{"paper_id": 26121240, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "Understanding the molecular basis of species formation is an important goal in evolutionary genetics, and Dobzhansky-Muller incompatibilities are thought to be a common source of postzygotic reproductive isolation between closely related lineages. However, the evolutionary forces that lead to the accumulation of such incompatibilities between diverging taxa are poorly understood. Segregation distorters are believed to be an important source of Dobzhansky-Muller incompatibilities between hybridizing species of Drosophila as well as hybridizing crop plants, but it remains unclear if these selfish genetic elements contribute to reproductive isolation in other taxa. Here, we collected viable sperm from first-generation hybrid male progeny of Mus musculus castaneus and M. m. domesticus, two subspecies of rodent in the earliest stages of speciation. We then genotyped millions of single nucleotide polymorphisms in these gamete pools and tested for a skew in the frequency of parental alleles across the genome. We show that segregation distorters are not measurable contributors to observed infertility in these hybrid males, despite sufficient statistical power to detect even weak segregation distortion with our novel method. Thus, reduced hybrid male fertility in crosses between these nascent species is attributable to other evolutionary forces.", "journal": "PloS one", "sentences": ["Understanding the molecular basis of species formation is an important goal in evolutionary genetics, and Dobzhansky-Muller incompatibilities are thought to be a common source of postzygotic reproductive isolation between closely related lineages.", "However, the evolutionary forces that lead to the accumulation of such incompatibilities between diverging taxa are poorly understood.", "Segregation distorters are believed to be an important source of Dobzhansky-Muller incompatibilities between hybridizing species of Drosophila as well as hybridizing crop plants, but it remains unclear if these selfish genetic elements contribute to reproductive isolation in other taxa.", "Here, we collected viable sperm from first-generation hybrid male progeny of Mus musculus castaneus and M. m. domesticus, two subspecies of rodent in the earliest stages of speciation.", "We then genotyped millions of single nucleotide polymorphisms in these gamete pools and tested for a skew in the frequency of parental alleles across the genome.", "We show that segregation distorters are not measurable contributors to observed infertility in these hybrid males, despite sufficient statistical power to detect even weak segregation distortion with our novel method.", "Thus, reduced hybrid male fertility in crosses between these nascent species is attributable to other evolutionary forces."], "title": "Direct Gamete Sequencing Reveals No Evidence for Segregation Distortion in House Mouse Hybrids."}
{"paper_id": 25202725, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "To evaluate the effects of extrusion process on the trans fatty acids (TFAs) formation in soybean crude oils, three different extrusion parameters, namely, extrusion temperature (80-160 \u00b0C), feed moisture (10-26%), and screw speed (100-500 rpm), were carried out. It was found that only five different types of TFAs were detected out using gas chromatography-mass spectrometry. Before the extrusion started, the initial amount of total TFAs was 3.04 g/100 g. However, after extruding under every level of any variable, the total amounts of TFAs were significantly higher than those in the control sample (P < 0.05). For example, taking the effect of extrusion temperature into account, we can find that the highest amount of total of trans fatty acid (TTFA) was 1.62 times the amount of that in the control sample, whereas the lowest amount of TTFA was 1.54 times the amount of that in the control sample. Importantly, it was observed that the amounts of every type of trans fatty acid were not continuously increasing with the increase of the level of any extrusion variable. This phenomenon demonstrated that the formation and diversification were intricate during extruding process and need to be further studied.", "journal": "TheScientificWorldJournal", "sentences": ["To evaluate the effects of extrusion process on the trans fatty acids (TFAs) formation in soybean crude oils, three different extrusion parameters, namely, extrusion temperature (80-160 \u00b0C), feed moisture (10-26%), and screw speed (100-500 rpm), were carried out.", "It was found that only five different types of TFAs were detected out using gas chromatography-mass spectrometry.", "Before the extrusion started, the initial amount of total TFAs was 3.04 g/100 g. However, after extruding under every level of any variable, the total amounts of TFAs were significantly higher than those in the control sample (P < 0.05).", "For example, taking the effect of extrusion temperature into account, we can find that the highest amount of total of trans fatty acid (TTFA) was 1.62 times the amount of that in the control sample, whereas the lowest amount of TTFA was 1.54 times the amount of that in the control sample.", "Importantly, it was observed that the amounts of every type of trans fatty acid were not continuously increasing with the increase of the level of any extrusion variable.", "This phenomenon demonstrated that the formation and diversification were intricate during extruding process and need to be further studied."], "title": "Effect of extruding full-fat soy flakes on trans fat content."}
{"paper_id": 24232458, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Ionizing radiation triggers diverse responses in human cells encompassing apoptosis, necrosis, stress-induced premature senescence (SIPS), autophagy, and endopolyploidy (e.g., multinucleation). Most of these responses result in loss of colony-forming ability in the clonogenic survival assay. However, not all modes of so-called clonogenic cell \"death\" are necessarily advantageous for therapeutic outcome in cancer radiotherapy. For example, the crosstalk between SIPS and autophagy is considered to influence the capacity of the tumor cells to maintain a prolonged state of growth inhibition that unfortunately can be succeeded by tumor regrowth and disease recurrence. Likewise, endopolyploid giant cells are able to segregate into near diploid descendants that continue mitotic activities. Herein we review the current knowledge on the roles that the p53 and p21(WAF1) tumor suppressors play in determining the fate of human fibroblasts (normal and Li-Fraumeni syndrome) and solid tumor-derived cells after exposure to ionizing radiation. In addition, we discuss the important role of WIP1, a p53-regulated oncogene, in the temporal regulation of the DNA damage response and its contribution to p53 dynamics post-irradiation. This article highlights the complexity of the DNA damage response and provides an impetus for rethinking the nature of cancer cell resistance to therapeutic agents.", "journal": "International journal of molecular sciences", "sentences": ["Ionizing radiation triggers diverse responses in human cells encompassing apoptosis, necrosis, stress-induced premature senescence (SIPS), autophagy, and endopolyploidy (e.g., multinucleation).", "Most of these responses result in loss of colony-forming ability in the clonogenic survival assay.", "However, not all modes of so-called clonogenic cell \"death\" are necessarily advantageous for therapeutic outcome in cancer radiotherapy.", "For example, the crosstalk between SIPS and autophagy is considered to influence the capacity of the tumor cells to maintain a prolonged state of growth inhibition that unfortunately can be succeeded by tumor regrowth and disease recurrence.", "Likewise, endopolyploid giant cells are able to segregate into near diploid descendants that continue mitotic activities.", "Herein we review the current knowledge on the roles that the p53 and p21(WAF1) tumor suppressors play in determining the fate of human fibroblasts (normal and Li-Fraumeni syndrome) and solid tumor-derived cells after exposure to ionizing radiation.", "In addition, we discuss the important role of WIP1, a p53-regulated oncogene, in the temporal regulation of the DNA damage response and its contribution to p53 dynamics post-irradiation.", "This article highlights the complexity of the DNA damage response and provides an impetus for rethinking the nature of cancer cell resistance to therapeutic agents."], "title": "Ionizing radiation-induced responses in human cells with differing TP53 status."}
{"paper_id": 27058143, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Emerging studies have shown that pharmacological activation of adenosine monophosphate-activated protein kinase (AMPK) produces potent analgesic effects in different animal pain models. Currently, the spinal molecular and synaptic mechanism by which AMPK regulates the pain signaling system remains unclear. To address this issue, we utilized the Cre-LoxP system to conditionally knockout the AMPK\u03b11 gene in the nervous system of mice. We demonstrated that AMPK\u03b11 is imperative for maintaining normal nociception, and mice deficient for AMPK\u03b11 exhibit mechanical allodynia. This is concomitantly associated with increased glutamatergic synaptic activities in neurons located in the superficial spinal dorsal horn, which results from the increased glutamate release from presynaptic terminals and function of ligand-gated glutamate receptors at the postsynaptic neurons. Additionally, AMPK\u03b11 knockout mice have increased activities of extracellular signal-regulated kinases (ERK) and p38 mitogen-activated protein kinases (p38), as well as elevated levels of interleukin-1\u03b2 (IL-1\u03b2), reactive oxygen species (ROS), and heme oxygenase 1 (HO-1) in the spinal dorsal horn. Systemic administration of a non-specific ROS scavenger (phenyl-N-tert-butylnitrone, PBN) or a HO-1 activator (Cobalt protoporphyrin IX, CoPP) attenuated allodynia in AMPK\u03b11 knockout mice. Bath-perfusion of the ROS scavenger or HO-1 activator effectively attenuated the increased ROS levels and glutamatergic synaptic activities in the spinal dorsal horn. Our findings suggest that ROS are the key down-stream signaling molecules mediating the behavioral hypersensitivity in AMPK\u03b11 knockout mice. Thus, targeting AMPK\u03b11 may represent an effective approach for the treatment of pathological pain conditions associated with neuroinflammation at the spinal dorsal horn.", "journal": "Neuroscience", "sentences": ["Emerging studies have shown that pharmacological activation of adenosine monophosphate-activated protein kinase (AMPK) produces potent analgesic effects in different animal pain models.", "Currently, the spinal molecular and synaptic mechanism by which AMPK regulates the pain signaling system remains unclear.", "To address this issue, we utilized the Cre-LoxP system to conditionally knockout the AMPK\u03b11 gene in the nervous system of mice.", "We demonstrated that AMPK\u03b11 is imperative for maintaining normal nociception, and mice deficient for AMPK\u03b11 exhibit mechanical allodynia.", "This is concomitantly associated with increased glutamatergic synaptic activities in neurons located in the superficial spinal dorsal horn, which results from the increased glutamate release from presynaptic terminals and function of ligand-gated glutamate receptors at the postsynaptic neurons.", "Additionally, AMPK\u03b11 knockout mice have increased activities of extracellular signal-regulated kinases (ERK) and p38 mitogen-activated protein kinases (p38), as well as elevated levels of interleukin-1\u03b2 (IL-1\u03b2), reactive oxygen species (ROS), and heme oxygenase 1 (HO-1) in the spinal dorsal horn.", "Systemic administration of a non-specific ROS scavenger (phenyl-N-tert-butylnitrone, PBN) or a HO-1 activator (Cobalt protoporphyrin IX, CoPP) attenuated allodynia in AMPK\u03b11 knockout mice.", "Bath-perfusion of the ROS scavenger or HO-1 activator effectively attenuated the increased ROS levels and glutamatergic synaptic activities in the spinal dorsal horn.", "Our findings suggest that ROS are the key down-stream signaling molecules mediating the behavioral hypersensitivity in AMPK\u03b11 knockout mice.", "Thus, targeting AMPK\u03b11 may represent an effective approach for the treatment of pathological pain conditions associated with neuroinflammation at the spinal dorsal horn."], "title": "AMPK\u03b11 knockout enhances nociceptive behaviors and spinal glutamatergic synaptic activities via production of reactive oxygen species in the spinal dorsal horn."}
{"paper_id": 26418811, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "Optical coherence tomography (OCT) is a useful imaging modality for detecting and monitoring diseases of the gastrointestinal tract and other tubular structures. The non-destructiveness of OCT enables time-serial studies in animal models. While turnkey commercial research OCT systems are plenty, researchers often require custom imaging probes. We describe the integration of a custom endoscope with a commercial swept-source OCT system and generalize this description to any imaging probe and OCT system. A numerical dispersion compensation method is also described. Example images demonstrate that OCT can visualize the mouse colon crypt structure and detect adenoma in vivo.", "journal": "PloS one", "sentences": ["Optical coherence tomography (OCT) is a useful imaging modality for detecting and monitoring diseases of the gastrointestinal tract and other tubular structures.", "The non-destructiveness of OCT enables time-serial studies in animal models.", "While turnkey commercial research OCT systems are plenty, researchers often require custom imaging probes.", "We describe the integration of a custom endoscope with a commercial swept-source OCT system and generalize this description to any imaging probe and OCT system.", "A numerical dispersion compensation method is also described.", "Example images demonstrate that OCT can visualize the mouse colon crypt structure and detect adenoma in vivo."], "title": "Expanding Functionality of Commercial Optical Coherence Tomography Systems by Integrating a Custom Endoscope."}
{"paper_id": 19892407, "labels": ["0", "0", "0", "0", "0"], "abstract": "Previous studies have found haplotypic association of HTR4 variants and schizophrenia. Examining case-control pairs, G-G of rs7713886 was associated with schizophrenia risk. The A-A-G-G-G-A-A rs9325104-rs1422636-rs7715569-rs6873382-rs7711800-rs10078551-rs2068190 haplotype was overrepresented in the schizophrenia cases. The associations were no longer significant after corrections for multiple comparisons. No association was found in the family sample.", "journal": "Psychiatry research", "sentences": ["Previous studies have found haplotypic association of HTR4 variants and schizophrenia.", "Examining case-control pairs, G-G of rs7713886 was associated with schizophrenia risk.", "The A-A-G-G-G-A-A rs9325104-rs1422636-rs7715569-rs6873382-rs7711800-rs10078551-rs2068190 haplotype was overrepresented in the schizophrenia cases.", "The associations were no longer significant after corrections for multiple comparisons.", "No association was found in the family sample."], "title": "Lack of association between HTR4 gene polymorphisms and schizophrenia in case-control and family-based samples."}
{"paper_id": 26957605, "labels": ["0", "1", "1", "1", "1"], "abstract": "C/D box small nucleolar RNAs (SNORDs) are small noncoding RNAs, and their best-understood function is to target the methyltransferase fibrillarin to rRNA (for example,SNORD27performs 2'-O-methylation of A27 in 18S rRNA). Unexpectedly, we found a subset of SNORDs, includingSNORD27, in soluble nuclear extract made under native conditions, where fibrillarin was not detected, indicating that a fraction of theSNORD27RNA likely forms a protein complex different from canonical snoRNAs found in the insoluble nuclear fraction. As part of this previously unidentified complex,SNORD27regulates the alternative splicing of the transcription factorE2F7pre-mRNA through direct RNA-RNA interaction without methylating the RNA, likely by competing withU1small nuclear ribonucleoprotein (snRNP). Furthermore, knockdown ofSNORD27activates previously \"silent\" exons in several other genes through base complementarity across the entireSNORD27sequence, not just the antisense boxes. Thus, some SNORDs likely function in both rRNA and pre-mRNA processing, which increases the repertoire of splicing regulators and links both processes.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["C/D box small nucleolar RNAs (SNORDs) are small noncoding RNAs, and their best-understood function is to target the methyltransferase fibrillarin to rRNA (for example,SNORD27performs 2'-O-methylation of A27 in 18S rRNA).", "Unexpectedly, we found a subset of SNORDs, includingSNORD27, in soluble nuclear extract made under native conditions, where fibrillarin was not detected, indicating that a fraction of theSNORD27RNA likely forms a protein complex different from canonical snoRNAs found in the insoluble nuclear fraction.", "As part of this previously unidentified complex,SNORD27regulates the alternative splicing of the transcription factorE2F7pre-mRNA through direct RNA-RNA interaction without methylating the RNA, likely by competing withU1small nuclear ribonucleoprotein (snRNP).", "Furthermore, knockdown ofSNORD27activates previously \"silent\" exons in several other genes through base complementarity across the entireSNORD27sequence, not just the antisense boxes.", "Thus, some SNORDs likely function in both rRNA and pre-mRNA processing, which increases the repertoire of splicing regulators and links both processes."], "title": "Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing."}
{"paper_id": 22938449, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Despite clinical advances in anticancer therapy, there is still a need for novel anticancer metabolites, with higher efficacy and lesser side effects. Oroxylum indicum (L.) Vent. is a small tree of the Bignoniaceae family which is well known for its food and medicinal properties. In present study, the chemopreventive properties of O. indicum hot and cold non-polar extracts (petroleum ether and chloroform) were investigated with MDA- MB-231 (cancer cells) and WRL-68 (non-tumor cells) by XTT assay. All the extracts, and particularly the petroleum ether hot extract (PHO), exhibited significantly (P<0.05) higher cytotoxicity in MDA-MB-231 when compared to WRL-68 cells. PHO was then tested for apoptosis induction in estrogen receptor (ER)-negative (MDA-MB-231) and ER-positive (MCF-7) breast cancer cells by cellular DNA fragmentation ELISA, where it proved more efficient in the MDA-MB-231 cells. Further, when PHO was tested for anti-metastatic potential in a cell migration inhibition assay, it exhibited beneficial effects. Thus non-polar extracts of O. indicum (especially PHO) can effectively target ER-negative breast cancer cells to induce apoptosis, without harming normal cells by cancer-specific cytotoxicity. Hence, it could be considered as an extract with candidate precursors to possibly harness or alleviate ER-negative breast cancer progression even in advanced stages of malignancy.", "journal": "Asian Pacific journal of cancer prevention : APJCP", "sentences": ["Despite clinical advances in anticancer therapy, there is still a need for novel anticancer metabolites, with higher efficacy and lesser side effects.", "Oroxylum indicum (L.) Vent.", "is a small tree of the Bignoniaceae family which is well known for its food and medicinal properties.", "In present study, the chemopreventive properties of O. indicum hot and cold non-polar extracts (petroleum ether and chloroform) were investigated with MDA- MB-231 (cancer cells) and WRL-68 (non-tumor cells) by XTT assay.", "All the extracts, and particularly the petroleum ether hot extract (PHO), exhibited significantly (P<0.05) higher cytotoxicity in MDA-MB-231 when compared to WRL-68 cells.", "PHO was then tested for apoptosis induction in estrogen receptor (ER)-negative (MDA-MB-231) and ER-positive (MCF-7) breast cancer cells by cellular DNA fragmentation ELISA, where it proved more efficient in the MDA-MB-231 cells.", "Further, when PHO was tested for anti-metastatic potential in a cell migration inhibition assay, it exhibited beneficial effects.", "Thus non-polar extracts of O. indicum (especially PHO) can effectively target ER-negative breast cancer cells to induce apoptosis, without harming normal cells by cancer-specific cytotoxicity.", "Hence, it could be considered as an extract with candidate precursors to possibly harness or alleviate ER-negative breast cancer progression even in advanced stages of malignancy."], "title": "Cytotoxicity, apoptosis induction and anti-metastatic potential of Oroxylum indicum in human breast cancer cells."}
{"paper_id": 26556853, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Increasing evidences have implicated somatic gain-of-function mutations at the telomerase reverse transcriptase (TERT) promoter as one of the major mechanisms that promote transcriptional activation of TERT and subsequently maintain telomere length in human cancers including glioma. To investigate the prognostic value of these mutations and telomere length, individually and their coexistence, in gliomas, we analyzed two somatic mutations C228T and C250T in the TERT promoter, relative telomere length (RTL), IDH1 mutation and MGMT methylation in 389 glioma patients, and explored their associations with patient characteristics and clinical outcomes. Our data showed that C228T and C250T mutations were found in 17.0% (66 of 389) and 11.8% (46 of 389) of gliomas, respectively, and these two mutations were mutually exclusive in this cancer. Moreover, they were significantly associated with WHO grade. We also found that the RTL was significant longer in gliomas than in meningiomas and normal brain tissues (Median, 0.89 vs. 0.44 and 0.50; P < 0.001), and demonstrated that the RTL was strongly correlated with tumor recurrence. Importantly, TERT promoter mutations or long RTL caused a significantly poorer survival than TERT wild-type or short RTL. Coexisting TERT promoter mutations and long RTL were more commonly associated with poor patient survival than they were individually. Notably, the patients with TERT promoter mutations particularly C228T or long RTL were resistant to radiotherapy. Collectively, TERT promoter mutations and long RTL are not only prognostic factors for poor clinical outcomes, but also the predictors of radiotherapy resistance in gliomas.", "journal": "Oncotarget", "sentences": ["Increasing evidences have implicated somatic gain-of-function mutations at the telomerase reverse transcriptase (TERT) promoter as one of the major mechanisms that promote transcriptional activation of TERT and subsequently maintain telomere length in human cancers including glioma.", "To investigate the prognostic value of these mutations and telomere length, individually and their coexistence, in gliomas, we analyzed two somatic mutations C228T and C250T in the TERT promoter, relative telomere length (RTL), IDH1 mutation and MGMT methylation in 389 glioma patients, and explored their associations with patient characteristics and clinical outcomes.", "Our data showed that C228T and C250T mutations were found in 17.0% (66 of 389) and 11.8% (46 of 389) of gliomas, respectively, and these two mutations were mutually exclusive in this cancer.", "Moreover, they were significantly associated with WHO grade.", "We also found that the RTL was significant longer in gliomas than in meningiomas and normal brain tissues (Median, 0.89 vs. 0.44 and 0.50; P < 0.001), and demonstrated that the RTL was strongly correlated with tumor recurrence.", "Importantly, TERT promoter mutations or long RTL caused a significantly poorer survival than TERT wild-type or short RTL.", "Coexisting TERT promoter mutations and long RTL were more commonly associated with poor patient survival than they were individually.", "Notably, the patients with TERT promoter mutations particularly C228T or long RTL were resistant to radiotherapy.", "Collectively, TERT promoter mutations and long RTL are not only prognostic factors for poor clinical outcomes, but also the predictors of radiotherapy resistance in gliomas."], "title": "TERT promoter mutations and long telomere length predict poor survival and radiotherapy resistance in gliomas."}
{"paper_id": 23405108, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Accumulation of \u03b1-synuclein (\u03b1-syn) fibrils in Lewy bodies and Lewy neurites is the pathological hallmark of Parkinson disease (PD). Ligands that bind \u03b1-syn fibrils could be utilized as imaging agents to improve the diagnosis of PD and to monitor disease progression. However, ligands for \u03b1-syn fibrils in PD brain tissue have not been previously identified and the feasibility of quantifying \u03b1-syn fibrils in brain tissue is unknown. We report the identification of the (125)I-labeled \u03b1-syn radioligand SIL23. [(125)I]SIL23 binds \u03b1-syn fibrils in postmortem brain tissue from PD patients as well as an \u03b1-syn transgenic mouse model for PD. The density of SIL23 binding sites correlates with the level of fibrillar \u03b1-syn in PD brain tissue, and [(125)I]SIL23 binding site densities in brain tissue are sufficiently high to enable in vivo imaging with high affinity ligands. These results identify a SIL23 binding site on \u03b1-syn fibrils that is a feasible target for development of an \u03b1-syn imaging agent. The affinity of SIL23 for \u03b1-syn and its selectivity for \u03b1-syn versus A\u03b2 and tau fibrils is not optimal for imaging fibrillar \u03b1-syn in vivo, but we show that SIL23 competitive binding assays can be used to screen additional ligands for suitable affinity and selectivity, which will accelerate the development of an \u03b1-syn imaging agent for PD.", "journal": "PloS one", "sentences": ["Accumulation of \u03b1-synuclein (\u03b1-syn) fibrils in Lewy bodies and Lewy neurites is the pathological hallmark of Parkinson disease (PD).", "Ligands that bind \u03b1-syn fibrils could be utilized as imaging agents to improve the diagnosis of PD and to monitor disease progression.", "However, ligands for \u03b1-syn fibrils in PD brain tissue have not been previously identified and the feasibility of quantifying \u03b1-syn fibrils in brain tissue is unknown.", "We report the identification of the (125)I-labeled \u03b1-syn radioligand SIL23.", "[(125)I]SIL23 binds \u03b1-syn fibrils in postmortem brain tissue from PD patients as well as an \u03b1-syn transgenic mouse model for PD.", "The density of SIL23 binding sites correlates with the level of fibrillar \u03b1-syn in PD brain tissue, and [(125)I]SIL23 binding site densities in brain tissue are sufficiently high to enable in vivo imaging with high affinity ligands.", "These results identify a SIL23 binding site on \u03b1-syn fibrils that is a feasible target for development of an \u03b1-syn imaging agent.", "The affinity of SIL23 for \u03b1-syn and its selectivity for \u03b1-syn versus A\u03b2 and tau fibrils is not optimal for imaging fibrillar \u03b1-syn in vivo, but we show that SIL23 competitive binding assays can be used to screen additional ligands for suitable affinity and selectivity, which will accelerate the development of an \u03b1-syn imaging agent for PD."], "title": "Binding of the radioligand SIL23 to \u03b1-synuclein fibrils in Parkinson disease brain tissue establishes feasibility and screening approaches for developing a Parkinson disease imaging agent."}
{"paper_id": 20613843, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Histone lysine acetylation and methylation have an important role during gene transcription in a chromatin context. Knowledge concerning the types of protein modules that can interact with acetyl-lysine has so far been limited to bromodomains. Recently, a tandem plant homeodomain (PHD) finger (PHD1-PHD2, or PHD12) of human DPF3b, which functions in association with the BAF chromatin remodelling complex to initiate gene transcription during heart and muscle development, was reported to bind histones H3 and H4 in an acetylation-sensitive manner, making it the first alternative to bromodomains for acetyl-lysine binding. Here we report the structural mechanism of acetylated histone binding by the double PHD fingers of DPF3b. Our three-dimensional solution structures and biochemical analysis of DPF3b highlight the molecular basis of the integrated tandem PHD finger, which acts as one functional unit in the sequence-specific recognition of lysine-14-acetylated histone H3 (H3K14ac). Whereas the interaction with H3 is promoted by acetylation at lysine 14, it is inhibited by methylation at lysine 4, and these opposing influences are important during transcriptional activation of the mouse DPF3b target genes Pitx2 and Jmjd1c. Binding of this tandem protein module to chromatin can thus be regulated by different histone modifications during the initiation of gene transcription.", "journal": "Nature", "sentences": ["Histone lysine acetylation and methylation have an important role during gene transcription in a chromatin context.", "Knowledge concerning the types of protein modules that can interact with acetyl-lysine has so far been limited to bromodomains.", "Recently, a tandem plant homeodomain (PHD) finger (PHD1-PHD2, or PHD12) of human DPF3b, which functions in association with the BAF chromatin remodelling complex to initiate gene transcription during heart and muscle development, was reported to bind histones H3 and H4 in an acetylation-sensitive manner, making it the first alternative to bromodomains for acetyl-lysine binding.", "Here we report the structural mechanism of acetylated histone binding by the double PHD fingers of DPF3b.", "Our three-dimensional solution structures and biochemical analysis of DPF3b highlight the molecular basis of the integrated tandem PHD finger, which acts as one functional unit in the sequence-specific recognition of lysine-14-acetylated histone H3 (H3K14ac).", "Whereas the interaction with H3 is promoted by acetylation at lysine 14, it is inhibited by methylation at lysine 4, and these opposing influences are important during transcriptional activation of the mouse DPF3b target genes Pitx2 and Jmjd1c.", "Binding of this tandem protein module to chromatin can thus be regulated by different histone modifications during the initiation of gene transcription."], "title": "Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b."}
{"paper_id": 22017755, "labels": ["0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Soil salinity is a major abiotic stress that limits plant growth and agriculture productivity. To cope with salt stress, plants have evolved complex salt-responsive signaling and metabolic processes at the cellular, organ, and whole-plant levels. Investigation of the physiological and molecular mechanisms underlying plant salinity tolerance will provide valuable information for effective engineering strategies. Current proteomics provides a high-throughput approach to study sophisticated molecular networks in plants. In this review, we describe a salt-responsive protein database by an integrated analysis of proteomics-based studies. The database contains 2171 salt-responsive protein identities representing 561 unique proteins. These proteins have been identified from leaves, roots, shoots, seedlings, unicells, grains, hypocotyls, radicles, and panicles from 34 plant species. The identified proteins provide invaluable information toward understanding the complex and fine-tuned plant salt-tolerance mechanisms in photosynthesis, reactive oxygen species (ROS) scavenging, ion homeostasis, osmotic modulation, signaling transduction, transcription, protein synthesis/turnover, cytoskeleton dynamics, and cross-tolerance to different stress conditions.", "journal": "Journal of proteome research", "sentences": ["Soil salinity is a major abiotic stress that limits plant growth and agriculture productivity.", "To cope with salt stress, plants have evolved complex salt-responsive signaling and metabolic processes at the cellular, organ, and whole-plant levels.", "Investigation of the physiological and molecular mechanisms underlying plant salinity tolerance will provide valuable information for effective engineering strategies.", "Current proteomics provides a high-throughput approach to study sophisticated molecular networks in plants.", "In this review, we describe a salt-responsive protein database by an integrated analysis of proteomics-based studies.", "The database contains 2171 salt-responsive protein identities representing 561 unique proteins.", "These proteins have been identified from leaves, roots, shoots, seedlings, unicells, grains, hypocotyls, radicles, and panicles from 34 plant species.", "The identified proteins provide invaluable information toward understanding the complex and fine-tuned plant salt-tolerance mechanisms in photosynthesis, reactive oxygen species (ROS) scavenging, ion homeostasis, osmotic modulation, signaling transduction, transcription, protein synthesis/turnover, cytoskeleton dynamics, and cross-tolerance to different stress conditions."], "title": "Mechanisms of plant salt response: insights from proteomics."}
{"paper_id": 26271832, "labels": ["0", "0", "0", "0", "1", "1"], "abstract": "Many in the scientific community agree that a randomized, placebo-controlled trial would offer the most scientifically rigorous study design for establishing the efficacy of a Group B Streptococcus (GBS) vaccine administered to pregnant women for the prevention of invasive GBS disease in young infants. There are compelling reasons to conduct such a trial in low-middle income countries (LMICs) with a high burden of disease, such as South Africa, and to adopt an add-on trial design in which participants are randomized to receive the GBS vaccine or placebo in addition to the locally available standard of care. Yet there is a longstanding debate about whether trials in LMICs should offer participants the worldwide best available standard of care. In this article, we examine both the risk-benefit profile and the potential for exploitation with an add-on trial design in the context of the locally available standard of care in South Africa. Our analysis suggests that providing the local standard of care to participants in this case may be not only more scientifically valuable but also more ethically acceptable than attempting to provide the worldwide best available standard of care in the South African setting. Moreover, the example of GBS in the South African setting can help to elucidate important ethical considerations for determining the acceptability of testing vaccine efficacy in the context of locally available rather than the worldwide best available standard of care in Phase III trials of other new maternal vaccines.", "journal": "Vaccine", "sentences": ["Many in the scientific community agree that a randomized, placebo-controlled trial would offer the most scientifically rigorous study design for establishing the efficacy of a Group B Streptococcus (GBS) vaccine administered to pregnant women for the prevention of invasive GBS disease in young infants.", "There are compelling reasons to conduct such a trial in low-middle income countries (LMICs) with a high burden of disease, such as South Africa, and to adopt an add-on trial design in which participants are randomized to receive the GBS vaccine or placebo in addition to the locally available standard of care.", "Yet there is a longstanding debate about whether trials in LMICs should offer participants the worldwide best available standard of care.", "In this article, we examine both the risk-benefit profile and the potential for exploitation with an add-on trial design in the context of the locally available standard of care in South Africa.", "Our analysis suggests that providing the local standard of care to participants in this case may be not only more scientifically valuable but also more ethically acceptable than attempting to provide the worldwide best available standard of care in the South African setting.", "Moreover, the example of GBS in the South African setting can help to elucidate important ethical considerations for determining the acceptability of testing vaccine efficacy in the context of locally available rather than the worldwide best available standard of care in Phase III trials of other new maternal vaccines."], "title": "Ethical considerations for designing GBS maternal vaccine efficacy trials in low-middle income countries."}
{"paper_id": 22125541, "labels": ["0", "0", "0", "0", "0"], "abstract": "According to prevailing views, brain organization is modulated by practice, e.g., during musical or linguistic training. Most recent results, using both neuropsychological tests and brain measures, revealed an intriguing connection between musical aptitude and second language linguistic abilities. A significant relationship between higher musical aptitude, better second language pronunciation skills, accurate chord discrimination ability, and more prominent sound-change-evoked brain activation in response to musical stimuli was found. Moreover, regular music practice may also have a modulatory effect on the brain's linguistic organization and alter hemispheric functioning in those who have regularly practised music for years. These findings, together with their implications, will be introduced and elaborated in our review.", "journal": "Frontiers in psychology", "sentences": ["According to prevailing views, brain organization is modulated by practice, e.g., during musical or linguistic training.", "Most recent results, using both neuropsychological tests and brain measures, revealed an intriguing connection between musical aptitude and second language linguistic abilities.", "A significant relationship between higher musical aptitude, better second language pronunciation skills, accurate chord discrimination ability, and more prominent sound-change-evoked brain activation in response to musical stimuli was found.", "Moreover, regular music practice may also have a modulatory effect on the brain's linguistic organization and alter hemispheric functioning in those who have regularly practised music for years.", "These findings, together with their implications, will be introduced and elaborated in our review."], "title": "The Interplay between Musical and Linguistic Aptitudes: A Review."}
{"paper_id": 20222668, "labels": ["0", "0", "0", "0", "0", "0", "1", "0"], "abstract": "We investigate the cause of the low activity of mitochondrial complex I found in ob/ob mice with nonalcoholic fatty liver disease. In mitochondrial proteins from ob/ob mice, we assessed complex I activity, fully assembled complex I, and its subunits, oxygen consumption, gene expression of complex I subunits, and oxidative damage to DNA. In mitochondrial proteins from the liver of ob/ob mice, complex I activity, fully assembly of this complex and complex I subunits were markedly reduced. Likewise, gene expression of mitochondrial DNA-encoded subunits was significantly decreased in obese mice, but not nuclear DNA-encoded subunits. Treatment of obese mice with uric acid, anti-TNFalpha antibody or a mimic of manganese superoxide dismutase normalized all these abnormalities. \"In vitro\" addition of peroxynitrite to mitochondrial proteins from wild-type mice reproduced the abnormalities found in ob/ob mice (decreased complex I activity, the amount of fully assembled complex I, and its subunits, and mitochondrial oxygen consumption). Low activity of complex I found in ob/ob mice can be ascribed to a reduced amount of fully assembled complex, which may be attributed to degradation and reduced synthesis of its subunits by peroxynitrite. Exposure of mitochondrial proteins from normal mice to peroxynitrite reproduced the proteomic abnormalities present in ob/ob mice.", "journal": "Journal of proteome research", "sentences": ["We investigate the cause of the low activity of mitochondrial complex I found in ob/ob mice with nonalcoholic fatty liver disease.", "In mitochondrial proteins from ob/ob mice, we assessed complex I activity, fully assembled complex I, and its subunits, oxygen consumption, gene expression of complex I subunits, and oxidative damage to DNA.", "In mitochondrial proteins from the liver of ob/ob mice, complex I activity, fully assembly of this complex and complex I subunits were markedly reduced.", "Likewise, gene expression of mitochondrial DNA-encoded subunits was significantly decreased in obese mice, but not nuclear DNA-encoded subunits.", "Treatment of obese mice with uric acid, anti-TNFalpha antibody or a mimic of manganese superoxide dismutase normalized all these abnormalities.", "\"In vitro\" addition of peroxynitrite to mitochondrial proteins from wild-type mice reproduced the abnormalities found in ob/ob mice (decreased complex I activity, the amount of fully assembled complex I, and its subunits, and mitochondrial oxygen consumption).", "Low activity of complex I found in ob/ob mice can be ascribed to a reduced amount of fully assembled complex, which may be attributed to degradation and reduced synthesis of its subunits by peroxynitrite.", "Exposure of mitochondrial proteins from normal mice to peroxynitrite reproduced the proteomic abnormalities present in ob/ob mice."], "title": "Mitochondrial complex I subunits are decreased in murine nonalcoholic fatty liver disease: implication of peroxynitrite."}
{"paper_id": 24734647, "labels": ["0", "0", "0", "0", "0"], "abstract": "In this paper, a facile synthetic route for the preparation of NaLn(MoO4)2:Eu3+ (Ln = Gd, Y) nanocrystals by a hydrothermal method is reported. The NaLn(MoO4)2:Eu3+ (Ln = Gd, Y) micro-powders were synthesized by a high temperature solid-state reaction. The optical properties of Eu3+ as a local structural probe are analyzed when being incorporated into NaLn(MoO4)2 (Ln = Gd, Y) micro-powders and nanocrystals. In NaLn(MoO4)2:Eu3+ (Ln = Gd, Y), the substitution of Ln3+ by Eu3+ is confirmed and the point symmetry of the site and crystal structure are analyzed. The luminescence mechanism and the size dependence of their fluorescence properties in NaLn(MoO4)2:Eu3+ (Ln = Gd, Y) micro-powders and nanocrystals are also discussed in detail.", "journal": "Journal of nanoscience and nanotechnology", "sentences": ["In this paper, a facile synthetic route for the preparation of NaLn(MoO4)2:Eu3+ (Ln = Gd, Y) nanocrystals by a hydrothermal method is reported.", "The NaLn(MoO4)2:Eu3+ (Ln = Gd, Y) micro-powders were synthesized by a high temperature solid-state reaction.", "The optical properties of Eu3+ as a local structural probe are analyzed when being incorporated into NaLn(MoO4)2 (Ln = Gd, Y) micro-powders and nanocrystals.", "In NaLn(MoO4)2:Eu3+ (Ln = Gd, Y), the substitution of Ln3+ by Eu3+ is confirmed and the point symmetry of the site and crystal structure are analyzed.", "The luminescence mechanism and the size dependence of their fluorescence properties in NaLn(MoO4)2:Eu3+ (Ln = Gd, Y) micro-powders and nanocrystals are also discussed in detail."], "title": "Photoluminescence properties and spectral structure analysis of NaLn(MoO4)2:Eu3+ (Ln = Gd, Y) phosphors."}
{"paper_id": 26986133, "labels": ["0", "0", "0", "0", "0"], "abstract": "Primary intraosseous cavernous hemangiomas (PICHs) are benign vascular tumors that may involve any part of the body. PICH occurs more frequently in the spine and less commonly in skull. The earliest description in the English literature was in 1845 by Toynbee, who reported a vascular tumor arising in the confines of the parietal bone. Skull PICHs do not always have typical radiologic features and should always be considered in the differential diagnosis of malignant skull lesions. We now reviewed and analyzed related literatures in detail with reporting a rare case of PICH in the left front bone that was surgically resected.", "journal": "Medicine", "sentences": ["Primary intraosseous cavernous hemangiomas (PICHs) are benign vascular tumors that may involve any part of the body.", "PICH occurs more frequently in the spine and less commonly in skull.", "The earliest description in the English literature was in 1845 by Toynbee, who reported a vascular tumor arising in the confines of the parietal bone.", "Skull PICHs do not always have typical radiologic features and should always be considered in the differential diagnosis of malignant skull lesions.", "We now reviewed and analyzed related literatures in detail with reporting a rare case of PICH in the left front bone that was surgically resected."], "title": "Primary Intraosseous Cavernous Hemangioma in the Skull."}
{"paper_id": 26973245, "labels": ["0", "0", "0", "1", "0", "0", "0", "0", "1"], "abstract": "Sterol-regulatory element-binding proteins (SREBPs) are key transcription factors regulating cholesterol and fatty acid biosynthesis. SREBP activity is tightly regulated to maintain lipid homeostasis, and is modulated upon extracellular stimuli such as growth factors. While the homeostatic SREBP regulation is well studied, stimuli-dependent regulatory mechanisms are still elusive. Here we demonstrate that SREBPs are regulated by a previously uncharacterized mechanism through transforming growth factor-\u03b2 activated kinase 1 (TAK1), a signaling molecule of inflammation. We found that TAK1 binds to and inhibits mature forms of SREBPs. In an in vivo setting, hepatocyte-specific Tak1 deletion upregulates liver lipid deposition and lipogenic enzymes in the mouse model. Furthermore, hepatic Tak1 deficiency causes steatosis pathologies including elevated blood triglyceride and cholesterol levels, which are established risk factors for the development of hepatocellular carcinoma (HCC) and are indeed correlated with Tak1-deficiency-induced HCC development. Pharmacological inhibition of SREBPs alleviated the steatosis and reduced the expression level of the HCC marker gene in the Tak1-deficient liver. Thus, TAK1 regulation of SREBP critically contributes to the maintenance of liver homeostasis to prevent steatosis, which is a potentially important mechanism to prevent HCC development.", "journal": "Oncogene", "sentences": ["Sterol-regulatory element-binding proteins (SREBPs) are key transcription factors regulating cholesterol and fatty acid biosynthesis.", "SREBP activity is tightly regulated to maintain lipid homeostasis, and is modulated upon extracellular stimuli such as growth factors.", "While the homeostatic SREBP regulation is well studied, stimuli-dependent regulatory mechanisms are still elusive.", "Here we demonstrate that SREBPs are regulated by a previously uncharacterized mechanism through transforming growth factor-\u03b2 activated kinase 1 (TAK1), a signaling molecule of inflammation.", "We found that TAK1 binds to and inhibits mature forms of SREBPs.", "In an in vivo setting, hepatocyte-specific Tak1 deletion upregulates liver lipid deposition and lipogenic enzymes in the mouse model.", "Furthermore, hepatic Tak1 deficiency causes steatosis pathologies including elevated blood triglyceride and cholesterol levels, which are established risk factors for the development of hepatocellular carcinoma (HCC) and are indeed correlated with Tak1-deficiency-induced HCC development.", "Pharmacological inhibition of SREBPs alleviated the steatosis and reduced the expression level of the HCC marker gene in the Tak1-deficient liver.", "Thus, TAK1 regulation of SREBP critically contributes to the maintenance of liver homeostasis to prevent steatosis, which is a potentially important mechanism to prevent HCC development."], "title": "TAK1 regulates hepatic lipid homeostasis through SREBP."}
{"paper_id": 22053217, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Tissue-specific manipulation of known copper transport genes in Drosophila tissues results in phenotypes that are presumably due to an alteration in copper levels in the targeted cells. However direct confirmation of this has to date been technically challenging. Measures of cellular copper content such as expression levels of copper-responsive genes or cuproenzyme activity levels, while useful, are indirect. First-generation copper-sensitive fluorophores show promise but currently lack the sensitivity required to detect subtle changes in copper levels. Moreover such techniques do not provide information regarding other relevant biometals such as zinc or iron. Traditional techniques for measuring elemental composition such as inductively coupled plasma mass spectroscopy are not sensitive enough for use with the small tissue amounts available in Drosophila research. Here we present synchrotron x-ray fluorescence microscopy analysis of two different Drosophila tissues, the larval wing imaginal disc, and sectioned adult fly heads and show that this technique can be used to detect changes in tissue copper levels caused by targeted manipulation of known copper homeostasis genes.", "journal": "PloS one", "sentences": ["Tissue-specific manipulation of known copper transport genes in Drosophila tissues results in phenotypes that are presumably due to an alteration in copper levels in the targeted cells.", "However direct confirmation of this has to date been technically challenging.", "Measures of cellular copper content such as expression levels of copper-responsive genes or cuproenzyme activity levels, while useful, are indirect.", "First-generation copper-sensitive fluorophores show promise but currently lack the sensitivity required to detect subtle changes in copper levels.", "Moreover such techniques do not provide information regarding other relevant biometals such as zinc or iron.", "Traditional techniques for measuring elemental composition such as inductively coupled plasma mass spectroscopy are not sensitive enough for use with the small tissue amounts available in Drosophila research.", "Here we present synchrotron x-ray fluorescence microscopy analysis of two different Drosophila tissues, the larval wing imaginal disc, and sectioned adult fly heads and show that this technique can be used to detect changes in tissue copper levels caused by targeted manipulation of known copper homeostasis genes."], "title": "Detection of genetically altered copper levels in Drosophila tissues by synchrotron x-ray fluorescence microscopy."}
{"paper_id": 22733746, "labels": ["0", "0", "1", "0", "0", "1", "1"], "abstract": "By microscopic analysis of fluorescent-labeled GalR, a regulon-specific transcription factor in Escherichia coli, we observed that GalR is present in the cell as aggregates (one to three fluorescent foci per cell) in nongrowing cells. To investigate whether these foci represent GalR-mediated association of some of the GalR specific DNA binding sites (gal operators), we used the chromosome conformation capture (3C) method in vivo. Our 3C data demonstrate that, in stationary phase cells, many of the operators distributed around the chromosome are interacted. By the use of atomic force microscopy, we showed that the observed remote chromosomal interconnections occur by direct interactions between DNA-bound GalR not involving any other factors. Mini plasmid DNA circles with three or five operators positioned at defined loci showed GalR-dependent loops of expected sizes of the intervening DNA segments. Our findings provide unique evidence that a transcription factor participates in organizing the chromosome in a three-dimensional structure. We believe that these chromosomal connections increase local concentration of GalR for coordinating the regulation of widely separated target genes, and organize the chromosome structure in space, thereby likely contributing to chromosome compaction.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["By microscopic analysis of fluorescent-labeled GalR, a regulon-specific transcription factor in Escherichia coli, we observed that GalR is present in the cell as aggregates (one to three fluorescent foci per cell) in nongrowing cells.", "To investigate whether these foci represent GalR-mediated association of some of the GalR specific DNA binding sites (gal operators), we used the chromosome conformation capture (3C) method in vivo.", "Our 3C data demonstrate that, in stationary phase cells, many of the operators distributed around the chromosome are interacted.", "By the use of atomic force microscopy, we showed that the observed remote chromosomal interconnections occur by direct interactions between DNA-bound GalR not involving any other factors.", "Mini plasmid DNA circles with three or five operators positioned at defined loci showed GalR-dependent loops of expected sizes of the intervening DNA segments.", "Our findings provide unique evidence that a transcription factor participates in organizing the chromosome in a three-dimensional structure.", "We believe that these chromosomal connections increase local concentration of GalR for coordinating the regulation of widely separated target genes, and organize the chromosome structure in space, thereby likely contributing to chromosome compaction."], "title": "Galactose repressor mediated intersegmental chromosomal connections in Escherichia coli."}
{"paper_id": 26578599, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Many effective agents used in cancer chemotherapy cause DNA interstrand crosslinks (ICLs), which covalently link both strands of the double helix together resulting in cytotoxicity. ICLs are thought to be processed by proteins from a variety of DNA repair pathways; however, a clear understanding of ICL recognition and repair processing in human cells is lacking. Previously, we found that the high mobility group box 1 (HMGB1) protein bound to triplex-directed psoralen ICLs (TFO-ICLs) in vitro, cooperatively with NER damage recognition proteins, promoted removal of UVC-induced lesions and facilitated error-free repair of TFO-ICLs in mouse fibroblasts. Here, we demonstrate that HMGB1 recognizes TFO-ICLs in human cells, and its depletion increases ICL-induced mutagenesis in human cells without altering the mutation spectra. In contrast, HMGB1 depletion in XPA-deficient human cells significantly altered the ICL-induced mutation spectrum from predominantly T\u2192A to T\u2192G transversions. Moreover, the recruitment of XPA and HMGB1 to the ICLs is co-dependent. Finally, we show that HMGB1 specifically introduces negative supercoils in ICL-containing plasmids in HeLa cell extracts. Taken together, our data suggest that in human cells, HMGB1 functions in association with XPA on ICLs and facilitates the formation of a favorable architectural environment for ICL repair processing.", "journal": "Nucleic acids research", "sentences": ["Many effective agents used in cancer chemotherapy cause DNA interstrand crosslinks (ICLs), which covalently link both strands of the double helix together resulting in cytotoxicity.", "ICLs are thought to be processed by proteins from a variety of DNA repair pathways; however, a clear understanding of ICL recognition and repair processing in human cells is lacking.", "Previously, we found that the high mobility group box 1 (HMGB1) protein bound to triplex-directed psoralen ICLs (TFO-ICLs) in vitro, cooperatively with NER damage recognition proteins, promoted removal of UVC-induced lesions and facilitated error-free repair of TFO-ICLs in mouse fibroblasts.", "Here, we demonstrate that HMGB1 recognizes TFO-ICLs in human cells, and its depletion increases ICL-induced mutagenesis in human cells without altering the mutation spectra.", "In contrast, HMGB1 depletion in XPA-deficient human cells significantly altered the ICL-induced mutation spectrum from predominantly T\u2192A to T\u2192G transversions.", "Moreover, the recruitment of XPA and HMGB1 to the ICLs is co-dependent.", "Finally, we show that HMGB1 specifically introduces negative supercoils in ICL-containing plasmids in HeLa cell extracts.", "Taken together, our data suggest that in human cells, HMGB1 functions in association with XPA on ICLs and facilitates the formation of a favorable architectural environment for ICL repair processing."], "title": "HMGB1 interacts with XPA to facilitate the processing of DNA interstrand crosslinks in human cells."}
{"paper_id": 25161285, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "The maintenance of the resident adult neural stem/progenitor cell (NSPC) pool depends on the precise balance of proliferation, differentiation, and maintenance of the undifferentiated state. Identifying the mechanisms that regulate this balance in adult hippocampal NSPCs can provide insight into basic stem cell self-renewal principles important for tissue homeostasis and preventing tumor formation. Pharmacological inhibition of histone deacetylases (HDACs), a class of histone-modifying enzymes, have promising effects in cancer cells, yet the specific roles of individual HDACs in stem cell proliferation is unclear. Here using conditional KO (cKO) mice and in vitro cell culture, we show that histone deacetylase 3 (HDAC3) is required for the proliferation of adult NSPCs. Detailed cell cycle analysis of NSPCs from Hdac3 cKO mice reveals a defect in cell cycle progression through the gap 2/mitosis (G2/M) but not the S phase. Moreover, HDAC3 controls G2/M phase progression mainly through posttranslational stabilization of the G2/M cyclin-dependent kinase 1 (CDK1). These results demonstrate that HDAC3 plays a critical role in NSPC proliferation and suggest that strategies aimed at pharmacological modulation of HDAC3 may be beneficial for tissue regeneration and controlling tumor cell growth.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["The maintenance of the resident adult neural stem/progenitor cell (NSPC) pool depends on the precise balance of proliferation, differentiation, and maintenance of the undifferentiated state.", "Identifying the mechanisms that regulate this balance in adult hippocampal NSPCs can provide insight into basic stem cell self-renewal principles important for tissue homeostasis and preventing tumor formation.", "Pharmacological inhibition of histone deacetylases (HDACs), a class of histone-modifying enzymes, have promising effects in cancer cells, yet the specific roles of individual HDACs in stem cell proliferation is unclear.", "Here using conditional KO (cKO) mice and in vitro cell culture, we show that histone deacetylase 3 (HDAC3) is required for the proliferation of adult NSPCs.", "Detailed cell cycle analysis of NSPCs from Hdac3 cKO mice reveals a defect in cell cycle progression through the gap 2/mitosis (G2/M) but not the S phase.", "Moreover, HDAC3 controls G2/M phase progression mainly through posttranslational stabilization of the G2/M cyclin-dependent kinase 1 (CDK1).", "These results demonstrate that HDAC3 plays a critical role in NSPC proliferation and suggest that strategies aimed at pharmacological modulation of HDAC3 may be beneficial for tissue regeneration and controlling tumor cell growth."], "title": "HDAC3 controls gap 2/mitosis progression in adult neural stem/progenitor cells by regulating CDK1 levels."}
{"paper_id": 26317649, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "In the current study we examined the combination of SAHA and SBE13 in cancer and non-cancer cells. HeLa cells displayed a synergistically reduced cell proliferation, which was much weaker in hTERT-RPE1 or NIH-3T3 cells. Cell cycle distribution differed in HeLa, hTERT-RPE1 and NIH-3T3 cells. SAHA-treated HeLa cells showed slightly increasing cell numbers in G2/M phase, but after combination with SBE13 strongly elevated cell numbers in G2/M and S phase, accompanied by decreasing G0/G1 percentages. hTERT-RPE1 and NIH-3T3 cells showed strongly enriched cell numbers in G0/G1 phase. Western blot and quantitative real time analyses revealed reduced Plk1 mRNA and protein in all cells. p21 protein was strongly induced in cancer, but not in non-cancer cells, corresponding to a different localization in immunofluorescence studies. Additionally, these revealed an abundantly present pRb protein in HeLa cells after any treatment but almost completely vanished pRb staining in treated hTERT-RPE1 cells. These differences could be approved in Western blots against Parp and Caspase 3, which were activated in HeLa, but not in hTERT-RPE1 cells. Thus, we observed for the first time a differential effect of cancer versus non-cancer cells after treatment with SAHA and SBE13, which might be due to the dual role of p21.", "journal": "Oncotarget", "sentences": ["In the current study we examined the combination of SAHA and SBE13 in cancer and non-cancer cells.", "HeLa cells displayed a synergistically reduced cell proliferation, which was much weaker in hTERT-RPE1 or NIH-3T3 cells.", "Cell cycle distribution differed in HeLa, hTERT-RPE1 and NIH-3T3 cells.", "SAHA-treated HeLa cells showed slightly increasing cell numbers in G2/M phase, but after combination with SBE13 strongly elevated cell numbers in G2/M and S phase, accompanied by decreasing G0/G1 percentages.", "hTERT-RPE1 and NIH-3T3 cells showed strongly enriched cell numbers in G0/G1 phase.", "Western blot and quantitative real time analyses revealed reduced Plk1 mRNA and protein in all cells.", "p21 protein was strongly induced in cancer, but not in non-cancer cells, corresponding to a different localization in immunofluorescence studies.", "Additionally, these revealed an abundantly present pRb protein in HeLa cells after any treatment but almost completely vanished pRb staining in treated hTERT-RPE1 cells.", "These differences could be approved in Western blots against Parp and Caspase 3, which were activated in HeLa, but not in hTERT-RPE1 cells.", "Thus, we observed for the first time a differential effect of cancer versus non-cancer cells after treatment with SAHA and SBE13, which might be due to the dual role of p21."], "title": "Survival of primary, but not of cancer cells after combined Plk1-HDAC inhibition."}
{"paper_id": 26317465, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "DNA-demethylating agents have shown clinical anti-tumor efficacy via an unknown mechanism of action. Using a combination of experimental and bioinformatics analyses in colorectal cancer cells, we demonstrate that low-dose 5-AZA-CdR targets colorectal cancer-initiating cells (CICs) by inducing viral mimicry. This is associated with induction of dsRNAs derived at\u00a0least in part from endogenous retroviral elements, activation of the MDA5/MAVS RNA recognition pathway, and downstream activation of IRF7. Indeed, disruption of virus recognition pathways, by individually knocking down MDA5, MAVS, or IRF7, inhibits the\u00a0ability of 5-AZA-CdR to target colorectal CICs and significantly decreases 5-AZA-CdR long-term growth effects. Moreover, transfection of dsRNA into CICs can mimic the effects of 5-AZA-CdR. Together, our results represent a major shift in understanding the anti-tumor mechanisms of DNA-demethylating agents and highlight the MDA5/MAVS/IRF7 pathway as a potentially druggable target against CICs.", "journal": "Cell", "sentences": ["DNA-demethylating agents have shown clinical anti-tumor efficacy via an unknown mechanism of action.", "Using a combination of experimental and bioinformatics analyses in colorectal cancer cells, we demonstrate that low-dose 5-AZA-CdR targets colorectal cancer-initiating cells (CICs) by inducing viral mimicry.", "This is associated with induction of dsRNAs derived at\u00a0least in part from endogenous retroviral elements, activation of the MDA5/MAVS RNA recognition pathway, and downstream activation of IRF7.", "Indeed, disruption of virus recognition pathways, by individually knocking down MDA5, MAVS, or IRF7, inhibits the\u00a0ability of 5-AZA-CdR to target colorectal CICs and significantly decreases 5-AZA-CdR long-term growth effects.", "Moreover, transfection of dsRNA into CICs can mimic the effects of 5-AZA-CdR.", "Together, our results represent a major shift in understanding the anti-tumor mechanisms of DNA-demethylating agents and highlight the MDA5/MAVS/IRF7 pathway as a potentially druggable target against CICs."], "title": "DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts."}
{"paper_id": 27434210, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Recent studies have demonstrated substantial effects of environmental stress that vary among clones. Exposure to ultraviolet radiation (UV) is an important abiotic stressor that is highly variable in aquatic ecosystems due to diel and seasonal variations in incident sunlight as well as to differences in the UV transparency of water among water bodies, the depth distribution of organisms, and the ability of organisms to detect and respond to UV. In contrast to the convention that all UV is damaging, evidence is accumulating for the beneficial effects of exposure to low levels of UV radiation. Whereas UV has been frequently observed as the primary light-related stressor, herein we present evidence that dark conditions may be similarly \"stressful\" (reduction of overall fitness), and stress responses vary among clones of the freshwater crustacean Daphnia parvula. We have identified a significant relationship between survivorship and reduced fecundity of clones maintained in dark conditions, but no correlation between tolerance of the clones to dark and UV radiation. Low tolerance to dark conditions can have negative effects not only on accumulated stresses in organisms (e.g. the repair of UV-induced damage in organisms with photolyase), but potentially on the overall physiology and fitness of organisms. Our results support recent evidence of the beneficial effects of low-level UV exposure for some organisms.", "journal": "PloS one", "sentences": ["Recent studies have demonstrated substantial effects of environmental stress that vary among clones.", "Exposure to ultraviolet radiation (UV) is an important abiotic stressor that is highly variable in aquatic ecosystems due to diel and seasonal variations in incident sunlight as well as to differences in the UV transparency of water among water bodies, the depth distribution of organisms, and the ability of organisms to detect and respond to UV.", "In contrast to the convention that all UV is damaging, evidence is accumulating for the beneficial effects of exposure to low levels of UV radiation.", "Whereas UV has been frequently observed as the primary light-related stressor, herein we present evidence that dark conditions may be similarly \"stressful\" (reduction of overall fitness), and stress responses vary among clones of the freshwater crustacean Daphnia parvula.", "We have identified a significant relationship between survivorship and reduced fecundity of clones maintained in dark conditions, but no correlation between tolerance of the clones to dark and UV radiation.", "Low tolerance to dark conditions can have negative effects not only on accumulated stresses in organisms (e.g.", "the repair of UV-induced damage in organisms with photolyase), but potentially on the overall physiology and fitness of organisms.", "Our results support recent evidence of the beneficial effects of low-level UV exposure for some organisms."], "title": "Effect of Clonal Selection on Daphnia Tolerance to Dark Experimental Conditions."}
{"paper_id": 19888575, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Pyranose dehydrogenase (PDH) is a flavin-dependant sugar oxidoreductase found in the family Agaricaceae, basidiomycetes that degrade lignocellulose-rich forest litter, and is catalytically related to the fungal enzymes pyranose 2-oxidase and cellobiose dehydrogenase. It has broad substrate specificity and displays similar activities with most sugar constituents of lignocellulose including disaccharides and oligosaccharides, a number of (substituted) quinones, and metal ions are suitable electron acceptors rather than molecular oxygen. In contrast to pyranose 2-oxidase and cellobiose dehydrogenase, which oxidize regioselectively at C-2 and C-1, respectively, PDH is capable of oxidation on C-1 to C-4 as well as double oxidations, depending on the nature of the substrate. This makes it a very interesting enzyme for biocatalytic applications, as many of the reaction products are otherwise unaccessible by chemical or enzymatic means. PDH was characterized in detail in a limited number of fungi, and the first encoding genes were isolated only recently. We report here, for the first time, the heterologous expression of one of these genes, encoding the major PDH protein in Agaricus meleagris, in the filamentous fungi Aspergillus nidulans, and Aspergillus niger.", "journal": "Applied microbiology and biotechnology", "sentences": ["Pyranose dehydrogenase (PDH) is a flavin-dependant sugar oxidoreductase found in the family Agaricaceae, basidiomycetes that degrade lignocellulose-rich forest litter, and is catalytically related to the fungal enzymes pyranose 2-oxidase and cellobiose dehydrogenase.", "It has broad substrate specificity and displays similar activities with most sugar constituents of lignocellulose including disaccharides and oligosaccharides, a number of (substituted) quinones, and metal ions are suitable electron acceptors rather than molecular oxygen.", "In contrast to pyranose 2-oxidase and cellobiose dehydrogenase, which oxidize regioselectively at C-2 and C-1, respectively, PDH is capable of oxidation on C-1 to C-4 as well as double oxidations, depending on the nature of the substrate.", "This makes it a very interesting enzyme for biocatalytic applications, as many of the reaction products are otherwise unaccessible by chemical or enzymatic means.", "PDH was characterized in detail in a limited number of fungi, and the first encoding genes were isolated only recently.", "We report here, for the first time, the heterologous expression of one of these genes, encoding the major PDH protein in Agaricus meleagris, in the filamentous fungi Aspergillus nidulans, and Aspergillus niger."], "title": "Heterologous expression of an Agaricus meleagris pyranose dehydrogenase-encoding gene in Aspergillus spp. and characterization of the recombinant enzyme."}
{"paper_id": 25819710, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Recently, Bacillus subtilis spores were shown to be endowed with strong adjuvant capacity when co-administered with purified antigenic proteins. In the present study we assessed whether spores possess adjuvant properties when combined with DNA vaccines. We showed that B. subtilis spores promoted the activation of dendritic cells in vitro and induced migration of pro-inflammatory cells after parenteral administration to mice. Likewise, co-administration of spores with a DNA vaccine encoding the human papillomavirus type 16 (HPV-16) E7 protein enhanced the activation of antigen-specific CD8(+) T cell responses in vivo. Mice immunized with the DNA vaccine admixed with spores presented a protective immunity increase to previously implanted tumor cells, capable of expressing HPV-16 oncoproteins. Finally, we observed that the adjuvant effect can vary accordingly to the number of co-administered spores which may be ascribed with the ability to induce. Collectively, the present results demonstrate for the first time that B. subtilis spores can also confer adjuvant effects to DNA vaccines.", "journal": "Vaccine", "sentences": ["Recently, Bacillus subtilis spores were shown to be endowed with strong adjuvant capacity when co-administered with purified antigenic proteins.", "In the present study we assessed whether spores possess adjuvant properties when combined with DNA vaccines.", "We showed that B. subtilis spores promoted the activation of dendritic cells in vitro and induced migration of pro-inflammatory cells after parenteral administration to mice.", "Likewise, co-administration of spores with a DNA vaccine encoding the human papillomavirus type 16 (HPV-16) E7 protein enhanced the activation of antigen-specific CD8(+) T cell responses in vivo.", "Mice immunized with the DNA vaccine admixed with spores presented a protective immunity increase to previously implanted tumor cells, capable of expressing HPV-16 oncoproteins.", "Finally, we observed that the adjuvant effect can vary accordingly to the number of co-administered spores which may be ascribed with the ability to induce.", "Collectively, the present results demonstrate for the first time that B. subtilis spores can also confer adjuvant effects to DNA vaccines."], "title": "Bacillus subtilis spores as adjuvants for DNA vaccines."}
{"paper_id": 25355213, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The local field potential (LFP) captures different neural processes, including integrative synaptic dynamics that cannot be observed by measuring only the spiking activity of small populations. Therefore, investigating how LFP power is modulated by external stimuli can offer important insights into sensory neural representations. However, gaining such insight requires developing data-driven computational models that can identify and disambiguate the neural contributions to the LFP. Here, we investigated how networks of excitatory and inhibitory integrate-and-fire neurons responding to time-dependent inputs can be used to interpret sensory modulations of LFP spectra. We computed analytically from such models the LFP spectra and the information that they convey about input and used these analytical expressions to fit the model to LFPs recorded in V1 of anesthetized macaques (Macaca mulatta) during the presentation of color movies. Our expressions explain 60%-98% of the variance of the LFP spectrum shape and its dependency upon movie scenes and we achieved this with realistic values for the best-fit parameters. In particular, synaptic best-fit parameters were compatible with experimental measurements and the predictions of firing rates, based only on the fit of LFP data, correlated with the multiunit spike rate recorded from the same location. Moreover, the parameters characterizing the input to the network across different movie scenes correlated with cross-scene changes of several image features. Our findings suggest that analytical descriptions of spiking neuron networks may become a crucial tool for the interpretation of field recordings.", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "sentences": ["The local field potential (LFP) captures different neural processes, including integrative synaptic dynamics that cannot be observed by measuring only the spiking activity of small populations.", "Therefore, investigating how LFP power is modulated by external stimuli can offer important insights into sensory neural representations.", "However, gaining such insight requires developing data-driven computational models that can identify and disambiguate the neural contributions to the LFP.", "Here, we investigated how networks of excitatory and inhibitory integrate-and-fire neurons responding to time-dependent inputs can be used to interpret sensory modulations of LFP spectra.", "We computed analytically from such models the LFP spectra and the information that they convey about input and used these analytical expressions to fit the model to LFPs recorded in V1 of anesthetized macaques (Macaca mulatta) during the presentation of color movies.", "Our expressions explain 60%-98% of the variance of the LFP spectrum shape and its dependency upon movie scenes and we achieved this with realistic values for the best-fit parameters.", "In particular, synaptic best-fit parameters were compatible with experimental measurements and the predictions of firing rates, based only on the fit of LFP data, correlated with the multiunit spike rate recorded from the same location.", "Moreover, the parameters characterizing the input to the network across different movie scenes correlated with cross-scene changes of several image features.", "Our findings suggest that analytical descriptions of spiking neuron networks may become a crucial tool for the interpretation of field recordings."], "title": "Stimulus dependence of local field potential spectra: experiment versus theory."}
{"paper_id": 21710492, "labels": ["0", "1", "0", "0", "0", "0", "1", "1"], "abstract": "Members of the extracellular signal-regulated kinase (ERK) family may have distinct roles in the development of cell injury and repair, differentiation and carcinogenesis. Here, we show, using a synthetic small-molecule MEK1/2 inhibitor (U0126) and RNA silencing of ERK1 and 2, comparatively, that ERK2 is critical to transformation and homeostasis of human epithelioid malignant mesotheliomas (MMs), asbestos-induced tumors with a poor prognosis. Although MM cell (HMESO) lines stably transfected with shERK1 or shERK2 both exhibited significant decreases in cell proliferation in vitro, injection of shERK2 cells, and not shERK1 cells, into immunocompromised severe combined immunodeficiency (SCID) mice showed significant attenuated tumor growth in comparison to shControl (shCon) cells. Inhibition of migration, invasion and colony formation occurred in shERK2 MM cells in vitro, suggesting multiple roles of ERK2 in neoplasia. Microarray and quantitative real-time PCR analyses revealed gene expression that was significantly increased (CASP1, TRAF1 and FAS) or decreased (SEMA3E, RPS6KA2, EGF and BCL2L1) in shERK2-transfected MM cells in contrast to shCon-transfected MM cells. Most striking decreases were observed in mRNA levels of Semaphorin 3 (SEMA3E), a candidate tumor suppressor gene linked to inhibition of angiogenesis. These studies demonstrate a key role of ERK2 in novel gene expression critical to the development of epithelioid MMs. After injection of sarcomatoid human MM (PPMMill) cells into SCID mice, both shERK1 and shERK2 lines showed significant decreased tumor growth, suggesting heterogeneous effects of ERKs in individual MMs.", "journal": "International journal of cancer", "sentences": ["Members of the extracellular signal-regulated kinase (ERK) family may have distinct roles in the development of cell injury and repair, differentiation and carcinogenesis.", "Here, we show, using a synthetic small-molecule MEK1/2 inhibitor (U0126) and RNA silencing of ERK1 and 2, comparatively, that ERK2 is critical to transformation and homeostasis of human epithelioid malignant mesotheliomas (MMs), asbestos-induced tumors with a poor prognosis.", "Although MM cell (HMESO) lines stably transfected with shERK1 or shERK2 both exhibited significant decreases in cell proliferation in vitro, injection of shERK2 cells, and not shERK1 cells, into immunocompromised severe combined immunodeficiency (SCID) mice showed significant attenuated tumor growth in comparison to shControl (shCon) cells.", "Inhibition of migration, invasion and colony formation occurred in shERK2 MM cells in vitro, suggesting multiple roles of ERK2 in neoplasia.", "Microarray and quantitative real-time PCR analyses revealed gene expression that was significantly increased (CASP1, TRAF1 and FAS) or decreased (SEMA3E, RPS6KA2, EGF and BCL2L1) in shERK2-transfected MM cells in contrast to shCon-transfected MM cells.", "Most striking decreases were observed in mRNA levels of Semaphorin 3 (SEMA3E), a candidate tumor suppressor gene linked to inhibition of angiogenesis.", "These studies demonstrate a key role of ERK2 in novel gene expression critical to the development of epithelioid MMs.", "After injection of sarcomatoid human MM (PPMMill) cells into SCID mice, both shERK1 and shERK2 lines showed significant decreased tumor growth, suggesting heterogeneous effects of ERKs in individual MMs."], "title": "ERK2 is essential for the growth of human epithelioid malignant mesotheliomas."}
{"paper_id": 22984083, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Phagocyte NADPH oxidase plays a key role in pathogen clearance via reactive oxygen species (ROS) production. Defects in oxidase function result in chronic granulomatous disease with hallmark recurrent microbial infections and inflammation. The oxidase's role in the adaptive immune response is not well understood. Class II presentation of cytoplasmic and exogenous Ag to CD4(+) T cells was impaired in human B cells with reduced oxidase p40(phox) subunit expression. Naturally arising mutations, which compromise p40(phox) function in a chronic granulomatous disease patient, also perturbed class II Ag presentation and intracellular ROS production. Reconstitution of patient B cells with a wild-type, but not a mutant, p40(phox) allele restored exogenous Ag presentation and intracellular ROS generation. Remarkably, class II presentation of epitopes from membrane Ag was robust in p40(phox)-deficient B cells. These studies reveal a role for NADPH oxidase and p40(phox) in skewing epitope selection and T cell recognition of self Ag.", "journal": "Journal of immunology (Baltimore, Md. : 1950)", "sentences": ["Phagocyte NADPH oxidase plays a key role in pathogen clearance via reactive oxygen species (ROS) production.", "Defects in oxidase function result in chronic granulomatous disease with hallmark recurrent microbial infections and inflammation.", "The oxidase's role in the adaptive immune response is not well understood.", "Class II presentation of cytoplasmic and exogenous Ag to CD4(+) T cells was impaired in human B cells with reduced oxidase p40(phox) subunit expression.", "Naturally arising mutations, which compromise p40(phox) function in a chronic granulomatous disease patient, also perturbed class II Ag presentation and intracellular ROS production.", "Reconstitution of patient B cells with a wild-type, but not a mutant, p40(phox) allele restored exogenous Ag presentation and intracellular ROS generation.", "Remarkably, class II presentation of epitopes from membrane Ag was robust in p40(phox)-deficient B cells.", "These studies reveal a role for NADPH oxidase and p40(phox) in skewing epitope selection and T cell recognition of self Ag."], "title": "Cutting edge: NADPH oxidase modulates MHC class II antigen presentation by B cells."}
{"paper_id": 26517809, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "The connection between colorectal cancer (CRC) and Wnt signaling pathway activation is well known, but full elucidation of the underlying regulation of the Wnt/\u03b2-catenin pathway and its biological functions in CRC pathogenesis is still needed. Here, the azoxymethane/dextran sulfate sodium salt (AOM/DSS) murine model has been used as an experimental platform able to mimic human sporadic CRC development with predictable timing. We performed genome-wide expression profiling of AOM/DSS-induced tumors and normal colon mucosa to identify potential novel CRC biomarkers. Remarkably, the enhanced expression of Notum, a conserved feedback antagonist of Wnt, was observed in tumors along with alterations in Glypican-1 and Glypican-3 levels. These findings were confirmed in a set of human CRC samples. Here, we provide the first demonstration of significant changes in Notum and glypicans gene expression during CRC development and present evidence to suggest them as potential new biomarkers of CRC pathogenesis.", "journal": "Oncotarget", "sentences": ["The connection between colorectal cancer (CRC) and Wnt signaling pathway activation is well known, but full elucidation of the underlying regulation of the Wnt/\u03b2-catenin pathway and its biological functions in CRC pathogenesis is still needed.", "Here, the azoxymethane/dextran sulfate sodium salt (AOM/DSS) murine model has been used as an experimental platform able to mimic human sporadic CRC development with predictable timing.", "We performed genome-wide expression profiling of AOM/DSS-induced tumors and normal colon mucosa to identify potential novel CRC biomarkers.", "Remarkably, the enhanced expression of Notum, a conserved feedback antagonist of Wnt, was observed in tumors along with alterations in Glypican-1 and Glypican-3 levels.", "These findings were confirmed in a set of human CRC samples.", "Here, we provide the first demonstration of significant changes in Notum and glypicans gene expression during CRC development and present evidence to suggest them as potential new biomarkers of CRC pathogenesis."], "title": "Novel insights into Notum and glypicans regulation in colorectal cancer."}
{"paper_id": 27385828, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The Ltn1 E3 ligase (listerin in mammals) has emerged as a paradigm for understanding ribosome-associated ubiquitylation. Ltn1 binds to 60S ribosomal subunits to ubiquitylate nascent polypeptides that become stalled during synthesis; among Ltn1's substrates are aberrant products of mRNA lacking stop codons [nonstop translation products (NSPs)]. Here, we report the reconstitution of NSP ubiquitylation in Neurospora crassa cell extracts. Upon translation in vitro, ribosome-stalled NSPs were ubiquitylated in an Ltn1-dependent manner, while still ribosome-associated. Furthermore, we provide biochemical evidence that the conserved N-terminal domain (NTD) plays a significant role in the binding of Ltn1 to 60S ribosomal subunits and that NTD mutations causing defective 60S binding also lead to defective NSP ubiquitylation, without affecting Ltn1's intrinsic E3 ligase activity. Finally, we report the crystal structure of the Ltn1 NTD at 2.4-\u00c5 resolution. The structure, combined with additional mutational studies, provides insight to NTD's role in binding stalled 60S subunits. Our findings show that Neurospora extracts can be used as a tool to dissect mechanisms underlying ribosome-associated protein quality control and are consistent with a model in which Ltn1 uses 60S subunits as adapters, at least in part via its NTD, to target stalled NSPs for ubiquitylation.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["The Ltn1 E3 ligase (listerin in mammals) has emerged as a paradigm for understanding ribosome-associated ubiquitylation.", "Ltn1 binds to 60S ribosomal subunits to ubiquitylate nascent polypeptides that become stalled during synthesis; among Ltn1's substrates are aberrant products of mRNA lacking stop codons [nonstop translation products (NSPs)].", "Here, we report the reconstitution of NSP ubiquitylation in Neurospora crassa cell extracts.", "Upon translation in vitro, ribosome-stalled NSPs were ubiquitylated in an Ltn1-dependent manner, while still ribosome-associated.", "Furthermore, we provide biochemical evidence that the conserved N-terminal domain (NTD) plays a significant role in the binding of Ltn1 to 60S ribosomal subunits and that NTD mutations causing defective 60S binding also lead to defective NSP ubiquitylation, without affecting Ltn1's intrinsic E3 ligase activity.", "Finally, we report the crystal structure of the Ltn1 NTD at 2.4-\u00c5 resolution.", "The structure, combined with additional mutational studies, provides insight to NTD's role in binding stalled 60S subunits.", "Our findings show that Neurospora extracts can be used as a tool to dissect mechanisms underlying ribosome-associated protein quality control and are consistent with a model in which Ltn1 uses 60S subunits as adapters, at least in part via its NTD, to target stalled NSPs for ubiquitylation."], "title": "Structure and function of the yeast listerin (Ltn1) conserved N-terminal domain in binding to stalled 60S ribosomal subunits."}
{"paper_id": 23626000, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "UNLABELLED\nTargeted therapies interfering with specifically one protein activity are promising strategies in the treatment of diseases like cancer. However, accumulated empirical experience has shown that targeting multiple proteins in signaling networks involved in the disease is often necessary. Thus, one important problem in biomedical research is the design and prioritization of optimal combinations of interventions to repress a pathological behavior, while minimizing side-effects. OCSANA (optimal combinations of interventions from network analysis) is a new software designed to identify and prioritize optimal and minimal combinations of interventions to disrupt the paths between source nodes and target nodes. When specified by the user, OCSANA seeks to additionally minimize the side effects that a combination of interventions can cause on specified off-target nodes. With the crucial ability to cope with very large networks, OCSANA includes an exact solution and a novel selective enumeration approach for the combinatorial interventions' problem.\n\n\nAVAILABILITY\nThe latest version of OCSANA, implemented as a plugin for Cytoscape and distributed under LGPL license, is available together with source code at http://bioinfo.curie.fr/projects/ocsana.", "journal": "Bioinformatics (Oxford, England)", "sentences": ["UNLABELLED\nTargeted therapies interfering with specifically one protein activity are promising strategies in the treatment of diseases like cancer.", "However, accumulated empirical experience has shown that targeting multiple proteins in signaling networks involved in the disease is often necessary.", "Thus, one important problem in biomedical research is the design and prioritization of optimal combinations of interventions to repress a pathological behavior, while minimizing side-effects.", "OCSANA (optimal combinations of interventions from network analysis) is a new software designed to identify and prioritize optimal and minimal combinations of interventions to disrupt the paths between source nodes and target nodes.", "When specified by the user, OCSANA seeks to additionally minimize the side effects that a combination of interventions can cause on specified off-target nodes.", "With the crucial ability to cope with very large networks, OCSANA includes an exact solution and a novel selective enumeration approach for the combinatorial interventions' problem.", "AVAILABILITY\nThe latest version of OCSANA, implemented as a plugin for Cytoscape and distributed under LGPL license, is available together with source code at http://bioinfo.curie.fr/projects/ocsana."], "title": "OCSANA: optimal combinations of interventions from network analysis."}
{"paper_id": 25162297, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "There are hundreds of proteins in saliva. Although it has long been hypothesized that these proteins modulate taste by interacting with taste receptors or taste stimuli, the functional impact of these proteins on feeding remains relatively unexplored. We have developed a new technique for saliva collection that does not interfere with daily behavioral testing and allows us to explore the relationship between feeding behavior and salivary protein expression. First, we monitored the alterations in salivary protein expression while simultaneously monitoring the animals' feeding behavior and meal patterns on a custom control diet or on the same diet mixed with 3% tannic acid. We demonstrated that six protein bands increased in density with dietary tannic acid exposure. Several of these bands were significantly correlated with behaviors thought to represent both orosensory and postingestive signaling. In a follow-up experiment, unconditioned licking to 0.01-3% tannic acid solutions was measured during a brief-access taste test before and after exposure to the tannic acid diet. In this experiment, rats with salivary proteins upregulated found the tannin solution less aversive (i.e., licked more) than those in the control condition. These data suggest a role for salivary proteins in mediating changes in both orosensory and postingestive feedback.", "journal": "PloS one", "sentences": ["There are hundreds of proteins in saliva.", "Although it has long been hypothesized that these proteins modulate taste by interacting with taste receptors or taste stimuli, the functional impact of these proteins on feeding remains relatively unexplored.", "We have developed a new technique for saliva collection that does not interfere with daily behavioral testing and allows us to explore the relationship between feeding behavior and salivary protein expression.", "First, we monitored the alterations in salivary protein expression while simultaneously monitoring the animals' feeding behavior and meal patterns on a custom control diet or on the same diet mixed with 3% tannic acid.", "We demonstrated that six protein bands increased in density with dietary tannic acid exposure.", "Several of these bands were significantly correlated with behaviors thought to represent both orosensory and postingestive signaling.", "In a follow-up experiment, unconditioned licking to 0.01-3% tannic acid solutions was measured during a brief-access taste test before and after exposure to the tannic acid diet.", "In this experiment, rats with salivary proteins upregulated found the tannin solution less aversive (i.e., licked more) than those in the control condition.", "These data suggest a role for salivary proteins in mediating changes in both orosensory and postingestive feedback."], "title": "Induction of salivary proteins modifies measures of both orosensory and postingestive feedback during exposure to a tannic acid diet."}
{"paper_id": 22565214, "labels": ["0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "The initial appraisal of treatment by inpatients with schizophrenia has been found to be a significant predictor of clinical outcomes. The study aim was to examine whether specific types of symptoms are associated with the initial appraisal of treatment after controlling other patient characteristics. Data of 2105 inpatients with schizophrenia (ICD-10 F20-9) were pooled from three national and international multi-centre studies. Patients were interviewed within the first week of their inpatient admission. Higher levels of manic and positive symptoms were significantly associated with a less favourable initial appraisal of treatment, whilst no association was found with depression/anxiety and negative symptoms. Detained patients had more negative initial treatment appraisals, and the association with manic symptoms was significantly stronger in detained patients compared to those admitted voluntarily. Whilst patient-reported outcomes in psychiatry are usually associated with mood symptoms, this appears not to be the case for the initial appraisal by inpatients with schizophrenia. The association with manic and positive symptoms may be explained by the influence of such symptoms on the hospital experience. Focusing on the initial management of mania and positive symptoms might improve patients' appraisal of treatment in the inpatient environment.", "journal": "Psychiatry research", "sentences": ["The initial appraisal of treatment by inpatients with schizophrenia has been found to be a significant predictor of clinical outcomes.", "The study aim was to examine whether specific types of symptoms are associated with the initial appraisal of treatment after controlling other patient characteristics.", "Data of 2105 inpatients with schizophrenia (ICD-10 F20-9) were pooled from three national and international multi-centre studies.", "Patients were interviewed within the first week of their inpatient admission.", "Higher levels of manic and positive symptoms were significantly associated with a less favourable initial appraisal of treatment, whilst no association was found with depression/anxiety and negative symptoms.", "Detained patients had more negative initial treatment appraisals, and the association with manic symptoms was significantly stronger in detained patients compared to those admitted voluntarily.", "Whilst patient-reported outcomes in psychiatry are usually associated with mood symptoms, this appears not to be the case for the initial appraisal by inpatients with schizophrenia.", "The association with manic and positive symptoms may be explained by the influence of such symptoms on the hospital experience.", "Focusing on the initial management of mania and positive symptoms might improve patients' appraisal of treatment in the inpatient environment."], "title": "Symptom levels and initial appraisal of hospital treatment in patients with schizophrenia."}
{"paper_id": 26587973, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Imatinib is the first-line drug for gastrointestinal stromal tumors (GISTs), as mutated KIT is closely associated with the occurrence of GIST. However, Imatinib resistance (IMA-resistance) occurs inevitably in most GIST patients. Although the over-expression of KIT in GIST is one of the major factors contributing to IMA-resistance, the underlying mechanism is still unclear. In this study, we demonstrate that p55PIK, an isoform of phosphoinositide 3-kinase (PI3K), increases KIT expression, leading to IMA-resistance in GISTs by activating NF-\u03baB signaling pathway. Furthermore, down-regulation of p55PIK significantly decreases KIT expression and re-sensitizes IMA-resistance-GIST cells to Imatinib in vitro and in vivo. Interestingly, the expression of both p55PIK and KIT proteins is significantly increased in tumor samples from IMA-resistance-GIST patients, suggesting that p55PIK up-regulation may be important for IMA-resistance in the clinical setting. Altogether, our data provide evidence that p55PIK-PI3K signaling can contribute to IMA-resistance in GIST by increasing KIT expression. Moreover, p55PIK may be a novel potential drug target for treating tumors that develop IMA-resistance.", "journal": "Oncotarget", "sentences": ["Imatinib is the first-line drug for gastrointestinal stromal tumors (GISTs), as mutated KIT is closely associated with the occurrence of GIST.", "However, Imatinib resistance (IMA-resistance) occurs inevitably in most GIST patients.", "Although the over-expression of KIT in GIST is one of the major factors contributing to IMA-resistance, the underlying mechanism is still unclear.", "In this study, we demonstrate that p55PIK, an isoform of phosphoinositide 3-kinase (PI3K), increases KIT expression, leading to IMA-resistance in GISTs by activating NF-\u03baB signaling pathway.", "Furthermore, down-regulation of p55PIK significantly decreases KIT expression and re-sensitizes IMA-resistance-GIST cells to Imatinib in vitro and in vivo.", "Interestingly, the expression of both p55PIK and KIT proteins is significantly increased in tumor samples from IMA-resistance-GIST patients, suggesting that p55PIK up-regulation may be important for IMA-resistance in the clinical setting.", "Altogether, our data provide evidence that p55PIK-PI3K signaling can contribute to IMA-resistance in GIST by increasing KIT expression.", "Moreover, p55PIK may be a novel potential drug target for treating tumors that develop IMA-resistance."], "title": "KIT over-expression by p55PIK-PI3K leads to Imatinib-resistance in patients with gastrointestinal stromal tumors."}
{"paper_id": 26488290, "labels": ["0", "0", "0", "0", "1"], "abstract": "The influence of spring stiffness and valve quality on the motion behaviors of reciprocating plunger pump discharge valves was investigated by fluid structure interaction (FSI) simulation and experimental analysis. The mathematical model of the discharge valve motion of a 2000-fracturing pump was developed and the discrete differential equations were solved according to FSI and results obtained by ANDINA software. Results indicate that spring stiffness influences the maximum lift, the opening resistance and shut-off lag angle, as well as the fluid velocity of the clearance, the impact stress and the volume efficiency of the pump valve in relation to the valve quality. An optimal spring stiffness parameter of 14.6 N/mm was obtained, and the volumetric efficiency of the pumping valve increased by 4\u2030 in comparison to results obtained with the original spring stiffness of 10.09N/mm. The experimental results indicated that the mathematical model and FSI method could provide an effective approach for the subsequent improvement of valve reliability, volumetric efficiency and lifespan.", "journal": "PloS one", "sentences": ["The influence of spring stiffness and valve quality on the motion behaviors of reciprocating plunger pump discharge valves was investigated by fluid structure interaction (FSI) simulation and experimental analysis.", "The mathematical model of the discharge valve motion of a 2000-fracturing pump was developed and the discrete differential equations were solved according to FSI and results obtained by ANDINA software.", "Results indicate that spring stiffness influences the maximum lift, the opening resistance and shut-off lag angle, as well as the fluid velocity of the clearance, the impact stress and the volume efficiency of the pump valve in relation to the valve quality.", "An optimal spring stiffness parameter of 14.6 N/mm was obtained, and the volumetric efficiency of the pumping valve increased by 4\u2030 in comparison to results obtained with the original spring stiffness of 10.09N/mm.", "The experimental results indicated that the mathematical model and FSI method could provide an effective approach for the subsequent improvement of valve reliability, volumetric efficiency and lifespan."], "title": "Dynamic Behavior of Reciprocating Plunger Pump Discharge Valve Based on Fluid Structure Interaction and Experimental Analysis."}
{"paper_id": 23852489, "labels": ["0", "0", "0", "0", "1", "1"], "abstract": "This study aimed to compare changes in skeletal muscle, prefrontal (PFC), and motor (MC) cortex hemodynamics during prolonged (i.e., 4-h) fatiguing whole-body exercise using multichannel near-infrared spectroscopy (NIRS). Ten subjects completed three successive 80-min cycling bouts at 45 % of their maximal power output. After the 4-h cycling, maximal voluntary contraction force of the leg was decreased by ~25 %. Muscle exhibited reproductive deoxygenation patterns during each of the three bouts, whereas intra-bout cerebral hemodynamics were different throughout the protocol. Results demonstrate that specific responses to fatiguing exercise are found between tissues but also between cortical sites involved in cycling, as shown by concomitant PFC hyperoxygenation and MC deoxygenation in the first 80 min of exercise. Further insights are needed to understand the consequences of these changes regarding the integrative control of motor output while fatigue develops over several hours.", "journal": "Advances in experimental medicine and biology", "sentences": ["This study aimed to compare changes in skeletal muscle, prefrontal (PFC), and motor (MC) cortex hemodynamics during prolonged (i.e., 4-h) fatiguing whole-body exercise using multichannel near-infrared spectroscopy (NIRS).", "Ten subjects completed three successive 80-min cycling bouts at 45 % of their maximal power output.", "After the 4-h cycling, maximal voluntary contraction force of the leg was decreased by ~25 %.", "Muscle exhibited reproductive deoxygenation patterns during each of the three bouts, whereas intra-bout cerebral hemodynamics were different throughout the protocol.", "Results demonstrate that specific responses to fatiguing exercise are found between tissues but also between cortical sites involved in cycling, as shown by concomitant PFC hyperoxygenation and MC deoxygenation in the first 80 min of exercise.", "Further insights are needed to understand the consequences of these changes regarding the integrative control of motor output while fatigue develops over several hours."], "title": "Muscle, prefrontal, and motor cortex oxygenation profiles during prolonged fatiguing exercise."}
{"paper_id": 26645829, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "We tested whether stereotypical situations would affect low-status group members' performance more strongly than high-status group members'. Experiment 1 and 2 tested this hypothesis using gender as a proxy of chronic social status and a gender-neutral task that has been randomly presented to favor boys (men superiority condition), favor girls (women superiority condition), or show no gender preference (control condition). Both experiments found that women's (Experiment 1) and girls' performance (Experiment 2) suffered more from the evoked stereotypes than did men's and boys' ones. This result was replicated in Experiment 3, indicating that short men (low-status group) were more affected compared to tall men (high-status group). Additionally, men were more affected compared to women when they perceived height as a threat. Hence, individuals are more or less vulnerable to identity threats as a function of the chronic social status at play; enjoying a high status provides protection and endorsing a low one weakens individual performance in stereotypical situations.", "journal": "PloS one", "sentences": ["We tested whether stereotypical situations would affect low-status group members' performance more strongly than high-status group members'.", "Experiment 1 and 2 tested this hypothesis using gender as a proxy of chronic social status and a gender-neutral task that has been randomly presented to favor boys (men superiority condition), favor girls (women superiority condition), or show no gender preference (control condition).", "Both experiments found that women's (Experiment 1) and girls' performance (Experiment 2) suffered more from the evoked stereotypes than did men's and boys' ones.", "This result was replicated in Experiment 3, indicating that short men (low-status group) were more affected compared to tall men (high-status group).", "Additionally, men were more affected compared to women when they perceived height as a threat.", "Hence, individuals are more or less vulnerable to identity threats as a function of the chronic social status at play; enjoying a high status provides protection and endorsing a low one weakens individual performance in stereotypical situations."], "title": "The Influence of Chronic and Situational Social Status on Stereotype Susceptibility."}
{"paper_id": 24376770, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "A growing number of studies are evaluating retinal progenitor cell (RPC) transplantation as an approach to repair retinal degeneration and restore visual function. To advance cell-replacement strategies for a practical retinal therapy, it is important to define the molecular and biochemical mechanisms guiding RPC motility. We have analyzed RPC expression of the epidermal growth factor receptor (EGFR) and evaluated whether exposure to epidermal growth factor (EGF) can coordinate motogenic activity in vitro. Using Boyden chamber analysis as an initial high-throughput screen, we determined that RPC motility was optimally stimulated by EGF concentrations in the range of 20-400 ng/ml, with decreased stimulation at higher concentrations, suggesting concentration-dependence of EGF-induced motility. Using bioinformatics analysis of the EGF ligand in a retina-specific gene network pathway, we predicted a chemotactic function for EGF involving the MAPK and JAK-STAT intracellular signaling pathways. Based on targeted inhibition studies, we show that ligand binding, phosphorylation of EGFR and activation of the intracellular STAT3 and PI3kinase signaling pathways are necessary to drive RPC motility. Using engineered microfluidic devices to generate quantifiable steady-state gradients of EGF coupled with live-cell tracking, we analyzed the dynamics of individual RPC motility. Microfluidic analysis, including center of mass and maximum accumulated distance, revealed that EGF induced motility is chemokinetic with optimal activity observed in response to low concentration gradients. Our combined results show that EGFR expressing RPCs exhibit enhanced chemokinetic motility in the presence of low nanomole levels of EGF. These findings may serve to inform further studies evaluating the extent to which EGFR activity, in response to endogenous ligand, drives motility and migration of RPCs in retinal transplantation paradigms.", "journal": "PloS one", "sentences": ["A growing number of studies are evaluating retinal progenitor cell (RPC) transplantation as an approach to repair retinal degeneration and restore visual function.", "To advance cell-replacement strategies for a practical retinal therapy, it is important to define the molecular and biochemical mechanisms guiding RPC motility.", "We have analyzed RPC expression of the epidermal growth factor receptor (EGFR) and evaluated whether exposure to epidermal growth factor (EGF) can coordinate motogenic activity in vitro.", "Using Boyden chamber analysis as an initial high-throughput screen, we determined that RPC motility was optimally stimulated by EGF concentrations in the range of 20-400 ng/ml, with decreased stimulation at higher concentrations, suggesting concentration-dependence of EGF-induced motility.", "Using bioinformatics analysis of the EGF ligand in a retina-specific gene network pathway, we predicted a chemotactic function for EGF involving the MAPK and JAK-STAT intracellular signaling pathways.", "Based on targeted inhibition studies, we show that ligand binding, phosphorylation of EGFR and activation of the intracellular STAT3 and PI3kinase signaling pathways are necessary to drive RPC motility.", "Using engineered microfluidic devices to generate quantifiable steady-state gradients of EGF coupled with live-cell tracking, we analyzed the dynamics of individual RPC motility.", "Microfluidic analysis, including center of mass and maximum accumulated distance, revealed that EGF induced motility is chemokinetic with optimal activity observed in response to low concentration gradients.", "Our combined results show that EGFR expressing RPCs exhibit enhanced chemokinetic motility in the presence of low nanomole levels of EGF.", "These findings may serve to inform further studies evaluating the extent to which EGFR activity, in response to endogenous ligand, drives motility and migration of RPCs in retinal transplantation paradigms."], "title": "Microfluidic generated EGF-gradients induce chemokinesis of transplantable retinal progenitor cells via the JAK/STAT and PI3kinase signaling pathways."}
{"paper_id": 23920621, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "In Denmark, two large regions cooperate in a public intervention process of acquiring a new eHealth-platform to support the daily clinical work of approximately 40,000 users in 14 hospitals. It is essential that the new platform, besides fulfilling comprehensive detailed specifications, supports the daily work practice consisting of numerous mixed tasks executed by many different clinical actors in various settings. Within health informatics it has proven beneficial to use human factors approaches in the design process to secure systems that are responsive to the actual field of application. While design methods are widely described, there are very limited descriptions of how to assess and compare different EHR-platforms and their support in work processes upon its procurement. This paper describes the method we have developed to undertake this task. It is discussed how the method differs and how it has been adjusted from existing assessment methods. Finally, future considerations are discussed.", "journal": "Studies in health technology and informatics", "sentences": ["In Denmark, two large regions cooperate in a public intervention process of acquiring a new eHealth-platform to support the daily clinical work of approximately 40,000 users in 14 hospitals.", "It is essential that the new platform, besides fulfilling comprehensive detailed specifications, supports the daily work practice consisting of numerous mixed tasks executed by many different clinical actors in various settings.", "Within health informatics it has proven beneficial to use human factors approaches in the design process to secure systems that are responsive to the actual field of application.", "While design methods are widely described, there are very limited descriptions of how to assess and compare different EHR-platforms and their support in work processes upon its procurement.", "This paper describes the method we have developed to undertake this task.", "It is discussed how the method differs and how it has been adjusted from existing assessment methods.", "Finally, future considerations are discussed."], "title": "Use of clinical simulation for assessment in EHR-procurement: design of method."}
{"paper_id": 26923876, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "The LT\u03b11\u03b22 and LIGHT TNF superfamily cytokines exert pleiotropic physiological functions through the activation of their cognate lymphotoxin-\u03b2 receptor (LT\u03b2R). Interestingly, since the discovery of these proteins, accumulating evidence has pinpointed a role for LT\u03b2R signaling in carcinogenesis. Early studies have shown a potential anti-tumoral role in a subset of solid cancers either by triggering apoptosis in malignant cells or by eliciting an anti-tumor immune response. However, more recent studies provided robust evidence that LT\u03b2R signaling is also involved in diverse cell-intrinsic and microenvironment-dependent pro-oncogenic mechanisms, affecting several solid and hematological malignancies. Consequently, the usefulness of LT\u03b2R signaling axis blockade has been investigated as a potential therapeutic approach for cancer. Considering the seemingly opposite roles of LT\u03b2R signaling in diverse cancer types and their key implications for therapy, we here extensively review the different mechanisms by which LT\u03b2R activation affects carcinogenesis, focusing on the diverse contexts and different models assessed.", "journal": "Biochimica et biophysica acta", "sentences": ["The LT\u03b11\u03b22 and LIGHT TNF superfamily cytokines exert pleiotropic physiological functions through the activation of their cognate lymphotoxin-\u03b2 receptor (LT\u03b2R).", "Interestingly, since the discovery of these proteins, accumulating evidence has pinpointed a role for LT\u03b2R signaling in carcinogenesis.", "Early studies have shown a potential anti-tumoral role in a subset of solid cancers either by triggering apoptosis in malignant cells or by eliciting an anti-tumor immune response.", "However, more recent studies provided robust evidence that LT\u03b2R signaling is also involved in diverse cell-intrinsic and microenvironment-dependent pro-oncogenic mechanisms, affecting several solid and hematological malignancies.", "Consequently, the usefulness of LT\u03b2R signaling axis blockade has been investigated as a potential therapeutic approach for cancer.", "Considering the seemingly opposite roles of LT\u03b2R signaling in diverse cancer types and their key implications for therapy, we here extensively review the different mechanisms by which LT\u03b2R activation affects carcinogenesis, focusing on the diverse contexts and different models assessed."], "title": "Context-dependent roles for lymphotoxin-\u03b2 receptor signaling in cancer development."}
{"paper_id": 20447696, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The present prospective high-risk study examined associations between childhood scores on five Wechsler Intelligence Scale for Children (WISC) subtests (vocabulary, similarities, block design, object assembly, and mazes) and later development of schizophrenia spectrum disorders (SSD). The sample comprised 244 high-risk or control children who were administered the WISC subtests at age 10 to 13 years in 1972. Adult psychiatric data were gathered from psychiatric interviews in 1992-93 and from the Danish Psychiatric Central Register in 2007. Thirty-two participants had developed SSD, 79 other psychiatric disorders (OPD), and 133 had no diagnosis (ND). The SSD group obtained lower scores than the ND group on all subtests and IQs, but when adjusted for sex and parental social status only significantly lower scores on similarities, object assembly, mazes, and total IQ. Compared with the ND group, the OPD group obtained significantly lower scores on similarities, vocabulary, verbal IQ, and total IQ. The only significant difference between the SSD and OPD groups was on object assembly (OPD performed at the level of ND). The results suggest a premorbid deficit in general intelligence in individuals who later develop SSD. The results for the OPD group support recent studies demonstrating that premorbid IQ deficits may characterize a wide range of psychiatric disorders.", "journal": "Psychiatry research", "sentences": ["The present prospective high-risk study examined associations between childhood scores on five Wechsler Intelligence Scale for Children (WISC) subtests (vocabulary, similarities, block design, object assembly, and mazes) and later development of schizophrenia spectrum disorders (SSD).", "The sample comprised 244 high-risk or control children who were administered the WISC subtests at age 10 to 13 years in 1972.", "Adult psychiatric data were gathered from psychiatric interviews in 1992-93 and from the Danish Psychiatric Central Register in 2007.", "Thirty-two participants had developed SSD, 79 other psychiatric disorders (OPD), and 133 had no diagnosis (ND).", "The SSD group obtained lower scores than the ND group on all subtests and IQs, but when adjusted for sex and parental social status only significantly lower scores on similarities, object assembly, mazes, and total IQ.", "Compared with the ND group, the OPD group obtained significantly lower scores on similarities, vocabulary, verbal IQ, and total IQ.", "The only significant difference between the SSD and OPD groups was on object assembly (OPD performed at the level of ND).", "The results suggest a premorbid deficit in general intelligence in individuals who later develop SSD.", "The results for the OPD group support recent studies demonstrating that premorbid IQ deficits may characterize a wide range of psychiatric disorders."], "title": "Premorbid IQ and adult schizophrenia spectrum disorder: verbal Performance subtests."}
{"paper_id": 24710172, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "The Neurospora clock protein FRQ forms a complex with casein kinase 1a (CK1a) and FRH, a DEAD box-containing RNA helicase with a clock-independent essential function in RNA metabolism. In the course of a circadian period, FRQ is progressively hyperphosphorylated and eventually degraded. Timed hyperphosphorylation of FRQ is crucial for timekeeping of the clock. Here we show that the ATPase activity of FRH attenuates the kinetics of CK1a-mediated hyperphosphorylation of FRQ. Hyperphosphorylation of FRQ is strictly dependent on site-specific recruitment of a CK1a molecule that is activated upon binding. The FRH ATPase cycle regulates the access of CK1a to phosphorylation sites in FRQ in cis, suggesting that FRH is an ATP-dependent remodelling factor acting on the protein complex. We show that the affinity of CK1a for FRQ decreases with increasing FRQ phosphorylation, suggesting functional inactivation of FRQ in the negative feedback loop of the circadian clock before and independent of its degradation.", "journal": "Nature communications", "sentences": ["The Neurospora clock protein FRQ forms a complex with casein kinase 1a (CK1a) and FRH, a DEAD box-containing RNA helicase with a clock-independent essential function in RNA metabolism.", "In the course of a circadian period, FRQ is progressively hyperphosphorylated and eventually degraded.", "Timed hyperphosphorylation of FRQ is crucial for timekeeping of the clock.", "Here we show that the ATPase activity of FRH attenuates the kinetics of CK1a-mediated hyperphosphorylation of FRQ.", "Hyperphosphorylation of FRQ is strictly dependent on site-specific recruitment of a CK1a molecule that is activated upon binding.", "The FRH ATPase cycle regulates the access of CK1a to phosphorylation sites in FRQ in cis, suggesting that FRH is an ATP-dependent remodelling factor acting on the protein complex.", "We show that the affinity of CK1a for FRQ decreases with increasing FRQ phosphorylation, suggesting functional inactivation of FRQ in the negative feedback loop of the circadian clock before and independent of its degradation."], "title": "The RNA helicase FRH is an ATP-dependent regulator of CK1a in the circadian clock of Neurospora crassa."}
{"paper_id": 20043871, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Non-alcoholic steatohepatitis (NASH) develops in a subset of patients with non-alcoholic fatty liver disease (NAFLD), but the exact mechanisms involved in the progression of NAFLD to NASH remain poorly understood. We investigated the role of tumor necrosis factor-alpha (TNF-alpha) in the apoptosis of hepatocytes that is related to the severity of NASH. We separated primary hepatocytes from the NAFLD liver caused by a high-fat diet. The production of intracellular reactive oxygen species was increased in steatotic hepatocytes, which were also sensitive to TNF-alpha. This factor induced significant apoptosis through the signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK) pathway. We describe here a novel culture model of steatotic hepatocytes separated from the NAFLD liver, and demonstrate that TNF-alpha induces their apoptosis in vitro.", "journal": "Biochemical and biophysical research communications", "sentences": ["Non-alcoholic steatohepatitis (NASH) develops in a subset of patients with non-alcoholic fatty liver disease (NAFLD), but the exact mechanisms involved in the progression of NAFLD to NASH remain poorly understood.", "We investigated the role of tumor necrosis factor-alpha (TNF-alpha) in the apoptosis of hepatocytes that is related to the severity of NASH.", "We separated primary hepatocytes from the NAFLD liver caused by a high-fat diet.", "The production of intracellular reactive oxygen species was increased in steatotic hepatocytes, which were also sensitive to TNF-alpha.", "This factor induced significant apoptosis through the signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK) pathway.", "We describe here a novel culture model of steatotic hepatocytes separated from the NAFLD liver, and demonstrate that TNF-alpha induces their apoptosis in vitro."], "title": "Tumor necrosis factor-alpha accelerates apoptosis of steatotic hepatocytes from a murine model of non-alcoholic fatty liver disease."}
{"paper_id": 26444690, "labels": ["0", "0", "0", "0", "1", "0"], "abstract": "This paper investigates a method to identify uncertain system parameters and unknown topological structure in general complex networks with or without time delay. A complex network, which has uncertain topology and unknown parameters, is designed as a drive network, and a known response complex network with an input controller is designed to identify the drive network. Under the proposed input controller, the drive network and the response network can achieve anticipatory projective synchronization when the system is steady. Lyapunov theorem and Barb\u01celat's lemma guarantee the stability of synchronization manifold between two networks. When the synchronization is achieved, the system parameters and topology in response network can be changed to equal with the parameters and topology in drive network. A numerical example is given to show the effectiveness of the proposed method.", "journal": "PloS one", "sentences": ["This paper investigates a method to identify uncertain system parameters and unknown topological structure in general complex networks with or without time delay.", "A complex network, which has uncertain topology and unknown parameters, is designed as a drive network, and a known response complex network with an input controller is designed to identify the drive network.", "Under the proposed input controller, the drive network and the response network can achieve anticipatory projective synchronization when the system is steady.", "Lyapunov theorem and Barb\u01celat's lemma guarantee the stability of synchronization manifold between two networks.", "When the synchronization is achieved, the system parameters and topology in response network can be changed to equal with the parameters and topology in drive network.", "A numerical example is given to show the effectiveness of the proposed method."], "title": "Structure Identification of Uncertain Complex Networks Based on Anticipatory Projective Synchronization."}
{"paper_id": 27632367, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "The recent availability of novel dyes and alternative light sources to facilitate complex tissue immunofluorescence studies such as multiplex labelling has not been matched by reports critically evaluating the considerations and relative benefits of these new tools, particularly in combination. Product information is often limited to wavelengths used for older fluorophores (FITC, TRITC & corresponding Alexa dyes family). Consequently, novel agents such as Quantum dots are not widely appreciated or used, despite highly favourable properties including extremely bright emission, stability and potentially reduced tissue autofluorescence at the excitation wavelength. Using spectral analysis, we report here a detailed critical appraisal and comparative evaluation of different light sources and fluorophores in multiplex immunofluorescence of clinical biopsy sections. The comparison includes mercury light, metal halide and 3 different LED-based systems, using 7 Qdots (525, 565, 585, 605, 625, 705), Cy3 and Cy5. We discuss the considerations relevant to achieving the best combination of light source and fluorophore for accurate multiplex fluorescence quantitation. We highlight practical limitations and confounders to quantitation with filter-based approaches.", "journal": "PloS one", "sentences": ["The recent availability of novel dyes and alternative light sources to facilitate complex tissue immunofluorescence studies such as multiplex labelling has not been matched by reports critically evaluating the considerations and relative benefits of these new tools, particularly in combination.", "Product information is often limited to wavelengths used for older fluorophores (FITC, TRITC & corresponding Alexa dyes family).", "Consequently, novel agents such as Quantum dots are not widely appreciated or used, despite highly favourable properties including extremely bright emission, stability and potentially reduced tissue autofluorescence at the excitation wavelength.", "Using spectral analysis, we report here a detailed critical appraisal and comparative evaluation of different light sources and fluorophores in multiplex immunofluorescence of clinical biopsy sections.", "The comparison includes mercury light, metal halide and 3 different LED-based systems, using 7 Qdots (525, 565, 585, 605, 625, 705), Cy3 and Cy5.", "We discuss the considerations relevant to achieving the best combination of light source and fluorophore for accurate multiplex fluorescence quantitation.", "We highlight practical limitations and confounders to quantitation with filter-based approaches."], "title": "Choice of Illumination System & Fluorophore for Multiplex Immunofluorescence on FFPE Tissue Sections."}
{"paper_id": 26528740, "labels": ["0", "0", "0", "0", "1"], "abstract": "In their study \"Vocal Learning in the Functionally Referential Food Grunts of Chimpanzees\", Watson et al.[1] claimed that they \"provide the first evidence for vocal learning in a referential call in non-humans\". We challenge this conclusion, on two counts. For one, we are not convinced that the authors controlled for arousal (or at least they did not report such data); furthermore, the vocal characteristics of the two groups largely overlapped already at the beginning of the study. Accordingly, we also question the authors' claim that their finding \"sheds new light on the evolutionary history of human referential words\".", "journal": "Current biology : CB", "sentences": ["In their study \"Vocal Learning in the Functionally Referential Food Grunts of Chimpanzees\", Watson et al.", "[1] claimed that they \"provide the first evidence for vocal learning in a referential call in non-humans\".", "We challenge this conclusion, on two counts.", "For one, we are not convinced that the authors controlled for arousal (or at least they did not report such data); furthermore, the vocal characteristics of the two groups largely overlapped already at the beginning of the study.", "Accordingly, we also question the authors' claim that their finding \"sheds new light on the evolutionary history of human referential words\"."], "title": "Is there any evidence for vocal learning in chimpanzee food calls?"}
{"paper_id": 21455315, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Bilingualism provides a unique opportunity for understanding the relative roles of proficiency and order of acquisition in determining how the brain represents language. In a previous study, we combined magnetoencephalography (MEG) and magnetic resonance imaging (MRI) to examine the spatiotemporal dynamics of word processing in a group of Spanish-English bilinguals who were more proficient in their native language. We found that from the earliest stages of lexical processing, words in the second language evoke greater activity in bilateral posterior visual regions, while activity to the native language is largely confined to classical left hemisphere fronto-temporal areas. In the present study, we sought to examine whether these effects relate to language proficiency or order of language acquisition by testing Spanish-English bilingual subjects who had become dominant in their second language. Additionally, we wanted to determine whether activity in bilateral visual regions was related to the presentation of written words in our previous study, so we presented subjects with both written and auditory words. We found greater activity for the less proficient native language in bilateral posterior visual regions for both the visual and auditory modalities, which started during the earliest word encoding stages and continued through lexico-semantic processing. In classical left fronto-temporal regions, the two languages evoked similar activity. Therefore, it is the lack of proficiency rather than secondary acquisition order that determines the recruitment of non-classical areas for word processing.", "journal": "PloS one", "sentences": ["Bilingualism provides a unique opportunity for understanding the relative roles of proficiency and order of acquisition in determining how the brain represents language.", "In a previous study, we combined magnetoencephalography (MEG) and magnetic resonance imaging (MRI) to examine the spatiotemporal dynamics of word processing in a group of Spanish-English bilinguals who were more proficient in their native language.", "We found that from the earliest stages of lexical processing, words in the second language evoke greater activity in bilateral posterior visual regions, while activity to the native language is largely confined to classical left hemisphere fronto-temporal areas.", "In the present study, we sought to examine whether these effects relate to language proficiency or order of language acquisition by testing Spanish-English bilingual subjects who had become dominant in their second language.", "Additionally, we wanted to determine whether activity in bilateral visual regions was related to the presentation of written words in our previous study, so we presented subjects with both written and auditory words.", "We found greater activity for the less proficient native language in bilateral posterior visual regions for both the visual and auditory modalities, which started during the earliest word encoding stages and continued through lexico-semantic processing.", "In classical left fronto-temporal regions, the two languages evoked similar activity.", "Therefore, it is the lack of proficiency rather than secondary acquisition order that determines the recruitment of non-classical areas for word processing."], "title": "Language proficiency modulates the recruitment of non-classical language areas in bilinguals."}
{"paper_id": 26786190, "labels": ["0", "1", "0", "0", "0", "0", "1", "1"], "abstract": "Chloride intracellular channel 4 (CLIC4) is a mammalian homologue of EXC-4 whose mutation is associated with cystic excretory canals in nematodes. Here we show that CLIC4-null mouse embryos exhibit impaired renal tubulogenesis. In both developing and developed kidneys, CLIC4 is specifically enriched in the proximal tubule epithelial cells, in which CLIC4 is important for luminal delivery, microvillus morphogenesis, and endolysosomal biogenesis. Adult CLIC4-null proximal tubules display aberrant dilation. In MDCK 3D cultures, CLIC4 is expressed on early endosome, recycling endosome and apical transport carriers before reaching its steady-state apical membrane localization in mature lumen. CLIC4 suppression causes impaired apical vesicle coalescence and central lumen formation, a phenotype that can be rescued by Rab8 and Cdc42. Furthermore, we show that retromer- and branched actin-mediated trafficking on early endosome regulates apical delivery during early luminogenesis. CLIC4 selectively modulates retromer-mediated apical transport by negatively regulating the formation of branched actin on early endosomes.", "journal": "Nature communications", "sentences": ["Chloride intracellular channel 4 (CLIC4) is a mammalian homologue of EXC-4 whose mutation is associated with cystic excretory canals in nematodes.", "Here we show that CLIC4-null mouse embryos exhibit impaired renal tubulogenesis.", "In both developing and developed kidneys, CLIC4 is specifically enriched in the proximal tubule epithelial cells, in which CLIC4 is important for luminal delivery, microvillus morphogenesis, and endolysosomal biogenesis.", "Adult CLIC4-null proximal tubules display aberrant dilation.", "In MDCK 3D cultures, CLIC4 is expressed on early endosome, recycling endosome and apical transport carriers before reaching its steady-state apical membrane localization in mature lumen.", "CLIC4 suppression causes impaired apical vesicle coalescence and central lumen formation, a phenotype that can be rescued by Rab8 and Cdc42.", "Furthermore, we show that retromer- and branched actin-mediated trafficking on early endosome regulates apical delivery during early luminogenesis.", "CLIC4 selectively modulates retromer-mediated apical transport by negatively regulating the formation of branched actin on early endosomes."], "title": "CLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking."}
{"paper_id": 24244604, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Helicobacter pylori infection is associated with extragastric diseases. The thyroid may be one of the targets of chronic inflammation. Here, we sought to investigate whether H. pylori infections were associated with the presence of thyroid nodules. A total of 988 euthyroid subjects from China were included in this cross-sectional study. Four hundred thirty-five (44.0%) subjects were diagnosed as having thyroid nodules, and 486 (49.2%) were diagnosed with H. pylori infections. The thyroid nodules group had a higher proportion of H. pylori infections than the control group (P = 0.002). Free thyroxine (FT4) levels were lower and the prevalence of thyroid nodules was higher in patients with H. pylori infection compared to those without infection, even after adjustment for age, gender, and body mass index (BMI; all P < 0.05). The prevalence of H. pylori infection showed a decreasing trend as serum FT4 level increased (P(trend) = 0.020). Stepwise logistic regression analysis showed that H. pylori infection was significantly associated with the risk of thyroid nodules (odds ratio: 1.390, 95% confidence interval: 1.059-1.824, P = 0.018). Our results suggested that H. pylori infections were positively associated with the presence of thyroid nodules in the euthyroid population, whose thyroid functions were in the reference range.", "journal": "PloS one", "sentences": ["Helicobacter pylori infection is associated with extragastric diseases.", "The thyroid may be one of the targets of chronic inflammation.", "Here, we sought to investigate whether H. pylori infections were associated with the presence of thyroid nodules.", "A total of 988 euthyroid subjects from China were included in this cross-sectional study.", "Four hundred thirty-five (44.0%) subjects were diagnosed as having thyroid nodules, and 486 (49.2%) were diagnosed with H. pylori infections.", "The thyroid nodules group had a higher proportion of H. pylori infections than the control group (P = 0.002).", "Free thyroxine (FT4) levels were lower and the prevalence of thyroid nodules was higher in patients with H. pylori infection compared to those without infection, even after adjustment for age, gender, and body mass index (BMI; all P < 0.05).", "The prevalence of H. pylori infection showed a decreasing trend as serum FT4 level increased (P(trend) = 0.020).", "Stepwise logistic regression analysis showed that H. pylori infection was significantly associated with the risk of thyroid nodules (odds ratio: 1.390, 95% confidence interval: 1.059-1.824, P = 0.018).", "Our results suggested that H. pylori infections were positively associated with the presence of thyroid nodules in the euthyroid population, whose thyroid functions were in the reference range."], "title": "Helicobacter pylori infection is associated with the presence of thyroid nodules in the euthyroid population."}
{"paper_id": 24498201, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Strong intercellular adhesion is critical for tissues that experience mechanical stress, such as the skin and heart. Desmosomes provide adhesive strength to tissues by anchoring desmosomal cadherins of neighboring cells to the intermediate filament cytoskeleton. Alterations in assembly and disassembly compromise desmosome function and may contribute to human diseases, such as the autoimmune skin blistering disease pemphigus vulgaris (PV). We previously demonstrated that PV auto-antibodies directed against the desmosomal cadherin desmoglein 3 (Dsg3) cause loss of adhesion by triggering membrane raft-mediated Dsg3 endocytosis. We hypothesized that raft membrane microdomains play a broader role in desmosome homeostasis by regulating the dynamics of desmosome assembly and disassembly. In human keratinocytes, Dsg3 is raft associated as determined by biochemical and super resolution immunofluorescence microscopy methods. Cholesterol depletion, which disrupts rafts, prevented desmosome assembly and adhesion, thus functionally linking rafts to desmosome formation. Interestingly, Dsg3 did not associate with rafts in cells lacking desmosomal proteins. Additionally, PV IgG-induced desmosome disassembly occurred by redistribution of Dsg3 into raft-containing endocytic membrane domains, resulting in cholesterol-dependent loss of adhesion. These findings demonstrate that membrane rafts are required for desmosome assembly and disassembly dynamics, suggesting therapeutic potential for raft targeting agents in desmosomal diseases such as PV.", "journal": "PloS one", "sentences": ["Strong intercellular adhesion is critical for tissues that experience mechanical stress, such as the skin and heart.", "Desmosomes provide adhesive strength to tissues by anchoring desmosomal cadherins of neighboring cells to the intermediate filament cytoskeleton.", "Alterations in assembly and disassembly compromise desmosome function and may contribute to human diseases, such as the autoimmune skin blistering disease pemphigus vulgaris (PV).", "We previously demonstrated that PV auto-antibodies directed against the desmosomal cadherin desmoglein 3 (Dsg3) cause loss of adhesion by triggering membrane raft-mediated Dsg3 endocytosis.", "We hypothesized that raft membrane microdomains play a broader role in desmosome homeostasis by regulating the dynamics of desmosome assembly and disassembly.", "In human keratinocytes, Dsg3 is raft associated as determined by biochemical and super resolution immunofluorescence microscopy methods.", "Cholesterol depletion, which disrupts rafts, prevented desmosome assembly and adhesion, thus functionally linking rafts to desmosome formation.", "Interestingly, Dsg3 did not associate with rafts in cells lacking desmosomal proteins.", "Additionally, PV IgG-induced desmosome disassembly occurred by redistribution of Dsg3 into raft-containing endocytic membrane domains, resulting in cholesterol-dependent loss of adhesion.", "These findings demonstrate that membrane rafts are required for desmosome assembly and disassembly dynamics, suggesting therapeutic potential for raft targeting agents in desmosomal diseases such as PV."], "title": "Desmosome assembly and disassembly are membrane raft-dependent."}
{"paper_id": 23886161, "labels": ["0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Along with rapid economic growth and enhanced agricultural productivity, particulate matter emissions in the northern cities of Thailand have been increasing for the past two decades. This trend is expected to continue in the coming decade. Emissions of particulate matter have brought about a series of public health concerns, particularly chronic respiratory diseases. It is well known that lung cancer incidence among northern Thai women is one of the highest in Asia (an annual age-adjusted incidence rate of 37.4 per 100,000). This fact has aroused serious concern among the public and the government and has drawn much attention and interest from the scientific community. To investigate the potential causes of this relatively high lung cancer incidence, this study employed Fourier transform infrared spectroscopy (FTIR) transmission spectroscopy to identify the chemical composition of the PM2.5 collected using Quartz Fibre Filters (QFFs) coupled with MiniVolTM portable air samplers (Airmetrics). PM2.5 samples collected in nine administrative provinces in northern Thailand before and after the \"Haze Episode\" in 2013 were categorised based on three-dimensional plots of a principal component analysis (PCA) with Varimax rotation. In addition, the incremental lifetime exposure to PM2.5 of both genders was calculated, and the first derivative of the FTIR spectrum of individual samples is here discussed.", "journal": "Asian Pacific journal of cancer prevention : APJCP", "sentences": ["Along with rapid economic growth and enhanced agricultural productivity, particulate matter emissions in the northern cities of Thailand have been increasing for the past two decades.", "This trend is expected to continue in the coming decade.", "Emissions of particulate matter have brought about a series of public health concerns, particularly chronic respiratory diseases.", "It is well known that lung cancer incidence among northern Thai women is one of the highest in Asia (an annual age-adjusted incidence rate of 37.4 per 100,000).", "This fact has aroused serious concern among the public and the government and has drawn much attention and interest from the scientific community.", "To investigate the potential causes of this relatively high lung cancer incidence, this study employed Fourier transform infrared spectroscopy (FTIR) transmission spectroscopy to identify the chemical composition of the PM2.5 collected using Quartz Fibre Filters (QFFs) coupled with MiniVolTM portable air samplers (Airmetrics).", "PM2.5 samples collected in nine administrative provinces in northern Thailand before and after the \"Haze Episode\" in 2013 were categorised based on three-dimensional plots of a principal component analysis (PCA) with Varimax rotation.", "In addition, the incremental lifetime exposure to PM2.5 of both genders was calculated, and the first derivative of the FTIR spectrum of individual samples is here discussed."], "title": "Chemical characterisation of organic functional group compositions in PM2.5 collected at nine administrative provinces in northern Thailand during the Haze Episode in 2013."}
{"paper_id": 23549080, "labels": ["0", "1", "0", "0", "0", "0", "1", "1"], "abstract": "Mycolactone is a diffusible lipid secreted by the human pathogen Mycobacterium ulcerans, which induces the formation of open skin lesions referred to as Buruli ulcers. Here, we show that mycolactone operates by hijacking the Wiskott-Aldrich syndrome protein (WASP) family of actin-nucleating factors. By disrupting WASP autoinhibition, mycolactone leads to uncontrolled activation of ARP2/3-mediated assembly of actin in the cytoplasm. In epithelial cells, mycolactone-induced stimulation of ARP2/3 concentrated in the perinuclear region, resulting in defective cell adhesion and directional migration. In vivo injection of mycolactone into mouse ears consistently altered the junctional organization and stratification of keratinocytes, leading to epidermal thinning, followed by rupture. This degradation process was efficiently suppressed by coadministration of the N-WASP inhibitor wiskostatin. These results elucidate the molecular basis of mycolactone activity and provide a mechanism for Buruli ulcer pathogenesis. Our findings should allow for the rationale design of competitive inhibitors of mycolactone binding to N-WASP, with anti-Buruli ulcer therapeutic potential.", "journal": "The Journal of clinical investigation", "sentences": ["Mycolactone is a diffusible lipid secreted by the human pathogen Mycobacterium ulcerans, which induces the formation of open skin lesions referred to as Buruli ulcers.", "Here, we show that mycolactone operates by hijacking the Wiskott-Aldrich syndrome protein (WASP) family of actin-nucleating factors.", "By disrupting WASP autoinhibition, mycolactone leads to uncontrolled activation of ARP2/3-mediated assembly of actin in the cytoplasm.", "In epithelial cells, mycolactone-induced stimulation of ARP2/3 concentrated in the perinuclear region, resulting in defective cell adhesion and directional migration.", "In vivo injection of mycolactone into mouse ears consistently altered the junctional organization and stratification of keratinocytes, leading to epidermal thinning, followed by rupture.", "This degradation process was efficiently suppressed by coadministration of the N-WASP inhibitor wiskostatin.", "These results elucidate the molecular basis of mycolactone activity and provide a mechanism for Buruli ulcer pathogenesis.", "Our findings should allow for the rationale design of competitive inhibitors of mycolactone binding to N-WASP, with anti-Buruli ulcer therapeutic potential."], "title": "Mycolactone activation of Wiskott-Aldrich syndrome proteins underpins Buruli ulcer formation."}
{"paper_id": 26356728, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "0"], "abstract": "Stress-induced hyperglycemia (SIH) has been independently associated with an increased risk of mortality in critically ill patients without diabetes. However, it is also necessary to consider preexisting hyperglycemia when investigating the relationship between SIH and mortality in patients with diabetes. We therefore assessed whether the gap between admission glucose and A1C-derived average glucose (ADAG) levels could be a predictor of mortality in critically ill patients with diabetes.We retrospectively reviewed the Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores and clinical outcomes of patients with diabetes admitted to our medical intensive care unit (ICU) between 2011 and 2014. The glycosylated hemoglobin (HbA1c) levels were converted to the ADAG by the equation, ADAG\u200a=\u200a[(28.7\u200a\u00d7\u200aHbA1c)\u200a-\u200a46.7]. We also used receiver operating characteristic (ROC) curves to determine the optimal cut-off value for the glycemic gap when predicting ICU mortality and used the net reclassification improvement (NRI) to measure the improvement in prediction performance gained by adding the glycemic gap to the APACHE-II score.We enrolled 518 patients, of which 87 (17.0%) died during their ICU stay. Nonsurvivors had significantly higher APACHE-II scores and glycemic gaps than survivors (P\u200a<\u200a0.001). Critically ill patients with diabetes and a glycemic gap \u226580\u200amg/dL had significantly higher ICU mortality and adverse outcomes than those with a glycemic gap <80\u200amg/dL (P\u200a<\u200a0.001). Incorporation of the glycemic gap into the APACHE-II score increased the discriminative performance for predicting ICU mortality by increasing the area under the ROC curve from 0.755 to 0.794 (NRI\u200a=\u200a13.6%, P\u200a=\u200a0.0013).The glycemic gap can be used to assess the severity and prognosis of critically ill patients with diabetes. The addition of the glycemic gap to the APACHE-II score significantly improved its ability to predict ICU mortality.", "journal": "Medicine", "sentences": ["Stress-induced hyperglycemia (SIH) has been independently associated with an increased risk of mortality in critically ill patients without diabetes.", "However, it is also necessary to consider preexisting hyperglycemia when investigating the relationship between SIH and mortality in patients with diabetes.", "We therefore assessed whether the gap between admission glucose and A1C-derived average glucose (ADAG) levels could be a predictor of mortality in critically ill patients with diabetes.We retrospectively reviewed the Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores and clinical outcomes of patients with diabetes admitted to our medical intensive care unit (ICU) between 2011 and 2014.", "The glycosylated hemoglobin (HbA1c) levels were converted to the ADAG by the equation, ADAG\u200a=\u200a[(28.7\u200a\u00d7\u200aHbA1c)\u200a-\u200a46.7].", "We also used receiver operating characteristic (ROC) curves to determine the optimal cut-off value for the glycemic gap when predicting ICU mortality and used the net reclassification improvement (NRI) to measure the improvement in prediction performance gained by adding the glycemic gap to the APACHE-II score.We enrolled 518 patients, of which 87 (17.0%) died during their ICU stay.", "Nonsurvivors had significantly higher APACHE-II scores and glycemic gaps than survivors (P\u200a<\u200a0.001).", "Critically ill patients with diabetes and a glycemic gap \u226580\u200amg/dL had significantly higher ICU mortality and adverse outcomes than those with a glycemic gap <80\u200amg/dL (P\u200a<\u200a0.001).", "Incorporation of the glycemic gap into the APACHE-II score increased the discriminative performance for predicting ICU mortality by increasing the area under the ROC curve from 0.755 to 0.794 (NRI\u200a=\u200a13.6%, P\u200a=\u200a0.0013).The glycemic gap can be used to assess the severity and prognosis of critically ill patients with diabetes.", "The addition of the glycemic gap to the APACHE-II score significantly improved its ability to predict ICU mortality."], "title": "Usefulness of Glycemic Gap to Predict ICU Mortality in Critically Ill Patients With Diabetes."}
{"paper_id": 26176702, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "Cancer can be viewed as an emergent behavior in terms of complex system theory and artificial life, Cellular Automata (CA) being the tool most used for studying and characterizing the emergent behavior. Different approaches with CA models were used to model cancer growth. The use of the abstract model of acquired cancer hallmarks permits the direct modeling at cellular level, where a cellular automaton defines the mitotic and apoptotic behavior of cells, and allows for an analysis of different dynamics of the cellular system depending on the presence of the different hallmarks. A CA model based on the presence of hallmarks in the cells, which includes a simulation of the behavior of Cancer Stem Cells (CSC) and their implications for the resultant growth behavior of the multicellular system, was employed. This modeling of cancer growth, in the avascular phase, was employed to analyze the effect of cancer treatments in a cancer stem cell context. The model clearly explains why, after treatment against non-stem cancer cells, the regrowth capability of CSCs generates a faster regrowth of tumor behavior, and also shows that a continuous low-intensity treatment does not favor CSC proliferation and differentiation, thereby allowing an unproblematic control of future tumor regrowth. The analysis performed indicates that, contrary to the current attempts at CSC control, trying to make CSC proliferation more difficult is an important point to consider, especially in the immediate period after a standard treatment for controlling non-stem cancer cell proliferation.", "journal": "PloS one", "sentences": ["Cancer can be viewed as an emergent behavior in terms of complex system theory and artificial life, Cellular Automata (CA) being the tool most used for studying and characterizing the emergent behavior.", "Different approaches with CA models were used to model cancer growth.", "The use of the abstract model of acquired cancer hallmarks permits the direct modeling at cellular level, where a cellular automaton defines the mitotic and apoptotic behavior of cells, and allows for an analysis of different dynamics of the cellular system depending on the presence of the different hallmarks.", "A CA model based on the presence of hallmarks in the cells, which includes a simulation of the behavior of Cancer Stem Cells (CSC) and their implications for the resultant growth behavior of the multicellular system, was employed.", "This modeling of cancer growth, in the avascular phase, was employed to analyze the effect of cancer treatments in a cancer stem cell context.", "The model clearly explains why, after treatment against non-stem cancer cells, the regrowth capability of CSCs generates a faster regrowth of tumor behavior, and also shows that a continuous low-intensity treatment does not favor CSC proliferation and differentiation, thereby allowing an unproblematic control of future tumor regrowth.", "The analysis performed indicates that, contrary to the current attempts at CSC control, trying to make CSC proliferation more difficult is an important point to consider, especially in the immediate period after a standard treatment for controlling non-stem cancer cell proliferation."], "title": "Treatment Analysis in a Cancer Stem Cell Context Using a Tumor Growth Model Based on Cellular Automata."}
{"paper_id": 22246035, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "HM1.24, an immunologic target for multiple myeloma (MM) cells, has not been effectively targeted with therapeutic monoclonal antibodies (mAbs). In this study, we investigated in vitro and in vivo anti-MM activities of XmAb5592, a humanized anti-HM1.24 mAb with Fc-domain engineered to significantly enhance Fc\u03b3R binding and associated immune effector functions. XmAb5592 increased antibody-dependent cellular cytotoxicity (ADCC) several fold relative to the anti-HM1.24 IgG1 analog against both MM cell lines and primary patient myeloma cells. XmAb5592 also augmented antibody dependent cellular phagocytosis (ADCP) by macrophages. Natural killer (NK) cells became more activated by XmAb5592 than the IgG1 analog, evidenced by increased cell surface expression of granzyme B-dependent CD107a and MM cell lysis, even in the presence of bone marrow stromal cells. XmAb5592 potently inhibited tumor growth in mice bearing human MM xenografts via Fc\u03b3R-dependent mechanisms, and was significantly more effective than the IgG1 analog. Lenalidomide synergistically enhanced in vitro ADCC against MM cells and in vivo tumor inhibition induced by XmAb5592. A single dose of 20 mg/kg XmAb5592 effectively depleted both blood and bone marrow plasma cells in cynomolgus monkeys. These results support clinical development of XmAb5592, both as a monotherapy and in combination with lenalidomide, to improve patient outcome of MM.", "journal": "Blood", "sentences": ["HM1.24, an immunologic target for multiple myeloma (MM) cells, has not been effectively targeted with therapeutic monoclonal antibodies (mAbs).", "In this study, we investigated in vitro and in vivo anti-MM activities of XmAb5592, a humanized anti-HM1.24 mAb with Fc-domain engineered to significantly enhance Fc\u03b3R binding and associated immune effector functions.", "XmAb5592 increased antibody-dependent cellular cytotoxicity (ADCC) several fold relative to the anti-HM1.24 IgG1 analog against both MM cell lines and primary patient myeloma cells.", "XmAb5592 also augmented antibody dependent cellular phagocytosis (ADCP) by macrophages.", "Natural killer (NK) cells became more activated by XmAb5592 than the IgG1 analog, evidenced by increased cell surface expression of granzyme B-dependent CD107a and MM cell lysis, even in the presence of bone marrow stromal cells.", "XmAb5592 potently inhibited tumor growth in mice bearing human MM xenografts via Fc\u03b3R-dependent mechanisms, and was significantly more effective than the IgG1 analog.", "Lenalidomide synergistically enhanced in vitro ADCC against MM cells and in vivo tumor inhibition induced by XmAb5592.", "A single dose of 20 mg/kg XmAb5592 effectively depleted both blood and bone marrow plasma cells in cynomolgus monkeys.", "These results support clinical development of XmAb5592, both as a monotherapy and in combination with lenalidomide, to improve patient outcome of MM."], "title": "Potent in vitro and in vivo activity of an Fc-engineered humanized anti-HM1.24 antibody against multiple myeloma via augmented effector function."}
{"paper_id": 25695377, "labels": ["0", "0", "1", "0", "0", "1"], "abstract": "Silicate glasses are durable materials, but are they sufficiently durable to confine highly radioactive wastes for hundreds of thousands years? Addressing this question requires a thorough understanding of the mechanisms underpinning aqueous corrosion of these materials. Here we show that in silica-saturated solution, a model glass of nuclear interest corrodes but at a rate that dramatically drops as a passivating layer forms. Water ingress into the glass, leading to the congruent release of mobile elements (B, Na and Ca), is followed by in situ repolymerization of the silicate network. This material is at equilibrium with pore and bulk solutions, and acts as a molecular sieve with a cutoff below 1\u2009nm. The low corrosion rate resulting from the formation of this stable passivating layer enables the objective of durability to be met, while progress in the fundamental understanding of corrosion unlocks the potential for optimizing the design of nuclear glass-geological disposal.", "journal": "Nature communications", "sentences": ["Silicate glasses are durable materials, but are they sufficiently durable to confine highly radioactive wastes for hundreds of thousands years?", "Addressing this question requires a thorough understanding of the mechanisms underpinning aqueous corrosion of these materials.", "Here we show that in silica-saturated solution, a model glass of nuclear interest corrodes but at a rate that dramatically drops as a passivating layer forms.", "Water ingress into the glass, leading to the congruent release of mobile elements (B, Na and Ca), is followed by in situ repolymerization of the silicate network.", "This material is at equilibrium with pore and bulk solutions, and acts as a molecular sieve with a cutoff below 1\u2009nm.", "The low corrosion rate resulting from the formation of this stable passivating layer enables the objective of durability to be met, while progress in the fundamental understanding of corrosion unlocks the potential for optimizing the design of nuclear glass-geological disposal."], "title": "Origin and consequences of silicate glass passivation by surface layers."}
{"paper_id": 24092019, "labels": ["0", "0", "0", "0", "1"], "abstract": "Hexagonal boron nitride is a two-dimensional layered material that can be stable at 1,500 \u00b0C in air and will not react with most chemicals. Here we demonstrate large-scale, ultrathin, oxidation-resistant coatings of high-quality hexagonal boron nitride layers with controlled thicknesses from double layers to bulk. We show that such ultrathin hexagonal boron nitride films are impervious to oxygen diffusion even at high temperatures and can serve as high-performance oxidation-resistant coatings for nickel up to 1,100 \u00b0C in oxidizing atmospheres. Furthermore, graphene layers coated with a few hexagonal boron nitride layers are also protected at similarly high temperatures. These hexagonal boron nitride atomic layer coatings, which can be synthesized via scalable chemical vapour deposition method down to only two layers, could be the thinnest coating ever shown to withstand such extreme environments and find applications as chemically stable high-temperature coatings.", "journal": "Nature communications", "sentences": ["Hexagonal boron nitride is a two-dimensional layered material that can be stable at 1,500 \u00b0C in air and will not react with most chemicals.", "Here we demonstrate large-scale, ultrathin, oxidation-resistant coatings of high-quality hexagonal boron nitride layers with controlled thicknesses from double layers to bulk.", "We show that such ultrathin hexagonal boron nitride films are impervious to oxygen diffusion even at high temperatures and can serve as high-performance oxidation-resistant coatings for nickel up to 1,100 \u00b0C in oxidizing atmospheres.", "Furthermore, graphene layers coated with a few hexagonal boron nitride layers are also protected at similarly high temperatures.", "These hexagonal boron nitride atomic layer coatings, which can be synthesized via scalable chemical vapour deposition method down to only two layers, could be the thinnest coating ever shown to withstand such extreme environments and find applications as chemically stable high-temperature coatings."], "title": "Ultrathin high-temperature oxidation-resistant coatings of hexagonal boron nitride."}
{"paper_id": 26791615, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Lekking is a rare, but iconic mating system where polygynous males aggregate and perform group displays to attract females. Existing theory postulates that demographic and environmental stability are required for lekking to be an evolutionarily viable reproductive strategy. However, we lack empirical tests for the hypotheses that lek stability is facilitated by age-specific variation in demographic rates, and by predictable, abundant resources. To address this knowledge gap, we use multistate models to examine how two demographic elements of lek stability-male survival and recruitment-vary with age, social status and phase of the El Ni\u00f1o Southern Oscillation (ENSO) in a Neotropical frugivorous bird, the wire-tailed manakin (Pipra filicauda). Our results show that demographic and environmental conditions were related to lek stability in the Ecuadorean Amazon. Apparent annual survival probability of territorial males was higher than that of non-territorial floaters, and recruitment probability increased as males progressed in an age-graded queue. Moreover, annual survival of territorial males and body condition of both floaters and territory holders were higher following years with El Ni\u00f1o conditions, associated with reduced rainfall and probably higher fruit production in the northern Neotropics, and lower after years with wet, La Ni\u00f1a conditions that predominated our study. Recruitment probabilities varied annually, independent of ENSO phase, and increased over our study period, but the annual mean number of territorial males per lek declined. Our results provide empirical support for hypothesized demographic and environmental drivers of lek dynamics. This study also suggests that climate-mediated changes in resource availability can affect demography and subsequent lek stability in a relatively buffered, lowland rainforest.", "journal": "Proceedings. Biological sciences / The Royal Society", "sentences": ["Lekking is a rare, but iconic mating system where polygynous males aggregate and perform group displays to attract females.", "Existing theory postulates that demographic and environmental stability are required for lekking to be an evolutionarily viable reproductive strategy.", "However, we lack empirical tests for the hypotheses that lek stability is facilitated by age-specific variation in demographic rates, and by predictable, abundant resources.", "To address this knowledge gap, we use multistate models to examine how two demographic elements of lek stability-male survival and recruitment-vary with age, social status and phase of the El Ni\u00f1o Southern Oscillation (ENSO) in a Neotropical frugivorous bird, the wire-tailed manakin (Pipra filicauda).", "Our results show that demographic and environmental conditions were related to lek stability in the Ecuadorean Amazon.", "Apparent annual survival probability of territorial males was higher than that of non-territorial floaters, and recruitment probability increased as males progressed in an age-graded queue.", "Moreover, annual survival of territorial males and body condition of both floaters and territory holders were higher following years with El Ni\u00f1o conditions, associated with reduced rainfall and probably higher fruit production in the northern Neotropics, and lower after years with wet, La Ni\u00f1a conditions that predominated our study.", "Recruitment probabilities varied annually, independent of ENSO phase, and increased over our study period, but the annual mean number of territorial males per lek declined.", "Our results provide empirical support for hypothesized demographic and environmental drivers of lek dynamics.", "This study also suggests that climate-mediated changes in resource availability can affect demography and subsequent lek stability in a relatively buffered, lowland rainforest."], "title": "Climate, demography and lek stability in an Amazonian bird."}
{"paper_id": 26605635, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "Absorption spectra of the green-to-red convertible fluorescent protein EosFP have been computed in a hybrid quantum mechanical/molecular mechanical (QM/MM) framework. The experimentally observed absorption maximum at \u223c390 nm is well reproduced by the protein with a neutral chromophore, and the anionic form is computed to absorb close to the experimentally determined maximum at \u223c500 nm. Absorption of a zwitterionic form is calculated to lie in the same spectral region; however, this species cannot be unambiguously assigned to the experimental spectra. Variation of the protonation states of residues surrounding the chromophore do not have significant impact on the positions of the absorption maxima. In particular, protonation of Glu212 leaves the calculated spectra largely unaffected. This is consistent with the spectra of the E212Q mutant, which differ from the wild-type spectra only in the intensities but not in the positions of the absorption bands.", "journal": "Journal of chemical theory and computation", "sentences": ["Absorption spectra of the green-to-red convertible fluorescent protein EosFP have been computed in a hybrid quantum mechanical/molecular mechanical (QM/MM) framework.", "The experimentally observed absorption maximum at \u223c390 nm is well reproduced by the protein with a neutral chromophore, and the anionic form is computed to absorb close to the experimentally determined maximum at \u223c500 nm.", "Absorption of a zwitterionic form is calculated to lie in the same spectral region; however, this species cannot be unambiguously assigned to the experimental spectra.", "Variation of the protonation states of residues surrounding the chromophore do not have significant impact on the positions of the absorption maxima.", "In particular, protonation of Glu212 leaves the calculated spectra largely unaffected.", "This is consistent with the spectra of the E212Q mutant, which differ from the wild-type spectra only in the intensities but not in the positions of the absorption bands."], "title": "Computational Study of Absorption Spectra of the Photoconvertible Fluorescent Protein EosFP in Different Protonation States."}
{"paper_id": 21456161, "labels": ["0", "0", "0", "0", "1"], "abstract": "The toxicity and biodistribution in vivo of various morphologies of Au nanoparticles (AuNPs) were studied by using KM mice. The quantitative analysis of Au in each tissue of mice was done by using the Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Sphere-shaped AuNPs displayed the best biocompatibility, compared with rod- and cube-shaped of AuNPs, and rod-shaped AuNPs was more toxic than cube-shaped AuNPs. In vivo biodistribution study revealed all AuNPs were preferentially accumulated in organ of liver and spleen. The findings from this study thus revealed that the toxicity and biodistribution in vivo of AuNPs are shape dependent.", "journal": "Journal of nanoscience and nanotechnology", "sentences": ["The toxicity and biodistribution in vivo of various morphologies of Au nanoparticles (AuNPs) were studied by using KM mice.", "The quantitative analysis of Au in each tissue of mice was done by using the Inductively Coupled Plasma Mass Spectrometry (ICP-MS).", "Sphere-shaped AuNPs displayed the best biocompatibility, compared with rod- and cube-shaped of AuNPs, and rod-shaped AuNPs was more toxic than cube-shaped AuNPs.", "In vivo biodistribution study revealed all AuNPs were preferentially accumulated in organ of liver and spleen.", "The findings from this study thus revealed that the toxicity and biodistribution in vivo of AuNPs are shape dependent."], "title": "Shape dependence of gold nanoparticles on in vivo acute toxicological effects and biodistribution."}
{"paper_id": 25147119, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Amyloid-\u03b2 (A\u03b2) peptide plays a major role in the pathogenesis of Alzheimer's disease (AD), and is generated by \u03b2- and \u03b3-secretase-mediated proteolytic processing of amyloid-\u03b2 protein precursor (A\u03b2PP). In the present study, we investigated the effect of 118 natural compounds on A\u03b2 production in the medium of HEK293 cells stably expressing human A\u03b2PP695 (HEK293-A\u03b2PP) using A\u03b242 sandwich ELISA to find natural compounds that can modulate A\u03b2 production. We found that a coumarin derivative of citrus fruits, auraptene, increased A\u03b2 production. Treatment of HEK293-A\u03b2PP cells and rat primary cortical neurons with auraptene significantly increased the secretion of A\u03b240, A\u03b242, and the A\u03b242/40 ratio. However, auraptene did not change the protein levels of the A\u03b2PP processing enzymes, a disintegrin and metalloproteinases 10 (ADAM10, \u03b1-secretase), \u03b2-site A\u03b2PP cleaving enzyme-1 (BACE-1, \u03b2-secretase), and presenilin 1 (PS1, \u03b3-secretase component). Auraptene increased the activity of \u03b3-secretase but not that of \u03b1- and \u03b2-secretase. Furthermore, auraptene enhanced \u03b3-secretase-mediated production of A\u03b2 from A\u03b2PP or A\u03b2PP-C99, but not through \u03b1- and \u03b2-secretase. Auraptene also phosphorylated c-Jun N-terminal kinase (JNK), and pretreatment with the JNK inhibitor, SP600125, reduced auraptene-induced \u03b3-secretase activity. Overall, our results suggest that auraptene-mediated activation of JNK may contribute to the production of A\u03b2 by promoting \u03b3-secretase activity.", "journal": "Journal of Alzheimer's disease : JAD", "sentences": ["Amyloid-\u03b2 (A\u03b2) peptide plays a major role in the pathogenesis of Alzheimer's disease (AD), and is generated by \u03b2- and \u03b3-secretase-mediated proteolytic processing of amyloid-\u03b2 protein precursor (A\u03b2PP).", "In the present study, we investigated the effect of 118 natural compounds on A\u03b2 production in the medium of HEK293 cells stably expressing human A\u03b2PP695 (HEK293-A\u03b2PP) using A\u03b242 sandwich ELISA to find natural compounds that can modulate A\u03b2 production.", "We found that a coumarin derivative of citrus fruits, auraptene, increased A\u03b2 production.", "Treatment of HEK293-A\u03b2PP cells and rat primary cortical neurons with auraptene significantly increased the secretion of A\u03b240, A\u03b242, and the A\u03b242/40 ratio.", "However, auraptene did not change the protein levels of the A\u03b2PP processing enzymes, a disintegrin and metalloproteinases 10 (ADAM10, \u03b1-secretase), \u03b2-site A\u03b2PP cleaving enzyme-1 (BACE-1, \u03b2-secretase), and presenilin 1 (PS1, \u03b3-secretase component).", "Auraptene increased the activity of \u03b3-secretase but not that of \u03b1- and \u03b2-secretase.", "Furthermore, auraptene enhanced \u03b3-secretase-mediated production of A\u03b2 from A\u03b2PP or A\u03b2PP-C99, but not through \u03b1- and \u03b2-secretase.", "Auraptene also phosphorylated c-Jun N-terminal kinase (JNK), and pretreatment with the JNK inhibitor, SP600125, reduced auraptene-induced \u03b3-secretase activity.", "Overall, our results suggest that auraptene-mediated activation of JNK may contribute to the production of A\u03b2 by promoting \u03b3-secretase activity."], "title": "Auraptene increases the production of amyloid-\u03b2 via c-Jun N-terminal kinase-dependent activation of \u03b3-secretase."}
{"paper_id": 22146822, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Principal component analysis (PCA) is capable of handling large sets of data. However, lack of consistent method in data pre-treatment and its importance are the limitations in PCA applications. This study examined pre-treatments methods (log (x + 1) transformation, outlier removal, and granulometric and geochemical normalization) on dataset of Mengkabong Lagoon, Sabah, mangrove surface sediment at high and low tides. The study revealed that geochemical normalization using Al with outliers removal resulted in a better classification of the mangrove surface sediment than that outliers removal, granulometric normalization using clay and log (x + 1) transformation. PCA output using geochemical normalization with outliers removal demonstrated associations between environmental variables and tides of mangrove surface sediment, Mengkabong Lagoon, Sabah. The PCA outputs at high and low tides also provided to better interpret information about the sediment and its controlling factors in the intertidal zone. The study showed data pre-treatment method to be a useful procedure to standardize the datasets and reducing the influence of outliers.", "journal": "Environmental monitoring and assessment", "sentences": ["Principal component analysis (PCA) is capable of handling large sets of data.", "However, lack of consistent method in data pre-treatment and its importance are the limitations in PCA applications.", "This study examined pre-treatments methods (log (x + 1) transformation, outlier removal, and granulometric and geochemical normalization) on dataset of Mengkabong Lagoon, Sabah, mangrove surface sediment at high and low tides.", "The study revealed that geochemical normalization using Al with outliers removal resulted in a better classification of the mangrove surface sediment than that outliers removal, granulometric normalization using clay and log (x + 1) transformation.", "PCA output using geochemical normalization with outliers removal demonstrated associations between environmental variables and tides of mangrove surface sediment, Mengkabong Lagoon, Sabah.", "The PCA outputs at high and low tides also provided to better interpret information about the sediment and its controlling factors in the intertidal zone.", "The study showed data pre-treatment method to be a useful procedure to standardize the datasets and reducing the influence of outliers."], "title": "Effect of data pre-treatment procedures on principal component analysis: a case study for mangrove surface sediment datasets."}
{"paper_id": 23675462, "labels": ["0", "0", "0", "0", "1", "0", "1", "1"], "abstract": "Mitogen- and stress-activated protein kinases 1 and 2 (MSK1 and MSK2), activated downstream of the ERK- and p38-mitogen-activated protein kinase pathways are involved in cell survival, proliferation and differentiation. Following mitogenic or stress stimuli, they mediate the nucleosomal response, which includes phosphorylation of histone H3 at serine 10 (H3S10ph) coupled with transcriptional activation of immediate-early genes. While MSK1 and MSK2 are closely related, their relative roles may vary with cellular context and/or stimuli. However, our knowledge of MSK2 recruitment to immediate-early genes is limited, as research has primarily focused on MSK1. Here, we demonstrate that both MSK1 and MSK2, regulate the phorbol ester 12-O-tetradecanoylphorbol-13-acetate induced expression of the breast cancer marker gene, trefoil factor 1 (TFF1), by phosphorylating H3S10 at its 5' regulatory regions. The MSK-mediated phosphorylation of H3S10 promotes the recruitment of 14-3-3 isoforms and BRG1, the ATPase subunit of the BAF/PBAF remodeling complex, to the enhancer and upstream promoter elements of TFF1. The recruited chromatin remodeling activity leads to the RNA polymerase II carboxy-terminal domain phosphorylation at the TFF1 promoter, initiating TFF1 expression in MCF-7 breast cancer cells. Moreover, we show that MSK1 or MSK2 is recruited to TFF1 regulatory regions, but as components of different multiprotein complexes.", "journal": "PloS one", "sentences": ["Mitogen- and stress-activated protein kinases 1 and 2 (MSK1 and MSK2), activated downstream of the ERK- and p38-mitogen-activated protein kinase pathways are involved in cell survival, proliferation and differentiation.", "Following mitogenic or stress stimuli, they mediate the nucleosomal response, which includes phosphorylation of histone H3 at serine 10 (H3S10ph) coupled with transcriptional activation of immediate-early genes.", "While MSK1 and MSK2 are closely related, their relative roles may vary with cellular context and/or stimuli.", "However, our knowledge of MSK2 recruitment to immediate-early genes is limited, as research has primarily focused on MSK1.", "Here, we demonstrate that both MSK1 and MSK2, regulate the phorbol ester 12-O-tetradecanoylphorbol-13-acetate induced expression of the breast cancer marker gene, trefoil factor 1 (TFF1), by phosphorylating H3S10 at its 5' regulatory regions.", "The MSK-mediated phosphorylation of H3S10 promotes the recruitment of 14-3-3 isoforms and BRG1, the ATPase subunit of the BAF/PBAF remodeling complex, to the enhancer and upstream promoter elements of TFF1.", "The recruited chromatin remodeling activity leads to the RNA polymerase II carboxy-terminal domain phosphorylation at the TFF1 promoter, initiating TFF1 expression in MCF-7 breast cancer cells.", "Moreover, we show that MSK1 or MSK2 is recruited to TFF1 regulatory regions, but as components of different multiprotein complexes."], "title": "Mitogen- and stress-activated protein kinases 1 and 2 are required for maximal trefoil factor 1 induction."}
{"paper_id": 26445439, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "The radial component is a network of interlamellar tight junctions (TJs) unique to central nervous system myelin. Ablation of claudin-11, a TJ protein, results in the absence of the radial component and compromises the passive electrical properties of myelin. Although TJs are known to regulate paracellular diffusion, this barrier function has not been directly demonstrated for the radial component, and some evidence suggests that the radial component may also mediate adhesion between myelin membranes. To investigate the physical properties of claudin-11 TJs, we compared fresh, unfixed Claudin 11-null and control nerves using x-ray and neutron diffraction. In Claudin 11-null tissue, we detected no changes in myelin structure, stability, or membrane interactions, which argues against the notion that myelin TJs exhibit significant adhesive properties. Moreover, our osmotic stressing and D2O-H2O exchange experiments demonstrate that myelin lacking claudin-11 is more permeable to water and small osmolytes. Thus, our data indicate that the radial component serves primarily as a diffusion barrier and elucidate the mechanism by which TJs govern myelin function.", "journal": "Biophysical journal", "sentences": ["The radial component is a network of interlamellar tight junctions (TJs) unique to central nervous system myelin.", "Ablation of claudin-11, a TJ protein, results in the absence of the radial component and compromises the passive electrical properties of myelin.", "Although TJs are known to regulate paracellular diffusion, this barrier function has not been directly demonstrated for the radial component, and some evidence suggests that the radial component may also mediate adhesion between myelin membranes.", "To investigate the physical properties of claudin-11 TJs, we compared fresh, unfixed Claudin 11-null and control nerves using x-ray and neutron diffraction.", "In Claudin 11-null tissue, we detected no changes in myelin structure, stability, or membrane interactions, which argues against the notion that myelin TJs exhibit significant adhesive properties.", "Moreover, our osmotic stressing and D2O-H2O exchange experiments demonstrate that myelin lacking claudin-11 is more permeable to water and small osmolytes.", "Thus, our data indicate that the radial component serves primarily as a diffusion barrier and elucidate the mechanism by which TJs govern myelin function."], "title": "Claudin-11 Tight Junctions in Myelin Are a Barrier to Diffusion and Lack Strong Adhesive Properties."}
{"paper_id": 24605057, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "In vitro microtubule assembly exhibits a rhythmic phenomenon, that is, fast growth periods alternating with slow growth periods. Mechanism underlying this phenomenon is unknown. Here a simple diffusion mechanism coupled with small diffusion coefficients is proposed to underlie this phenomenon. Calculations based on previously published results demonstrate that such a mechanism can explain the differences in the average duration of the interval encompassing a fast growth period and a slow growth period in in vitro microtubule assembly experiments in different conditions. Because no parameter unique to the microtubule assembly process is involved in the analysis, the proposed mechanism is expected to be generally applicable to heterogeneous chemical reactions. Also because biological systems are characterized by heterogeneous chemical reactions, the diffusion-based rhythmic characteristic of heterogeneous reactions is postulated to be a fundamental element in generating rhythmic behaviors in biological systems.", "journal": "TheScientificWorldJournal", "sentences": ["In vitro microtubule assembly exhibits a rhythmic phenomenon, that is, fast growth periods alternating with slow growth periods.", "Mechanism underlying this phenomenon is unknown.", "Here a simple diffusion mechanism coupled with small diffusion coefficients is proposed to underlie this phenomenon.", "Calculations based on previously published results demonstrate that such a mechanism can explain the differences in the average duration of the interval encompassing a fast growth period and a slow growth period in in vitro microtubule assembly experiments in different conditions.", "Because no parameter unique to the microtubule assembly process is involved in the analysis, the proposed mechanism is expected to be generally applicable to heterogeneous chemical reactions.", "Also because biological systems are characterized by heterogeneous chemical reactions, the diffusion-based rhythmic characteristic of heterogeneous reactions is postulated to be a fundamental element in generating rhythmic behaviors in biological systems."], "title": "Slow diffusion underlies alternation of fast and slow growth periods of microtubule assembly."}
{"paper_id": 27448149, "labels": ["0", "0", "1", "1", "1", "1"], "abstract": "Extensive research has established how miRNAs regulate target mRNAs by translation repression and/or endonucleolytic degradation in metazoans. However, information related to the effect of target mRNA on biogenesis and stability of corresponding miRNAs in animals is limited. Here we report regulated biogenesis of cognate miRNAs by their target mRNAs. Enhanced pre-miRNA processing by AGO-associated DICER1 contributes to this increased miRNP formation. The processed miRNAs are loaded onto AGO2 to form functionally competent miRISCs both in vivo and also in a cell-free in vitro system. Thus, we identify an additional layer of posttranscriptional regulation that helps the cell to maintain requisite levels of mature forms of respective miRNAs by modulating their processing in a target-dependent manner, a process happening for miR-122 during stress reversal in human hepatic cells.", "journal": "Nature communications", "sentences": ["Extensive research has established how miRNAs regulate target mRNAs by translation repression and/or endonucleolytic degradation in metazoans.", "However, information related to the effect of target mRNA on biogenesis and stability of corresponding miRNAs in animals is limited.", "Here we report regulated biogenesis of cognate miRNAs by their target mRNAs.", "Enhanced pre-miRNA processing by AGO-associated DICER1 contributes to this increased miRNP formation.", "The processed miRNAs are loaded onto AGO2 to form functionally competent miRISCs both in vivo and also in a cell-free in vitro system.", "Thus, we identify an additional layer of posttranscriptional regulation that helps the cell to maintain requisite levels of mature forms of respective miRNAs by modulating their processing in a target-dependent manner, a process happening for miR-122 during stress reversal in human hepatic cells."], "title": "Target-dependent biogenesis of cognate microRNAs in human cells."}
{"paper_id": 26589222, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "Psychological stress is an intrinsic part of life that affects all organs of the body through direct nervous system innervation and the release of neuroendocrine hormones. The field of PsychoNeuroImmunology (PNI) has clearly demonstrated that the physiological response to psychological stressors can dramatically impact the functioning of the immune system, thus identifying one way in which susceptibility to or severity of diseases are exacerbated during stressful periods. This chapter describes research at the interface between the fields of PNI and Microbial Endocrinology to demonstrate that natural barrier defenses, such as those provided by the commensal microflora, can be disrupted by exposure to psychological stressors. These stress effects are evident in the development of the intestinal microflora in animals born from stressful pregnancy conditions, and in older animals with fully developed microbial populations. Moreover, data are presented demonstrating that exposure to different types of stressors results in the translocation of microflora from cutaneous and mucosal surfaces into regional lymph nodes. When considered together, a scenario emerges in which psychological stressors induce a neuroendocrine response that has the potential to directly or indirectly affect commensal microflora populations, the integrity of barrier defenses, and the internalization of microbes. Finally, a hypothesis is put forth in which stressor-induced alterations of the microflora contribute to the observed stressor-induced increases in inflammatory markers in the absence of overt infection.", "journal": "Advances in experimental medicine and biology", "sentences": ["Psychological stress is an intrinsic part of life that affects all organs of the body through direct nervous system innervation and the release of neuroendocrine hormones.", "The field of PsychoNeuroImmunology (PNI) has clearly demonstrated that the physiological response to psychological stressors can dramatically impact the functioning of the immune system, thus identifying one way in which susceptibility to or severity of diseases are exacerbated during stressful periods.", "This chapter describes research at the interface between the fields of PNI and Microbial Endocrinology to demonstrate that natural barrier defenses, such as those provided by the commensal microflora, can be disrupted by exposure to psychological stressors.", "These stress effects are evident in the development of the intestinal microflora in animals born from stressful pregnancy conditions, and in older animals with fully developed microbial populations.", "Moreover, data are presented demonstrating that exposure to different types of stressors results in the translocation of microflora from cutaneous and mucosal surfaces into regional lymph nodes.", "When considered together, a scenario emerges in which psychological stressors induce a neuroendocrine response that has the potential to directly or indirectly affect commensal microflora populations, the integrity of barrier defenses, and the internalization of microbes.", "Finally, a hypothesis is put forth in which stressor-induced alterations of the microflora contribute to the observed stressor-induced increases in inflammatory markers in the absence of overt infection."], "title": "Psychological Stress, Immunity, and the Effects on Indigenous Microflora."}
{"paper_id": 26183018, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Stress has been implicated as a key contributor to poor health outcomes; however, few studies have examined how African American men and women explicitly describe the relationships among stress, coping, and African American men's health. In this paper, we explore strategies men use to cope with stress, and beliefs about the consequences of stress for African American men's health behaviors, morbidity and mortality from the perspectives of African American men and women. A phenomenological analytic approach was used to examine focus group data collected from 154 African American men (18 focus groups) and 77 African American women (8 focus groups). Women's perspectives were captured because women often observe men under stress and can provide support to men during stressful times. Our findings indicate that African American men in this study responded to stress by engaging in often identified coping behaviors (i.e., consumption of calorie dense food, exercise, spiritually-related activities). Men in our study, however, did not always view their responses to stress as explicit coping mechanisms. There was also some discordance between men's and women's perceptions of men's coping behaviors as there were occasions where they seemed to interpret the same behavior differently (e.g., resting vs. avoidance). Men and women believed that stress helped to explain why African American men had worse health than other groups. They identified mental, physical and social consequences of stress. We conclude by detailing implications for conceptualizing and measuring coping and we outline key considerations for interventions and further research about stress, coping and health.", "journal": "Social science & medicine (1982)", "sentences": ["Stress has been implicated as a key contributor to poor health outcomes; however, few studies have examined how African American men and women explicitly describe the relationships among stress, coping, and African American men's health.", "In this paper, we explore strategies men use to cope with stress, and beliefs about the consequences of stress for African American men's health behaviors, morbidity and mortality from the perspectives of African American men and women.", "A phenomenological analytic approach was used to examine focus group data collected from 154 African American men (18 focus groups) and 77 African American women (8 focus groups).", "Women's perspectives were captured because women often observe men under stress and can provide support to men during stressful times.", "Our findings indicate that African American men in this study responded to stress by engaging in often identified coping behaviors (i.e., consumption of calorie dense food, exercise, spiritually-related activities).", "Men in our study, however, did not always view their responses to stress as explicit coping mechanisms.", "There was also some discordance between men's and women's perceptions of men's coping behaviors as there were occasions where they seemed to interpret the same behavior differently (e.g., resting vs. avoidance).", "Men and women believed that stress helped to explain why African American men had worse health than other groups.", "They identified mental, physical and social consequences of stress.", "We conclude by detailing implications for conceptualizing and measuring coping and we outline key considerations for interventions and further research about stress, coping and health."], "title": "\"If you do nothing about stress, the next thing you know, you're shattered\": Perspectives on African American men's stress, coping and health from African American men and key women in their lives."}
{"paper_id": 22261019, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The mechanism underlying the decline of age-related learning and memory remains unclear. Brain-region-specific changes of synaptic proteins and decreased thyroid hormones (THs) have been implied involving this decline. During normal aging, however, the relationships among synaptic proteins, THs and abilities of learning and memory remain to be elucidated. In this study, the age-related spatial learning and memory ability of 41 Kunming mice (KM) (14 mice aged 6 months, 13 mice aged 11 months, 14 mice aged 22 months) was measured with radial six-arm water maze. The levels of SNAP-25 and Munc18-1 in brain regions were semi-quantified by Western blotting and the serum THs were detected by radioimmunoassay. Our results showed the old Kunming mice had marked impairment of spatial learning and memory, with decreased serum free triiodothyronine (FT3) and increased SNAP-25 and Munc18-1 in dorsal hippocampus (DH), ventral hippocampus (VH) and frontal lobe (F). The Pearson's correlation test showed the impairment of spatial learning ability positively correlated with SNAP-25 in DH and Munc18-1 in DH and VH. While, the levels of SNAP-25 (DH, VH and F) and Munc18-1 (DH) negatively correlated with the serum FT3 level, and the spatial memory decline marginal negatively correlate with serum THs. These results suggested that increased hippocampal SNAP-25 and Munc18-1 which seemingly result from decreased serum THs might involve the age-related impairment of spatial learning and memory.", "journal": "Behavioural brain research", "sentences": ["The mechanism underlying the decline of age-related learning and memory remains unclear.", "Brain-region-specific changes of synaptic proteins and decreased thyroid hormones (THs) have been implied involving this decline.", "During normal aging, however, the relationships among synaptic proteins, THs and abilities of learning and memory remain to be elucidated.", "In this study, the age-related spatial learning and memory ability of 41 Kunming mice (KM) (14 mice aged 6 months, 13 mice aged 11 months, 14 mice aged 22 months) was measured with radial six-arm water maze.", "The levels of SNAP-25 and Munc18-1 in brain regions were semi-quantified by Western blotting and the serum THs were detected by radioimmunoassay.", "Our results showed the old Kunming mice had marked impairment of spatial learning and memory, with decreased serum free triiodothyronine (FT3) and increased SNAP-25 and Munc18-1 in dorsal hippocampus (DH), ventral hippocampus (VH) and frontal lobe (F).", "The Pearson's correlation test showed the impairment of spatial learning ability positively correlated with SNAP-25 in DH and Munc18-1 in DH and VH.", "While, the levels of SNAP-25 (DH, VH and F) and Munc18-1 (DH) negatively correlated with the serum FT3 level, and the spatial memory decline marginal negatively correlate with serum THs.", "These results suggested that increased hippocampal SNAP-25 and Munc18-1 which seemingly result from decreased serum THs might involve the age-related impairment of spatial learning and memory."], "title": "Reduced thyroid hormones with increased hippocampal SNAP-25 and Munc18-1 might involve cognitive impairment during aging."}
{"paper_id": 26837577, "labels": ["0", "0", "0", "0", "1", "1", "1"], "abstract": "A central goal of synthetic biology is to implement diverse cellular functions by predictably controlling gene expression. Though research has focused more on protein regulators than RNA regulators, recent advances in our understanding of RNA folding and functions have motivated the use of RNA regulators. RNA regulators provide an advantage because they are easier to design and engineer than protein regulators, potentially have a lower burden on the cell and are highly orthogonal. Here, we combine the CRISPR system from Streptococcus pyogenes and synthetic antisense RNAs (asRNAs) in Escherichia coli strains to repress or derepress a target gene in a programmable manner. Specifically, we demonstrate for the first time that the gene target repressed by the CRISPR system can be derepressed by expressing an asRNA that sequesters a small guide RNA (sgRNA). Furthermore, we demonstrate that tunable levels of derepression can be achieved (up to 95%) by designing asRNAs that target different regions of a sgRNA and by altering the hybridization free energy of the sgRNA-asRNA complex. This new system, which we call the combined CRISPR and asRNA system, can be used to reversibly repress or derepress multiple target genes simultaneously, allowing for rational reprogramming of cellular functions.", "journal": "Nucleic acids research", "sentences": ["A central goal of synthetic biology is to implement diverse cellular functions by predictably controlling gene expression.", "Though research has focused more on protein regulators than RNA regulators, recent advances in our understanding of RNA folding and functions have motivated the use of RNA regulators.", "RNA regulators provide an advantage because they are easier to design and engineer than protein regulators, potentially have a lower burden on the cell and are highly orthogonal.", "Here, we combine the CRISPR system from Streptococcus pyogenes and synthetic antisense RNAs (asRNAs) in Escherichia coli strains to repress or derepress a target gene in a programmable manner.", "Specifically, we demonstrate for the first time that the gene target repressed by the CRISPR system can be derepressed by expressing an asRNA that sequesters a small guide RNA (sgRNA).", "Furthermore, we demonstrate that tunable levels of derepression can be achieved (up to 95%) by designing asRNAs that target different regions of a sgRNA and by altering the hybridization free energy of the sgRNA-asRNA complex.", "This new system, which we call the combined CRISPR and asRNA system, can be used to reversibly repress or derepress multiple target genes simultaneously, allowing for rational reprogramming of cellular functions."], "title": "Programmable control of bacterial gene expression with the combined CRISPR and antisense RNA system."}
{"paper_id": 22792241, "labels": ["0", "0", "0", "0", "0", "0", "1", "0", "0", "1"], "abstract": "The magnitude of community-wide dispersal is central to metacommunity models, yet dispersal is notoriously difficult to quantify in passive and cryptic dispersers such as many freshwater invertebrates. By overcoming the problem of quantifying dispersal rates, colonization rates into new habitats can provide a useful estimate of the magnitude of effective dispersal. Here we study the influence of spatial and local processes on colonization rates into new ponds that indicate differential dispersal limitation of major zooplankton taxa, with important implications for metacommunity dynamics. We identify regional and local factors that affect zooplankton colonization rates and spatial patterns in a large-scale experimental system. Our study differs from others in the unique setup of the experimental pond area by which we were able to test spatial and environmental variables at a large spatial scale. We quantified colonization rates separately for the Copepoda, Cladocera and Rotifera from samples collected over a period of 21 months in 48 newly constructed temporary ponds of 0.18-2.95 ha distributed in a restored wetland area of 2,700 ha in Do\u00f1ana National Park, Southern Spain. Species richness upon initial sampling of new ponds was about one third of that in reference ponds, although the rate of detection of new species from thereon were not significantly different, probably owing to high turnover in the dynamic, temporary reference ponds. Environmental heterogeneity had no detectable effect on colonization rates in new ponds. In contrast, connectivity, space (based on latitude and longitude) and surface area were key determinants of colonization rates for copepods and cladocerans. This suggests dispersal limitation in cladocerans and copepods, but not in rotifers, possibly due to differences in propagule size and abundance.", "journal": "PloS one", "sentences": ["The magnitude of community-wide dispersal is central to metacommunity models, yet dispersal is notoriously difficult to quantify in passive and cryptic dispersers such as many freshwater invertebrates.", "By overcoming the problem of quantifying dispersal rates, colonization rates into new habitats can provide a useful estimate of the magnitude of effective dispersal.", "Here we study the influence of spatial and local processes on colonization rates into new ponds that indicate differential dispersal limitation of major zooplankton taxa, with important implications for metacommunity dynamics.", "We identify regional and local factors that affect zooplankton colonization rates and spatial patterns in a large-scale experimental system.", "Our study differs from others in the unique setup of the experimental pond area by which we were able to test spatial and environmental variables at a large spatial scale.", "We quantified colonization rates separately for the Copepoda, Cladocera and Rotifera from samples collected over a period of 21 months in 48 newly constructed temporary ponds of 0.18-2.95 ha distributed in a restored wetland area of 2,700 ha in Do\u00f1ana National Park, Southern Spain.", "Species richness upon initial sampling of new ponds was about one third of that in reference ponds, although the rate of detection of new species from thereon were not significantly different, probably owing to high turnover in the dynamic, temporary reference ponds.", "Environmental heterogeneity had no detectable effect on colonization rates in new ponds.", "In contrast, connectivity, space (based on latitude and longitude) and surface area were key determinants of colonization rates for copepods and cladocerans.", "This suggests dispersal limitation in cladocerans and copepods, but not in rotifers, possibly due to differences in propagule size and abundance."], "title": "Strong spatial influence on colonization rates in a pioneer zooplankton metacommunity."}
{"paper_id": 25468348, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Along with microtubules and microfilaments, intermediate filaments are a major component of the eukaryotic cytoskeleton and play a key role in cell mechanics. In cells, keratin intermediate filaments form networks of bundles that are sparser in structure and have lower connectivity than, for example, actin networks. Because of this, bending and buckling play an important role in these networks. Buckling events, which occur due to compressive intracellular forces and cross-talk between the keratin network and other cytoskeletal components, are measured here in situ. By applying a mechanical model for the bundled filaments, we can access the mechanical properties of both the keratin bundles themselves and the surrounding cytosol. Bundling is characterized by a coupling parameter that describes the strength of the linkage between the individual filaments within a bundle. Our findings suggest that coupling between the filaments is mostly complete, although it becomes weaker for thicker bundles, with some relative movement allowed.", "journal": "Biophysical journal", "sentences": ["Along with microtubules and microfilaments, intermediate filaments are a major component of the eukaryotic cytoskeleton and play a key role in cell mechanics.", "In cells, keratin intermediate filaments form networks of bundles that are sparser in structure and have lower connectivity than, for example, actin networks.", "Because of this, bending and buckling play an important role in these networks.", "Buckling events, which occur due to compressive intracellular forces and cross-talk between the keratin network and other cytoskeletal components, are measured here in situ.", "By applying a mechanical model for the bundled filaments, we can access the mechanical properties of both the keratin bundles themselves and the surrounding cytosol.", "Bundling is characterized by a coupling parameter that describes the strength of the linkage between the individual filaments within a bundle.", "Our findings suggest that coupling between the filaments is mostly complete, although it becomes weaker for thicker bundles, with some relative movement allowed."], "title": "Mechanics of individual keratin bundles in living cells."}
{"paper_id": 20831911, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Human enterovirus 71 (EV71) is a cause of hand, foot and mouth disease (HMFD) in children under 6 years old, and could cause serious neurological complications in some patients. Numerous large outbreaks of EV71 caused HMFD have occurred recently in Asia, especially in China. The cross-reactivity of EV71 with human brain tissue was observed and the cross-reactivity inducing regions were identified in previously study, which suggested that there were two regions in structural proteins of virus should be avoided in the vaccine. Six peptides without cross-reactivity were selected and combined into three vaccine candidates and applied in further evaluation in neonatal mice. The Vac6 comprising the peptides of P(70-159), P(140-249), P(324-443) and P(746-876) of the structural proteins could provide effective protection on pups against virus infection, as shown in viral copies detection and histopathology examination. Immunohistochemical staining results indicated that Vac6 had no cross-reactivity with human brain tissues. Our results suggested that Vac6 could have potential clinical value against EV71 epidemics caused mainly by C4 strains in the mainland of China.", "journal": "Vaccine", "sentences": ["Human enterovirus 71 (EV71) is a cause of hand, foot and mouth disease (HMFD) in children under 6 years old, and could cause serious neurological complications in some patients.", "Numerous large outbreaks of EV71 caused HMFD have occurred recently in Asia, especially in China.", "The cross-reactivity of EV71 with human brain tissue was observed and the cross-reactivity inducing regions were identified in previously study, which suggested that there were two regions in structural proteins of virus should be avoided in the vaccine.", "Six peptides without cross-reactivity were selected and combined into three vaccine candidates and applied in further evaluation in neonatal mice.", "The Vac6 comprising the peptides of P(70-159), P(140-249), P(324-443) and P(746-876) of the structural proteins could provide effective protection on pups against virus infection, as shown in viral copies detection and histopathology examination.", "Immunohistochemical staining results indicated that Vac6 had no cross-reactivity with human brain tissues.", "Our results suggested that Vac6 could have potential clinical value against EV71 epidemics caused mainly by C4 strains in the mainland of China."], "title": "Combined peptides of human enterovirus 71 protect against virus infection in mice."}
{"paper_id": 25970428, "labels": ["0", "0", "0", "0", "1", "0"], "abstract": "The importance of assigning an accurate estimate of age and sex to elephant carcasses found in the wild has increased in recent years with the escalation in levels of poaching throughout Africa. Irregularities identified in current ageing techniques prompted the development of a new method to describe molar progression throughout life. Elephant mandibles (n = 323) were studied and a point near the distal dental alveolus was identified as being most useful in ranking each jaw according to molar progression. These 'Age Reference Lines' were then associated with an age scale based on previous studies and Zimbabwean mandibles of known age. The new ranking produced a single age scale that proved useful for both male and female mandibles up to the maximum lifespan age of 70-75 years. Methods to aid in molar identification and the sexing of found jaws were also identified.", "journal": "PloS one", "sentences": ["The importance of assigning an accurate estimate of age and sex to elephant carcasses found in the wild has increased in recent years with the escalation in levels of poaching throughout Africa.", "Irregularities identified in current ageing techniques prompted the development of a new method to describe molar progression throughout life.", "Elephant mandibles (n = 323) were studied and a point near the distal dental alveolus was identified as being most useful in ranking each jaw according to molar progression.", "These 'Age Reference Lines' were then associated with an age scale based on previous studies and Zimbabwean mandibles of known age.", "The new ranking produced a single age scale that proved useful for both male and female mandibles up to the maximum lifespan age of 70-75 years.", "Methods to aid in molar identification and the sexing of found jaws were also identified."], "title": "A Novel Objective Method of Estimating the Age of Mandibles from African Elephants (Loxodonta africana Africana)."}
{"paper_id": 26665001, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "Next-generation sequencing (NGS) technologies have greatly impacted on every field of molecular research mainly because they reduce costs and increase throughput of DNA sequencing. These features, together with the technology's flexibility, have opened the way to a variety of applications including the study of the molecular basis of human diseases. Several analytical approaches have been developed to selectively enrich regions of interest from the whole genome in order to identify germinal and/or somatic sequence variants and to study DNA methylation. These approaches are now widely used in research, and they are already being used in routine molecular diagnostics. However, some issues are still controversial, namely, standardization of methods, data analysis and storage, and ethical aspects. Besides providing an overview of the NGS-based approaches most frequently used to study the molecular basis of human diseases at DNA level, we discuss the principal challenges and applications of NGS in the field of human genomics.", "journal": "BioMed research international", "sentences": ["Next-generation sequencing (NGS) technologies have greatly impacted on every field of molecular research mainly because they reduce costs and increase throughput of DNA sequencing.", "These features, together with the technology's flexibility, have opened the way to a variety of applications including the study of the molecular basis of human diseases.", "Several analytical approaches have been developed to selectively enrich regions of interest from the whole genome in order to identify germinal and/or somatic sequence variants and to study DNA methylation.", "These approaches are now widely used in research, and they are already being used in routine molecular diagnostics.", "However, some issues are still controversial, namely, standardization of methods, data analysis and storage, and ethical aspects.", "Besides providing an overview of the NGS-based approaches most frequently used to study the molecular basis of human diseases at DNA level, we discuss the principal challenges and applications of NGS in the field of human genomics."], "title": "Cracking the Code of Human Diseases Using Next-Generation Sequencing: Applications, Challenges, and Perspectives."}
{"paper_id": 24757984, "labels": ["0", "0", "1", "0", "0", "0", "1"], "abstract": "Zinc oxide nanowires are integrated onto carbon microfibers using a two-step approach which includes electrochemical deposition of zinc and its thermal oxidation. Such nano-on-micro hybrid architecture is then used as resistive gas sensor. Some properties like mechanical flexibility, low cost and large-area fabrication make this design appealing for different applications. The huge surface-to-volume ratio of such structure comes from being structured at both microscale and nanoscale (ZnO nanowires and C microfiber) and leads to a strong and rapid response/recovery times when it is used as a gas sensor. The fabrication process of the ZnO-microC device is very simple and doesn't involve any expensive lithographic step. The sensors show excellent liquefied petroleum gas sensing properties, with very fast response on gas exposure (about 3 s) and very good reversibility (less than 2%). In addition, the carbon microfiber substrate allows the use of the ZnO-microC sensor also in applications where flexibility is required (for example integrated in fabric).", "journal": "Journal of nanoscience and nanotechnology", "sentences": ["Zinc oxide nanowires are integrated onto carbon microfibers using a two-step approach which includes electrochemical deposition of zinc and its thermal oxidation.", "Such nano-on-micro hybrid architecture is then used as resistive gas sensor.", "Some properties like mechanical flexibility, low cost and large-area fabrication make this design appealing for different applications.", "The huge surface-to-volume ratio of such structure comes from being structured at both microscale and nanoscale (ZnO nanowires and C microfiber) and leads to a strong and rapid response/recovery times when it is used as a gas sensor.", "The fabrication process of the ZnO-microC device is very simple and doesn't involve any expensive lithographic step.", "The sensors show excellent liquefied petroleum gas sensing properties, with very fast response on gas exposure (about 3 s) and very good reversibility (less than 2%).", "In addition, the carbon microfiber substrate allows the use of the ZnO-microC sensor also in applications where flexibility is required (for example integrated in fabric)."], "title": "ZnO nanowires-C microfiber hybrid nanosensor for liquefied petroleum gas detection."}
{"paper_id": 23785119, "labels": ["0", "0", "0", "0", "1", "1", "1"], "abstract": "Invariant NKT (iNKT) cells are glycolipid-specific innate lymphocytes emerging as critical players in the immune response to diverse infections and disease. iNKT cells are activated through cognate interactions with lipid-loaded APCs, by Ag-independent cytokine-mediated signaling pathways, or a combination of both. Although each of these modes of iNKT cell activation plays an important role in directing the humoral and cell-mediated immune response, the spatio-temporal nature of these interactions and the cellular requirements for activation are largely undefined. Combining novel in situ confocal imaging of \u03b1Galactosylceramide-loaded CD1d tetramer labeling to localize the endogenous iNKT cell population with cytokine reporter mice, we reveal the choreography of early murine splenic iNKT cell activation across diverse settings of glycolipid immunization and systemic infection with Streptococcus pneumoniae. We find that iNKT cells consolidate in the marginal zone and require dendritic cells lining the splenic marginal zone for activation following administration of cognate glycolipids and during systemic infection but not following exogenous cytokine administration. Although further establishing the importance of cognate iNKT cell interactions with APCs, we also show that noncognate iNKT-dependent mechanisms are sufficient to mediate effector outcomes, such as STAT signaling and dendritic cell licensing throughout the splenic parenchyma. Collectively, these data provide new insight into how iNKT cells may serve as a natural adjuvant in facilitating adaptive immune responses, irrespective of their tissue localization.", "journal": "Journal of immunology (Baltimore, Md. : 1950)", "sentences": ["Invariant NKT (iNKT) cells are glycolipid-specific innate lymphocytes emerging as critical players in the immune response to diverse infections and disease.", "iNKT cells are activated through cognate interactions with lipid-loaded APCs, by Ag-independent cytokine-mediated signaling pathways, or a combination of both.", "Although each of these modes of iNKT cell activation plays an important role in directing the humoral and cell-mediated immune response, the spatio-temporal nature of these interactions and the cellular requirements for activation are largely undefined.", "Combining novel in situ confocal imaging of \u03b1Galactosylceramide-loaded CD1d tetramer labeling to localize the endogenous iNKT cell population with cytokine reporter mice, we reveal the choreography of early murine splenic iNKT cell activation across diverse settings of glycolipid immunization and systemic infection with Streptococcus pneumoniae.", "We find that iNKT cells consolidate in the marginal zone and require dendritic cells lining the splenic marginal zone for activation following administration of cognate glycolipids and during systemic infection but not following exogenous cytokine administration.", "Although further establishing the importance of cognate iNKT cell interactions with APCs, we also show that noncognate iNKT-dependent mechanisms are sufficient to mediate effector outcomes, such as STAT signaling and dendritic cell licensing throughout the splenic parenchyma.", "Collectively, these data provide new insight into how iNKT cells may serve as a natural adjuvant in facilitating adaptive immune responses, irrespective of their tissue localization."], "title": "The mechanism of splenic invariant NKT cell activation dictates localization in vivo."}
{"paper_id": 24742466, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Components of neural circuits are often repurposed so that the same biological hardware can be used for distinct computations. This flexibility in circuit operation is required to account for the changes in sensory computations that accompany changes in input signals. Yet we know little about how such changes in circuit operation are implemented. Here we show that a single retinal ganglion cell performs a different computation in dim light--averaging contrast within its receptive field--than in brighter light, when the cell becomes sensitive to fine spatial detail. This computational change depends on interactions between two parallel circuits that control the ganglion cell's excitatory synaptic inputs. Specifically, steady-state interactions through dendro-axonal gap junctions control rectification of the synapses providing excitatory input to the ganglion cell. These findings provide a clear example of how a simple synaptic mechanism can repurpose a neural circuit to perform diverse computations.", "journal": "Neuron", "sentences": ["Components of neural circuits are often repurposed so that the same biological hardware can be used for distinct computations.", "This flexibility in circuit operation is required to account for the changes in sensory computations that accompany changes in input signals.", "Yet we know little about how such changes in circuit operation are implemented.", "Here we show that a single retinal ganglion cell performs a different computation in dim light--averaging contrast within its receptive field--than in brighter light, when the cell becomes sensitive to fine spatial detail.", "This computational change depends on interactions between two parallel circuits that control the ganglion cell's excitatory synaptic inputs.", "Specifically, steady-state interactions through dendro-axonal gap junctions control rectification of the synapses providing excitatory input to the ganglion cell.", "These findings provide a clear example of how a simple synaptic mechanism can repurpose a neural circuit to perform diverse computations."], "title": "The synaptic and circuit mechanisms underlying a change in spatial encoding in the retina."}
{"paper_id": 26307964, "labels": ["0", "0", "0", "1", "1"], "abstract": "Previous studies in our laboratory found that the extract from seeds of Amorpha fruticosa in the Leguminosae family had lethal effects against mosquito larvae, and an insecticidal compound amorphigenin was isolated. In this study, the inhibitory effects of amorphigenin against the mitochondrial complex I of Culex pipiens pallens (Diptera: Culicidae) were investigated and compared with that of rotenone. The results showed that amorphigenin and rotenone can decrease the mitochondrial complex I activity both in vivo and in vitro as the in vivo IC50 values (the inhibitor concentrations leading to 50% of the enzyme activity lost) were determined to be 2.4329 and 2.5232 \u03bcmol/L, respectively, while the in vitro IC50 values were 2.8592 and 3.1375 \u03bcmol/L, respectively. Both amorphigenin and rotenone were shown to be reversible and mixed-I type inhibitors of the mitochondrial complex I of Cx. pipiens pallens, indicating that amorphigenin and rotenone inhibited the enzyme activity not only by binding with the free enzyme but also with the enzyme-substrate complex, and the values of KI and KIS for amorphigenin were determined to be 20.58 and 87.55 \u03bcM, respectively, while the values for rotenone were 14.04 and 69.23 \u03bcM, respectively.", "journal": "International journal of molecular sciences", "sentences": ["Previous studies in our laboratory found that the extract from seeds of Amorpha fruticosa in the Leguminosae family had lethal effects against mosquito larvae, and an insecticidal compound amorphigenin was isolated.", "In this study, the inhibitory effects of amorphigenin against the mitochondrial complex I of Culex pipiens pallens (Diptera: Culicidae) were investigated and compared with that of rotenone.", "The results showed that amorphigenin and rotenone can decrease the mitochondrial complex I activity both in vivo and in vitro as the in vivo IC50 values (the inhibitor concentrations leading to 50% of the enzyme activity lost) were determined to be 2.4329 and 2.5232 \u03bcmol/L, respectively, while the in vitro IC50 values were 2.8592 and 3.1375 \u03bcmol/L, respectively.", "Both amorphigenin and rotenone were shown to be reversible and mixed-I type inhibitors of the mitochondrial complex I of Cx.", "pipiens pallens, indicating that amorphigenin and rotenone inhibited the enzyme activity not only by binding with the free enzyme but also with the enzyme-substrate complex, and the values of KI and KIS for amorphigenin were determined to be 20.58 and 87.55 \u03bcM, respectively, while the values for rotenone were 14.04 and 69.23 \u03bcM, respectively."], "title": "Inhibitory Effects of Amorphigenin on the Mitochondrial Complex I of Culex pipiens pallens Coquillett (Diptera: Culicidae)."}
{"paper_id": 25170878, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Research in psychology and affective neuroscience often relies on film as a standardized and reliable method for evoking emotion. However, clip validation is not undertaken regularly. This presents a challenge for research with adolescent and young adult samples who are exposed routinely to high-definition (HD) three-dimensional (3D) stimuli and may not respond to older, validated film clips. Studies with young people inform understanding of emotional development, dysregulated affect, and psychopathology, making it critical to assess whether technological advances improve the study of emotion. In the present study, we examine whether 3D film is more evocative than 2D using a tightly controlled within-subjects design. Participants (n \u200a=\u200a 408) viewed clips during a concurrent psychophysiological assessment. Results indicate that both 2D and 3D technology are highly effective tools for emotion elicitation. However, 3D does not add incremental benefit over 2D, even when individual differences in anxiety, emotion dysregulation, and novelty seeking are considered.", "journal": "PloS one", "sentences": ["Research in psychology and affective neuroscience often relies on film as a standardized and reliable method for evoking emotion.", "However, clip validation is not undertaken regularly.", "This presents a challenge for research with adolescent and young adult samples who are exposed routinely to high-definition (HD) three-dimensional (3D) stimuli and may not respond to older, validated film clips.", "Studies with young people inform understanding of emotional development, dysregulated affect, and psychopathology, making it critical to assess whether technological advances improve the study of emotion.", "In the present study, we examine whether 3D film is more evocative than 2D using a tightly controlled within-subjects design.", "Participants (n \u200a=\u200a 408) viewed clips during a concurrent psychophysiological assessment.", "Results indicate that both 2D and 3D technology are highly effective tools for emotion elicitation.", "However, 3D does not add incremental benefit over 2D, even when individual differences in anxiety, emotion dysregulation, and novelty seeking are considered."], "title": "Testing the effectiveness of 3D film for laboratory-based studies of emotion."}
{"paper_id": 27258194, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Echo planar imaging (EPI) suffers from geometric distortions caused by magnetic field inhomogeneities, which can be time-varying as a result of small amounts of head motion that occur over seconds and minutes during fMRI experiments, also known as \"dynamic geometric distortion\". Phase Labeling for Additional Coordinate Encoding (PLACE) is a promising technique for geometric distortion correction without reduced temporal resolution and in principle can be used to correct for motion-induced dynamic geometric distortion. PLACE requires at least two EPI images of the same anatomy that are ideally acquired with no variation in the magnetic field inhomogeneities. However, head motion and lung ventilation during the respiratory cycle can cause changes in magnetic field inhomogeneities within the EPI pair used for PLACE. In this work, we exploited dynamic off-resonance in k-space (DORK) and averaging to correct the within EPI pair magnetic field inhomogeneities; and hence proposed a combined technique (DORK+PLACE+averaging) to mitigate dynamic geometric distortion in EPI-based fMRI while preserving the temporal resolution. The performance of the combined DORK, PLACE and averaging technique was characterized through several imaging experiments involving test phantoms and six healthy adult volunteers. Phantom data illustrate reduced temporal standard deviation of fMRI signal intensities after use of combined dynamic PLACE, DORK and averaging compared to the standard processing and static geometric distortion correction. The combined technique also substantially improved the temporal standard deviation and activation maps obtained from human fMRI data in comparison to the results obtained by standard processing and static geometric distortion correction, highlighting the utility of the approach.", "journal": "PloS one", "sentences": ["Echo planar imaging (EPI) suffers from geometric distortions caused by magnetic field inhomogeneities, which can be time-varying as a result of small amounts of head motion that occur over seconds and minutes during fMRI experiments, also known as \"dynamic geometric distortion\".", "Phase Labeling for Additional Coordinate Encoding (PLACE) is a promising technique for geometric distortion correction without reduced temporal resolution and in principle can be used to correct for motion-induced dynamic geometric distortion.", "PLACE requires at least two EPI images of the same anatomy that are ideally acquired with no variation in the magnetic field inhomogeneities.", "However, head motion and lung ventilation during the respiratory cycle can cause changes in magnetic field inhomogeneities within the EPI pair used for PLACE.", "In this work, we exploited dynamic off-resonance in k-space (DORK) and averaging to correct the within EPI pair magnetic field inhomogeneities; and hence proposed a combined technique (DORK+PLACE+averaging) to mitigate dynamic geometric distortion in EPI-based fMRI while preserving the temporal resolution.", "The performance of the combined DORK, PLACE and averaging technique was characterized through several imaging experiments involving test phantoms and six healthy adult volunteers.", "Phantom data illustrate reduced temporal standard deviation of fMRI signal intensities after use of combined dynamic PLACE, DORK and averaging compared to the standard processing and static geometric distortion correction.", "The combined technique also substantially improved the temporal standard deviation and activation maps obtained from human fMRI data in comparison to the results obtained by standard processing and static geometric distortion correction, highlighting the utility of the approach."], "title": "Suppressing Respiration Effects when Geometric Distortion Is Corrected Dynamically by Phase Labeling for Additional Coordinate Encoding (PLACE) during Functional MRI."}
{"paper_id": 26610474, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Helicobacter pylori (H. pylori)-induced oxidative stress has been shown to play a very important role in the inflammation of the gastric mucosa and increases the risk of developing gastric cancer. Resveratrol has many biological functions and activities, including antioxidant and anti-inflammatory effect. The purpose of this study was to probe whether resveratrol inhibits H. pylori-induced gastric inflammation and to elucidate the underlying mechanisms of any effect in mice. A mouse model of H. pylori infection was established via oral inoculation with H. pylori. After one week, mice were administered resveratrol (100 mg/kg body weight/day) orally for six weeks. The mRNA and protein levels of iNOS and IL-8 were assessed using RT-PCR, Western blot and ELISA. The expression levels of I\u03baB\u03b1 and phosphorylated I\u03baB\u03b1 (which embodies the level and activation of NF-\u03baB), Heme Oxygenase-1 (HO-1; a potent antioxidant enzyme) and nuclear factor-erythroid 2 related factor 2 (Nrf2) were determined using Western blot, and lipid peroxide (LPO) level and myeloperoxidase (MPO) activity were examined using an MPO colorimetric activity assay, thiobarbituric acid reaction, and histological-grade using HE staining of the gastric mucosa. The results showed that resveratrol improved the histological infiltration score and decreased LPO level and MPO activity in the gastric mucosa. Resveratrol down-regulated the H. pylori-induced mRNA transcription and protein expression levels of IL-8 and iNOS, suppressed H. pylori-induced phosphorylation of I\u03baB\u03b1, and increased the levels of HO-1 and Nrf2. In conclusion, resveratrol treatment exerted significant effects against oxidative stress and inflammation in H. pylori-infected mucosa through the suppression of IL-8, iNOS, and NF-\u03baB, and moreover through the activation of the Nrf2/HO-1 pathway.", "journal": "International journal of molecular sciences", "sentences": ["Helicobacter pylori (H. pylori)-induced oxidative stress has been shown to play a very important role in the inflammation of the gastric mucosa and increases the risk of developing gastric cancer.", "Resveratrol has many biological functions and activities, including antioxidant and anti-inflammatory effect.", "The purpose of this study was to probe whether resveratrol inhibits H. pylori-induced gastric inflammation and to elucidate the underlying mechanisms of any effect in mice.", "A mouse model of H. pylori infection was established via oral inoculation with H. pylori.", "After one week, mice were administered resveratrol (100 mg/kg body weight/day) orally for six weeks.", "The mRNA and protein levels of iNOS and IL-8 were assessed using RT-PCR, Western blot and ELISA.", "The expression levels of I\u03baB\u03b1 and phosphorylated I\u03baB\u03b1 (which embodies the level and activation of NF-\u03baB), Heme Oxygenase-1 (HO-1; a potent antioxidant enzyme) and nuclear factor-erythroid 2 related factor 2 (Nrf2) were determined using Western blot, and lipid peroxide (LPO) level and myeloperoxidase (MPO) activity were examined using an MPO colorimetric activity assay, thiobarbituric acid reaction, and histological-grade using HE staining of the gastric mucosa.", "The results showed that resveratrol improved the histological infiltration score and decreased LPO level and MPO activity in the gastric mucosa.", "Resveratrol down-regulated the H. pylori-induced mRNA transcription and protein expression levels of IL-8 and iNOS, suppressed H. pylori-induced phosphorylation of I\u03baB\u03b1, and increased the levels of HO-1 and Nrf2.", "In conclusion, resveratrol treatment exerted significant effects against oxidative stress and inflammation in H. pylori-infected mucosa through the suppression of IL-8, iNOS, and NF-\u03baB, and moreover through the activation of the Nrf2/HO-1 pathway."], "title": "Resveratrol Protects against Helicobacter pylori-Associated Gastritis by Combating Oxidative Stress."}
{"paper_id": 20686617, "labels": ["0", "0", "0", "1", "0", "0", "0"], "abstract": "SNP markers provide the primary data for population structure analysis. In this study, we employed whole-genome autosomal SNPs as a marker set (54,836 SNP markers) and tested their possible effects on genetic ancestry using 320 subjects covering 24 regional groups including Northern (=16) and Southern (=3) Asians, Amerindians (=1), and four HapMap populations (YRI, CEU, JPT, and CHB). Additionally, we evaluated the effectiveness and robustness of 50K autosomal SNPs with various clustering methods, along with their dependencies on recombination hotspots (RH), linkage disequilibrium (LD), missing calls and regional specific markers. The RH- and LD-free multi-dimensional scaling (MDS) method showed a broad picture of human migration from Africa to North-East Asia on our genome map, supporting results from previous haploid DNA studies. Of the Asian groups, the East Asian group showed greater differentiation than the Northern and Southern Asian groups with respect to Fst statistics. By extension, the analysis of monomorphic markers implied that nine out of ten historical regions in South Korea, and Tokyo in Japan, showed signs of genetic drift caused by the later settlement of East Asia (South Korea, Japan and China), while Gyeongju in South East Korea showed signs of the earliest settlement in East Asia. In the genome map, the gene flow to the Korean Peninsula from its neighboring countries indicated that some genetic signals from Northern populations such as the Siberians and Mongolians still remain in the South East and West regions, while few signals remain from the early Southern lineages.", "journal": "PloS one", "sentences": ["SNP markers provide the primary data for population structure analysis.", "In this study, we employed whole-genome autosomal SNPs as a marker set (54,836 SNP markers) and tested their possible effects on genetic ancestry using 320 subjects covering 24 regional groups including Northern (=16) and Southern (=3) Asians, Amerindians (=1), and four HapMap populations (YRI, CEU, JPT, and CHB).", "Additionally, we evaluated the effectiveness and robustness of 50K autosomal SNPs with various clustering methods, along with their dependencies on recombination hotspots (RH), linkage disequilibrium (LD), missing calls and regional specific markers.", "The RH- and LD-free multi-dimensional scaling (MDS) method showed a broad picture of human migration from Africa to North-East Asia on our genome map, supporting results from previous haploid DNA studies.", "Of the Asian groups, the East Asian group showed greater differentiation than the Northern and Southern Asian groups with respect to Fst statistics.", "By extension, the analysis of monomorphic markers implied that nine out of ten historical regions in South Korea, and Tokyo in Japan, showed signs of genetic drift caused by the later settlement of East Asia (South Korea, Japan and China), while Gyeongju in South East Korea showed signs of the earliest settlement in East Asia.", "In the genome map, the gene flow to the Korean Peninsula from its neighboring countries indicated that some genetic signals from Northern populations such as the Siberians and Mongolians still remain in the South East and West regions, while few signals remain from the early Southern lineages."], "title": "Gene flow between the Korean peninsula and its neighboring countries."}
{"paper_id": 23951041, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The widespread mass extinctions at the end of the Cretaceous caused world-wide disruption of ecosystems, and faunal responses to the one-two punch of severe environmental perturbation and ecosystem collapse are still unclear. Here we report the discovery of in situ terrestrial fossil burrows from just above the impact-defined Cretaceous-Paleogene (K/Pg) boundary in southwestern North Dakota. The crisscrossing networks of horizontal burrows occur at the interface of a lignitic coal and silty sandstone, and reveal intense faunal activity within centimeters of the boundary clay. Estimated rates of sedimentation and coal formation suggest that the burrows were made less than ten thousand years after the end-Cretaceous impact. The burrow characteristics are most consistent with burrows of extant earthworms. Moreover, the burrowing and detritivorous habits of these annelids fit models that predict the trophic and sheltering lifestyles of terrestrial animals that survived the K/Pg extinction event. In turn, such detritus-eaters would have played a critical role in supporting secondary consumers. Thus, some of the carnivorous vertebrates that radiated after the K/Pg extinction may owe their evolutionary success to thriving populations of earthworms.", "journal": "PloS one", "sentences": ["The widespread mass extinctions at the end of the Cretaceous caused world-wide disruption of ecosystems, and faunal responses to the one-two punch of severe environmental perturbation and ecosystem collapse are still unclear.", "Here we report the discovery of in situ terrestrial fossil burrows from just above the impact-defined Cretaceous-Paleogene (K/Pg) boundary in southwestern North Dakota.", "The crisscrossing networks of horizontal burrows occur at the interface of a lignitic coal and silty sandstone, and reveal intense faunal activity within centimeters of the boundary clay.", "Estimated rates of sedimentation and coal formation suggest that the burrows were made less than ten thousand years after the end-Cretaceous impact.", "The burrow characteristics are most consistent with burrows of extant earthworms.", "Moreover, the burrowing and detritivorous habits of these annelids fit models that predict the trophic and sheltering lifestyles of terrestrial animals that survived the K/Pg extinction event.", "In turn, such detritus-eaters would have played a critical role in supporting secondary consumers.", "Thus, some of the carnivorous vertebrates that radiated after the K/Pg extinction may owe their evolutionary success to thriving populations of earthworms."], "title": "Fossil worm burrows reveal very early terrestrial animal activity and shed light on trophic resources after the end-cretaceous mass extinction."}
{"paper_id": 24971506, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The MYB transcription factors are involved in various plant biochemistry and physiology processes and play a central role in plant defense response. In the present study, a full-length cDNA sequence of a MYB gene, designated as SpMYB, was isolated from tomato. SpMYB encodes the R2R3-type protein consisting of 328 amino acids. The expression level of SpMYB was strongly induced by fungal pathogens. Transgenic tobacco plants overexpressing SpMYB had an enhanced salt and drought stress tolerance compared with wild-type plants, and showed significantly improved resistance to Alternaria alternate. Further analysis revealed that transgenic tobaccos exhibited less accumulation of malondialdehyde (MDA) and more accumulation of superoxide dismutase (SOD), peroxidase (POD) and phenylalanine ammonia-lyase (PAL) after inoculation with A. alternate. Meanwhile, changes in some photosynthetic parameters, such as photosynthetic rate (Pn), transpiration rate (Tr) and intercellular CO2 concentration (Ci) were also found in the transgenic tobaccos. Furthermore, transgenic tobaccos constitutively accumulated higher levels of pathogenesis-related (PR) gene transcripts, such as PR1 and PR2. The results suggested that the tomato SpMYB transcription factor plays an important role in responses to abiotic and biotic stress.", "journal": "Gene", "sentences": ["The MYB transcription factors are involved in various plant biochemistry and physiology processes and play a central role in plant defense response.", "In the present study, a full-length cDNA sequence of a MYB gene, designated as SpMYB, was isolated from tomato.", "SpMYB encodes the R2R3-type protein consisting of 328 amino acids.", "The expression level of SpMYB was strongly induced by fungal pathogens.", "Transgenic tobacco plants overexpressing SpMYB had an enhanced salt and drought stress tolerance compared with wild-type plants, and showed significantly improved resistance to Alternaria alternate.", "Further analysis revealed that transgenic tobaccos exhibited less accumulation of malondialdehyde (MDA) and more accumulation of superoxide dismutase (SOD), peroxidase (POD) and phenylalanine ammonia-lyase (PAL) after inoculation with A. alternate.", "Meanwhile, changes in some photosynthetic parameters, such as photosynthetic rate (Pn), transpiration rate (Tr) and intercellular CO2 concentration (Ci) were also found in the transgenic tobaccos.", "Furthermore, transgenic tobaccos constitutively accumulated higher levels of pathogenesis-related (PR) gene transcripts, such as PR1 and PR2.", "The results suggested that the tomato SpMYB transcription factor plays an important role in responses to abiotic and biotic stress."], "title": "SpMYB overexpression in tobacco plants leads to altered abiotic and biotic stress responses."}
{"paper_id": 25992770, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies with the acute toxicity induced by photosensitizers after exposure to NIR-light. Herein, we evaluate the efficacy of NIR-PIT in preventing lung metastases in a mouse model. Lung is one of the most common sites for developing metastases, but it also has the deepest tissue light penetration. Thus, lung is the ideal site for treating early metastases by using a light-based strategy. In vitro NIR-PIT cytotoxicity was assessed with dead cell staining, luciferase activity, and a decrease in cytoplasmic GFP fluorescence in 3T3/HER2-luc-GFP cells incubated with an anti-HER2 antibody photosensitizer conjugate. Cell-specific killing was demonstrated in mixed 2D/3D cell cultures of 3T3/HER2-luc-GFP (target) and 3T3-RFP (non-target) cells. In vivo NIR-PIT was performed in the left lung in a mouse model of lung metastases, and the number of metastasis nodules, tumor fluorescence, and luciferase activity were all evaluated. All three evaluations demonstrated that the NIR-PIT-treated lung had significant reductions in metastatic disease (*p < 0.0001, Mann-Whitney U-test) and that NIR-PIT did not damage non-target tumors or normal lung tissue. Thus, NIR-PIT can specifically prevent early metastases and is a promising anti-metastatic therapy.", "journal": "Oncotarget", "sentences": ["Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies with the acute toxicity induced by photosensitizers after exposure to NIR-light.", "Herein, we evaluate the efficacy of NIR-PIT in preventing lung metastases in a mouse model.", "Lung is one of the most common sites for developing metastases, but it also has the deepest tissue light penetration.", "Thus, lung is the ideal site for treating early metastases by using a light-based strategy.", "In vitro NIR-PIT cytotoxicity was assessed with dead cell staining, luciferase activity, and a decrease in cytoplasmic GFP fluorescence in 3T3/HER2-luc-GFP cells incubated with an anti-HER2 antibody photosensitizer conjugate.", "Cell-specific killing was demonstrated in mixed 2D/3D cell cultures of 3T3/HER2-luc-GFP (target) and 3T3-RFP (non-target) cells.", "In vivo NIR-PIT was performed in the left lung in a mouse model of lung metastases, and the number of metastasis nodules, tumor fluorescence, and luciferase activity were all evaluated.", "All three evaluations demonstrated that the NIR-PIT-treated lung had significant reductions in metastatic disease (*p < 0.0001, Mann-Whitney U-test) and that NIR-PIT did not damage non-target tumors or normal lung tissue.", "Thus, NIR-PIT can specifically prevent early metastases and is a promising anti-metastatic therapy."], "title": "Near infrared photoimmunotherapy prevents lung cancer metastases in a murine model."}
{"paper_id": 26248370, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen associated with nosocomial pneumonia and is an increasing threat for severe community-acquired pneumonia. We have now investigated the role of interleukin-12 (IL-12) in protective immunity against lung infection with MRSA. The importance of IL-12 in protection from pulmonary MRSA infection was demonstrated by the finding that IL-12p35-deficient mice had a lower survival rate, higher bacterial burdens in lung and spleen, and decreased expression of interferon gamma (IFN-\u03b3) in the lung compared to wild-type mice. These effects were completely reversed by replacement intranasal therapy with recombinant IL-12. Furthermore, exogenous IL-12 treatment of wild-type mice 24 h before pulmonary challenge with a lethal dose of MRSA significantly improved bacterial clearance and resulted in protection from death. The IL-12-treated mice had increased numbers of lung natural killer (NK) cells and neutrophils and higher levels of IFN-\u03b3 in the lung and serum compared to untreated mice. The major source of IL-12-driven IFN-\u03b3 expression in the lung was the NK cell, and the direct target of pulmonary IFN-\u03b3 was the lung macrophage, as shown using mice with a macrophage-specific defect in interferon gamma (IFN-\u03b3) signaling (MIIG mice). Importantly, combination therapy with linezolid and IL-12 following intranasal MRSA infection significantly increased survival compared to that of mice receiving linezolid or IL-12 alone. These results indicate that IL-12-based immunotherapy may hold promise for treatment of MRSA pneumonia.", "journal": "Antimicrobial agents and chemotherapy", "sentences": ["Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen associated with nosocomial pneumonia and is an increasing threat for severe community-acquired pneumonia.", "We have now investigated the role of interleukin-12 (IL-12) in protective immunity against lung infection with MRSA.", "The importance of IL-12 in protection from pulmonary MRSA infection was demonstrated by the finding that IL-12p35-deficient mice had a lower survival rate, higher bacterial burdens in lung and spleen, and decreased expression of interferon gamma (IFN-\u03b3) in the lung compared to wild-type mice.", "These effects were completely reversed by replacement intranasal therapy with recombinant IL-12.", "Furthermore, exogenous IL-12 treatment of wild-type mice 24 h before pulmonary challenge with a lethal dose of MRSA significantly improved bacterial clearance and resulted in protection from death.", "The IL-12-treated mice had increased numbers of lung natural killer (NK) cells and neutrophils and higher levels of IFN-\u03b3 in the lung and serum compared to untreated mice.", "The major source of IL-12-driven IFN-\u03b3 expression in the lung was the NK cell, and the direct target of pulmonary IFN-\u03b3 was the lung macrophage, as shown using mice with a macrophage-specific defect in interferon gamma (IFN-\u03b3) signaling (MIIG mice).", "Importantly, combination therapy with linezolid and IL-12 following intranasal MRSA infection significantly increased survival compared to that of mice receiving linezolid or IL-12 alone.", "These results indicate that IL-12-based immunotherapy may hold promise for treatment of MRSA pneumonia."], "title": "Role of Interleukin-12 in Protection against Pulmonary Infection with Methicillin-Resistant Staphylococcus aureus."}
{"paper_id": 23675357, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "A review of the literature indicates that empirical researchers have difficulty translating Freud's theory on depression into appropriate research questions and hypotheses. In their attempt to do so, the level of complexity in Freud's work is often lost. As a result, what is empirically tested is no more than a caricature of the original theory. To help researchers avoid such problems, this study presents a conceptual analysis of Freud's theory of depression as it is presented in Mourning and Melancholia (Freud, 1917). In analyzing Freud's theory on the etiology of depression, it is essential to differentiate between (1) an identification with the satisfying and frustrating aspects of the love object, (2) the inter- and an intrapersonal loss of the love object, and (3) conscious and unconscious dynamics. A schematic representation of the mechanism of depression is put forward and a research design by which this schema can be empirically investigated is outlined.", "journal": "Frontiers in psychology", "sentences": ["A review of the literature indicates that empirical researchers have difficulty translating Freud's theory on depression into appropriate research questions and hypotheses.", "In their attempt to do so, the level of complexity in Freud's work is often lost.", "As a result, what is empirically tested is no more than a caricature of the original theory.", "To help researchers avoid such problems, this study presents a conceptual analysis of Freud's theory of depression as it is presented in Mourning and Melancholia (Freud, 1917).", "In analyzing Freud's theory on the etiology of depression, it is essential to differentiate between (1) an identification with the satisfying and frustrating aspects of the love object, (2) the inter- and an intrapersonal loss of the love object, and (3) conscious and unconscious dynamics.", "A schematic representation of the mechanism of depression is put forward and a research design by which this schema can be empirically investigated is outlined."], "title": "Some Preliminary Notes on an Empirical Test of Freud's Theory on Depression."}
{"paper_id": 26620840, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "DNA vaccination is a promising alternative strategy for developing new human and animal vaccines. The massive efforts made these past 25 years to increase the immunizing potential of this kind of vaccine are still ongoing. A relatively small number of studies concerning poultry have been published. Even though there is a need for new poultry vaccines, five parameters must nevertheless be taken into account for their development: the vaccine has to be very effective, safe, inexpensive, suitable for mass vaccination and able to induce immune responses in the presence of maternal antibodies (when appropriate). DNA vaccination should meet these requirements. This review describes studies in this field performed exclusively on birds (chickens, ducks and turkeys). No evaluations of avian DNA vaccine efficacy performed on mice as preliminary tests have been taken into consideration. The review first describes the state of the art for DNA vaccination in poultry: pathogens targeted, plasmids used and different routes of vaccine administration. Second, it presents strategies designed to improve DNA vaccine efficacy: influence of the route of administration, plasmid dose and age of birds on their first inoculation; increasing plasmid uptake by host cells; addition of immunomodulators; optimization of plasmid backbones and codon usage; association of vaccine antigens and finally, heterologous prime-boost regimens. The final part will indicate additional properties of DNA vaccines in poultry: fate of the plasmids upon inoculation, immunological considerations and the use of DNA vaccines for purposes other than preventing infectious diseases.", "journal": "Vaccine", "sentences": ["DNA vaccination is a promising alternative strategy for developing new human and animal vaccines.", "The massive efforts made these past 25 years to increase the immunizing potential of this kind of vaccine are still ongoing.", "A relatively small number of studies concerning poultry have been published.", "Even though there is a need for new poultry vaccines, five parameters must nevertheless be taken into account for their development: the vaccine has to be very effective, safe, inexpensive, suitable for mass vaccination and able to induce immune responses in the presence of maternal antibodies (when appropriate).", "DNA vaccination should meet these requirements.", "This review describes studies in this field performed exclusively on birds (chickens, ducks and turkeys).", "No evaluations of avian DNA vaccine efficacy performed on mice as preliminary tests have been taken into consideration.", "The review first describes the state of the art for DNA vaccination in poultry: pathogens targeted, plasmids used and different routes of vaccine administration.", "Second, it presents strategies designed to improve DNA vaccine efficacy: influence of the route of administration, plasmid dose and age of birds on their first inoculation; increasing plasmid uptake by host cells; addition of immunomodulators; optimization of plasmid backbones and codon usage; association of vaccine antigens and finally, heterologous prime-boost regimens.", "The final part will indicate additional properties of DNA vaccines in poultry: fate of the plasmids upon inoculation, immunological considerations and the use of DNA vaccines for purposes other than preventing infectious diseases."], "title": "DNA vaccination of poultry: The current status in 2015."}
{"paper_id": 23009841, "labels": ["0", "0", "0", "0", "0", "1", "1", "0"], "abstract": "Biomembranes are thin capacitors with the unique feature of displaying phase transitions in a physiologically relevant regime. We investigate the voltage and lateral pressure dependence of their capacitance close to their chain melting transition. Because the gel and the fluid membrane have different area and thickness, the capacitance of the two membrane phases is different. In the presence of external fields, charges exert forces that can influence the state of the membrane, thereby influencing the transition temperature. This phenomenon is called \"electrostriction\". We show that this effect allows us to introduce a capacitive susceptibility that assumes a maximum in the melting transition with an associated excess charge. As a consequence, voltage regimes exist in which a small change in voltage can lead to a large uptake of charge and a large capacitive current. Furthermore, we consider electromechanical behavior such as pressure-induced changes in capacitance, and the application of such concepts in biology.", "journal": "Biophysical journal", "sentences": ["Biomembranes are thin capacitors with the unique feature of displaying phase transitions in a physiologically relevant regime.", "We investigate the voltage and lateral pressure dependence of their capacitance close to their chain melting transition.", "Because the gel and the fluid membrane have different area and thickness, the capacitance of the two membrane phases is different.", "In the presence of external fields, charges exert forces that can influence the state of the membrane, thereby influencing the transition temperature.", "This phenomenon is called \"electrostriction\".", "We show that this effect allows us to introduce a capacitive susceptibility that assumes a maximum in the melting transition with an associated excess charge.", "As a consequence, voltage regimes exist in which a small change in voltage can lead to a large uptake of charge and a large capacitive current.", "Furthermore, we consider electromechanical behavior such as pressure-induced changes in capacitance, and the application of such concepts in biology."], "title": "The capacitance and electromechanical coupling of lipid membranes close to transitions: the effect of electrostriction."}
{"paper_id": 26551322, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "Oxidized pterins, efficient photosensitizers under UVA irradiation, accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder. Soybean phosphatidylcholine (SoyPC) liposomes were employed as model membranes to investigate if pterin (Ptr), the parent compound of oxidized pterins, is able to photoinduced lipid peroxidation. Size exclusion chromatography and dialysis experiments showed that Ptr is not encapsulated inside the liposomes and the lipid membrane is permeable to this compound. The formation of conjugated dienes and trienes, upon UVA irradiation, was followed by absorption at 234 and 270 nm, respectively. The photoproducts were characterized by mass spectrometry and oxygenation of SoyPC was demonstrated. In addition, analysis of MS/MS spectra suggested the formation hydroperoxides. Finally, the biological implications of the findings are discussed.", "journal": "Biochimica et biophysica acta", "sentences": ["Oxidized pterins, efficient photosensitizers under UVA irradiation, accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder.", "Soybean phosphatidylcholine (SoyPC) liposomes were employed as model membranes to investigate if pterin (Ptr), the parent compound of oxidized pterins, is able to photoinduced lipid peroxidation.", "Size exclusion chromatography and dialysis experiments showed that Ptr is not encapsulated inside the liposomes and the lipid membrane is permeable to this compound.", "The formation of conjugated dienes and trienes, upon UVA irradiation, was followed by absorption at 234 and 270 nm, respectively.", "The photoproducts were characterized by mass spectrometry and oxygenation of SoyPC was demonstrated.", "In addition, analysis of MS/MS spectra suggested the formation hydroperoxides.", "Finally, the biological implications of the findings are discussed."], "title": "Soybean phosphatidylcholine liposomes as model membranes to study lipid peroxidation photoinduced by pterin."}
{"paper_id": 21390252, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "The major virulence factor of the neuroinvasive pathogen Escherichia coli K1 is the K1 capsule composed of \u03b12,8-linked polysialic acid (polySia). K1 strains harboring the CUS-3 prophage modify their capsular polysaccharide by phase-variable O-acetylation, a step that is associated with increased virulence. Here we present the crystal structure of the prophage-encoded polysialate O-acetyltransferase NeuO. The homotrimeric enzyme belongs to the left-handed \u03b2-helix (L\u03b2H) family of acyltransferases and is characterized by an unusual funnel-shaped outline. Comparison with other members of the L\u03b2H family allowed the identification of active site residues and proposal of a catalytic mechanism and highlighted structural characteristics of polySia specific O-acetyltransferases. As a unique feature of NeuO, the enzymatic activity linearly increases with the length of the N-terminal poly-\u03c8-domain which is composed of a variable number of tandem copies of an RLKTQDS heptad. Since the poly-\u03c8-domain was not resolved in the crystal structure it is assumed to be unfolded in the apo-enzyme.", "journal": "PloS one", "sentences": ["The major virulence factor of the neuroinvasive pathogen Escherichia coli K1 is the K1 capsule composed of \u03b12,8-linked polysialic acid (polySia).", "K1 strains harboring the CUS-3 prophage modify their capsular polysaccharide by phase-variable O-acetylation, a step that is associated with increased virulence.", "Here we present the crystal structure of the prophage-encoded polysialate O-acetyltransferase NeuO.", "The homotrimeric enzyme belongs to the left-handed \u03b2-helix (L\u03b2H) family of acyltransferases and is characterized by an unusual funnel-shaped outline.", "Comparison with other members of the L\u03b2H family allowed the identification of active site residues and proposal of a catalytic mechanism and highlighted structural characteristics of polySia specific O-acetyltransferases.", "As a unique feature of NeuO, the enzymatic activity linearly increases with the length of the N-terminal poly-\u03c8-domain which is composed of a variable number of tandem copies of an RLKTQDS heptad.", "Since the poly-\u03c8-domain was not resolved in the crystal structure it is assumed to be unfolded in the apo-enzyme."], "title": "Crystal structure analysis of the polysialic acid specific O-acetyltransferase NeuO."}
{"paper_id": 21070744, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Cell-penetrating peptides (CPPs) are a promising group of delivery vectors for various therapeutic agents but their application is often hampered by poor stability in the presence of serum. Different strategies to improve peptide stability have been exploited, one of them being \"retro-inversion\" (RI) of natural peptides. With this approach the stability of CPPs has been increased, thereby making them more efficient transporters. Several RI-CPPs were here assessed and compared to the corresponding parent peptides in different cell-lines. Surprisingly, treatment of cells with these peptides induced trypsin insensitivity and rapid severe toxicity in contrast to L-peptides. This was measured as reduced metabolic activity and condensed cell nuclei, in parity with the apoptosis inducing agent staurosporine. Furthermore, effects on mitochondrial network, focal adhesions, actin cytoskeleton and caspase-3 activation were analyzed and adverse effects were evident at 20 \u03bcM peptide concentration within 4 h while parent L-peptides had negligible effects. To our knowledge this is the first time RI peptides are reported to cause cellular toxicity, displayed by decreased metabolic activity, morphological changes and induction of apoptosis. Considering the wide range of research areas that involves the use of RI-peptides, this finding is of major importance and needs to be taken under consideration in applications of RI-peptides.", "journal": "Biochimica et biophysica acta", "sentences": ["Cell-penetrating peptides (CPPs) are a promising group of delivery vectors for various therapeutic agents but their application is often hampered by poor stability in the presence of serum.", "Different strategies to improve peptide stability have been exploited, one of them being \"retro-inversion\" (RI) of natural peptides.", "With this approach the stability of CPPs has been increased, thereby making them more efficient transporters.", "Several RI-CPPs were here assessed and compared to the corresponding parent peptides in different cell-lines.", "Surprisingly, treatment of cells with these peptides induced trypsin insensitivity and rapid severe toxicity in contrast to L-peptides.", "This was measured as reduced metabolic activity and condensed cell nuclei, in parity with the apoptosis inducing agent staurosporine.", "Furthermore, effects on mitochondrial network, focal adhesions, actin cytoskeleton and caspase-3 activation were analyzed and adverse effects were evident at 20 \u03bcM peptide concentration within 4 h while parent L-peptides had negligible effects.", "To our knowledge this is the first time RI peptides are reported to cause cellular toxicity, displayed by decreased metabolic activity, morphological changes and induction of apoptosis.", "Considering the wide range of research areas that involves the use of RI-peptides, this finding is of major importance and needs to be taken under consideration in applications of RI-peptides."], "title": "Retro-inversion of certain cell-penetrating peptides causes severe cellular toxicity."}
{"paper_id": 26984528, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Fluoroquinolones form drug-topoisomerase-DNA complexes that rapidly block transcription and replication. Crystallographic and biochemical studies show that quinolone binding involves a water/metal-ion bridge between the quinolone C3-C4 keto-acid and amino acids in helix-4 of the target proteins, GyrA (gyrase) and ParC (topoisomerase IV). A recent cross-linking study revealed a second drug-binding mode in which the other end of the quinolone, the C7 ring system, interacts with GyrA. We report that addition of a dinitrophenyl (DNP) moiety to the C7 end of ciprofloxacin (Cip-DNP) reduced protection due to resistance substitutions in Escherichia coli GyrA helix-4, consistent with the existence of a second drug-binding mode not evident in X-ray structures of drug-topoisomerase-DNA complexes. Several other C7 aryl fluoroquinolones behaved in a similar manner with particular GyrA mutants. Treatment of E. coli cultures with Cip-DNP selectively enriched an uncommon variant, GyrA-A119E, a change that may impede binding of the dinitrophenyl group at or near the GyrA-GyrA interface. Collectively the data support the existence of a secondary quinolone-binding mode in which the quinolone C7 ring system interacts with GyrA; the data also identify C7 aryl derivatives as a new way to obtain fluoroquinolones that overcome existing GyrA-mediated quinolone resistance.", "journal": "Nucleic acids research", "sentences": ["Fluoroquinolones form drug-topoisomerase-DNA complexes that rapidly block transcription and replication.", "Crystallographic and biochemical studies show that quinolone binding involves a water/metal-ion bridge between the quinolone C3-C4 keto-acid and amino acids in helix-4 of the target proteins, GyrA (gyrase) and ParC (topoisomerase IV).", "A recent cross-linking study revealed a second drug-binding mode in which the other end of the quinolone, the C7 ring system, interacts with GyrA.", "We report that addition of a dinitrophenyl (DNP) moiety to the C7 end of ciprofloxacin (Cip-DNP) reduced protection due to resistance substitutions in Escherichia coli GyrA helix-4, consistent with the existence of a second drug-binding mode not evident in X-ray structures of drug-topoisomerase-DNA complexes.", "Several other C7 aryl fluoroquinolones behaved in a similar manner with particular GyrA mutants.", "Treatment of E. coli cultures with Cip-DNP selectively enriched an uncommon variant, GyrA-A119E, a change that may impede binding of the dinitrophenyl group at or near the GyrA-GyrA interface.", "Collectively the data support the existence of a secondary quinolone-binding mode in which the quinolone C7 ring system interacts with GyrA; the data also identify C7 aryl derivatives as a new way to obtain fluoroquinolones that overcome existing GyrA-mediated quinolone resistance."], "title": "Suppression of gyrase-mediated resistance by C7 aryl fluoroquinolones."}
{"paper_id": 27073845, "labels": ["0", "0", "1", "0", "1", "1"], "abstract": "Intestinal microbiota play a significant role in nutrient metabolism, modulation of the immune system, obesity, and possibly in carcinogenesis, although the underlying mechanisms resulting in disease or impacts on longevity caused by different intestinal microbiota are mostly unknown. Herein we use isogenic Atm-deficient and wild type mice as models to interrogate changes in the metabolic profiles of urine and feces of these mice, which are differing in their intestinal microbiota. Using high resolution mass spectrometry approach we show that the composition of intestinal microbiota modulates specific metabolic perturbations resulting in a possible alleviation of a glycolytic phenotype. Metabolites including 3-methylbutyrolactone, kyneurenic acid and 3-methyladenine known to be onco-protective are elevated in Atm-deficient and wild type mice with restricted intestinal microbiota. Thus our approach has broad applicability to study the direct influence of gut microbiome on host metabolism and resultant phenotype. These results for the first time suggest a possible correlation of metabolic alterations and carcinogenesis, modulated by intestinal microbiota in A-T mice.", "journal": "PloS one", "sentences": ["Intestinal microbiota play a significant role in nutrient metabolism, modulation of the immune system, obesity, and possibly in carcinogenesis, although the underlying mechanisms resulting in disease or impacts on longevity caused by different intestinal microbiota are mostly unknown.", "Herein we use isogenic Atm-deficient and wild type mice as models to interrogate changes in the metabolic profiles of urine and feces of these mice, which are differing in their intestinal microbiota.", "Using high resolution mass spectrometry approach we show that the composition of intestinal microbiota modulates specific metabolic perturbations resulting in a possible alleviation of a glycolytic phenotype.", "Metabolites including 3-methylbutyrolactone, kyneurenic acid and 3-methyladenine known to be onco-protective are elevated in Atm-deficient and wild type mice with restricted intestinal microbiota.", "Thus our approach has broad applicability to study the direct influence of gut microbiome on host metabolism and resultant phenotype.", "These results for the first time suggest a possible correlation of metabolic alterations and carcinogenesis, modulated by intestinal microbiota in A-T mice."], "title": "Chemopreventive Metabolites Are Correlated with a Change in Intestinal Microbiota Measured in A-T Mice and Decreased Carcinogenesis."}
{"paper_id": 24743745, "labels": ["0", "0", "0", "0", "1", "1", "1"], "abstract": "The mitogen-activated protein kinase (MAPK) family, including extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK)1/2 and p38 MAPK, is known to be activated by ultraviolet (UV) radiation in melanocytes to regulate melanin production. Reactive oxygen species (ROS) play important roles in the pathway of ERK and JNK activation. It has been established that the essential oil of Achillea millefolium L. (AM-EO) has activities that suppress the oxidative stress and inflammatory responses. Thus, we analyzed the effects of AM-EO on melanogenesis in melanocyte stimulating hormone (\u03b1-MSH) treated melanoma cells. The results demonstrated that AM-EO suppresses melanin production by decreasing tyrosinase activity through the regulation of the JNK and ERK signaling pathways. This effect might be associated with the AM-EO activity leading to the suppression of ROS, and linalyl acetate is its major functional component. Therefore, we propose that AM-EO has the potential to treat hyperpigmentation in the future.", "journal": "PloS one", "sentences": ["The mitogen-activated protein kinase (MAPK) family, including extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK)1/2 and p38 MAPK, is known to be activated by ultraviolet (UV) radiation in melanocytes to regulate melanin production.", "Reactive oxygen species (ROS) play important roles in the pathway of ERK and JNK activation.", "It has been established that the essential oil of Achillea millefolium L. (AM-EO) has activities that suppress the oxidative stress and inflammatory responses.", "Thus, we analyzed the effects of AM-EO on melanogenesis in melanocyte stimulating hormone (\u03b1-MSH) treated melanoma cells.", "The results demonstrated that AM-EO suppresses melanin production by decreasing tyrosinase activity through the regulation of the JNK and ERK signaling pathways.", "This effect might be associated with the AM-EO activity leading to the suppression of ROS, and linalyl acetate is its major functional component.", "Therefore, we propose that AM-EO has the potential to treat hyperpigmentation in the future."], "title": "The melanogenesis alteration effects of Achillea millefolium L. essential oil and linalyl acetate: involvement of oxidative stress and the JNK and ERK signaling pathways in melanoma cells."}
{"paper_id": 20102953, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "In aortic stenosis (AS), the increased afterload results in progressive structural and functional changes that precede the development of symptoms. We hypothesized that the detection of abnormalities in left ventricular long-axis function could identify patients with asymptomatic AS at increased risk of events. We prospectively examined the outcome of 126 patients with asymptomatic AS who underwent a comprehensive echocardiographic examination, including tissue Doppler imaging. B-type natriuretic peptide (BNP) was measured in all patients. During a median follow-up period of 20.3 + or - 17.8 months, 6 patients died, 8 developed symptoms but did not undergo surgery, and 48 underwent aortic valve replacement. On multivariate Cox regression analysis, the parameters associated with the predefined outcome were gender (p = 0.048), left atrial area index (p = 0.011), systolic annular velocity (p = 0.016), E/Ea ratio (p = 0.024), late diastolic annular velocity (p = 0.023), and BNP (p = 0.012). Using receiver operating characteristics curve analysis, a left atrial area index of > or = 12.4 cm(2)/m(2), systolic annular velocity of < or = 4.5 cm/s, E/Ea ratio >13.8, late diastolic annular velocity of < or = 9 cm/s, and BNP of > or = 61 pg/ml were identified as the best cutoff values to predict events. In conclusion, in asymptomatic AS, tissue Doppler imaging and BNP measurements provide prognostic information beyond that from clinical and conventional echocardiographic parameters.", "journal": "The American journal of cardiology", "sentences": ["In aortic stenosis (AS), the increased afterload results in progressive structural and functional changes that precede the development of symptoms.", "We hypothesized that the detection of abnormalities in left ventricular long-axis function could identify patients with asymptomatic AS at increased risk of events.", "We prospectively examined the outcome of 126 patients with asymptomatic AS who underwent a comprehensive echocardiographic examination, including tissue Doppler imaging.", "B-type natriuretic peptide (BNP) was measured in all patients.", "During a median follow-up period of 20.3 + or - 17.8 months, 6 patients died, 8 developed symptoms but did not undergo surgery, and 48 underwent aortic valve replacement.", "On multivariate Cox regression analysis, the parameters associated with the predefined outcome were gender (p = 0.048), left atrial area index (p = 0.011), systolic annular velocity (p = 0.016), E/Ea ratio (p = 0.024), late diastolic annular velocity (p = 0.023), and BNP (p = 0.012).", "Using receiver operating characteristics curve analysis, a left atrial area index of > or = 12.4 cm(2)/m(2), systolic annular velocity of < or = 4.5 cm/s, E/Ea ratio >13.8, late diastolic annular velocity of < or = 9 cm/s, and BNP of > or = 61 pg/ml were identified as the best cutoff values to predict events.", "In conclusion, in asymptomatic AS, tissue Doppler imaging and BNP measurements provide prognostic information beyond that from clinical and conventional echocardiographic parameters."], "title": "Prognostic effect of long-axis left ventricular dysfunction and B-type natriuretic peptide levels in asymptomatic aortic stenosis."}
{"paper_id": 26797624, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Radiological hazards associated with exposure to Naturally Occurring Radionuclides Materials from gold mine tailings in the province of Gauteng in South Africa were evaluated. A comparison was made with soil samples from a control area. In this study, gamma spectroscopy was used to measure the activity concentrations of these radionuclides in 56 soil samples from the mine tailings and 10 soil samples from the control area. The average activity concentrations in Bq\u2219kg(-1) for Uranium-238, Thorium-232, and Potassium-40 from the mine tailings were found to be 785.3 \u00b1 13.7, 43.9 \u00b1 1.0 and 427.0 \u00b1 13.1, respectively. On the other hand, the average activity concentrations in Bq\u2219kg(-1) for Uranium-238, Thorium-232, and Potassium-40 from the control area were found to be 17.0.1 \u00b1 0.4, 22.2 \u00b1 0.5 and 496.8 \u00b1 15.2, respectively. Radiological hazard parameters calculated from these activity concentrations were higher than recommended safe limits. In particular, calculated average values for the external hazard (Hex) and the internal hazard (Hin) from the mine tailings were found to be 2.4 and 4.5. Both these values were higher than unity, posing a significant health risk to the population in the area.", "journal": "International journal of environmental research and public health", "sentences": ["Radiological hazards associated with exposure to Naturally Occurring Radionuclides Materials from gold mine tailings in the province of Gauteng in South Africa were evaluated.", "A comparison was made with soil samples from a control area.", "In this study, gamma spectroscopy was used to measure the activity concentrations of these radionuclides in 56 soil samples from the mine tailings and 10 soil samples from the control area.", "The average activity concentrations in Bq\u2219kg(-1) for Uranium-238, Thorium-232, and Potassium-40 from the mine tailings were found to be 785.3 \u00b1 13.7, 43.9 \u00b1 1.0 and 427.0 \u00b1 13.1, respectively.", "On the other hand, the average activity concentrations in Bq\u2219kg(-1) for Uranium-238, Thorium-232, and Potassium-40 from the control area were found to be 17.0.1 \u00b1 0.4, 22.2 \u00b1 0.5 and 496.8 \u00b1 15.2, respectively.", "Radiological hazard parameters calculated from these activity concentrations were higher than recommended safe limits.", "In particular, calculated average values for the external hazard (Hex) and the internal hazard (Hin) from the mine tailings were found to be 2.4 and 4.5.", "Both these values were higher than unity, posing a significant health risk to the population in the area."], "title": "An Assessment of Radiological Hazards from Gold Mine Tailings in the Province of Gauteng in South Africa."}
{"paper_id": 23849281, "labels": ["0", "0", "0", "0", "0", "1", "0", "0", "1"], "abstract": "Partnership is a prominent approach to delivering healthcare globally, with advocates arguing that partnership has distinctive advantages over alternatives such as hierarchies or markets. There is much debate as to whether partnerships represent a distinctive mode of coordination in practice, however. Furthermore, despite evidence from diverse settings of the challenges of putting partnerships into practice, there has been little cross-pollination between literature from different fields. We bring together existing literature and two partnership case studies in the contrasting contexts of the UK National Health Service and an internationally-funded health intervention in Cambodia. The case studies were conducted between 2005 and 2008. Based on our synthesis of the literature, we propose an analytical distinction between instrumental and transformative partnerships, arguing that it is transformative partnerships that can deliver the unique advantages set out in theory. Comparative analysis of the cases illustrates that although both were able to achieve some valuable successes, they fell short of realising their transformative potential. We identify five common issues that impeded or facilitated transformative partnership-working, at micro, meso- and macro-levels: starting conditions; programme set-up; funding asymmetries and interdependence; accountability mechanisms; and relationships and distance from the field. Through systematic comparison we offer a more nuanced understanding of how programmes themselves create particular architectures for partnership, how underlying globalised institutional logics of managerialism promote instrumental partnerships, and how local-level, interpersonal relationships may help to overcome barriers to partnership's transformative potential.", "journal": "Social science & medicine (1982)", "sentences": ["Partnership is a prominent approach to delivering healthcare globally, with advocates arguing that partnership has distinctive advantages over alternatives such as hierarchies or markets.", "There is much debate as to whether partnerships represent a distinctive mode of coordination in practice, however.", "Furthermore, despite evidence from diverse settings of the challenges of putting partnerships into practice, there has been little cross-pollination between literature from different fields.", "We bring together existing literature and two partnership case studies in the contrasting contexts of the UK National Health Service and an internationally-funded health intervention in Cambodia.", "The case studies were conducted between 2005 and 2008.", "Based on our synthesis of the literature, we propose an analytical distinction between instrumental and transformative partnerships, arguing that it is transformative partnerships that can deliver the unique advantages set out in theory.", "Comparative analysis of the cases illustrates that although both were able to achieve some valuable successes, they fell short of realising their transformative potential.", "We identify five common issues that impeded or facilitated transformative partnership-working, at micro, meso- and macro-levels: starting conditions; programme set-up; funding asymmetries and interdependence; accountability mechanisms; and relationships and distance from the field.", "Through systematic comparison we offer a more nuanced understanding of how programmes themselves create particular architectures for partnership, how underlying globalised institutional logics of managerialism promote instrumental partnerships, and how local-level, interpersonal relationships may help to overcome barriers to partnership's transformative potential."], "title": "Realising the transformative potential of healthcare partnerships: insights from divergent literatures and contrasting cases in high- and low-income country contexts."}
{"paper_id": 26690079, "labels": ["0", "0", "0", "0", "0", "0", "1", "1", "0", "0"], "abstract": "In this study, the levels of 16 USEPA-prioritized polycyclic aromatic hydrocarbons (PAHs) were quantified in various environmental matrices in Ikpa River Basin and nearby dumpsites using gas chromatography-mass spectrometry (GC-MS). The levels of the contaminants were further subjected to models to estimate possible sources and potential risks. The results obtained revealed that nearby dumpsites could be the major source of contamination of the Ikpa River Basin. The total sum of PAHs in water and sediment samples gave 926.6 \u03bcg/l and 1099.7 \u03bcg/kg, respectively. Higher concentrations, 3025.8 \u03bcg/kg, 3645.7 \u03bcg/kg, and 2457.2 \u03bcg/l, were recorded for nearby municipal dumpsite soil, hospital dumpsite soil, and landfill leachates, respectively. Hierarchical cluster analysis (HCA) and PAH molecular diagnostic ratios (MDRs) suggest that PAH loading in the river basin were mostly of pyrogenic origin. The risk assessment indicated that exposure to PAHs through dermal contact with sediments was most significant than oral ingestion of water and children were the most vulnerable group. Non-cancer (toxic) risks due to exposure to PAHs by oral ingestion of water from Ikpa River were within acceptable limits as the calculated hazard quotients (HQs) and hazard indexes (HIs) were below unity, suggesting negligible or no toxic risk. However, toxic risks through dermal contact with sediments reached unacceptable limits as HI values exceeded unity for all sample stations. Estimated cancer risks due to oral ingestion of water reached the USEPA minimum risk level (3.14\u2009\u00d7\u200910(-5)) requiring public notification while risks due to dermal adsorption of PAHs from the sediments reached levels (2.10\u2009\u00d7\u200910(-1)) requiring remediation actions.", "journal": "Environmental monitoring and assessment", "sentences": ["In this study, the levels of 16 USEPA-prioritized polycyclic aromatic hydrocarbons (PAHs) were quantified in various environmental matrices in Ikpa River Basin and nearby dumpsites using gas chromatography-mass spectrometry (GC-MS).", "The levels of the contaminants were further subjected to models to estimate possible sources and potential risks.", "The results obtained revealed that nearby dumpsites could be the major source of contamination of the Ikpa River Basin.", "The total sum of PAHs in water and sediment samples gave 926.6 \u03bcg/l and 1099.7 \u03bcg/kg, respectively.", "Higher concentrations, 3025.8 \u03bcg/kg, 3645.7 \u03bcg/kg, and 2457.2 \u03bcg/l, were recorded for nearby municipal dumpsite soil, hospital dumpsite soil, and landfill leachates, respectively.", "Hierarchical cluster analysis (HCA) and PAH molecular diagnostic ratios (MDRs) suggest that PAH loading in the river basin were mostly of pyrogenic origin.", "The risk assessment indicated that exposure to PAHs through dermal contact with sediments was most significant than oral ingestion of water and children were the most vulnerable group.", "Non-cancer (toxic) risks due to exposure to PAHs by oral ingestion of water from Ikpa River were within acceptable limits as the calculated hazard quotients (HQs) and hazard indexes (HIs) were below unity, suggesting negligible or no toxic risk.", "However, toxic risks through dermal contact with sediments reached unacceptable limits as HI values exceeded unity for all sample stations.", "Estimated cancer risks due to oral ingestion of water reached the USEPA minimum risk level (3.14\u2009\u00d7\u200910(-5)) requiring public notification while risks due to dermal adsorption of PAHs from the sediments reached levels (2.10\u2009\u00d7\u200910(-1)) requiring remediation actions."], "title": "Polycyclic aromatic hydrocarbons loads and potential risks in freshwater ecosystem of the Ikpa River Basin, Niger Delta-Nigeria."}
{"paper_id": 22293203, "labels": ["0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "CD38 is a multifunctional enzyme that can not only generate cyclic adenosine diphosphate-ribose (cADPR) - a key Ca(2+) -mobilizing second messenger - by consuming NAD(+), but also hydrolyze extracellular NAD(+). There have been only a small number of studies on the functions of CD38 in the CNS. Brain inflammation plays critical roles in ischemic brain injury and multiple other neurological diseases, in which microglia activation is a key event. In this study we determined the roles of CD38 in the basal survival of mouse BV2 microglia cells by applying CD38 siRNA. Our study found that silencing of CD38 led to significantly decreased survival of the cells. We also found that decreased CD38 levels can lead to apoptosis of the microglial cells, as assessed by flow cytometry-based Annexin V/7-AAD assay, caspase-3 immunostaining and Hoechst staining assays. Our study has further indicated that the CD38 silencing-induced apoptosis is mainly caspase 3-dependent. Collectively, our study has provided the first evidence suggesting that CD38 plays a critical role in the basal survival of microglia, and decreased CD38 can lead to caspase 3-dependent apoptosis of the cells. These results suggest that CD38 may become a therapeutic target for modulating microglial survival in neurological diseases.", "journal": "Biochemical and biophysical research communications", "sentences": ["CD38 is a multifunctional enzyme that can not only generate cyclic adenosine diphosphate-ribose (cADPR) - a key Ca(2+) -mobilizing second messenger - by consuming NAD(+), but also hydrolyze extracellular NAD(+).", "There have been only a small number of studies on the functions of CD38 in the CNS.", "Brain inflammation plays critical roles in ischemic brain injury and multiple other neurological diseases, in which microglia activation is a key event.", "In this study we determined the roles of CD38 in the basal survival of mouse BV2 microglia cells by applying CD38 siRNA.", "Our study found that silencing of CD38 led to significantly decreased survival of the cells.", "We also found that decreased CD38 levels can lead to apoptosis of the microglial cells, as assessed by flow cytometry-based Annexin V/7-AAD assay, caspase-3 immunostaining and Hoechst staining assays.", "Our study has further indicated that the CD38 silencing-induced apoptosis is mainly caspase 3-dependent.", "Collectively, our study has provided the first evidence suggesting that CD38 plays a critical role in the basal survival of microglia, and decreased CD38 can lead to caspase 3-dependent apoptosis of the cells.", "These results suggest that CD38 may become a therapeutic target for modulating microglial survival in neurological diseases."], "title": "CD38 is a key enzyme for the survival of mouse microglial BV2 cells."}
{"paper_id": 25646724, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Light microscopy enables noninvasive imaging of fluorescent species in biological specimens, but resolution is generally limited by diffraction to ~200-250 nm. Many biological processes occur on smaller length scales, highlighting the importance of techniques that can image below the diffraction limit and provide valuable single-molecule information. In recent years, imaging techniques have been developed which can achieve resolution below the diffraction limit. Utilizing one such technique, fluorescence photoactivation localization microscopy (FPALM), we demonstrated its ability to construct super-resolution images from single molecules in a living zebrafish embryo, expanding the realm of previous super-resolution imaging to a living vertebrate organism. We imaged caveolin-1 in vivo, in living zebrafish embryos. Our results demonstrate the successful image acquisition of super-resolution images in a living vertebrate organism, opening several opportunities to answer more dynamic biological questions in vivo at the previously inaccessible nanoscale.", "journal": "PloS one", "sentences": ["Light microscopy enables noninvasive imaging of fluorescent species in biological specimens, but resolution is generally limited by diffraction to ~200-250 nm.", "Many biological processes occur on smaller length scales, highlighting the importance of techniques that can image below the diffraction limit and provide valuable single-molecule information.", "In recent years, imaging techniques have been developed which can achieve resolution below the diffraction limit.", "Utilizing one such technique, fluorescence photoactivation localization microscopy (FPALM), we demonstrated its ability to construct super-resolution images from single molecules in a living zebrafish embryo, expanding the realm of previous super-resolution imaging to a living vertebrate organism.", "We imaged caveolin-1 in vivo, in living zebrafish embryos.", "Our results demonstrate the successful image acquisition of super-resolution images in a living vertebrate organism, opening several opportunities to answer more dynamic biological questions in vivo at the previously inaccessible nanoscale."], "title": "Nanoscale imaging of caveolin-1 membrane domains in vivo."}
{"paper_id": 27196096, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Aspergillus flavus is a well-known pathogenic fungus for both crops and human beings. The acquisition of resistance to azoles by A. flavus is leading to more failures occurring in the prevention of infection by A. flavus. In this study, we found that thymol, one of the major chemical constituents of the essential oil of Monarda punctate, had efficient fungicidal activity against A. flavus and led to sporular lysis. Further studies indicated that thymol treatment induced the generation of both ROS and NO in spores, whereas NO accumulation was far later than ROS accumulation in response to thymol. By blocking ROS production with the inhibitors of NADPH oxidase, NO generation was also significantly inhibited in the presence of thymol, which indicated that ROS induced NO generation in A. flavus in response to thymol treatment. Moreover, the removal of either ROS or NO attenuated lysis and death of spores exposed to thymol. The addition of SNP (exogenous NO donor) eliminated the protective effects of the inhibitors of NADPH oxidase on thymol-induced lysis and death of spores. Taken together, it could be concluded that ROS is involved in spore death induced by thymol via the induction of NO.", "journal": "PloS one", "sentences": ["Aspergillus flavus is a well-known pathogenic fungus for both crops and human beings.", "The acquisition of resistance to azoles by A. flavus is leading to more failures occurring in the prevention of infection by A. flavus.", "In this study, we found that thymol, one of the major chemical constituents of the essential oil of Monarda punctate, had efficient fungicidal activity against A. flavus and led to sporular lysis.", "Further studies indicated that thymol treatment induced the generation of both ROS and NO in spores, whereas NO accumulation was far later than ROS accumulation in response to thymol.", "By blocking ROS production with the inhibitors of NADPH oxidase, NO generation was also significantly inhibited in the presence of thymol, which indicated that ROS induced NO generation in A. flavus in response to thymol treatment.", "Moreover, the removal of either ROS or NO attenuated lysis and death of spores exposed to thymol.", "The addition of SNP (exogenous NO donor) eliminated the protective effects of the inhibitors of NADPH oxidase on thymol-induced lysis and death of spores.", "Taken together, it could be concluded that ROS is involved in spore death induced by thymol via the induction of NO."], "title": "ROS Involves the Fungicidal Actions of Thymol against Spores of Aspergillus flavus via the Induction of Nitric Oxide."}
{"paper_id": 24631674, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The atrial volume receptor reflex arc serves to regulate plasma volume. Atrial volume receptors located in the endocardium of the atrial wall undergo mechanical deformation as blood is returned to the atria of the heart. The mechanosensitive channel(s) responsible for regulating plasma volume remain to be determined. Here we report that the TRP channel family members TRPC1 and TRPV4 were expressed in sensory nerve endings in the atrial endocardium. Furthermore, TRPC1 and TRPV4 were coincident with the nerve ending vesicle marker synaptophysin. Calcitonin gene-related peptide was exclusively confined to the myo- and epicardium of the atria. The small conductance Ca(2+)-activated K(+) channels (SK2 and SK4) were also present, however there was no relationship between SK and TRP channels. SK2 channels were expressed in nerves in the epicardium, while SK4 channels were in some regions of the endocardium but appeared to be present in epithelial cells rather than sensory endings. In conclusion, we have provided the first evidence for TRPC1 and TRPV4 channels as potential contributors to mechanosensation in the atrial volume receptors.", "journal": "Neuroscience", "sentences": ["The atrial volume receptor reflex arc serves to regulate plasma volume.", "Atrial volume receptors located in the endocardium of the atrial wall undergo mechanical deformation as blood is returned to the atria of the heart.", "The mechanosensitive channel(s) responsible for regulating plasma volume remain to be determined.", "Here we report that the TRP channel family members TRPC1 and TRPV4 were expressed in sensory nerve endings in the atrial endocardium.", "Furthermore, TRPC1 and TRPV4 were coincident with the nerve ending vesicle marker synaptophysin.", "Calcitonin gene-related peptide was exclusively confined to the myo- and epicardium of the atria.", "The small conductance Ca(2+)-activated K(+) channels (SK2 and SK4) were also present, however there was no relationship between SK and TRP channels.", "SK2 channels were expressed in nerves in the epicardium, while SK4 channels were in some regions of the endocardium but appeared to be present in epithelial cells rather than sensory endings.", "In conclusion, we have provided the first evidence for TRPC1 and TRPV4 channels as potential contributors to mechanosensation in the atrial volume receptors."], "title": "Expression of transient receptor potential channels TRPC1 and TRPV4 in venoatrial endocardium of the rat heart."}
{"paper_id": 21430780, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation.", "journal": "Nature", "sentences": ["Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest.", "It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma.", "We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage.", "Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate.", "To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma.", "One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells.", "Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth.", "When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies.", "Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation."], "title": "DHODH modulates transcriptional elongation in the neural crest and melanoma."}
{"paper_id": 26360597, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "A range of single classifiers have been proposed to classify crop types using time series vegetation indices, and hybrid classifiers are used to improve discriminatory power. Traditional fusion rules use the product of multi-single classifiers, but that strategy cannot integrate the classification output of machine learning classifiers. In this research, the performance of two hybrid strategies, multiple voting (M-voting) and probabilistic fusion (P-fusion), for crop classification using NDVI time series were tested with different training sample sizes at both pixel and object levels, and two representative counties in north Xinjiang were selected as study area. The single classifiers employed in this research included Random Forest (RF), Support Vector Machine (SVM), and See 5 (C 5.0). The results indicated that classification performance improved (increased the mean overall accuracy by 5%~10%, and reduced standard deviation of overall accuracy by around 1%) substantially with the training sample number, and when the training sample size was small (50 or 100 training samples), hybrid classifiers substantially outperformed single classifiers with higher mean overall accuracy (1%~2%). However, when abundant training samples (4,000) were employed, single classifiers could achieve good classification accuracy, and all classifiers obtained similar performances. Additionally, although object-based classification did not improve accuracy, it resulted in greater visual appeal, especially in study areas with a heterogeneous cropping pattern.", "journal": "PloS one", "sentences": ["A range of single classifiers have been proposed to classify crop types using time series vegetation indices, and hybrid classifiers are used to improve discriminatory power.", "Traditional fusion rules use the product of multi-single classifiers, but that strategy cannot integrate the classification output of machine learning classifiers.", "In this research, the performance of two hybrid strategies, multiple voting (M-voting) and probabilistic fusion (P-fusion), for crop classification using NDVI time series were tested with different training sample sizes at both pixel and object levels, and two representative counties in north Xinjiang were selected as study area.", "The single classifiers employed in this research included Random Forest (RF), Support Vector Machine (SVM), and See 5 (C 5.0).", "The results indicated that classification performance improved (increased the mean overall accuracy by 5%~10%, and reduced standard deviation of overall accuracy by around 1%) substantially with the training sample number, and when the training sample size was small (50 or 100 training samples), hybrid classifiers substantially outperformed single classifiers with higher mean overall accuracy (1%~2%).", "However, when abundant training samples (4,000) were employed, single classifiers could achieve good classification accuracy, and all classifiers obtained similar performances.", "Additionally, although object-based classification did not improve accuracy, it resulted in greater visual appeal, especially in study areas with a heterogeneous cropping pattern."], "title": "Comparison of Hybrid Classifiers for Crop Classification Using Normalized Difference Vegetation Index Time Series: A Case Study for Major Crops in North Xinjiang, China."}
{"paper_id": 22567121, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Diatoms and other algae not only survive, but thrive in sea ice. Among sea ice diatoms, all species examined so far produce ice-binding proteins (IBPs), whereas no such proteins are found in non-ice-associated diatoms, which strongly suggests that IBPs are essential for survival in ice. The restricted occurrence also raises the question of how the IBP genes were acquired. Proteins with similar sequences and ice-binding activities are produced by ice-associated bacteria, and so it has previously been speculated that the genes were acquired by horizontal transfer (HGT) from bacteria. Here we report several new IBP sequences from three types of ice algae, which together with previously determined sequences reveal a phylogeny that is completely incongruent with algal phylogeny, and that can be most easily explained by HGT. HGT is also supported by the finding that the closest matches to the algal IBP genes are all bacterial genes and that the algal IBP genes lack introns. We also describe a highly freeze-tolerant bacterium from the bottom layer of Antarctic sea ice that produces an IBP with 47% amino acid identity to a diatom IBP from the same layer, demonstrating at least an opportunity for gene transfer. Together, these results suggest that the success of diatoms and other algae in sea ice can be at least partly attributed to their acquisition of prokaryotic IBP genes.", "journal": "PloS one", "sentences": ["Diatoms and other algae not only survive, but thrive in sea ice.", "Among sea ice diatoms, all species examined so far produce ice-binding proteins (IBPs), whereas no such proteins are found in non-ice-associated diatoms, which strongly suggests that IBPs are essential for survival in ice.", "The restricted occurrence also raises the question of how the IBP genes were acquired.", "Proteins with similar sequences and ice-binding activities are produced by ice-associated bacteria, and so it has previously been speculated that the genes were acquired by horizontal transfer (HGT) from bacteria.", "Here we report several new IBP sequences from three types of ice algae, which together with previously determined sequences reveal a phylogeny that is completely incongruent with algal phylogeny, and that can be most easily explained by HGT.", "HGT is also supported by the finding that the closest matches to the algal IBP genes are all bacterial genes and that the algal IBP genes lack introns.", "We also describe a highly freeze-tolerant bacterium from the bottom layer of Antarctic sea ice that produces an IBP with 47% amino acid identity to a diatom IBP from the same layer, demonstrating at least an opportunity for gene transfer.", "Together, these results suggest that the success of diatoms and other algae in sea ice can be at least partly attributed to their acquisition of prokaryotic IBP genes."], "title": "Possible role of horizontal gene transfer in the colonization of sea ice by algae."}
{"paper_id": 26993169, "labels": ["0", "0", "0", "0", "1", "0", "1"], "abstract": "Mitochondrial diseases encompass a wide variety of pathologies characterized by a dysfunction of the mitochondrial respiratory chain resulting in an energy deficiency. The respiratory chain consists of five multi-protein complexes providing coupling between nutrient oxidation and phosphorylation of ADP to ATP. In the present report, we studied mitochondrial genes of complex I, III, IV and V in 2 Tunisian patients with mitochondrial neuromuscular disorders. In the first patient, we detected the m.8392C>T variation (P136S) in the mitochondrial ATPase6 gene and the m.8527A>G transition at the junction MT-ATP6/MT-ATP8 which change the initiation codon AUG to GUG. The presence of these two variations in such an important gene could probably affect the ATP synthesis in the studied patient. In the second patient, we detected several known variations in addition to a mitochondrial deletion in the major arc of the mtDNA eliminating tRNA and respiratory chain protein genes. This deletion could be responsible of an inefficient translation leading to an inefficient mitochondrial protein synthesis in P2.", "journal": "Biochemical and biophysical research communications", "sentences": ["Mitochondrial diseases encompass a wide variety of pathologies characterized by a dysfunction of the mitochondrial respiratory chain resulting in an energy deficiency.", "The respiratory chain consists of five multi-protein complexes providing coupling between nutrient oxidation and phosphorylation of ADP to ATP.", "In the present report, we studied mitochondrial genes of complex I, III, IV and V in 2 Tunisian patients with mitochondrial neuromuscular disorders.", "In the first patient, we detected the m.8392C>T variation (P136S) in the mitochondrial ATPase6 gene and the m.8527A>G transition at the junction MT-ATP6/MT-ATP8 which change the initiation codon AUG to GUG.", "The presence of these two variations in such an important gene could probably affect the ATP synthesis in the studied patient.", "In the second patient, we detected several known variations in addition to a mitochondrial deletion in the major arc of the mtDNA eliminating tRNA and respiratory chain protein genes.", "This deletion could be responsible of an inefficient translation leading to an inefficient mitochondrial protein synthesis in P2."], "title": "Mutational analysis in patients with neuromuscular disorders: Detection of mitochondrial deletion and double mutations in the MT-ATP6 gene."}
{"paper_id": 23516621, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Escherichia coli, as one of the gut microbiota, can evoke severe inflammatory diseases including peritonitis and sepsis. Gram-negative bacteria including E. coli constitutively release nano-sized outer membrane vesicles (OMVs). Although E. coli OMVs can induce the inflammatory responses without live bacteria, the effect of E. coli OMVs in vivo on endothelial cell function has not been previously elucidated. In this study, we show that bacteria-free OMVs increased the expression of endothelial intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1, and enhanced the leukocyte binding on human microvascular endothelial cells in vitro. Inhibition of NF-\u03baB and TLR4 reduced the expression of cell adhesion molecules in vitro. OMVs given intraperitoneally to the mice induced ICAM-1 expression and neutrophil sequestration in the lung endothelium, and the effects were reduced in ICAM-1(-/-) and TLR4(-/-) mice. When compared to free lipopolysaccharide, OMVs were more potent in inducing both ICAM-1 expression as well as leukocyte adhesion in vitro, and ICAM-1 expression and neutrophil sequestration in the lungs in vivo. This study shows that OMVs potently up-regulate functional cell adhesion molecules via NF-\u03baB- and TLR4-dependent pathways, and that OMVs are more potent than free lipopolysaccharide.", "journal": "PloS one", "sentences": ["Escherichia coli, as one of the gut microbiota, can evoke severe inflammatory diseases including peritonitis and sepsis.", "Gram-negative bacteria including E. coli constitutively release nano-sized outer membrane vesicles (OMVs).", "Although E. coli OMVs can induce the inflammatory responses without live bacteria, the effect of E. coli OMVs in vivo on endothelial cell function has not been previously elucidated.", "In this study, we show that bacteria-free OMVs increased the expression of endothelial intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1, and enhanced the leukocyte binding on human microvascular endothelial cells in vitro.", "Inhibition of NF-\u03baB and TLR4 reduced the expression of cell adhesion molecules in vitro.", "OMVs given intraperitoneally to the mice induced ICAM-1 expression and neutrophil sequestration in the lung endothelium, and the effects were reduced in ICAM-1(-/-) and TLR4(-/-) mice.", "When compared to free lipopolysaccharide, OMVs were more potent in inducing both ICAM-1 expression as well as leukocyte adhesion in vitro, and ICAM-1 expression and neutrophil sequestration in the lungs in vivo.", "This study shows that OMVs potently up-regulate functional cell adhesion molecules via NF-\u03baB- and TLR4-dependent pathways, and that OMVs are more potent than free lipopolysaccharide."], "title": "Outer membrane vesicles derived from Escherichia coli up-regulate expression of endothelial cell adhesion molecules in vitro and in vivo."}
{"paper_id": 26028034, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "HOXA9 is a homeodomain-containing transcription factor that has an important role in hematopoietic stem cell expansion and is commonly deregulated in acute leukemias. A variety of upstream genetic alterations in acute myeloid leukemia lead to overexpression of HOXA9, which is a strong predictor of poor prognosis. In many cases, HOXA9 has been shown to be necessary for maintaining leukemic transformation; however, the molecular mechanisms through which it promotes leukemogenesis remain elusive. Recent work has established that HOXA9 regulates downstream gene expression through binding at promoter distal enhancers along with a subset of cell-specific cofactor and collaborator proteins. Increasing efforts are being made to identify both the critical cofactors and target genes required for maintaining transformation in HOXA9-overexpressing leukemias. With continued advances in understanding HOXA9-mediated transformation, there is a wealth of opportunity for developing novel therapeutics that would be applicable for greater than 50% of AML with overexpression of HOXA9.", "journal": "Oncogene", "sentences": ["HOXA9 is a homeodomain-containing transcription factor that has an important role in hematopoietic stem cell expansion and is commonly deregulated in acute leukemias.", "A variety of upstream genetic alterations in acute myeloid leukemia lead to overexpression of HOXA9, which is a strong predictor of poor prognosis.", "In many cases, HOXA9 has been shown to be necessary for maintaining leukemic transformation; however, the molecular mechanisms through which it promotes leukemogenesis remain elusive.", "Recent work has established that HOXA9 regulates downstream gene expression through binding at promoter distal enhancers along with a subset of cell-specific cofactor and collaborator proteins.", "Increasing efforts are being made to identify both the critical cofactors and target genes required for maintaining transformation in HOXA9-overexpressing leukemias.", "With continued advances in understanding HOXA9-mediated transformation, there is a wealth of opportunity for developing novel therapeutics that would be applicable for greater than 50% of AML with overexpression of HOXA9."], "title": "Role of HOXA9 in leukemia: dysregulation, cofactors and essential targets."}
{"paper_id": 24498150, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "It has become increasingly clear that the current taxonomy of clinical phenotypes is mixed with molecular heterogeneity, which potentially affects the treatment effect for involved patients. Defining the hidden molecular-distinct diseases using modern large-scale genomic approaches is therefore useful for refining clinical practice and improving intervention strategies. Given that microRNA expression profiling has provided a powerful way to dissect hidden genetic heterogeneity for complex diseases, the aim of the study was to develop a bioinformatics approach that identifies microRNA features leading to the hidden subtyping of complex clinical phenotypes. The basic strategy of the proposed method was to identify optimal miRNA clusters by iteratively partitioning the sample and feature space using the two-ways super-paramagnetic clustering technique. We evaluated the obtained optimal miRNA cluster by determining the consistency of co-expression and the chromosome location among the within-cluster microRNAs, and concluded that the optimal miRNA cluster could lead to a natural partition of disease samples. We applied the proposed method to a publicly available microarray dataset of breast cancer patients that have notoriously heterogeneous phenotypes. We obtained a feature subset of 13 microRNAs that could classify the 71 breast cancer patients into five subtypes with significantly different five-year overall survival rates (45%, 82.4%, 70.6%, 100% and 60% respectively; p\u200a=\u200a0.008). By building a multivariate Cox proportional-hazards prediction model for the feature subset, we identified has-miR-146b as one of the most significant predictor (p\u200a=\u200a0.045; hazard ratios\u200a=\u200a0.39). The proposed algorithm is a promising computational strategy for dissecting hidden genetic heterogeneity for complex diseases, and will be of value for improving cancer diagnosis and treatment.", "journal": "PloS one", "sentences": ["It has become increasingly clear that the current taxonomy of clinical phenotypes is mixed with molecular heterogeneity, which potentially affects the treatment effect for involved patients.", "Defining the hidden molecular-distinct diseases using modern large-scale genomic approaches is therefore useful for refining clinical practice and improving intervention strategies.", "Given that microRNA expression profiling has provided a powerful way to dissect hidden genetic heterogeneity for complex diseases, the aim of the study was to develop a bioinformatics approach that identifies microRNA features leading to the hidden subtyping of complex clinical phenotypes.", "The basic strategy of the proposed method was to identify optimal miRNA clusters by iteratively partitioning the sample and feature space using the two-ways super-paramagnetic clustering technique.", "We evaluated the obtained optimal miRNA cluster by determining the consistency of co-expression and the chromosome location among the within-cluster microRNAs, and concluded that the optimal miRNA cluster could lead to a natural partition of disease samples.", "We applied the proposed method to a publicly available microarray dataset of breast cancer patients that have notoriously heterogeneous phenotypes.", "We obtained a feature subset of 13 microRNAs that could classify the 71 breast cancer patients into five subtypes with significantly different five-year overall survival rates (45%, 82.4%, 70.6%, 100% and 60% respectively; p\u200a=\u200a0.008).", "By building a multivariate Cox proportional-hazards prediction model for the feature subset, we identified has-miR-146b as one of the most significant predictor (p\u200a=\u200a0.045; hazard ratios\u200a=\u200a0.39).", "The proposed algorithm is a promising computational strategy for dissecting hidden genetic heterogeneity for complex diseases, and will be of value for improving cancer diagnosis and treatment."], "title": "Unraveling the hidden heterogeneities of breast cancer based on functional miRNA cluster."}
{"paper_id": 24248344, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "Northern Hemisphere sea ice has been declining sharply over the past decades and 2012 exhibited the lowest Arctic summer sea-ice cover in historic times. Whereas ongoing changes are closely monitored through satellite observations, we have only limited data of past Arctic sea-ice cover derived from short historical records, indirect terrestrial proxies, and low-resolution marine sediment cores. A multicentury time series from extremely long-lived annual increment-forming crustose coralline algal buildups now provides the first high-resolution in situ marine proxy for sea-ice cover. Growth and Mg/Ca ratios of these Arctic-wide occurring calcified algae are sensitive to changes in both temperature and solar radiation. Growth sharply declines with increasing sea-ice blockage of light from the benthic algal habitat. The 646-y multisite record from the Canadian Arctic indicates that during the Little Ice Age, sea ice was extensive but highly variable on subdecadal time scales and coincided with an expansion of ice-dependent Thule/Labrador Inuit sea mammal hunters in the region. The past 150 y instead have been characterized by sea ice exhibiting multidecadal variability with a long-term decline distinctly steeper than at any time since the 14th century.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Northern Hemisphere sea ice has been declining sharply over the past decades and 2012 exhibited the lowest Arctic summer sea-ice cover in historic times.", "Whereas ongoing changes are closely monitored through satellite observations, we have only limited data of past Arctic sea-ice cover derived from short historical records, indirect terrestrial proxies, and low-resolution marine sediment cores.", "A multicentury time series from extremely long-lived annual increment-forming crustose coralline algal buildups now provides the first high-resolution in situ marine proxy for sea-ice cover.", "Growth and Mg/Ca ratios of these Arctic-wide occurring calcified algae are sensitive to changes in both temperature and solar radiation.", "Growth sharply declines with increasing sea-ice blockage of light from the benthic algal habitat.", "The 646-y multisite record from the Canadian Arctic indicates that during the Little Ice Age, sea ice was extensive but highly variable on subdecadal time scales and coincided with an expansion of ice-dependent Thule/Labrador Inuit sea mammal hunters in the region.", "The past 150 y instead have been characterized by sea ice exhibiting multidecadal variability with a long-term decline distinctly steeper than at any time since the 14th century."], "title": "Arctic sea-ice decline archived by multicentury annual-resolution record from crustose coralline algal proxy."}
{"paper_id": 22790986, "labels": ["0", "1", "0", "0", "1", "1"], "abstract": "Monte Carlo simulations of a mesoscale model of oligonucleosomes are analyzed to examine the role of dynamic-linker histone (LH) binding/unbinding in high monovalent salt with divalent ions, and to further interpret noted chromatin fiber softening by dynamic LH in monovalent salt conditions. We find that divalent ions produce a fiber stiffening effect that competes with, but does not overshadow, the dramatic softening triggered by dynamic-LH behavior. Indeed, we find that in typical in vivo conditions, dynamic-LH binding/unbinding reduces fiber stiffening dramatically (by a factor of almost 5, as measured by the elasticity modulus) compared with rigidly fixed LH, and also the force needed to initiate chromatin unfolding, making it consistent with those of molecular motors. Our data also show that, during unfolding, divalent ions together with LHs induce linker-DNA bending and DNA-DNA repulsion screening, which guarantee formation of heteromorphic superbeads-on-a-string structures that combine regions of loose and compact fiber independently of the characteristics of the LH-core bond. These structures might be important for gene regulation as they expose regions of the DNA selectively. Dynamic control of LH binding/unbinding, either globally or locally, in the presence of divalent ions, might constitute a mechanism for regulation of gene expression.", "journal": "Nucleic acids research", "sentences": ["Monte Carlo simulations of a mesoscale model of oligonucleosomes are analyzed to examine the role of dynamic-linker histone (LH) binding/unbinding in high monovalent salt with divalent ions, and to further interpret noted chromatin fiber softening by dynamic LH in monovalent salt conditions.", "We find that divalent ions produce a fiber stiffening effect that competes with, but does not overshadow, the dramatic softening triggered by dynamic-LH behavior.", "Indeed, we find that in typical in vivo conditions, dynamic-LH binding/unbinding reduces fiber stiffening dramatically (by a factor of almost 5, as measured by the elasticity modulus) compared with rigidly fixed LH, and also the force needed to initiate chromatin unfolding, making it consistent with those of molecular motors.", "Our data also show that, during unfolding, divalent ions together with LHs induce linker-DNA bending and DNA-DNA repulsion screening, which guarantee formation of heteromorphic superbeads-on-a-string structures that combine regions of loose and compact fiber independently of the characteristics of the LH-core bond.", "These structures might be important for gene regulation as they expose regions of the DNA selectively.", "Dynamic control of LH binding/unbinding, either globally or locally, in the presence of divalent ions, might constitute a mechanism for regulation of gene expression."], "title": "Crucial role of dynamic linker histone binding and divalent ions for DNA accessibility and gene regulation revealed by mesoscale modeling of oligonucleosomes."}
{"paper_id": 20871596, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity. Recurrent translocation of BRD4 is observed in a genetically-defined, incurable subtype of human squamous carcinoma. Competitive binding by JQ1 displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models. These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family.", "journal": "Nature", "sentences": ["Epigenetic proteins are intently pursued targets in ligand discovery.", "So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'.", "Potent inhibitors of histone binding modules have not yet been described.", "Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains.", "High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity.", "Recurrent translocation of BRD4 is observed in a genetically-defined, incurable subtype of human squamous carcinoma.", "Competitive binding by JQ1 displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models.", "These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family."], "title": "Selective inhibition of BET bromodomains."}
{"paper_id": 26139369, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Fighting pathogens and maintaining tissue homeostasis are prerequisites for survival. Both of these functions are upheld by the immune system, though the latter is often overlooked in the context of the CNS. The mere presence of immune cells in the CNS was long considered a hallmark of pathology, but this view has been recently challenged by studies demonstrating that immunological signaling can confer pivotal neuroprotective effects on the injured CNS. In this review, we describe the temporal sequence of immunological events that follow CNS injury. Beginning with immediate changes at the injury site, including death of neural cells and release of damage-associated molecular patterns (DAMPs), and progressing through innate and adaptive immune responses, we describe the cascade of inflammatory mediators and the implications of their post-injury effects. We conclude by proposing a revised interpretation of immune privilege in the brain, which takes beneficial neuro-immune communications into account.", "journal": "Neuron", "sentences": ["Fighting pathogens and maintaining tissue homeostasis are prerequisites for survival.", "Both of these functions are upheld by the immune system, though the latter is often overlooked in the context of the CNS.", "The mere presence of immune cells in the CNS was long considered a hallmark of pathology, but this view has been recently challenged by studies demonstrating that immunological signaling can confer pivotal neuroprotective effects on the injured CNS.", "In this review, we describe the temporal sequence of immunological events that follow CNS injury.", "Beginning with immediate changes at the injury site, including death of neural cells and release of damage-associated molecular patterns (DAMPs), and progressing through innate and adaptive immune responses, we describe the cascade of inflammatory mediators and the implications of their post-injury effects.", "We conclude by proposing a revised interpretation of immune privilege in the brain, which takes beneficial neuro-immune communications into account."], "title": "Dealing with Danger in the CNS: The Response of the Immune System to Injury."}
{"paper_id": 26502286, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The Hepatitis C virus (HCV) infection exhibits a high global prevalence frequently associated with hepatocellular carcinoma, taking years to develop. Despite the standardization of highly sensitive HCV quantitative RT-PCR (qRT-PCR) detection methods, false-negative diagnoses may be generated with current methods, mainly due to the presence of PCR inhibitors and/or low viral loads in the patient's sample. These false-negative diagnoses impact both public health systems, in developing countries, and an in lesser extent, in developed countries, including both the risk of virus transmission during organ transplantation and/or blood transfusion and the quality of the antiviral treatment monitoring. To adopt an appropriate therapeutic strategy to improve the patient's prognosis, it is urgent to increase the HCV detection sensitivity. Based upon previous studies on HBV, we worked on the capacity of the scavenger acute phase protein, Apolipoprotein H (ApoH) to interact with HCV. Using different approaches, including immunoassays, antibody-inhibition, oxidation, ultracentrifugation, electron microscopy and RT-PCR analyses, we demonstrated specific interactions between HCV particles and ApoH. Moreover, when using a two-step HCV detection process, including capture of HCV by ApoH-coated nanomagnetic beads and a home-made real-time HCV-RT-PCR, we confirmed the presence of HCV for all samples from a clinical collection of HCV-seropositive patients exhibiting an RT-PCR COBAS\u00ae TaqMan\u00ae HCV Test, v2.0 (COBAS)-positive result. In contrast, for HCV-seropositive patients with either low HCV-load as determined with COBAS or exhibiting HCV-negative COBAS results, the addition of the two-step ApoH-HCV-capture and HCV-detection process was able to increase the sensitivity of HCV detection or more interestingly, detect in a genotype sequence-independent manner, a high-proportion (44%) of HCV/RNA-positive among the COBAS HCV-negative patients. Thus, the immune interaction between ApoH and HCV could be used as a sample preparation tool to enrich and/or cleanse HCV patient's samples to enhance the detection sensitivity of HCV and therefore significantly reduce the numbers of false-negative HCV diagnosis results.", "journal": "PloS one", "sentences": ["The Hepatitis C virus (HCV) infection exhibits a high global prevalence frequently associated with hepatocellular carcinoma, taking years to develop.", "Despite the standardization of highly sensitive HCV quantitative RT-PCR (qRT-PCR) detection methods, false-negative diagnoses may be generated with current methods, mainly due to the presence of PCR inhibitors and/or low viral loads in the patient's sample.", "These false-negative diagnoses impact both public health systems, in developing countries, and an in lesser extent, in developed countries, including both the risk of virus transmission during organ transplantation and/or blood transfusion and the quality of the antiviral treatment monitoring.", "To adopt an appropriate therapeutic strategy to improve the patient's prognosis, it is urgent to increase the HCV detection sensitivity.", "Based upon previous studies on HBV, we worked on the capacity of the scavenger acute phase protein, Apolipoprotein H (ApoH) to interact with HCV.", "Using different approaches, including immunoassays, antibody-inhibition, oxidation, ultracentrifugation, electron microscopy and RT-PCR analyses, we demonstrated specific interactions between HCV particles and ApoH.", "Moreover, when using a two-step HCV detection process, including capture of HCV by ApoH-coated nanomagnetic beads and a home-made real-time HCV-RT-PCR, we confirmed the presence of HCV for all samples from a clinical collection of HCV-seropositive patients exhibiting an RT-PCR COBAS\u00ae TaqMan\u00ae HCV Test, v2.0 (COBAS)-positive result.", "In contrast, for HCV-seropositive patients with either low HCV-load as determined with COBAS or exhibiting HCV-negative COBAS results, the addition of the two-step ApoH-HCV-capture and HCV-detection process was able to increase the sensitivity of HCV detection or more interestingly, detect in a genotype sequence-independent manner, a high-proportion (44%) of HCV/RNA-positive among the COBAS HCV-negative patients.", "Thus, the immune interaction between ApoH and HCV could be used as a sample preparation tool to enrich and/or cleanse HCV patient's samples to enhance the detection sensitivity of HCV and therefore significantly reduce the numbers of false-negative HCV diagnosis results."], "title": "Interactions between Hepatitis C Virus and the Human Apolipoprotein H Acute Phase Protein: A Tool for a Sensitive Detection of the Virus."}
{"paper_id": 24557948, "labels": ["0", "0", "1", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The emergence of Staphylococcus aureus strains that are resistant to glycopeptides has led to alarming scenarios where serious staphylococcal infections cannot be treated. The bacterium expresses many small regulatory RNAs (sRNAs) that have unknown biological functions for the most part. Here we show that an S. aureus sRNA, SprX (alias RsaOR), shapes bacterial resistance to glycopeptides, the invaluable treatments for Methicillin-resistant staphylococcal infections. Modifying SprX expression levels influences Vancomycin and Teicoplanin glycopeptide resistance. Comparative proteomic studies have identified that SprX specifically downregulates stage V sporulation protein G, SpoVG. SpoVG is produced from the yabJ-spoVG operon and contributes to S. aureus glycopeptide resistance. SprX negatively regulates SpoVG expression by direct antisense pairings at the internal translation initiation signals of the second operon gene, without modifying bicistronic mRNA expression levels or affecting YabJ translation. The SprX and yabJ-spoVG mRNA domains involved in the interaction have been identified, highlighting the importance of a CU-rich loop of SprX in the control of SpoVG expression. We have shown that SpoVG might not be the unique SprX target involved in the glycopeptide resistance and demonstrated that the regulation of glycopeptide sensitivity involves the CU-rich domain of SprX. Here we report the case of a sRNA influencing antibiotic resistance of a major human pathogen.", "journal": "Nucleic acids research", "sentences": ["The emergence of Staphylococcus aureus strains that are resistant to glycopeptides has led to alarming scenarios where serious staphylococcal infections cannot be treated.", "The bacterium expresses many small regulatory RNAs (sRNAs) that have unknown biological functions for the most part.", "Here we show that an S. aureus sRNA, SprX (alias RsaOR), shapes bacterial resistance to glycopeptides, the invaluable treatments for Methicillin-resistant staphylococcal infections.", "Modifying SprX expression levels influences Vancomycin and Teicoplanin glycopeptide resistance.", "Comparative proteomic studies have identified that SprX specifically downregulates stage V sporulation protein G, SpoVG.", "SpoVG is produced from the yabJ-spoVG operon and contributes to S. aureus glycopeptide resistance.", "SprX negatively regulates SpoVG expression by direct antisense pairings at the internal translation initiation signals of the second operon gene, without modifying bicistronic mRNA expression levels or affecting YabJ translation.", "The SprX and yabJ-spoVG mRNA domains involved in the interaction have been identified, highlighting the importance of a CU-rich loop of SprX in the control of SpoVG expression.", "We have shown that SpoVG might not be the unique SprX target involved in the glycopeptide resistance and demonstrated that the regulation of glycopeptide sensitivity involves the CU-rich domain of SprX.", "Here we report the case of a sRNA influencing antibiotic resistance of a major human pathogen."], "title": "A small RNA controls a protein regulator involved in antibiotic resistance in Staphylococcus aureus."}
{"paper_id": 27082608, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Fetal-type Minamata disease is caused by the exposure to high concentrations of methylmercury in the fetal period and shows cerebral palsy-like clinical features. Relief of spasticity is a major task of rehabilitation to improve their activities of daily living.Here we report the effect of long-term vibration therapy on bilateral lower-limb spasticity in 3 patients with fetal-type Minamata disease. We used a simple, inexpensive, and noninvasive approach with hand-held vibration massagers, which were applied to the plantar fascia at 90\u200aHz for 15\u200aminutes.The effect was observed soon after the first treatment and resulted in better performance of the repetitive facilitation. Vibration therapy for 1 year improved Modified Ashworth Scale for the ankle flexors in 2 cases. The labored gait improved and gait speed increased in another case. Continued vibration therapy for another 1 year further improved Modified Ashworth Scale score and range of motion of ankle dorsiflexion in 1 case. This case showed the decreased amplitude of soleus H-reflex after the 15-minute vibration therapy, suggesting that \u03b1-motor neuron excitability was suppressed.Vibration therapy using a hand-held vibration massager may offer safe and effective treatment for lower-limb spasticity in patients with chronic neurological disorders.", "journal": "Medicine", "sentences": ["Fetal-type Minamata disease is caused by the exposure to high concentrations of methylmercury in the fetal period and shows cerebral palsy-like clinical features.", "Relief of spasticity is a major task of rehabilitation to improve their activities of daily living.Here we report the effect of long-term vibration therapy on bilateral lower-limb spasticity in 3 patients with fetal-type Minamata disease.", "We used a simple, inexpensive, and noninvasive approach with hand-held vibration massagers, which were applied to the plantar fascia at 90\u200aHz for 15\u200aminutes.The effect was observed soon after the first treatment and resulted in better performance of the repetitive facilitation.", "Vibration therapy for 1 year improved Modified Ashworth Scale for the ankle flexors in 2 cases.", "The labored gait improved and gait speed increased in another case.", "Continued vibration therapy for another 1 year further improved Modified Ashworth Scale score and range of motion of ankle dorsiflexion in 1 case.", "This case showed the decreased amplitude of soleus H-reflex after the 15-minute vibration therapy, suggesting that \u03b1-motor neuron excitability was suppressed.Vibration therapy using a hand-held vibration massager may offer safe and effective treatment for lower-limb spasticity in patients with chronic neurological disorders."], "title": "Three Case Reports of Successful Vibration Therapy of the Plantar Fascia for Spasticity Due to Cerebral Palsy-Like Syndrome, Fetal-Type Minamata Disease."}
{"paper_id": 20688509, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "An ultrasensitive electrochemical immunosensor based on graphene sheet (GS) has been developed. GS was used to immobilize mediator thionine (TH), horseradish peroxidase (HRP) and secondary anti-prostate-specific antigen (PSA) antibody (Ab2) and the resulting nanostructure (GS-TH-HRP-Ab2) was used as the label for the immunosensor. With primary anti-PSA antibody (Ab1) also immobilized onto the GS, the immunosensor displayed a wide range of linear response (0.002-10 ng/mL), low detection limit (1 pg/mL), good reproducibility, selectivity and stability. The good performance of the immunosensor is attributed to the graphene sheet's high surface-to-volume ratio which allows the immobilization of a high-level of Ab1, Ab2, TH and HRP and its good electrical conductivity which can improve the electron transfer among TH, HRP, H2O2 and electrode. The immunosensor was used to detect the PSA contents in serum samples from patients and satisfactory test results were obtained in comparison with the ELISA test results. Thus, graphene-based labels may provide many potential applications for the detection of different cancer biomarkers.", "journal": "Biosensors & bioelectronics", "sentences": ["An ultrasensitive electrochemical immunosensor based on graphene sheet (GS) has been developed.", "GS was used to immobilize mediator thionine (TH), horseradish peroxidase (HRP) and secondary anti-prostate-specific antigen (PSA) antibody (Ab2) and the resulting nanostructure (GS-TH-HRP-Ab2) was used as the label for the immunosensor.", "With primary anti-PSA antibody (Ab1) also immobilized onto the GS, the immunosensor displayed a wide range of linear response (0.002-10 ng/mL), low detection limit (1 pg/mL), good reproducibility, selectivity and stability.", "The good performance of the immunosensor is attributed to the graphene sheet's high surface-to-volume ratio which allows the immobilization of a high-level of Ab1, Ab2, TH and HRP and its good electrical conductivity which can improve the electron transfer among TH, HRP, H2O2 and electrode.", "The immunosensor was used to detect the PSA contents in serum samples from patients and satisfactory test results were obtained in comparison with the ELISA test results.", "Thus, graphene-based labels may provide many potential applications for the detection of different cancer biomarkers."], "title": "Ultrasensitive immunosensor for the detection of cancer biomarker based on graphene sheet."}
{"paper_id": 26390037, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Recently, the stable light products and radiance calibrated products from Defense Meteorological Satellite Program's (DMSP) Operational Linescan System (OLS) have been useful for mapping global fossil fuel carbon dioxide (CO2) emissions at fine spatial resolution. However, few studies on this subject were conducted with the new-generation nighttime light data from the Visible Infrared Imaging Radiometer Suite (VIIRS) sensor on the Suomi National Polar-orbiting Partnership (NPP) Satellite, which has a higher spatial resolution and a wider radiometric detection range than the traditional DMSP-OLS nighttime light data. Therefore, this study performed the first evaluation of the potential of NPP-VIIRS data in estimating the spatial distributions of global CO2 emissions (excluding power plant emissions). Through a disaggregating model, three global emission maps were then derived from population counts and three different types of nighttime lights data (NPP-VIIRS, the stable light data and radiance calibrated data of DMSP-OLS) for a comparative analysis. The results compared with the reference data of land cover in Beijing, Shanghai and Guangzhou show that the emission areas of map from NPP-VIIRS data have higher spatial consistency of the artificial surfaces and exhibit a more reasonable distribution of CO2 emission than those of other two maps from DMSP-OLS data. Besides, in contrast to two maps from DMSP-OLS data, the emission map from NPP-VIIRS data is closer to the Vulcan inventory and exhibits a better agreement with the actual statistical data of CO2 emissions at the level of sub-administrative units of the United States. This study demonstrates that the NPP-VIIRS data can be a powerful tool for studying the spatial distributions of CO2 emissions, as well as the socioeconomic indicators at multiple scales.", "journal": "PloS one", "sentences": ["Recently, the stable light products and radiance calibrated products from Defense Meteorological Satellite Program's (DMSP) Operational Linescan System (OLS) have been useful for mapping global fossil fuel carbon dioxide (CO2) emissions at fine spatial resolution.", "However, few studies on this subject were conducted with the new-generation nighttime light data from the Visible Infrared Imaging Radiometer Suite (VIIRS) sensor on the Suomi National Polar-orbiting Partnership (NPP) Satellite, which has a higher spatial resolution and a wider radiometric detection range than the traditional DMSP-OLS nighttime light data.", "Therefore, this study performed the first evaluation of the potential of NPP-VIIRS data in estimating the spatial distributions of global CO2 emissions (excluding power plant emissions).", "Through a disaggregating model, three global emission maps were then derived from population counts and three different types of nighttime lights data (NPP-VIIRS, the stable light data and radiance calibrated data of DMSP-OLS) for a comparative analysis.", "The results compared with the reference data of land cover in Beijing, Shanghai and Guangzhou show that the emission areas of map from NPP-VIIRS data have higher spatial consistency of the artificial surfaces and exhibit a more reasonable distribution of CO2 emission than those of other two maps from DMSP-OLS data.", "Besides, in contrast to two maps from DMSP-OLS data, the emission map from NPP-VIIRS data is closer to the Vulcan inventory and exhibits a better agreement with the actual statistical data of CO2 emissions at the level of sub-administrative units of the United States.", "This study demonstrates that the NPP-VIIRS data can be a powerful tool for studying the spatial distributions of CO2 emissions, as well as the socioeconomic indicators at multiple scales."], "title": "Evaluation of NPP-VIIRS Nighttime Light Data for Mapping Global Fossil Fuel Combustion CO2 Emissions: A Comparison with DMSP-OLS Nighttime Light Data."}
{"paper_id": 26109668, "labels": ["0", "0", "0", "0", "1"], "abstract": "Primary afferents are sensitized to mechanical stimuli following in vivo inflammation, but whether sensitization of mechanically gated ion channels contributes to this phenomenon is unknown. Here we identified two populations of murine A fiber-type sensory neurons that display markedly different responses to focal mechanical stimuli of the membrane based on their expression of calcitonin gene-related peptide (CGRP). Following inflammation of the hindpaw, myelinated, CGRP-positive neurons projecting to the paw skin displayed elevated mechanical currents in response to mechanical stimuli. Conversely, muscle inflammation markedly amplified mechanical currents in myelinated, CGRP-negative neurons projecting to muscle. These data show, for the first time, that mechanically gated currents are amplified following in vivo tissue inflammation, and also suggest that mechanical sensitization can occur in myelinated neurons after inflammation.", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "sentences": ["Primary afferents are sensitized to mechanical stimuli following in vivo inflammation, but whether sensitization of mechanically gated ion channels contributes to this phenomenon is unknown.", "Here we identified two populations of murine A fiber-type sensory neurons that display markedly different responses to focal mechanical stimuli of the membrane based on their expression of calcitonin gene-related peptide (CGRP).", "Following inflammation of the hindpaw, myelinated, CGRP-positive neurons projecting to the paw skin displayed elevated mechanical currents in response to mechanical stimuli.", "Conversely, muscle inflammation markedly amplified mechanical currents in myelinated, CGRP-negative neurons projecting to muscle.", "These data show, for the first time, that mechanically gated currents are amplified following in vivo tissue inflammation, and also suggest that mechanical sensitization can occur in myelinated neurons after inflammation."], "title": "Amplified Mechanically Gated Currents in Distinct Subsets of Myelinated Sensory Neurons following In Vivo Inflammation of Skin and Muscle."}
{"paper_id": 25951283, "labels": ["0", "0", "0", "0", "1", "1", "0", "1"], "abstract": "Observations of the south pole of the Saturnian moon Enceladus revealed large rifts in the south-polar terrain, informally called 'tiger stripes', named Alexandria, Baghdad, Cairo and Damascus Sulci. These fractures have been shown to be the sources of the observed jets of water vapour and icy particles and to exhibit higher temperatures than the surrounding terrain. Subsequent observations have focused on obtaining close-up imaging of this region to better characterize these emissions. Recent work examined those newer data sets and used triangulation of discrete jets to produce maps of jetting activity at various times. Here we show that much of the eruptive activity can be explained by broad, curtain-like eruptions. Optical illusions in the curtain eruptions resulting from a combination of viewing direction and local fracture geometry produce image features that were probably misinterpreted previously as discrete jets. We present maps of the total emission along the fractures, rather than just the jet-like component, for five times during an approximately one-year period in 2009 and 2010. An accurate picture of the style, timing and spatial distribution of the south-polar eruptions is crucial to evaluating theories for the mechanism controlling the eruptions.", "journal": "Nature", "sentences": ["Observations of the south pole of the Saturnian moon Enceladus revealed large rifts in the south-polar terrain, informally called 'tiger stripes', named Alexandria, Baghdad, Cairo and Damascus Sulci.", "These fractures have been shown to be the sources of the observed jets of water vapour and icy particles and to exhibit higher temperatures than the surrounding terrain.", "Subsequent observations have focused on obtaining close-up imaging of this region to better characterize these emissions.", "Recent work examined those newer data sets and used triangulation of discrete jets to produce maps of jetting activity at various times.", "Here we show that much of the eruptive activity can be explained by broad, curtain-like eruptions.", "Optical illusions in the curtain eruptions resulting from a combination of viewing direction and local fracture geometry produce image features that were probably misinterpreted previously as discrete jets.", "We present maps of the total emission along the fractures, rather than just the jet-like component, for five times during an approximately one-year period in 2009 and 2010.", "An accurate picture of the style, timing and spatial distribution of the south-polar eruptions is crucial to evaluating theories for the mechanism controlling the eruptions."], "title": "Curtain eruptions from Enceladus' south-polar terrain."}
{"paper_id": 25231022, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "Ecological assessments of surface water bodies are essential in order to evaluate the level of degradation in freshwater ecosystems and to address the subsequent decline in services they provide. These assessments cover multiple aspects of the aquatic environment, particularly biological elements due to their ability to respond to all pressures within an ecosystem. Such assessments can enable the identification of the multiple pressures which threaten water bodies, facilitating sustainable decisions regarding their management to be identified. Here, the design requirements of the networks which facilitate ecological assessments are presented. A river basin district in England is used as a case study to investigate the number of elements monitored, the number of failing elements and the relationship between failing elements. Findings demonstrate the value of ensuring that monitoring networks are risk based and appropriately designed to meet their objectives. This therefore requires that monitoring is not only for the communicating of compliance but also for use iteratively so that the design of monitoring networks and ultimately management can be continually improved.", "journal": "Environmental monitoring and assessment", "sentences": ["Ecological assessments of surface water bodies are essential in order to evaluate the level of degradation in freshwater ecosystems and to address the subsequent decline in services they provide.", "These assessments cover multiple aspects of the aquatic environment, particularly biological elements due to their ability to respond to all pressures within an ecosystem.", "Such assessments can enable the identification of the multiple pressures which threaten water bodies, facilitating sustainable decisions regarding their management to be identified.", "Here, the design requirements of the networks which facilitate ecological assessments are presented.", "A river basin district in England is used as a case study to investigate the number of elements monitored, the number of failing elements and the relationship between failing elements.", "Findings demonstrate the value of ensuring that monitoring networks are risk based and appropriately designed to meet their objectives.", "This therefore requires that monitoring is not only for the communicating of compliance but also for use iteratively so that the design of monitoring networks and ultimately management can be continually improved."], "title": "Ecological assessments of surface water bodies at the river basin level: a case study from England."}
{"paper_id": 26934580, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Autism spectrum disorder (ASD) is one phenotypic aspect of many monogenic, hereditary cancer syndromes. Pleiotropic effects of cancer genes on the autism phenotype could lead to repurposing of oncology medications to treat this increasingly prevalent neurodevelopmental condition for which there is currently no treatment. To explore this hypothesis we sought to discover whether autistic patients more often have rare coding, single-nucleotide variants within tumor suppressor and oncogenes and whether autistic patients are more often diagnosed with neoplasms. Exome-sequencing data from the ARRA Autism Sequencing Collaboration was compared to that of a control cohort from the Exome Variant Server database revealing that rare, coding variants within oncogenes were enriched for in the ARRA ASD cohort (p<1.0x10-8). In contrast, variants were not significantly enriched in tumor suppressor genes. Phenotypically, children and adults with ASD exhibited a protective effect against cancer, with a frequency of 1.3% vs. 3.9% (p<0.001), but the protective effect decreased with age. The odds ratio of neoplasm for those with ASD relative to controls was 0.06 (95% CI: 0.02, 0.19; p<0.0001) in the 0 to 14 age group; 0.35 (95% CI: 0.14, 0.87; p = 0.024) in the 15 to 29 age group; 0.41 (95% CI: 0.15, 1.17; p = 0.095) in the 30 to 54 age group; and 0.49 (95% CI: 0.14, 1.74; p = 0.267) in those 55 and older. Both males and females demonstrated the protective effect. These findings suggest that defects in cellular proliferation, and potentially senescence, might influence both autism and neoplasm, and already approved drugs targeting oncogenic pathways might also have therapeutic value for treating autism.", "journal": "PloS one", "sentences": ["Autism spectrum disorder (ASD) is one phenotypic aspect of many monogenic, hereditary cancer syndromes.", "Pleiotropic effects of cancer genes on the autism phenotype could lead to repurposing of oncology medications to treat this increasingly prevalent neurodevelopmental condition for which there is currently no treatment.", "To explore this hypothesis we sought to discover whether autistic patients more often have rare coding, single-nucleotide variants within tumor suppressor and oncogenes and whether autistic patients are more often diagnosed with neoplasms.", "Exome-sequencing data from the ARRA Autism Sequencing Collaboration was compared to that of a control cohort from the Exome Variant Server database revealing that rare, coding variants within oncogenes were enriched for in the ARRA ASD cohort (p<1.0x10-8).", "In contrast, variants were not significantly enriched in tumor suppressor genes.", "Phenotypically, children and adults with ASD exhibited a protective effect against cancer, with a frequency of 1.3% vs. 3.9% (p<0.001), but the protective effect decreased with age.", "The odds ratio of neoplasm for those with ASD relative to controls was 0.06 (95% CI: 0.02, 0.19; p<0.0001) in the 0 to 14 age group; 0.35 (95% CI: 0.14, 0.87; p = 0.024) in the 15 to 29 age group; 0.41 (95% CI: 0.15, 1.17; p = 0.095) in the 30 to 54 age group; and 0.49 (95% CI: 0.14, 1.74; p = 0.267) in those 55 and older.", "Both males and females demonstrated the protective effect.", "These findings suggest that defects in cellular proliferation, and potentially senescence, might influence both autism and neoplasm, and already approved drugs targeting oncogenic pathways might also have therapeutic value for treating autism."], "title": "Autism Linked to Increased Oncogene Mutations but Decreased Cancer Rate."}
{"paper_id": 25430564, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Oxaliplatin is a key drug commonly used in colorectal cancer treatment. Despite high clinical efficacy, its therapeutic application is limited by common, dose-limiting occurrence of neuropathy. As usual symptomatic neuropathy treatments fail to improve the patients' condition, there is an urgent need to advance our understanding of the pathogenesis of neuropathy to propose effective therapy and ensure adequate pain management. Oxaliplatin-induced neuropathy was recently reported to be associated with protein kinase C (PKC) activation. It is unclear, however, whether PKC inhibition can prevent neuropathy. In our current studies, we found that a PKC inhibitor, tamoxifen, inhibited oxaliplatin-induced neuropathy via the PKC/extracellular signal-regulated kinase (ERK)/c-Fos pathway in lumbar spinal cords (lumbar segments 4-6). Additionally, tamoxifen was shown to act in synergy with oxaliplatin to inhibit growth in tumor cells-implanted mice. Moreover, mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, PD0325901, suppressed oxaliplatin-induced neuropathy and enhanced oxaliplatin efficacy. Our results indicate that oxaliplatin-induced neuropathy is associated with PKC/ERK/c-Fos pathway in lumbar spinal cord. Additionally, we demonstrate that disruption of this pathway by PKC and MEK inhibitors suppresses oxaliplatin-induced neuropathy, thereby suggesting that PKC and MEK inhibitors may be therapeutically useful in preventing oxaliplatin-induced neuropathy and could aid in combination antitumor pharmacotherapy.", "journal": "International journal of cancer", "sentences": ["Oxaliplatin is a key drug commonly used in colorectal cancer treatment.", "Despite high clinical efficacy, its therapeutic application is limited by common, dose-limiting occurrence of neuropathy.", "As usual symptomatic neuropathy treatments fail to improve the patients' condition, there is an urgent need to advance our understanding of the pathogenesis of neuropathy to propose effective therapy and ensure adequate pain management.", "Oxaliplatin-induced neuropathy was recently reported to be associated with protein kinase C (PKC) activation.", "It is unclear, however, whether PKC inhibition can prevent neuropathy.", "In our current studies, we found that a PKC inhibitor, tamoxifen, inhibited oxaliplatin-induced neuropathy via the PKC/extracellular signal-regulated kinase (ERK)/c-Fos pathway in lumbar spinal cords (lumbar segments 4-6).", "Additionally, tamoxifen was shown to act in synergy with oxaliplatin to inhibit growth in tumor cells-implanted mice.", "Moreover, mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, PD0325901, suppressed oxaliplatin-induced neuropathy and enhanced oxaliplatin efficacy.", "Our results indicate that oxaliplatin-induced neuropathy is associated with PKC/ERK/c-Fos pathway in lumbar spinal cord.", "Additionally, we demonstrate that disruption of this pathway by PKC and MEK inhibitors suppresses oxaliplatin-induced neuropathy, thereby suggesting that PKC and MEK inhibitors may be therapeutically useful in preventing oxaliplatin-induced neuropathy and could aid in combination antitumor pharmacotherapy."], "title": "PKC/MEK inhibitors suppress oxaliplatin-induced neuropathy and potentiate the antitumor effects."}
{"paper_id": 20410364, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Although human cognition often occurs during dynamic motor actions, most studies of human brain dynamics examine subjects in static seated or prone conditions. EEG signals have historically been considered to be too noise prone to allow recording of brain dynamics during human locomotion. Here we applied a channel-based artifact template regression procedure and a subsequent spatial filtering approach to remove gait-related movement artifact from EEG signals recorded during walking and running. We first used stride time warping to remove gait artifact from high-density EEG recorded during a visual oddball discrimination task performed while walking and running. Next, we applied infomax independent component analysis (ICA) to parse the channel-based noise reduced EEG signals into maximally independent components (ICs) and then performed component-based template regression. Applying channel-based or channel-based plus component-based artifact rejection significantly reduced EEG spectral power in the 1.5- to 8.5-Hz frequency range during walking and running. In walking conditions, gait-related artifact was insubstantial: event-related potentials (ERPs), which were nearly identical to visual oddball discrimination events while standing, were visible before and after applying noise reduction. In the running condition, gait-related artifact severely compromised the EEG signals: stable average ERP time-courses of IC processes were only detectable after artifact removal. These findings show that high-density EEG can be used to study brain dynamics during whole body movements and that mechanical artifact from rhythmic gait events may be minimized using a template regression procedure.", "journal": "Journal of neurophysiology", "sentences": ["Although human cognition often occurs during dynamic motor actions, most studies of human brain dynamics examine subjects in static seated or prone conditions.", "EEG signals have historically been considered to be too noise prone to allow recording of brain dynamics during human locomotion.", "Here we applied a channel-based artifact template regression procedure and a subsequent spatial filtering approach to remove gait-related movement artifact from EEG signals recorded during walking and running.", "We first used stride time warping to remove gait artifact from high-density EEG recorded during a visual oddball discrimination task performed while walking and running.", "Next, we applied infomax independent component analysis (ICA) to parse the channel-based noise reduced EEG signals into maximally independent components (ICs) and then performed component-based template regression.", "Applying channel-based or channel-based plus component-based artifact rejection significantly reduced EEG spectral power in the 1.5- to 8.5-Hz frequency range during walking and running.", "In walking conditions, gait-related artifact was insubstantial: event-related potentials (ERPs), which were nearly identical to visual oddball discrimination events while standing, were visible before and after applying noise reduction.", "In the running condition, gait-related artifact severely compromised the EEG signals: stable average ERP time-courses of IC processes were only detectable after artifact removal.", "These findings show that high-density EEG can be used to study brain dynamics during whole body movements and that mechanical artifact from rhythmic gait events may be minimized using a template regression procedure."], "title": "Removal of movement artifact from high-density EEG recorded during walking and running."}
{"paper_id": 24982881, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "This study examined the immunogenic properties of the fusion protein fimbria 2 of Bordetella pertussis (Fim2)-cholera toxin B subunit (CTB) in the intranasal murine model of infection. To this end B. pertussis Fim2 coding sequence was cloned downstream of the cholera toxin B subunit coding sequence. The expression and assembly of the fusion protein into pentameric structures (CTB-Fim2) were evaluated by SDS-PAGE and monosialotetrahexosylgaglioside (GM1-ganglioside) enzyme-linked immunosorbent assay (ELISA). To evaluate the protective capacity of CTB-Fim2, an intraperitoneal or intranasal mouse immunization schedule was performed with 50\u2009\u03bcg of CTB-Fim2. Recombinant (rFim2) or purified (BpFim2) Fim2, CTB, and phosphate-buffered saline (PBS) were used as controls. The results showed that mice immunized with BpFim2 or CTB-Fim2 intraperitoneally or intranasally presented a significant reduction in bacterial lung counts compared to control groups (P < 0.01 or P < 0.001 , resp.). Moreover, intranasal immunization with CTB-Fim2 induced significant levels of Fim2-specific IgG in serum and bronchoalveolar lavage (BAL) and Fim2-specific IgA in BAL. Analysis of IgG isotypes and cytokines mRNA levels showed that CTB-Fim2 results in a mixed Th1/Th2 (T-helper) response. The data presented here provide support for CTB-Fim2 as a promising recombinant antigen against Bordetella pertussis infection.", "journal": "BioMed research international", "sentences": ["This study examined the immunogenic properties of the fusion protein fimbria 2 of Bordetella pertussis (Fim2)-cholera toxin B subunit (CTB) in the intranasal murine model of infection.", "To this end B. pertussis Fim2 coding sequence was cloned downstream of the cholera toxin B subunit coding sequence.", "The expression and assembly of the fusion protein into pentameric structures (CTB-Fim2) were evaluated by SDS-PAGE and monosialotetrahexosylgaglioside (GM1-ganglioside) enzyme-linked immunosorbent assay (ELISA).", "To evaluate the protective capacity of CTB-Fim2, an intraperitoneal or intranasal mouse immunization schedule was performed with 50\u2009\u03bcg of CTB-Fim2.", "Recombinant (rFim2) or purified (BpFim2) Fim2, CTB, and phosphate-buffered saline (PBS) were used as controls.", "The results showed that mice immunized with BpFim2 or CTB-Fim2 intraperitoneally or intranasally presented a significant reduction in bacterial lung counts compared to control groups (P < 0.01 or P < 0.001 , resp.).", "Moreover, intranasal immunization with CTB-Fim2 induced significant levels of Fim2-specific IgG in serum and bronchoalveolar lavage (BAL) and Fim2-specific IgA in BAL.", "Analysis of IgG isotypes and cytokines mRNA levels showed that CTB-Fim2 results in a mixed Th1/Th2 (T-helper) response.", "The data presented here provide support for CTB-Fim2 as a promising recombinant antigen against Bordetella pertussis infection."], "title": "Immunization with the recombinant Cholera toxin B fused to Fimbria 2 protein protects against Bordetella pertussis infection."}
{"paper_id": 21131278, "labels": ["0", "1", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Structured RNA regions are important gene control elements in prokaryotes and eukaryotes. Here, we show that the mRNA of a cyanobacterial heat shock gene contains a built-in thermosensor critical for photosynthetic activity under stress conditions. The exceptionally short 5'-untranslated region is comprised of a single hairpin with an internal asymmetric loop. It inhibits translation of the Synechocystis hsp17 transcript at normal growth conditions, permits translation initiation under stress conditions and shuts down Hsp17 production in the recovery phase. Point mutations that stabilized or destabilized the RNA structure deregulated reporter gene expression in vivo and ribosome binding in vitro. Introduction of such point mutations into the Synechocystis genome produced severe phenotypic defects. Reversible formation of the open and closed structure was beneficial for viability, integrity of the photosystem and oxygen evolution. Continuous production of Hsp17 was detrimental when the stress declined indicating that shutting-off heat shock protein production is an important, previously unrecognized function of RNA thermometers. We discovered a simple biosensor that strictly adjusts the cellular level of a molecular chaperone to the physiological need.", "journal": "Nucleic acids research", "sentences": ["Structured RNA regions are important gene control elements in prokaryotes and eukaryotes.", "Here, we show that the mRNA of a cyanobacterial heat shock gene contains a built-in thermosensor critical for photosynthetic activity under stress conditions.", "The exceptionally short 5'-untranslated region is comprised of a single hairpin with an internal asymmetric loop.", "It inhibits translation of the Synechocystis hsp17 transcript at normal growth conditions, permits translation initiation under stress conditions and shuts down Hsp17 production in the recovery phase.", "Point mutations that stabilized or destabilized the RNA structure deregulated reporter gene expression in vivo and ribosome binding in vitro.", "Introduction of such point mutations into the Synechocystis genome produced severe phenotypic defects.", "Reversible formation of the open and closed structure was beneficial for viability, integrity of the photosystem and oxygen evolution.", "Continuous production of Hsp17 was detrimental when the stress declined indicating that shutting-off heat shock protein production is an important, previously unrecognized function of RNA thermometers.", "We discovered a simple biosensor that strictly adjusts the cellular level of a molecular chaperone to the physiological need."], "title": "Translation on demand by a simple RNA-based thermosensor."}
{"paper_id": 21187374, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "The essential mineral nutrient potassium (K(+)) is the most important inorganic cation for plants and is recognized as a limiting factor for crop yield and quality. Nonetheless, it is only partially understood how K(+) contributes to plant productivity. K(+) is used as a major active solute to maintain turgor and to drive irreversible and reversible changes in cell volume. K(+) also plays an important role in numerous metabolic processes, for example, by serving as an essential cofactor of enzymes. Here, we provide evidence for an additional, previously unrecognized role of K(+) in plant growth. By combining diverse experimental approaches with computational cell simulation, we show that K(+) circulating in the phloem serves as a decentralized energy storage that can be used to overcome local energy limitations. Posttranslational modification of the phloem-expressed Arabidopsis K(+) channel AKT2 taps this \"potassium battery,\" which then efficiently assists the plasma membrane H(+)-ATPase in energizing the transmembrane phloem (re)loading processes.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["The essential mineral nutrient potassium (K(+)) is the most important inorganic cation for plants and is recognized as a limiting factor for crop yield and quality.", "Nonetheless, it is only partially understood how K(+) contributes to plant productivity.", "K(+) is used as a major active solute to maintain turgor and to drive irreversible and reversible changes in cell volume.", "K(+) also plays an important role in numerous metabolic processes, for example, by serving as an essential cofactor of enzymes.", "Here, we provide evidence for an additional, previously unrecognized role of K(+) in plant growth.", "By combining diverse experimental approaches with computational cell simulation, we show that K(+) circulating in the phloem serves as a decentralized energy storage that can be used to overcome local energy limitations.", "Posttranslational modification of the phloem-expressed Arabidopsis K(+) channel AKT2 taps this \"potassium battery,\" which then efficiently assists the plasma membrane H(+)-ATPase in energizing the transmembrane phloem (re)loading processes."], "title": "Potassium (K+) gradients serve as a mobile energy source in plant vascular tissues."}
{"paper_id": 25083868, "labels": ["0", "0", "1", "0", "1", "1", "0", "1"], "abstract": "Stromal cells within the tumor microenvironment are\u00a0essential for tumor progression and metastasis. Surprisingly little is known about the factors that drive the transcriptional reprogramming of stromal cells within tumors. We report that the transcriptional regulator heat shock factor 1 (HSF1) is frequently activated in cancer-associated fibroblasts (CAFs), where it is a potent enabler of malignancy. HSF1 drives a transcriptional program in CAFs that complements, yet is completely different from, the program it drives in adjacent cancer cells. This CAF program is uniquely structured to support malignancy in a non-cell-autonomous way. Two central stromal signaling molecules-TGF-\u03b2 and SDF1-play a critical role. In early-stage breast and lung cancer, high stromal HSF1 activation is strongly associated with poor patient outcome. Thus, tumors co-opt the ancient survival functions of HSF1 to orchestrate malignancy in both cell-autonomous and non-cell-autonomous ways, with far-reaching therapeutic implications.", "journal": "Cell", "sentences": ["Stromal cells within the tumor microenvironment are\u00a0essential for tumor progression and metastasis.", "Surprisingly little is known about the factors that drive the transcriptional reprogramming of stromal cells within tumors.", "We report that the transcriptional regulator heat shock factor 1 (HSF1) is frequently activated in cancer-associated fibroblasts (CAFs), where it is a potent enabler of malignancy.", "HSF1 drives a transcriptional program in CAFs that complements, yet is completely different from, the program it drives in adjacent cancer cells.", "This CAF program is uniquely structured to support malignancy in a non-cell-autonomous way.", "Two central stromal signaling molecules-TGF-\u03b2 and SDF1-play a critical role.", "In early-stage breast and lung cancer, high stromal HSF1 activation is strongly associated with poor patient outcome.", "Thus, tumors co-opt the ancient survival functions of HSF1 to orchestrate malignancy in both cell-autonomous and non-cell-autonomous ways, with far-reaching therapeutic implications."], "title": "The reprogramming of tumor stroma by HSF1 is a potent enabler of malignancy."}
{"paper_id": 25501057, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "This study was designed to assess the effect of the addition of low-dose spironolactone on blood pressure (BP) in patients with resistant arterial hypertension. Patients with office systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg despite treatment with at least 3 antihypertensive drugs, including a diuretic, were enrolled in this double-blind, placebo-controlled, multicentre trial. One hundred sixty-one patients in outpatient internal medicine departments of 6 hospitals in the Czech Republic were randomly assigned to receive 25 mg of spironolactone (N = 81) or a placebo (N = 80) once daily as an add-on to their antihypertensive medication, using simple randomization. This study was registered with ClinicalTrials.gov, number NCT00524615. A nalyses were done with 150 patients who finished the follow-up (74 in the spironolactone and 76 in the placebo group). At 8 weeks, BP values were decreased more by spironolactone, with differences in mean fall of SBP of -9.8, -13.0, -10.5, and -9.9 mm Hg (P < 0.001 for all) in daytime, nighttime, and 24-hour ambulatory BP monitoring and in the office. The respective DBP differences were -3.2, -6.4, -3.5, and -3.0 mm Hg (P = 0.013, P < 0.001, P = 0.005, and P = 0.003). Adverse events in both groups were comparable. The office SBP goal <14 mm Hg at 8 weeks was reached in 73% of patients using spironolactone and 41% using placebo (P = 0.001). Spironolactone in patients with resistant arterial hypertension leads to a significant decrease of both SBP and DBP and markedly improves BP control.", "journal": "Medicine", "sentences": ["This study was designed to assess the effect of the addition of low-dose spironolactone on blood pressure (BP) in patients with resistant arterial hypertension.", "Patients with office systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg despite treatment with at least 3 antihypertensive drugs, including a diuretic, were enrolled in this double-blind, placebo-controlled, multicentre trial.", "One hundred sixty-one patients in outpatient internal medicine departments of 6 hospitals in the Czech Republic were randomly assigned to receive 25 mg of spironolactone (N = 81) or a placebo (N = 80) once daily as an add-on to their antihypertensive medication, using simple randomization.", "This study was registered with ClinicalTrials.gov, number NCT00524615.", "A nalyses were done with 150 patients who finished the follow-up (74 in the spironolactone and 76 in the placebo group).", "At 8 weeks, BP values were decreased more by spironolactone, with differences in mean fall of SBP of -9.8, -13.0, -10.5, and -9.9 mm Hg (P < 0.001 for all) in daytime, nighttime, and 24-hour ambulatory BP monitoring and in the office.", "The respective DBP differences were -3.2, -6.4, -3.5, and -3.0 mm Hg (P = 0.013, P < 0.001, P = 0.005, and P = 0.003).", "Adverse events in both groups were comparable.", "The office SBP goal <14 mm Hg at 8 weeks was reached in 73% of patients using spironolactone and 41% using placebo (P = 0.001).", "Spironolactone in patients with resistant arterial hypertension leads to a significant decrease of both SBP and DBP and markedly improves BP control."], "title": "Effect of spironolactone in resistant arterial hypertension: a randomized, double-blind, placebo-controlled trial (ASPIRANT-EXT)."}
{"paper_id": 26338970, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Despite being an attractive molecular target for both lymphoid and myeloid leukemias characterized by activated tyrosine kinases, the molecular and physiological consequences of reduced signal transducer and activator of transcription-5 (Stat5) during leukemogenesis are not well known. Stat5 is a critical regulator of mouse hematopoietic stem cell (HSC) self-renewal and is essential for normal lymphocyte development. We report that pan-hematopoietic deletion in viable adult Vav1-Cre conditional knockout mice as well as Stat5abnull/null fetal liver transplant chimeras generated HSCs with reduced expression of quiescence regulating genes (Tie2, Mpl, Slamf1, Spi1, Cited2) and increased expression of B-cell development genes (Satb1, Dntt, Btla, Flk2). Using a classical murine B-cell acute lymphoblastic leukemia (B-ALL) model, we demonstrate that these HSCs were also poised to produce a burst of B-cell precursors upon expression of Bcl-2 combined with oncogenic Myc. This strong selective advantage for leukemic transformation in the background of Stat5 deficient hematopoiesis was permissive for faster initiation of Myc-induced transformation to B-ALL. However, once established, the B-ALL progression in secondary transplant recipients was Stat5-independent. Overall, these studies suggest that Stat5 can play multiple important roles that not only preserve the HSC compartment but can limit accumulation of potential pre-leukemic lymphoid populations.", "journal": "Oncotarget", "sentences": ["Despite being an attractive molecular target for both lymphoid and myeloid leukemias characterized by activated tyrosine kinases, the molecular and physiological consequences of reduced signal transducer and activator of transcription-5 (Stat5) during leukemogenesis are not well known.", "Stat5 is a critical regulator of mouse hematopoietic stem cell (HSC) self-renewal and is essential for normal lymphocyte development.", "We report that pan-hematopoietic deletion in viable adult Vav1-Cre conditional knockout mice as well as Stat5abnull/null fetal liver transplant chimeras generated HSCs with reduced expression of quiescence regulating genes (Tie2, Mpl, Slamf1, Spi1, Cited2) and increased expression of B-cell development genes (Satb1, Dntt, Btla, Flk2).", "Using a classical murine B-cell acute lymphoblastic leukemia (B-ALL) model, we demonstrate that these HSCs were also poised to produce a burst of B-cell precursors upon expression of Bcl-2 combined with oncogenic Myc.", "This strong selective advantage for leukemic transformation in the background of Stat5 deficient hematopoiesis was permissive for faster initiation of Myc-induced transformation to B-ALL.", "However, once established, the B-ALL progression in secondary transplant recipients was Stat5-independent.", "Overall, these studies suggest that Stat5 can play multiple important roles that not only preserve the HSC compartment but can limit accumulation of potential pre-leukemic lymphoid populations."], "title": "Stat5-deficient hematopoiesis is permissive for Myc-induced B-cell leukemogenesis."}
{"paper_id": 25105550, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Transportation decisions have health consequences that are often not incorporated into policy-making processes. Health Impact Assessment (HIA) is a process that can be used to evaluate health effects of transportation policy. We present a rapid HIA, conducted over eight weeks, evaluating health and economic effects of proposed fare increases and service cuts to Boston, Massachusetts' public transportation system. We used transportation modeling in concert with tools allowing for quantification and monetization of multiple pathways. We estimated health and economic costs of proposed public transportation system changes to be hundreds of millions of dollars per year, exceeding the budget gap the public transportation authority was required to close. Significant health pathways included crashes, air pollution, and physical activity. The HIA enabled stakeholders to advocate for more modest fare increases and service cuts, which were eventually adopted by decision makers. This HIA was among the first to quantify and monetize multiple pathways linking transportation decisions with health and economic outcomes, using approaches that could be applied in different settings. Including health costs in transportation decisions can lead to policy choices with both economic and public health benefits.", "journal": "International journal of environmental research and public health", "sentences": ["Transportation decisions have health consequences that are often not incorporated into policy-making processes.", "Health Impact Assessment (HIA) is a process that can be used to evaluate health effects of transportation policy.", "We present a rapid HIA, conducted over eight weeks, evaluating health and economic effects of proposed fare increases and service cuts to Boston, Massachusetts' public transportation system.", "We used transportation modeling in concert with tools allowing for quantification and monetization of multiple pathways.", "We estimated health and economic costs of proposed public transportation system changes to be hundreds of millions of dollars per year, exceeding the budget gap the public transportation authority was required to close.", "Significant health pathways included crashes, air pollution, and physical activity.", "The HIA enabled stakeholders to advocate for more modest fare increases and service cuts, which were eventually adopted by decision makers.", "This HIA was among the first to quantify and monetize multiple pathways linking transportation decisions with health and economic outcomes, using approaches that could be applied in different settings.", "Including health costs in transportation decisions can lead to policy choices with both economic and public health benefits."], "title": "A health impact assessment of proposed public transportation service cuts and fare increases in Boston, Massachusetts (U.S.A.)."}
{"paper_id": 24459437, "labels": ["0", "0", "0", "0", "0", "1", "0", "0"], "abstract": "Internal erosion is known as the most important cause of dam failure after overtopping. It is important to improve the erosion resistance of the erodible soil by selecting an effective technique along with the reasonable costs. To prevent internal erosion of embankment dams the use of chemical stabilizers that reduce the soil erodibility potential is highly recommended. In the present study, a lignin-based chemical, known as lignosulfonate, is used to improve the erodibility of clayey sand specimen. The clayey sand was tested in various hydraulic heads in terms of internal erosion in its natural state as well as when it is mixed with the different percentages of lignosulfonate. The results show that erodibility of collected clayey sand is very high and is dramatically reduced by adding lignosulfonate. Adding 3% of lignosulfonate to clayey sand can reduce the coefficient of soil erosion from 0.01020 to 0.000017. It is also found that the qualitative erodibility of stabilized soil with 3% lignosulfonate is altered from the group of extremely rapid to the group of moderately slow.", "journal": "TheScientificWorldJournal", "sentences": ["Internal erosion is known as the most important cause of dam failure after overtopping.", "It is important to improve the erosion resistance of the erodible soil by selecting an effective technique along with the reasonable costs.", "To prevent internal erosion of embankment dams the use of chemical stabilizers that reduce the soil erodibility potential is highly recommended.", "In the present study, a lignin-based chemical, known as lignosulfonate, is used to improve the erodibility of clayey sand specimen.", "The clayey sand was tested in various hydraulic heads in terms of internal erosion in its natural state as well as when it is mixed with the different percentages of lignosulfonate.", "The results show that erodibility of collected clayey sand is very high and is dramatically reduced by adding lignosulfonate.", "Adding 3% of lignosulfonate to clayey sand can reduce the coefficient of soil erosion from 0.01020 to 0.000017.", "It is also found that the qualitative erodibility of stabilized soil with 3% lignosulfonate is altered from the group of extremely rapid to the group of moderately slow."], "title": "Investigating the effect of lignosulfonate on erosion rate of the embankments constructed with clayey sand."}
{"paper_id": 24244398, "labels": ["0", "0", "0", "0", "1"], "abstract": "Stem bromelain, a cysteine protease isolated from pineapples, is a natural anti-inflammatory treatment, yet its mechanism of action remains unclear. Curious as to whether bromelain might affect selectin-mediated leukocyte rolling, we studied the ability of bromelain-treated human neutrophils to tether to substrates presenting immobilized P-selectin or E-selectin under shear stress. Bromelain treatment attenuated P-selectin-mediated tethering but had no effect on neutrophil recruitment on E-selectin substrates. Flow cytometric analysis of human neutrophils, using two antibodies against distinct epitopes within the P-selectin glycoprotein ligand-1 (PSGL-1) active site, revealed that bromelain cleaves PSGL-1 to remove one of two sites required for P-selectin binding, while leaving the region required for E-selectin binding intact. These findings suggest one molecular mechanism by which bromelain may exert its anti-inflammatory effects is via selective cleavage of PSGL-1 to reduce P-selectin-mediated neutrophil recruitment.", "journal": "PloS one", "sentences": ["Stem bromelain, a cysteine protease isolated from pineapples, is a natural anti-inflammatory treatment, yet its mechanism of action remains unclear.", "Curious as to whether bromelain might affect selectin-mediated leukocyte rolling, we studied the ability of bromelain-treated human neutrophils to tether to substrates presenting immobilized P-selectin or E-selectin under shear stress.", "Bromelain treatment attenuated P-selectin-mediated tethering but had no effect on neutrophil recruitment on E-selectin substrates.", "Flow cytometric analysis of human neutrophils, using two antibodies against distinct epitopes within the P-selectin glycoprotein ligand-1 (PSGL-1) active site, revealed that bromelain cleaves PSGL-1 to remove one of two sites required for P-selectin binding, while leaving the region required for E-selectin binding intact.", "These findings suggest one molecular mechanism by which bromelain may exert its anti-inflammatory effects is via selective cleavage of PSGL-1 to reduce P-selectin-mediated neutrophil recruitment."], "title": "Bromelain decreases neutrophil interactions with P-selectin, but not E-selectin, in vitro by proteolytic cleavage of P-selectin glycoprotein ligand-1."}
{"paper_id": 24392102, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The hypocholesterolemic effect of tomato juice has been investigated in an intervention study with rats, along with the possible inhibition effect of bioactive tomato compounds binding to the HMGCR enzyme. Two experimental groups (n\u200a=\u200a8 Sprague-Dawley rats) were fed ad libitum for five weeks, with water or tomato juice provided to the control and intervention groups, respectively. Total, LDL and HDL cholesterol, and total triglycerides were analysed in plasma, and the lycopene content and the expression and activity of the enzyme HMGCR were determined in liver samples. A computational molecular modelling was carried out to determine the interactions between HMGCR and lycopene, chlorogenic acid and naringenin. Total, LDL and HDL cholesterol were significantly lower in the intervention group after the intake of tomato juice. In addition, a significant reduction in HMGCR activity was observed, although this was not accompanied by changes in gene expression. The molecular modelling showed that components of tomato can bind to the active site of the enzyme and compete with the ligand HMGCoA. Lycopene, from tomato juice, accumulates in the liver and can inhibit the activity of the rate-limiting enzyme of cholesterol biosynthesis, HMGCR.", "journal": "PloS one", "sentences": ["The hypocholesterolemic effect of tomato juice has been investigated in an intervention study with rats, along with the possible inhibition effect of bioactive tomato compounds binding to the HMGCR enzyme.", "Two experimental groups (n\u200a=\u200a8 Sprague-Dawley rats) were fed ad libitum for five weeks, with water or tomato juice provided to the control and intervention groups, respectively.", "Total, LDL and HDL cholesterol, and total triglycerides were analysed in plasma, and the lycopene content and the expression and activity of the enzyme HMGCR were determined in liver samples.", "A computational molecular modelling was carried out to determine the interactions between HMGCR and lycopene, chlorogenic acid and naringenin.", "Total, LDL and HDL cholesterol were significantly lower in the intervention group after the intake of tomato juice.", "In addition, a significant reduction in HMGCR activity was observed, although this was not accompanied by changes in gene expression.", "The molecular modelling showed that components of tomato can bind to the active site of the enzyme and compete with the ligand HMGCoA.", "Lycopene, from tomato juice, accumulates in the liver and can inhibit the activity of the rate-limiting enzyme of cholesterol biosynthesis, HMGCR."], "title": "The inhibitory effects of bioactive compounds of tomato juice binding to hepatic HMGCR: in vivo study and molecular modelling."}
{"paper_id": 26147648, "labels": ["0", "0", "0", "1", "1", "1"], "abstract": "A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development.", "journal": "PloS one", "sentences": ["A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults.", "The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups.", "An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences.", "By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults.", "Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults.", "Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development."], "title": "Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults."}
{"paper_id": 25495225, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "In bottom-up mass spectrometry-based proteomics analyses, variability at any step of the process, particularly during sample proteolysis, directly affects the sensitivity, accuracy, and precision of peptide detection and quantification. Currently, no generic internal standards are available to control the quality of sample processing steps. This makes it difficult to assess the comparability of MS proteomic data obtained under different experimental conditions. Here, we describe the design, synthesis, and validation of a universal protein standard, called DIGESTIF, that can be added to any biological sample. The DIGESTIF standard consists of a soluble recombinant protein scaffold to which a set of 11 artificial peptides (iRT peptides) with good ionization properties has been incorporated. In the protein scaffold, the amino acids flanking iRT peptide cleavage sites were selected either to favor or hinder protease cleavage. After sample processing, the retention time and relative intensity pattern of the released iRT peptides can be used to assess the quality of sample workup, the extent of digestion, and the performance of the LC-MS system. Thus, DIGESTIF can be used to standardize a broad spectrum of applications, ranging from simple replicate measurements to large-scale biomarker screening in biomedical applications.", "journal": "Journal of proteome research", "sentences": ["In bottom-up mass spectrometry-based proteomics analyses, variability at any step of the process, particularly during sample proteolysis, directly affects the sensitivity, accuracy, and precision of peptide detection and quantification.", "Currently, no generic internal standards are available to control the quality of sample processing steps.", "This makes it difficult to assess the comparability of MS proteomic data obtained under different experimental conditions.", "Here, we describe the design, synthesis, and validation of a universal protein standard, called DIGESTIF, that can be added to any biological sample.", "The DIGESTIF standard consists of a soluble recombinant protein scaffold to which a set of 11 artificial peptides (iRT peptides) with good ionization properties has been incorporated.", "In the protein scaffold, the amino acids flanking iRT peptide cleavage sites were selected either to favor or hinder protease cleavage.", "After sample processing, the retention time and relative intensity pattern of the released iRT peptides can be used to assess the quality of sample workup, the extent of digestion, and the performance of the LC-MS system.", "Thus, DIGESTIF can be used to standardize a broad spectrum of applications, ranging from simple replicate measurements to large-scale biomarker screening in biomedical applications."], "title": "DIGESTIF: a universal quality standard for the control of bottom-up proteomics experiments."}
{"paper_id": 26588137, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "Nonlocal (NL) van der Waals correlation has been incorporated into the spin-component and spin-opposite scaled double-hybrid density functionals (DHDFs) for noncovalent interactions. The short-range attenuation parameters for the tested DHDFs with the NL correlations are optimized by minimizing the mean absolute deviations (MADs) against the S66 database. And consequently, the obtained DHDFs with the NL correlations are denoted as PWPB95-NL, DSD-BLYP-NL, DSD-PBEP86-NL, and DOD-PBEP86-NL. These four DHDFs with the NL correlations are further assessed with the S22B, NCCE31, and ADIM6 databases. On the basis of our benchmark computations, the cooperation of the NL correlation and the spin-component and spin-opposite scaled DHDFs is successful for noncovalent interactions. However, the performances of the four aforementioned DHDFs with the NL correlations on the charge transfer interactions are less than satisfactory.", "journal": "Journal of chemical theory and computation", "sentences": ["Nonlocal (NL) van der Waals correlation has been incorporated into the spin-component and spin-opposite scaled double-hybrid density functionals (DHDFs) for noncovalent interactions.", "The short-range attenuation parameters for the tested DHDFs with the NL correlations are optimized by minimizing the mean absolute deviations (MADs) against the S66 database.", "And consequently, the obtained DHDFs with the NL correlations are denoted as PWPB95-NL, DSD-BLYP-NL, DSD-PBEP86-NL, and DOD-PBEP86-NL.", "These four DHDFs with the NL correlations are further assessed with the S22B, NCCE31, and ADIM6 databases.", "On the basis of our benchmark computations, the cooperation of the NL correlation and the spin-component and spin-opposite scaled DHDFs is successful for noncovalent interactions.", "However, the performances of the four aforementioned DHDFs with the NL correlations on the charge transfer interactions are less than satisfactory."], "title": "Spin-Component-Scaled Double-Hybrid Density Functionals with Nonlocal van der Waals Correlations for Noncovalent Interactions."}
{"paper_id": 22553313, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The BM microenvironment is required for the maintenance, proliferation, and mobilization of hematopoietic stem and progenitor cells (HSPCs), both during steady-state conditions and hematopoietic recovery after myeloablation. The ECM meshwork has long been recognized as a major anatomical component of the BM microenvironment; however, the molecular signatures and functions of the ECM to support HSPCs are poorly understood. Of the many ECM proteins, the expression of tenascin-C (TN-C) was found to be dramatically up-regulated during hematopoietic recovery after myeloablation. The TN-C gene was predominantly expressed in stromal cells and endothelial cells, known as BM niche cells, supporting the function of HSPCs. Mice lacking TN-C (TN-C(-/-)) mice showed normal steady-state hematopoiesis; however, they failed to reconstitute hematopoiesis after BM ablation and showed high lethality. The capacity to support transplanted wild-type hematopoietic cells to regenerate hematopoiesis was reduced in TN-C(-/-) recipient mice. In vitro culture on a TN-C substratum promoted the proliferation of HSPCs in an integrin \u03b19-dependent manner and up-regulated the expression of the cyclins (cyclinD1 and cyclinE1) and down-regulated the expression of the cyclin-dependent kinase inhibitors (p57(Kip2), p21(Cip1), p16(Ink4a)). These results identify TN-C as a critical component of the BM microenvironment that is required for hematopoietic regeneration.", "journal": "Blood", "sentences": ["The BM microenvironment is required for the maintenance, proliferation, and mobilization of hematopoietic stem and progenitor cells (HSPCs), both during steady-state conditions and hematopoietic recovery after myeloablation.", "The ECM meshwork has long been recognized as a major anatomical component of the BM microenvironment; however, the molecular signatures and functions of the ECM to support HSPCs are poorly understood.", "Of the many ECM proteins, the expression of tenascin-C (TN-C) was found to be dramatically up-regulated during hematopoietic recovery after myeloablation.", "The TN-C gene was predominantly expressed in stromal cells and endothelial cells, known as BM niche cells, supporting the function of HSPCs.", "Mice lacking TN-C (TN-C(-/-)) mice showed normal steady-state hematopoiesis; however, they failed to reconstitute hematopoiesis after BM ablation and showed high lethality.", "The capacity to support transplanted wild-type hematopoietic cells to regenerate hematopoiesis was reduced in TN-C(-/-) recipient mice.", "In vitro culture on a TN-C substratum promoted the proliferation of HSPCs in an integrin \u03b19-dependent manner and up-regulated the expression of the cyclins (cyclinD1 and cyclinE1) and down-regulated the expression of the cyclin-dependent kinase inhibitors (p57(Kip2), p21(Cip1), p16(Ink4a)).", "These results identify TN-C as a critical component of the BM microenvironment that is required for hematopoietic regeneration."], "title": "Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration."}
{"paper_id": 26881841, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "Usher syndrome type III (USH3A) is an autosomal recessive disorder caused by mutations in clarin-1 (CLRN1) gene, leading to progressive retinal degeneration and sensorineural deafness. Efforts to develop therapies for preventing photoreceptor cell loss are hampered by the lack of a retinal phenotype in the existing USH3 mouse models and by conflicting reports regarding the endogenous retinal localization of clarin-1, a transmembrane protein of unknown function. In this study, we used an AAV-based approach to express CLRN1 in the mouse retina in order to determine the pattern of its subcellular localization in different cell types. We found that all major classes of retinal cells express AAV-delivered CLRN1 driven by the ubiquitous, constitutive small chicken \u03b2-actin promoter, which has important implications for the design of future USH3 gene therapy studies. Within photoreceptor cells, AAV-expressed CLRN1 is mainly localized at the inner segment region and outer plexiform layer, similar to the endogenous expression of other usher proteins. Subretinal delivery using a full strength viral titer led to significant loss of retinal function as evidenced by ERG analysis, suggesting that there is a critical limit for CLRN1 expression in photoreceptor cells. Taken together, these results suggest that CLRN1 expression is potentially supported by a variety of retinal cells, and the right combination of AAV vector dose, promoter, and delivery method needs to be selected to develop safe therapies for USH3 disorder.", "journal": "PloS one", "sentences": ["Usher syndrome type III (USH3A) is an autosomal recessive disorder caused by mutations in clarin-1 (CLRN1) gene, leading to progressive retinal degeneration and sensorineural deafness.", "Efforts to develop therapies for preventing photoreceptor cell loss are hampered by the lack of a retinal phenotype in the existing USH3 mouse models and by conflicting reports regarding the endogenous retinal localization of clarin-1, a transmembrane protein of unknown function.", "In this study, we used an AAV-based approach to express CLRN1 in the mouse retina in order to determine the pattern of its subcellular localization in different cell types.", "We found that all major classes of retinal cells express AAV-delivered CLRN1 driven by the ubiquitous, constitutive small chicken \u03b2-actin promoter, which has important implications for the design of future USH3 gene therapy studies.", "Within photoreceptor cells, AAV-expressed CLRN1 is mainly localized at the inner segment region and outer plexiform layer, similar to the endogenous expression of other usher proteins.", "Subretinal delivery using a full strength viral titer led to significant loss of retinal function as evidenced by ERG analysis, suggesting that there is a critical limit for CLRN1 expression in photoreceptor cells.", "Taken together, these results suggest that CLRN1 expression is potentially supported by a variety of retinal cells, and the right combination of AAV vector dose, promoter, and delivery method needs to be selected to develop safe therapies for USH3 disorder."], "title": "AAV-Mediated Clarin-1 Expression in the Mouse Retina: Implications for USH3A Gene Therapy."}
{"paper_id": 25521299, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "This research examines the relationships between El Ni\u00f1o Southern Oscillation (ENSO), water level, precipitation patterns and carbon dioxide (CO2) exchange rates in the freshwater wetland ecosystems of the Florida Everglades. Data was obtained over a 5-year study period (2009-2013) from two freshwater marsh sites located in Everglades National Park that differ in hydrology. At the short-hydroperiod site (Taylor Slough; TS) and the long-hydroperiod site (Shark River Slough; SRS) fluctuations in precipitation patterns occurred with changes in ENSO phase, suggesting that extreme ENSO phases alter Everglades hydrology which is known to have a substantial influence on ecosystem carbon dynamics. Variations in both ENSO phase and annual net CO2 exchange rates co-occurred with changes in wet and dry season length and intensity. Combined with site-specific seasonality in CO2 exchanges rates, El Ni\u00f1o and La Ni\u00f1a phases magnified season intensity and CO2 exchange rates at both sites. At TS, net CO2 uptake rates were higher in the dry season, whereas SRS had greater rates of carbon sequestration during the wet season. As La Ni\u00f1a phases were concurrent with drought years and extended dry seasons, TS became a greater sink for CO2 on an annual basis (-11 to -110 g CO2 m-2 yr-1) compared to El Ni\u00f1o and neutral years (-5 to -43.5 g CO2 m-2 yr-1). SRS was a small source for CO2 annually (1.81 to 80 g CO2 m-2 yr-1) except in one exceptionally wet year that was associated with an El Ni\u00f1o phase (-16 g CO2 m-2 yr-1). Considering that future climate predictions suggest a higher frequency and intensity in El Ni\u00f1o and La Ni\u00f1a phases, these results indicate that changes in extreme ENSO phases will significantly alter CO2 dynamics in the Florida Everglades.", "journal": "PloS one", "sentences": ["This research examines the relationships between El Ni\u00f1o Southern Oscillation (ENSO), water level, precipitation patterns and carbon dioxide (CO2) exchange rates in the freshwater wetland ecosystems of the Florida Everglades.", "Data was obtained over a 5-year study period (2009-2013) from two freshwater marsh sites located in Everglades National Park that differ in hydrology.", "At the short-hydroperiod site (Taylor Slough; TS) and the long-hydroperiod site (Shark River Slough; SRS) fluctuations in precipitation patterns occurred with changes in ENSO phase, suggesting that extreme ENSO phases alter Everglades hydrology which is known to have a substantial influence on ecosystem carbon dynamics.", "Variations in both ENSO phase and annual net CO2 exchange rates co-occurred with changes in wet and dry season length and intensity.", "Combined with site-specific seasonality in CO2 exchanges rates, El Ni\u00f1o and La Ni\u00f1a phases magnified season intensity and CO2 exchange rates at both sites.", "At TS, net CO2 uptake rates were higher in the dry season, whereas SRS had greater rates of carbon sequestration during the wet season.", "As La Ni\u00f1a phases were concurrent with drought years and extended dry seasons, TS became a greater sink for CO2 on an annual basis (-11 to -110 g CO2 m-2 yr-1) compared to El Ni\u00f1o and neutral years (-5 to -43.5 g CO2 m-2 yr-1).", "SRS was a small source for CO2 annually (1.81 to 80 g CO2 m-2 yr-1) except in one exceptionally wet year that was associated with an El Ni\u00f1o phase (-16 g CO2 m-2 yr-1).", "Considering that future climate predictions suggest a higher frequency and intensity in El Ni\u00f1o and La Ni\u00f1a phases, these results indicate that changes in extreme ENSO phases will significantly alter CO2 dynamics in the Florida Everglades."], "title": "El Ni\u00f1o Southern Oscillation (ENSO) enhances CO2 exchange rates in freshwater Marsh ecosystems in the Florida everglades."}
{"paper_id": 24687550, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The high mobility group nucleosome binding domain 5 (HMGN5) is a member of the high mobility group proteins family and highly expressed in multiple malignancies. Nevertheless, the role of HMGN5 in osteosarcoma remains unclear. This study aimed to investigate the expression and clinical significance of HMGN5 in human osteosarcoma, confirm the oncogenic role of HMGN5 and explore the mechanism by which HMGN5 contributes to invasion and metastasis. HMGN5 expression was detected in osteosarcoma tissues and corresponding adjacent non-cancerous tissues (ANCTs) from 52 patients by immunohistochemical (IHC) assay and the clinicopathologic characteristics of all patients were also recorded. Next, osteosarcoma cells were transfected by HMGN5 RNA interference and cell viability, apoptosis and invasion were detected by cell vitality test, flow cytometry and transwell assay, respectively. As a result, IHC assay showed strong immunized activity of HMGN5 in the nucleus in all osteosarcoma tissues compared with the ANCT (53.5 \u00b1 4.3 % vs. 17.0 \u00b1 3.9 %, P < 0.01). HMGN5 expression level was associated with pathologic staging and TNM staging. Knockdown of HMGN5 induced cell cycle arrest, inhibited invasion and increased sensitivity to doxorubicin-induced cell apoptosis in U2-OS and SaO2 cells. Western blot analysis demonstrated that there were increased expressions of cleaved caspase-3, cleaved PARP and decreased expressions of PCNA, PI3Kp85\u03b1, p-AKT, MMP-9, and cyclin B1 in U2-OS and SaO2 cells depleted of HMGN5. HMGN5 plays oncogenic role in osteosarcoma by promoting cell proliferation and invasion, and could be exploited as a target for therapy in osteosarcoma.", "journal": "Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine", "sentences": ["The high mobility group nucleosome binding domain 5 (HMGN5) is a member of the high mobility group proteins family and highly expressed in multiple malignancies.", "Nevertheless, the role of HMGN5 in osteosarcoma remains unclear.", "This study aimed to investigate the expression and clinical significance of HMGN5 in human osteosarcoma, confirm the oncogenic role of HMGN5 and explore the mechanism by which HMGN5 contributes to invasion and metastasis.", "HMGN5 expression was detected in osteosarcoma tissues and corresponding adjacent non-cancerous tissues (ANCTs) from 52 patients by immunohistochemical (IHC) assay and the clinicopathologic characteristics of all patients were also recorded.", "Next, osteosarcoma cells were transfected by HMGN5 RNA interference and cell viability, apoptosis and invasion were detected by cell vitality test, flow cytometry and transwell assay, respectively.", "As a result, IHC assay showed strong immunized activity of HMGN5 in the nucleus in all osteosarcoma tissues compared with the ANCT (53.5 \u00b1 4.3 % vs. 17.0 \u00b1 3.9 %, P < 0.01).", "HMGN5 expression level was associated with pathologic staging and TNM staging.", "Knockdown of HMGN5 induced cell cycle arrest, inhibited invasion and increased sensitivity to doxorubicin-induced cell apoptosis in U2-OS and SaO2 cells.", "Western blot analysis demonstrated that there were increased expressions of cleaved caspase-3, cleaved PARP and decreased expressions of PCNA, PI3Kp85\u03b1, p-AKT, MMP-9, and cyclin B1 in U2-OS and SaO2 cells depleted of HMGN5.", "HMGN5 plays oncogenic role in osteosarcoma by promoting cell proliferation and invasion, and could be exploited as a target for therapy in osteosarcoma."], "title": "The expression and clinical significance of high mobility group nucleosome binding domain 5 in human osteosarcoma."}
{"paper_id": 27082593, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The peripheral blood mononuclear cell (PBMC) count is a routinely used and meaningful index for infection and blood diseases. PBMCs may be closely related to osteoclasts and include osteoclast precursors; we examined the association between the PBMC count and bone health. This research included 2806 community men aged \u226550 years who underwent full health examinations from October 2007 through December 2011 in four medical centers. The PBMC count was significantly high among subjects with \"at least osteopenia\" compared with controls. In analysis of covariance adjusted for potential confounders, the bone mineral density (BMD) value and T-score had a significant decreasing trend across the quartiles of PBMC count. In univariate analysis, the PBMC count had a strong association with \"at least osteopenia\" (odds ratio [OR] = 2.520, 95% confidence interval [CI]: 1.397-4.547). After adjustment for confounding factors (multivariate analysis) from Model 1 to 4, PBMC count remained as an independent risk factor for \"at least osteopenia\" (OR\u200a=\u200a2.481, 95% CI: 1.176-5.236). Moreover, after adjusting for all confounding variables, participants had a significantly high OR in the body mass index (BMI) <25 group (OR\u200a=\u200a2.798, CI: 1.122-6.973; P\u200a=\u200a0.027) and systolic blood pressure (SBP) <140 group (OR\u200a=\u200a2.519, CI: 1.059-5.993; P\u200a=\u200a0.037). In conclusion, the PBMC count is significantly associated with bone loss in elderly men and the exact mechanism requires further clarification.", "journal": "Medicine", "sentences": ["The peripheral blood mononuclear cell (PBMC) count is a routinely used and meaningful index for infection and blood diseases.", "PBMCs may be closely related to osteoclasts and include osteoclast precursors; we examined the association between the PBMC count and bone health.", "This research included 2806 community men aged \u226550 years who underwent full health examinations from October 2007 through December 2011 in four medical centers.", "The PBMC count was significantly high among subjects with \"at least osteopenia\" compared with controls.", "In analysis of covariance adjusted for potential confounders, the bone mineral density (BMD) value and T-score had a significant decreasing trend across the quartiles of PBMC count.", "In univariate analysis, the PBMC count had a strong association with \"at least osteopenia\" (odds ratio [OR] = 2.520, 95% confidence interval [CI]: 1.397-4.547).", "After adjustment for confounding factors (multivariate analysis) from Model 1 to 4, PBMC count remained as an independent risk factor for \"at least osteopenia\" (OR\u200a=\u200a2.481, 95% CI: 1.176-5.236).", "Moreover, after adjusting for all confounding variables, participants had a significantly high OR in the body mass index (BMI) <25 group (OR\u200a=\u200a2.798, CI: 1.122-6.973; P\u200a=\u200a0.027) and systolic blood pressure (SBP) <140 group (OR\u200a=\u200a2.519, CI: 1.059-5.993; P\u200a=\u200a0.037).", "In conclusion, the PBMC count is significantly associated with bone loss in elderly men and the exact mechanism requires further clarification."], "title": "The Peripheral Blood Mononuclear Cell Count Is Associated With Bone Health in Elderly Men: A Cross-Sectional Population-Based Study."}
{"paper_id": 25254549, "labels": ["0", "0", "0", "1", "0", "0", "0", "0", "1"], "abstract": "Polycomb group (PcG) proteins bind to and repress genes in embryonic stem cells through lineage commitment to the terminal differentiated state. PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark H3K27me3, catalyzed by the Polycomb repressive complex 2. Here, we present in vivo evidence for a previously unrecognized plasticity of PcG-repressed genes in terminally differentiated brain neurons of parkisonian mice. We show that acute administration of the dopamine precursor, L-DOPA, induces a remarkable increase in H3K27me3S28 phosphorylation. The induction of the H3K27me3S28p histone mark specifically occurs in medium spiny neurons expressing dopamine D1 receptors and is dependent on Msk1 kinase activity and DARPP-32-mediated inhibition of protein phosphatase-1. Chromatin immunoprecipitation (ChIP) experiments showed that increased H3K27me3S28p was accompanied by reduced PcG binding to regulatory regions of genes. An analysis of the genome wide distribution of L-DOPA-induced H3K27me3S28 phosphorylation by ChIP sequencing (ChIP-seq) in combination with expression analysis by RNA-sequencing (RNA-seq) showed that the induction of H3K27me3S28p correlated with increased expression of a subset of PcG repressed genes. We found that induction of H3K27me3S28p persisted during chronic L-DOPA administration to parkisonian mice and correlated with aberrant gene expression. We propose that dopaminergic transmission can activate PcG repressed genes in the adult brain and thereby contribute to long-term maladaptive responses including the motor complications, or dyskinesia, caused by prolonged administration of L-DOPA in Parkinson's disease.", "journal": "PLoS genetics", "sentences": ["Polycomb group (PcG) proteins bind to and repress genes in embryonic stem cells through lineage commitment to the terminal differentiated state.", "PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark H3K27me3, catalyzed by the Polycomb repressive complex 2.", "Here, we present in vivo evidence for a previously unrecognized plasticity of PcG-repressed genes in terminally differentiated brain neurons of parkisonian mice.", "We show that acute administration of the dopamine precursor, L-DOPA, induces a remarkable increase in H3K27me3S28 phosphorylation.", "The induction of the H3K27me3S28p histone mark specifically occurs in medium spiny neurons expressing dopamine D1 receptors and is dependent on Msk1 kinase activity and DARPP-32-mediated inhibition of protein phosphatase-1.", "Chromatin immunoprecipitation (ChIP) experiments showed that increased H3K27me3S28p was accompanied by reduced PcG binding to regulatory regions of genes.", "An analysis of the genome wide distribution of L-DOPA-induced H3K27me3S28 phosphorylation by ChIP sequencing (ChIP-seq) in combination with expression analysis by RNA-sequencing (RNA-seq) showed that the induction of H3K27me3S28p correlated with increased expression of a subset of PcG repressed genes.", "We found that induction of H3K27me3S28p persisted during chronic L-DOPA administration to parkisonian mice and correlated with aberrant gene expression.", "We propose that dopaminergic transmission can activate PcG repressed genes in the adult brain and thereby contribute to long-term maladaptive responses including the motor complications, or dyskinesia, caused by prolonged administration of L-DOPA in Parkinson's disease."], "title": "Dopamine signaling leads to loss of Polycomb repression and aberrant gene activation in experimental parkinsonism."}
{"paper_id": 22755077, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "A new rod-like thermotropic liquid crystalline polyester (TLCP) material and its nanocomposites based on different concentrations of graphene were synthesized by in-situ high-temperature solution polymerization. The resulting nanocomposites were characterized using XRD, microscopic analysis (POM, SEM, and TEM), spectroscopic analysis (FT-IR, UV-Vis, and fluorescence), and thermal analysis (TGA and DSC). The XRD and POM methods showed that the composite materials exhibited only the nematic phase. The TEM images revealed that the graphene were distributed in the polymer with sizes ranging from 100 to 200 nm. The absorption spectroscopy data showed that the electronic properties of graphene were mostly retained without damaging their two-dimensional electronic properties, together with the analysis of the maximum absorption spectrum and concentration of the composites in terms of the Lambert-Beer law. The fluorescence from the TLCP moiety was almost completely quenched and red shifted by graphene, indicating that the linkage mode facilitated effective energy and electron transfer between the rod-like TLCP and the extended pi-system of graphene. Therefore, this novel nanocomposite material exhibits excellent thermal properties based on the thermogravimetric analysis.", "journal": "Journal of nanoscience and nanotechnology", "sentences": ["A new rod-like thermotropic liquid crystalline polyester (TLCP) material and its nanocomposites based on different concentrations of graphene were synthesized by in-situ high-temperature solution polymerization.", "The resulting nanocomposites were characterized using XRD, microscopic analysis (POM, SEM, and TEM), spectroscopic analysis (FT-IR, UV-Vis, and fluorescence), and thermal analysis (TGA and DSC).", "The XRD and POM methods showed that the composite materials exhibited only the nematic phase.", "The TEM images revealed that the graphene were distributed in the polymer with sizes ranging from 100 to 200 nm.", "The absorption spectroscopy data showed that the electronic properties of graphene were mostly retained without damaging their two-dimensional electronic properties, together with the analysis of the maximum absorption spectrum and concentration of the composites in terms of the Lambert-Beer law.", "The fluorescence from the TLCP moiety was almost completely quenched and red shifted by graphene, indicating that the linkage mode facilitated effective energy and electron transfer between the rod-like TLCP and the extended pi-system of graphene.", "Therefore, this novel nanocomposite material exhibits excellent thermal properties based on the thermogravimetric analysis."], "title": "Synthesis and characterization of liquid crystalline polyester/graphene and a study of their properties."}
{"paper_id": 20854799, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "0", "1"], "abstract": "Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive death of substantia nigra dopaminergic neurons that results in a regional loss of striatal dopamine (DA) levels. Dental pulp contains ex vivo-expandable cells called dental pulp stem cells (DPSCs), with the capacity to differentiate into multiple cell lineages. More interestingly, due to their embryonic origin, DPSCs express neurotrophic factors such as brain-derived neurotrophic factor, nerve growth factor and glial cell-derived neurotrophic factor. The aim of the present study was to investigate the neuroprotective effects of DPSCs against MPP+ (2.5, 5, and 10 \u03bcM) and rotenone (0.25, 0.5 and 1 \u03bcM) in an in vitro model of PD, using an indirect co-culture system with mesencephalic cell cultures. When mesencephalic cultures were challenged with MPP+ or rotenone, in the presence of DPSCs a statistically significant protective effect was observed at all the tested doses in terms of DA uptake. DPSCs protective effect on DA neurons was also confirmed by immunocytochemistry: an increased number of spared tyrosine hydroxylase (TH)+ cells was observed in co-culture conditions compared to controls, and neurons showed longer processes in comparison with mesencephalic cells grown without DPSCs. In conclusion, the co-culture with DPSCs significantly attenuated MPP+ or rotenone-induced toxicity in primary cultures of mesencephalic neurons. Considering that the direct contact between the two cell types was prevented, it can be speculated that neuroprotection could be due to soluble factors such as BDNF and NGF, released by DPSCs. Blocking BDNF and NGF with neutralizing antibodies, the neuroprotecting effect of DPSCs was completely abolished. Therefore DPSCs can be viewed as possible candidates for studies on cell-based therapy in neurodegenerative disorders.", "journal": "Brain research", "sentences": ["Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive death of substantia nigra dopaminergic neurons that results in a regional loss of striatal dopamine (DA) levels.", "Dental pulp contains ex vivo-expandable cells called dental pulp stem cells (DPSCs), with the capacity to differentiate into multiple cell lineages.", "More interestingly, due to their embryonic origin, DPSCs express neurotrophic factors such as brain-derived neurotrophic factor, nerve growth factor and glial cell-derived neurotrophic factor.", "The aim of the present study was to investigate the neuroprotective effects of DPSCs against MPP+ (2.5, 5, and 10 \u03bcM) and rotenone (0.25, 0.5 and 1 \u03bcM) in an in vitro model of PD, using an indirect co-culture system with mesencephalic cell cultures.", "When mesencephalic cultures were challenged with MPP+ or rotenone, in the presence of DPSCs a statistically significant protective effect was observed at all the tested doses in terms of DA uptake.", "DPSCs protective effect on DA neurons was also confirmed by immunocytochemistry: an increased number of spared tyrosine hydroxylase (TH)+ cells was observed in co-culture conditions compared to controls, and neurons showed longer processes in comparison with mesencephalic cells grown without DPSCs.", "In conclusion, the co-culture with DPSCs significantly attenuated MPP+ or rotenone-induced toxicity in primary cultures of mesencephalic neurons.", "Considering that the direct contact between the two cell types was prevented, it can be speculated that neuroprotection could be due to soluble factors such as BDNF and NGF, released by DPSCs.", "Blocking BDNF and NGF with neutralizing antibodies, the neuroprotecting effect of DPSCs was completely abolished.", "Therefore DPSCs can be viewed as possible candidates for studies on cell-based therapy in neurodegenerative disorders."], "title": "Human dental pulp stem cells protect mouse dopaminergic neurons against MPP+ or rotenone."}
{"paper_id": 24550298, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Brain ischemia and reperfusion activate the immune system. The abrupt development of brain ischemic lesions suggests that innate immune cells may shape the outcome of stroke. Natural killer (NK) cells are innate lymphocytes that can be swiftly mobilized during the earliest phases of immune responses, but their role during stroke remains unknown. Herein, we found that NK cells infiltrated the ischemic lesions of the human brain. In a mouse model of cerebral ischemia, ischemic neuron-derived fractalkine recruited NK cells, which subsequently determined the size of brain lesions in a T and B cell-independent manner. NK cell-mediated exacerbation of brain infarction occurred rapidly after ischemia via the disruption of NK cell tolerance, augmenting local inflammation and neuronal hyperactivity. Therefore, NK cells catalyzed neuronal death in the ischemic brain.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Brain ischemia and reperfusion activate the immune system.", "The abrupt development of brain ischemic lesions suggests that innate immune cells may shape the outcome of stroke.", "Natural killer (NK) cells are innate lymphocytes that can be swiftly mobilized during the earliest phases of immune responses, but their role during stroke remains unknown.", "Herein, we found that NK cells infiltrated the ischemic lesions of the human brain.", "In a mouse model of cerebral ischemia, ischemic neuron-derived fractalkine recruited NK cells, which subsequently determined the size of brain lesions in a T and B cell-independent manner.", "NK cell-mediated exacerbation of brain infarction occurred rapidly after ischemia via the disruption of NK cell tolerance, augmenting local inflammation and neuronal hyperactivity.", "Therefore, NK cells catalyzed neuronal death in the ischemic brain."], "title": "Ischemic neurons recruit natural killer cells that accelerate brain infarction."}
{"paper_id": 26814368, "labels": ["0", "1", "0", "0", "1", "1"], "abstract": "Direct observations indicate that the magnitude of the Earth's magnetic axial dipole has decreased over the past 175 years; it is now 9% weaker than it was in 1840. Here we show how the rate of dipole decay may be controlled by a planetary-scale gyre in the liquid metal outer core. The gyre's meridional limbs on average transport normal polarity magnetic flux equatorward and reverse polarity flux poleward. Asymmetry in the geomagnetic field, due to the South Atlantic Anomaly, is essential to the proposed mechanism. We find that meridional flux advection accounts for the majority of the dipole decay since 1840, especially during times of rapid decline, with magnetic diffusion making an almost steady contribution generally of smaller magnitude. Based on the morphology of the present field, and the persistent nature of the gyre, the current episode of dipole decay looks set to continue, at least for the next few decades.", "journal": "Nature communications", "sentences": ["Direct observations indicate that the magnitude of the Earth's magnetic axial dipole has decreased over the past 175 years; it is now 9% weaker than it was in 1840.", "Here we show how the rate of dipole decay may be controlled by a planetary-scale gyre in the liquid metal outer core.", "The gyre's meridional limbs on average transport normal polarity magnetic flux equatorward and reverse polarity flux poleward.", "Asymmetry in the geomagnetic field, due to the South Atlantic Anomaly, is essential to the proposed mechanism.", "We find that meridional flux advection accounts for the majority of the dipole decay since 1840, especially during times of rapid decline, with magnetic diffusion making an almost steady contribution generally of smaller magnitude.", "Based on the morphology of the present field, and the persistent nature of the gyre, the current episode of dipole decay looks set to continue, at least for the next few decades."], "title": "Gyre-driven decay of the Earth's magnetic dipole."}
{"paper_id": 26717984, "labels": ["0", "0", "0", "0", "0", "0", "1", "0"], "abstract": "This report evaluates the pro-mutagenic behavior of 8-oxo-guanine (8-oxo-G) by quantifying the ability of high-fidelity and specialized DNA polymerases to incorporate natural and modified nucleotides opposite this lesion. Although high-fidelity DNA polymerases such as pol \u03b4 and the bacteriophage T4 DNA polymerase replicating 8-oxo-G in an error-prone manner, they display remarkably low efficiencies for TLS compared to normal DNA synthesis. In contrast, pol \u03b7 shows a combination of high efficiency and low fidelity when replicating 8-oxo-G. These combined properties are consistent with a pro-mutagenic role for pol \u03b7 when replicating this DNA lesion. Studies using modified nucleotide analogs show that pol \u03b7 relies heavily on hydrogen-bonding interactions during translesion DNA synthesis. However, nucleobase modifications such as alkylation to the N2 position of guanine significantly increase error-prone synthesis catalyzed by pol \u03b7 when replicating 8-oxo-G. Molecular modeling studies demonstrate the existence of a hydrophobic pocket in pol \u03b7 that participates in the increased utilization of certain hydrophobic nucleotides. A model is proposed for enhanced pro-mutagenic replication catalyzed by pol \u03b7 that couples efficient incorporation of damaged nucleotides opposite oxidized DNA lesions created by reactive oxygen species. The biological implications of this model toward increasing mutagenic events in lung cancer are discussed.", "journal": "Nucleic acids research", "sentences": ["This report evaluates the pro-mutagenic behavior of 8-oxo-guanine (8-oxo-G) by quantifying the ability of high-fidelity and specialized DNA polymerases to incorporate natural and modified nucleotides opposite this lesion.", "Although high-fidelity DNA polymerases such as pol \u03b4 and the bacteriophage T4 DNA polymerase replicating 8-oxo-G in an error-prone manner, they display remarkably low efficiencies for TLS compared to normal DNA synthesis.", "In contrast, pol \u03b7 shows a combination of high efficiency and low fidelity when replicating 8-oxo-G.", "These combined properties are consistent with a pro-mutagenic role for pol \u03b7 when replicating this DNA lesion.", "Studies using modified nucleotide analogs show that pol \u03b7 relies heavily on hydrogen-bonding interactions during translesion DNA synthesis.", "However, nucleobase modifications such as alkylation to the N2 position of guanine significantly increase error-prone synthesis catalyzed by pol \u03b7 when replicating 8-oxo-G. Molecular modeling studies demonstrate the existence of a hydrophobic pocket in pol \u03b7 that participates in the increased utilization of certain hydrophobic nucleotides.", "A model is proposed for enhanced pro-mutagenic replication catalyzed by pol \u03b7 that couples efficient incorporation of damaged nucleotides opposite oxidized DNA lesions created by reactive oxygen species.", "The biological implications of this model toward increasing mutagenic events in lung cancer are discussed."], "title": "The use of modified and non-natural nucleotides provide unique insights into pro-mutagenic replication catalyzed by polymerase eta."}
{"paper_id": 25690941, "labels": ["0", "0", "0", "1", "0", "0", "1"], "abstract": "Cellular senescence can modulate various pathologies and is associated with irreparable DNA double-strand breaks (IrrDSBs). Extracellular senescence metabolomes (ESMs) were generated from fibroblasts rendered senescent by proliferative exhaustion (PEsen) or 20 Gy of \u03b3 rays (IrrDSBsen) and compared with those of young proliferating cells, confluent cells, quiescent cells, and cells exposed to repairable levels of DNA damage to identify novel noninvasive markers of senescent cells. ESMs of PEsen and IrrDSBsen overlapped and showed increased levels of citrate, molecules involved in oxidative stress, a sterol, monohydroxylipids, tryptophan metabolism, phospholipid, and nucleotide catabolism, as well as reduced levels of dipeptides containing branched chain amino acids. The ESM overlaps with the aging and disease body fluid metabolomes, supporting their utility in the noninvasive detection of human senescent cells in vivo and by implication the detection of a variety of human pathologies. Intracellular metabolites of senescent cells showed a relative increase in glycolysis, gluconeogenesis, the pentose-phosphate pathway, and, consistent with this, pyruvate dehydrogenase kinase transcripts. In contrast, tricarboxylic acid cycle enzyme transcript levels were unchanged and their metabolites were depleted. These results are surprising because glycolysis antagonizes senescence entry but are consistent with established senescent cells entering a state of low oxidative stress.", "journal": "Journal of proteome research", "sentences": ["Cellular senescence can modulate various pathologies and is associated with irreparable DNA double-strand breaks (IrrDSBs).", "Extracellular senescence metabolomes (ESMs) were generated from fibroblasts rendered senescent by proliferative exhaustion (PEsen) or 20 Gy of \u03b3 rays (IrrDSBsen) and compared with those of young proliferating cells, confluent cells, quiescent cells, and cells exposed to repairable levels of DNA damage to identify novel noninvasive markers of senescent cells.", "ESMs of PEsen and IrrDSBsen overlapped and showed increased levels of citrate, molecules involved in oxidative stress, a sterol, monohydroxylipids, tryptophan metabolism, phospholipid, and nucleotide catabolism, as well as reduced levels of dipeptides containing branched chain amino acids.", "The ESM overlaps with the aging and disease body fluid metabolomes, supporting their utility in the noninvasive detection of human senescent cells in vivo and by implication the detection of a variety of human pathologies.", "Intracellular metabolites of senescent cells showed a relative increase in glycolysis, gluconeogenesis, the pentose-phosphate pathway, and, consistent with this, pyruvate dehydrogenase kinase transcripts.", "In contrast, tricarboxylic acid cycle enzyme transcript levels were unchanged and their metabolites were depleted.", "These results are surprising because glycolysis antagonizes senescence entry but are consistent with established senescent cells entering a state of low oxidative stress."], "title": "Senescent human fibroblasts show increased glycolysis and redox homeostasis with extracellular metabolomes that overlap with those of irreparable DNA damage, aging, and disease."}
{"paper_id": 26157118, "labels": ["0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "UNLABELLED\nThe propensity for transspecies prion transmission is related to the structural characteristics of the enciphering and new host PrP, although the exact mechanism remains incompletely understood. The effects of variability in prion protein on cross-species prion transmission have been studied with animal bioassays, but the influence of prion protein structure versus that of host cofactors (e.g., cellular constituents, trafficking, and innate immune interactions) remains difficult to dissect. To isolate the effects of protein-protein interactions on transspecies conversion, we used recombinant PrP(C) and real-time quaking-induced conversion (RT-QuIC) and compared chronic wasting disease (CWD) and classical bovine spongiform encephalopathy (cBSE) prions. To assess the impact of transmission to a new species, we studied feline CWD (fCWD) and feline BSE (i.e., feline spongiform encephalopathy [FSE]). We cross-seeded fCWD and FSE into each species' full-length, recombinant PrP(C) and measured the time required for conversion to the amyloid (PrP(Res)) form, which we describe here as the rate of amyloid conversion. These studies revealed the following: (i) CWD and BSE seeded their homologous species' PrP best; (ii) fCWD was a more efficient seed for feline rPrP than for white-tailed deer rPrP; (iii) conversely, FSE more efficiently converted bovine than feline rPrP; (iv) and CWD, fCWD, BSE, and FSE all converted human rPrP, although not as efficiently as homologous sCJD prions. These results suggest that (i) at the level of protein-protein interactions, CWD adapts to a new species more readily than does BSE and (ii) the barrier preventing transmission of CWD to humans may be less robust than estimated.\n\n\nIMPORTANCE\nWe demonstrate that bovine spongiform encephalopathy prions maintain their transspecies conversion characteristics upon passage to cats but that chronic wasting disease prions adapt to the cat and are distinguishable from the original prion. Additionally, we showed that chronic wasting disease prions are effective at seeding the conversion of normal human prion protein to an amyloid conformation, perhaps the first step in crossing the species barrier.", "journal": "Journal of virology", "sentences": ["UNLABELLED\nThe propensity for transspecies prion transmission is related to the structural characteristics of the enciphering and new host PrP, although the exact mechanism remains incompletely understood.", "The effects of variability in prion protein on cross-species prion transmission have been studied with animal bioassays, but the influence of prion protein structure versus that of host cofactors (e.g., cellular constituents, trafficking, and innate immune interactions) remains difficult to dissect.", "To isolate the effects of protein-protein interactions on transspecies conversion, we used recombinant PrP(C) and real-time quaking-induced conversion (RT-QuIC) and compared chronic wasting disease (CWD) and classical bovine spongiform encephalopathy (cBSE) prions.", "To assess the impact of transmission to a new species, we studied feline CWD (fCWD) and feline BSE (i.e., feline spongiform encephalopathy [FSE]).", "We cross-seeded fCWD and FSE into each species' full-length, recombinant PrP(C) and measured the time required for conversion to the amyloid (PrP(Res)) form, which we describe here as the rate of amyloid conversion.", "These studies revealed the following: (i) CWD and BSE seeded their homologous species' PrP best; (ii) fCWD was a more efficient seed for feline rPrP than for white-tailed deer rPrP; (iii) conversely, FSE more efficiently converted bovine than feline rPrP; (iv) and CWD, fCWD, BSE, and FSE all converted human rPrP, although not as efficiently as homologous sCJD prions.", "These results suggest that (i) at the level of protein-protein interactions, CWD adapts to a new species more readily than does BSE and (ii) the barrier preventing transmission of CWD to humans may be less robust than estimated.", "IMPORTANCE\nWe demonstrate that bovine spongiform encephalopathy prions maintain their transspecies conversion characteristics upon passage to cats but that chronic wasting disease prions adapt to the cat and are distinguishable from the original prion.", "Additionally, we showed that chronic wasting disease prions are effective at seeding the conversion of normal human prion protein to an amyloid conformation, perhaps the first step in crossing the species barrier."], "title": "Insights into Chronic Wasting Disease and Bovine Spongiform Encephalopathy Species Barriers by Use of Real-Time Conversion."}
{"paper_id": 25799492, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Coordination between actin cytoskeleton assembly and localized polarization of intracellular trafficking routes is crucial for cancer cell migration. ARF6 has been implicated in the endocytic recycling of surface receptors and membrane components and in actin cytoskeleton remodeling. Here we show that overexpression of an ARF6 fast-cycling mutant in MDA-MB-231 breast cancer-derived cells to mimick ARF6 hyperactivation observed in invasive breast tumors induced a striking rearrangement of the actin cytoskeleton at the ventral cell surface. This phenotype consisted in the formation of dynamic actin-based podosome rosette-like structures expanding outward as wave positive for F-actin and actin cytoskeleton regulatory components including cortactin, Arp2/3 and SCAR/WAVE complexes and upstream Rac1 regulator. Ventral rosette-like structures were similarly induced in MDA-MB-231 cells in response to epidermal growth factor (EGF) stimulation and to Rac1 hyperactivation. In addition, interference with ARF6 expression attenuated activation and plasma membrane targeting of Rac1 in response to EGF treatment. Our data suggest a role for ARF6 in linking EGF-receptor signaling to Rac1 recruitment and activation at the plasma membrane to promote breast cancer cell directed migration.", "journal": "PloS one", "sentences": ["Coordination between actin cytoskeleton assembly and localized polarization of intracellular trafficking routes is crucial for cancer cell migration.", "ARF6 has been implicated in the endocytic recycling of surface receptors and membrane components and in actin cytoskeleton remodeling.", "Here we show that overexpression of an ARF6 fast-cycling mutant in MDA-MB-231 breast cancer-derived cells to mimick ARF6 hyperactivation observed in invasive breast tumors induced a striking rearrangement of the actin cytoskeleton at the ventral cell surface.", "This phenotype consisted in the formation of dynamic actin-based podosome rosette-like structures expanding outward as wave positive for F-actin and actin cytoskeleton regulatory components including cortactin, Arp2/3 and SCAR/WAVE complexes and upstream Rac1 regulator.", "Ventral rosette-like structures were similarly induced in MDA-MB-231 cells in response to epidermal growth factor (EGF) stimulation and to Rac1 hyperactivation.", "In addition, interference with ARF6 expression attenuated activation and plasma membrane targeting of Rac1 in response to EGF treatment.", "Our data suggest a role for ARF6 in linking EGF-receptor signaling to Rac1 recruitment and activation at the plasma membrane to promote breast cancer cell directed migration."], "title": "ARF6 promotes the formation of Rac1 and WAVE-dependent ventral F-actin rosettes in breast cancer cells in response to epidermal growth factor."}
{"paper_id": 23451172, "labels": ["0", "0", "0", "0", "1", "1", "1"], "abstract": "In contrast to male genitalia that typically exhibit patterns of rapid and divergent evolution among internally fertilizing animals, female genitalia have been less well studied and are generally thought to evolve slowly among closely-related species. As a result, few cases of male-female genital coevolution have been documented. In Drosophila, female copulatory structures have been claimed to be mostly invariant compared to male structures. Here, we re-examined male and female genitalia in the nine species of the D. melanogaster subgroup. We describe several new species-specific female genital structures that appear to coevolve with male genital structures, and provide evidence that the coevolving structures contact each other during copulation. Several female structures might be defensive shields against apparently harmful male structures, such as cercal teeth, phallic hooks and spines. Evidence for male-female morphological coevolution in Drosophila has previously been shown at the post-copulatory level (e.g., sperm length and sperm storage organ size), and our results provide support for male-female coevolution at the copulatory level.", "journal": "PloS one", "sentences": ["In contrast to male genitalia that typically exhibit patterns of rapid and divergent evolution among internally fertilizing animals, female genitalia have been less well studied and are generally thought to evolve slowly among closely-related species.", "As a result, few cases of male-female genital coevolution have been documented.", "In Drosophila, female copulatory structures have been claimed to be mostly invariant compared to male structures.", "Here, we re-examined male and female genitalia in the nine species of the D. melanogaster subgroup.", "We describe several new species-specific female genital structures that appear to coevolve with male genital structures, and provide evidence that the coevolving structures contact each other during copulation.", "Several female structures might be defensive shields against apparently harmful male structures, such as cercal teeth, phallic hooks and spines.", "Evidence for male-female morphological coevolution in Drosophila has previously been shown at the post-copulatory level (e.g., sperm length and sperm storage organ size), and our results provide support for male-female coevolution at the copulatory level."], "title": "Coevolution between male and female genitalia in the Drosophila melanogaster species subgroup."}
{"paper_id": 25993270, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The single-cell green alga Chlamydomonas reinhardtii harbors twelve truncated hemoglobins (Cr-TrHbs). Cr-TrHb1-1 and Cr-TrHb1-8 have been postulated to be parts of the nitrogen assimilation pathway, and of a NO-dependent signaling pathway, respectively. Here, spectroscopic and reactivity properties of Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4, all belonging to clsss 1 (previously known as group N or group I), are reported. The ferric form of Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 displays a stable 6cLS heme-Fe atom, whereas the hexa-coordination of the ferrous derivative appears less strongly stabilized. Accordingly, kinetics of azide binding to ferric Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 are independent of the ligand concentration. Conversely, kinetics of CO or NO2- binding to ferrous Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 are ligand-dependent at low CO or NO2- concentrations, tending to level off at high ligand concentrations, suggesting the presence of a rate-limiting step. In agreement with the different heme-Fe environments, the pH-dependent kinetics for CO and NO2-binding to ferrous Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 are characterized by different ligand-linked protonation events. This raises the question of whether the simultaneous presence in C. reinhardtii of multiple TrHb1s may be related to different regulatory roles.", "journal": "PloS one", "sentences": ["The single-cell green alga Chlamydomonas reinhardtii harbors twelve truncated hemoglobins (Cr-TrHbs).", "Cr-TrHb1-1 and Cr-TrHb1-8 have been postulated to be parts of the nitrogen assimilation pathway, and of a NO-dependent signaling pathway, respectively.", "Here, spectroscopic and reactivity properties of Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4, all belonging to clsss 1 (previously known as group N or group I), are reported.", "The ferric form of Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 displays a stable 6cLS heme-Fe atom, whereas the hexa-coordination of the ferrous derivative appears less strongly stabilized.", "Accordingly, kinetics of azide binding to ferric Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 are independent of the ligand concentration.", "Conversely, kinetics of CO or NO2- binding to ferrous Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 are ligand-dependent at low CO or NO2- concentrations, tending to level off at high ligand concentrations, suggesting the presence of a rate-limiting step.", "In agreement with the different heme-Fe environments, the pH-dependent kinetics for CO and NO2-binding to ferrous Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 are characterized by different ligand-linked protonation events.", "This raises the question of whether the simultaneous presence in C. reinhardtii of multiple TrHb1s may be related to different regulatory roles."], "title": "Functional and Spectroscopic Characterization of Chlamydomonas reinhardtii Truncated Hemoglobins."}
{"paper_id": 22022566, "labels": ["0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "To test the hypothesis that the myosin II motor domain (S1) preferentially binds to specific subsets of actin filaments in vivo, we expressed GFP-fused S1 with mutations that enhanced its affinity for actin in Dictyostelium cells. Consistent with the hypothesis, the GFP-S1 mutants were localized along specific portions of the cell cortex. Comparison with rhodamine-phalloidin staining in fixed cells demonstrated that the GFP-S1 probes preferentially bound to actin filaments in the rear cortex and cleavage furrows, where actin filaments are stretched by interaction with endogenous myosin II filaments. The GFP-S1 probes were similarly enriched in the cortex stretched passively by traction forces in the absence of myosin II or by external forces using a microcapillary. The preferential binding of GFP-S1 mutants to stretched actin filaments did not depend on cortexillin I or PTEN, two proteins previously implicated in the recruitment of myosin II filaments to stretched cortex. These results suggested that it is the stretching of the actin filaments itself that increases their affinity for the myosin II motor domain. In contrast, the GFP-fused myosin I motor domain did not localize to stretched actin filaments, which suggests different preferences of the motor domains for different structures of actin filaments play a role in distinct intracellular localizations of myosin I and II. We propose a scheme in which the stretching of actin filaments, the preferential binding of myosin II filaments to stretched actin filaments, and myosin II-dependent contraction form a positive feedback loop that contributes to the stabilization of cell polarity and to the responsiveness of the cells to external mechanical stimuli.", "journal": "PloS one", "sentences": ["To test the hypothesis that the myosin II motor domain (S1) preferentially binds to specific subsets of actin filaments in vivo, we expressed GFP-fused S1 with mutations that enhanced its affinity for actin in Dictyostelium cells.", "Consistent with the hypothesis, the GFP-S1 mutants were localized along specific portions of the cell cortex.", "Comparison with rhodamine-phalloidin staining in fixed cells demonstrated that the GFP-S1 probes preferentially bound to actin filaments in the rear cortex and cleavage furrows, where actin filaments are stretched by interaction with endogenous myosin II filaments.", "The GFP-S1 probes were similarly enriched in the cortex stretched passively by traction forces in the absence of myosin II or by external forces using a microcapillary.", "The preferential binding of GFP-S1 mutants to stretched actin filaments did not depend on cortexillin I or PTEN, two proteins previously implicated in the recruitment of myosin II filaments to stretched cortex.", "These results suggested that it is the stretching of the actin filaments itself that increases their affinity for the myosin II motor domain.", "In contrast, the GFP-fused myosin I motor domain did not localize to stretched actin filaments, which suggests different preferences of the motor domains for different structures of actin filaments play a role in distinct intracellular localizations of myosin I and II.", "We propose a scheme in which the stretching of actin filaments, the preferential binding of myosin II filaments to stretched actin filaments, and myosin II-dependent contraction form a positive feedback loop that contributes to the stabilization of cell polarity and to the responsiveness of the cells to external mechanical stimuli."], "title": "Stretching actin filaments within cells enhances their affinity for the myosin II motor domain."}
{"paper_id": 27136381, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "The upper and lower airways of healthy humans are reported to harbor stable and consistent bacterial populations, and the composition of these communities is altered in individuals affected with several respiratory diseases. Data regarding the presence of airway microbiota in other animals are scant and a better understanding of the composition and metabolic function of such bacterial populations is essential for the development of novel therapeutic and diagnostic modalities for use in both veterinary and human medicine. Based on targeted next-generation sequencing of feces and samples collected at multiple levels of the airways from 16 healthy female dogs, we demonstrate that canine airways harbor a topographically continuous microbiota with increasing relative abundance of proteobacterial species from the upper to lower airways. The lung-associated microbiota, as assessed via bronchoalveolar lavage fluid (BALF), was the most consistent between dogs and was dominated by three distinct taxa, two of which were resolved to the species level and one to the level of family. The gene content of the nasal, oropharyngeal, and lung-associated microbiota, predicted using the Phylogenetic Investigations into Communities by Reconstruction of Unobserved States (PICRUSt) software, provided information regarding the glyoxylate and citrate cycle metabolic pathways utilized by these bacterial populations to colonize such nutrient-poor, low-throughput environments. These data generated in healthy subjects provide context for future analysis of diseased canine airways. Moreover, as dogs have similar respiratory anatomy, physiology, and immune systems as humans, are exposed to many of the same environmental stimuli, and spontaneously develop similar respiratory diseases, these data support the use of dogs as a model species for prospective studies of the airway microbiota, with findings translatable to the human condition.", "journal": "PloS one", "sentences": ["The upper and lower airways of healthy humans are reported to harbor stable and consistent bacterial populations, and the composition of these communities is altered in individuals affected with several respiratory diseases.", "Data regarding the presence of airway microbiota in other animals are scant and a better understanding of the composition and metabolic function of such bacterial populations is essential for the development of novel therapeutic and diagnostic modalities for use in both veterinary and human medicine.", "Based on targeted next-generation sequencing of feces and samples collected at multiple levels of the airways from 16 healthy female dogs, we demonstrate that canine airways harbor a topographically continuous microbiota with increasing relative abundance of proteobacterial species from the upper to lower airways.", "The lung-associated microbiota, as assessed via bronchoalveolar lavage fluid (BALF), was the most consistent between dogs and was dominated by three distinct taxa, two of which were resolved to the species level and one to the level of family.", "The gene content of the nasal, oropharyngeal, and lung-associated microbiota, predicted using the Phylogenetic Investigations into Communities by Reconstruction of Unobserved States (PICRUSt) software, provided information regarding the glyoxylate and citrate cycle metabolic pathways utilized by these bacterial populations to colonize such nutrient-poor, low-throughput environments.", "These data generated in healthy subjects provide context for future analysis of diseased canine airways.", "Moreover, as dogs have similar respiratory anatomy, physiology, and immune systems as humans, are exposed to many of the same environmental stimuli, and spontaneously develop similar respiratory diseases, these data support the use of dogs as a model species for prospective studies of the airway microbiota, with findings translatable to the human condition."], "title": "Composition and Predicted Metabolic Capacity of Upper and Lower Airway Microbiota of Healthy Dogs in Relation to the Fecal Microbiota."}
{"paper_id": 21039047, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Although bone marrow micrometastasis may remain silent, its detection changes the staging and management of lung cancer. In the present study conducted in West Bengal, India, 74 diagnosed bronchogenic carcinoma cases (28 squamous cell carcinomas, 20 adenocarcinomas, 9 small cell carcinomas, 4 large cell carcinomas, 13 unclassified) in early stages (stage I, II and IIIA) were included. Complete hemograms, bone marrow aspiration and cell blocks of aspirated material, trephine biopsy were done for detection of micrometastasis. Overall micrometastases in bone marrow were noted in 17 cases (23.0%). We detected marrow metastasis in 44.4% cases of small cell carcinomas and 21.2% cases of non small cell lung cancer (50% of large cell carcinomas, 20% of adenocarcinomas, 17.9% of squamous cell carcinomas) and 15.4% cases of unclassified carcinoma. We found a statistically significant correlation between marrow metastasis and low platelet count (P=0.0001) and high ESR (P=0.0003), but no significant correlation with hemoglobin percentage (P=0.36), total leukocyte count (P=0.58) and eosinophil count (P=0.44). A definite correlation noted between micrometastasis with the clinical stage (no case in Stage I, 12.5% in Stage II, 30.4% in Stage IIIA patients). We emphasize that detection of micrometastasis is essential particularly in non small cell cancers, where treatment with curative intent is planned, which can be suitably done by morphological study of bone marrow aspirate and biopsy in countries like India.", "journal": "Asian Pacific journal of cancer prevention : APJCP", "sentences": ["Although bone marrow micrometastasis may remain silent, its detection changes the staging and management of lung cancer.", "In the present study conducted in West Bengal, India, 74 diagnosed bronchogenic carcinoma cases (28 squamous cell carcinomas, 20 adenocarcinomas, 9 small cell carcinomas, 4 large cell carcinomas, 13 unclassified) in early stages (stage I, II and IIIA) were included.", "Complete hemograms, bone marrow aspiration and cell blocks of aspirated material, trephine biopsy were done for detection of micrometastasis.", "Overall micrometastases in bone marrow were noted in 17 cases (23.0%).", "We detected marrow metastasis in 44.4% cases of small cell carcinomas and 21.2% cases of non small cell lung cancer (50% of large cell carcinomas, 20% of adenocarcinomas, 17.9% of squamous cell carcinomas) and 15.4% cases of unclassified carcinoma.", "We found a statistically significant correlation between marrow metastasis and low platelet count (P=0.0001) and high ESR (P=0.0003), but no significant correlation with hemoglobin percentage (P=0.36), total leukocyte count (P=0.58) and eosinophil count (P=0.44).", "A definite correlation noted between micrometastasis with the clinical stage (no case in Stage I, 12.5% in Stage II, 30.4% in Stage IIIA patients).", "We emphasize that detection of micrometastasis is essential particularly in non small cell cancers, where treatment with curative intent is planned, which can be suitably done by morphological study of bone marrow aspirate and biopsy in countries like India."], "title": "Occult micrometastasis to bone marrow in early lung cancer: a clinicopathologic study from West Bengal, India."}
{"paper_id": 25512253, "labels": ["0", "0", "0", "1", "1", "1"], "abstract": "Supercritical water is fundamental in many fields of applications and a precise characterization of the supercritical state is of uttermost importance for this liquid. In a fluid, when moving from the critical point into the single-phase region, the thermodynamic response functions show maxima reminiscent of the critical divergence. Here we study the thermodynamic properties of water in the supercritical region by analysing both available experimental data and our computer simulation results. We find that the lines connecting the maxima of the response functions converge on approaching the critical point in a single line, the Widom line. We further show that the Widom line coincides with a crossover from a liquid-like to a gas-like behaviour clearly visible in the transport properties. These thermodynamic and dynamic features show that the supercritical state in water is far more complex than what was so far believed, indicating a new perspective in the characterization of the thermodynamics of this state.", "journal": "Nature communications", "sentences": ["Supercritical water is fundamental in many fields of applications and a precise characterization of the supercritical state is of uttermost importance for this liquid.", "In a fluid, when moving from the critical point into the single-phase region, the thermodynamic response functions show maxima reminiscent of the critical divergence.", "Here we study the thermodynamic properties of water in the supercritical region by analysing both available experimental data and our computer simulation results.", "We find that the lines connecting the maxima of the response functions converge on approaching the critical point in a single line, the Widom line.", "We further show that the Widom line coincides with a crossover from a liquid-like to a gas-like behaviour clearly visible in the transport properties.", "These thermodynamic and dynamic features show that the supercritical state in water is far more complex than what was so far believed, indicating a new perspective in the characterization of the thermodynamics of this state."], "title": "Widom line and dynamical crossovers as routes to understand supercritical water."}
{"paper_id": 25367368, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The Skyrme-particle, the skyrmion, was introduced over half a century ago in the context of dense nuclear matter. But with skyrmions being mathematical objects--special types of topological solitons--they can emerge in much broader contexts. Recently skyrmions were observed in helimagnets, forming nanoscale spin-textures. Extending over length scales much larger than the interatomic spacing, they behave as large, classical objects, yet deep inside they are of quantum nature. Penetrating into their microscopic roots requires a multi-scale approach, spanning the full quantum to classical domain. Here, we achieve this for the first time in the skyrmionic Mott insulator Cu2OSeO3. We show that its magnetic building blocks are strongly fluctuating Cu4 tetrahedra, spawning a continuum theory that culminates in 51\u2009nm large skyrmions, in striking agreement with experiment. One of the further predictions that ensues is the temperature-dependent decay of skyrmions into half-skyrmions.", "journal": "Nature communications", "sentences": ["The Skyrme-particle, the skyrmion, was introduced over half a century ago in the context of dense nuclear matter.", "But with skyrmions being mathematical objects--special types of topological solitons--they can emerge in much broader contexts.", "Recently skyrmions were observed in helimagnets, forming nanoscale spin-textures.", "Extending over length scales much larger than the interatomic spacing, they behave as large, classical objects, yet deep inside they are of quantum nature.", "Penetrating into their microscopic roots requires a multi-scale approach, spanning the full quantum to classical domain.", "Here, we achieve this for the first time in the skyrmionic Mott insulator Cu2OSeO3.", "We show that its magnetic building blocks are strongly fluctuating Cu4 tetrahedra, spawning a continuum theory that culminates in 51\u2009nm large skyrmions, in striking agreement with experiment.", "One of the further predictions that ensues is the temperature-dependent decay of skyrmions into half-skyrmions."], "title": "The quantum nature of skyrmions and half-skyrmions in Cu2OSeO3."}
{"paper_id": 25063297, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "A mutant of the high fidelity family-B DNA polymerase from the archaeon Thermococcus gorgonarius (Tgo-Pol), able to replicate past DNA lesions, is described. Gain of function requires replacement of the three amino acid loop region in the fingers domain of Tgo-Pol with a longer version, found naturally in eukaryotic Pol \u03b6 (a family-B translesion synthesis polymerase). Inactivation of the 3'-5' proof-reading exonuclease activity is also necessary. The resulting Tgo-Pol Z1 variant is proficient at initiating replication from base mismatches and can read through damaged bases, such as abasic sites and thymine photo-dimers. Tgo-Pol Z1 is also proficient at extending from primers that terminate opposite aberrant bases. The fidelity of Tgo-Pol Z1 is reduced, with a marked tendency to make changes at G:C base pairs. Together, these results suggest that the loop region of the fingers domain may play a critical role in determining whether a family-B enzyme falls into the accurate genome-replicating category or is an error-prone translesion synthesis polymerase. Tgo-Pol Z1 may also be useful for amplification of damaged DNA.", "journal": "Nucleic acids research", "sentences": ["A mutant of the high fidelity family-B DNA polymerase from the archaeon Thermococcus gorgonarius (Tgo-Pol), able to replicate past DNA lesions, is described.", "Gain of function requires replacement of the three amino acid loop region in the fingers domain of Tgo-Pol with a longer version, found naturally in eukaryotic Pol \u03b6 (a family-B translesion synthesis polymerase).", "Inactivation of the 3'-5' proof-reading exonuclease activity is also necessary.", "The resulting Tgo-Pol Z1 variant is proficient at initiating replication from base mismatches and can read through damaged bases, such as abasic sites and thymine photo-dimers.", "Tgo-Pol Z1 is also proficient at extending from primers that terminate opposite aberrant bases.", "The fidelity of Tgo-Pol Z1 is reduced, with a marked tendency to make changes at G:C base pairs.", "Together, these results suggest that the loop region of the fingers domain may play a critical role in determining whether a family-B enzyme falls into the accurate genome-replicating category or is an error-prone translesion synthesis polymerase.", "Tgo-Pol Z1 may also be useful for amplification of damaged DNA."], "title": "An archaeal family-B DNA polymerase variant able to replicate past DNA damage: occurrence of replicative and translesion synthesis polymerases within the B family."}
{"paper_id": 27057893, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "The aim of the study is to evaluate the clinical characteristics of intraoperative retinal breaks (RBs) and postoperative retinal detachment (RRD) in patients undergoing pars plana vitrectomy (PPV) for macular disorders, who were treated preoperatively with prophylactic peripheral laser retinopexy.This observational cohort study comprised of 254 patients who underwent macular surgery and were preoperatively subjected to prophylactic laser retinopexy anterior to the equator. The main outcome measures were the incidence and characteristics of intraoperative RBs and postoperative RRD.Intraoperative RBs occurred in 14 patients (5.5%). Ten patients presented a sclerotomy-related RB (3.9%) and 4 patients a nonsclerotomy-related RB (1.6%). Two patients showed postoperative RRD (0.7%). Neither of the 2 patients with postoperative RRD was macula-off at presentation: one of them was successfully operated on with scleral buckling and the other was managed by observation alone. A significantly increased risk for the intraoperative development of sclerotomy-related RB was found in 20-gauge PPV compared with 23/25-gauge PPV.Preoperative prophylactic peripheral laser retinopexy does not guarantee the prevention of intraopertaive RBs or postoperative RRD. However, it might prevent the involvement of the macula when RRD occurs postoperatively.", "journal": "Medicine", "sentences": ["The aim of the study is to evaluate the clinical characteristics of intraoperative retinal breaks (RBs) and postoperative retinal detachment (RRD) in patients undergoing pars plana vitrectomy (PPV) for macular disorders, who were treated preoperatively with prophylactic peripheral laser retinopexy.This observational cohort study comprised of 254 patients who underwent macular surgery and were preoperatively subjected to prophylactic laser retinopexy anterior to the equator.", "The main outcome measures were the incidence and characteristics of intraoperative RBs and postoperative RRD.Intraoperative RBs occurred in 14 patients (5.5%).", "Ten patients presented a sclerotomy-related RB (3.9%) and 4 patients a nonsclerotomy-related RB (1.6%).", "Two patients showed postoperative RRD (0.7%).", "Neither of the 2 patients with postoperative RRD was macula-off at presentation: one of them was successfully operated on with scleral buckling and the other was managed by observation alone.", "A significantly increased risk for the intraoperative development of sclerotomy-related RB was found in 20-gauge PPV compared with 23/25-gauge PPV.Preoperative prophylactic peripheral laser retinopexy does not guarantee the prevention of intraopertaive RBs or postoperative RRD.", "However, it might prevent the involvement of the macula when RRD occurs postoperatively."], "title": "The Incidence of Rhegmatogenous Retinal Complications in Macular Surgery After Prophylactic Preoperative Laser Retinopexy: A Retrospective Study."}
{"paper_id": 26451375, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Fuchs endothelial corneal dystrophy (FECD) is a common corneal endotheliopathy with a complex and heterogeneous genetic background. Different variants in the TCF4 gene have been strongly associated with the development of FECD. TCF4 encodes the E2-2 transcription factor but the link between the strong susceptibility locus and disease mechanism remains elusive. Here, we confirm a strong positive association between TCF4 single nucleotide polymorphism rs613872 and FECD in Polish patients (OR = 12.95, 95% CI: 8.63-19.42, \u03c7 (2) = 189.5, p < 0.0001). We show that TCF4 expression at the mRNA level in corneal endothelium (n = 63) does not differ significantly between individuals with a particular TCF4 genotype. It is also not altered in FECD patients as compared to control samples. The data suggest that changes in the transcript level containing constitutive TCF4 exon encoding the amino-terminal part of the protein seem not to contribute to disease pathogenesis. However, considering the strong association of TCF4 allelic variants with FECD, genotyping of TCF4 risk alleles may be important in the clinical practice.", "journal": "BioMed research international", "sentences": ["Fuchs endothelial corneal dystrophy (FECD) is a common corneal endotheliopathy with a complex and heterogeneous genetic background.", "Different variants in the TCF4 gene have been strongly associated with the development of FECD.", "TCF4 encodes the E2-2 transcription factor but the link between the strong susceptibility locus and disease mechanism remains elusive.", "Here, we confirm a strong positive association between TCF4 single nucleotide polymorphism rs613872 and FECD in Polish patients (OR = 12.95, 95% CI: 8.63-19.42, \u03c7 (2) = 189.5, p < 0.0001).", "We show that TCF4 expression at the mRNA level in corneal endothelium (n = 63) does not differ significantly between individuals with a particular TCF4 genotype.", "It is also not altered in FECD patients as compared to control samples.", "The data suggest that changes in the transcript level containing constitutive TCF4 exon encoding the amino-terminal part of the protein seem not to contribute to disease pathogenesis.", "However, considering the strong association of TCF4 allelic variants with FECD, genotyping of TCF4 risk alleles may be important in the clinical practice."], "title": "Fuchs Endothelial Corneal Dystrophy: Strong Association with rs613872 Not Paralleled by Changes in Corneal Endothelial TCF4 mRNA Level."}
{"paper_id": 26739564, "labels": ["0", "0", "0", "0", "1", "0", "1", "1"], "abstract": "Metastatic dissemination of breast cancer cells represents a significant clinical obstacle to curative therapy. The loss of function of metastasis suppressor genes is a major rate-limiting step in breast cancer progression that prevents the formation of new colonies at distal sites. However, the discovery of new metastasis suppressor genes in breast cancer using genomic efforts has been slow, potentially due to their primary regulation by epigenetic mechanisms. Here, we report the use of model cell lines with the same genetic lineage for the identification of a novel metastasis suppressor gene, serum deprivation response (SDPR), localized to 2q32-33, a region reported to be associated with significant loss of heterozygosity in breast cancer. In silico metaanalysis of publicly available gene expression datasets suggests that the loss of expression of SDPR correlates with significantly reduced distant-metastasis-free and relapse-free survival of breast cancer patients who underwent therapy. Furthermore, we found that stable SDPR overexpression in highly metastatic breast cancer model cell lines inhibited prosurvival pathways, shifted the balance of Bcl-2 family proteins in favor of apoptosis, and decreased migration and intravasation/extravasation potential, with a corresponding drastic suppression of metastatic nodule formation in the lungs of NOD/SCID mice. Moreover, SDPR expression is silenced by promoter DNA methylation, and as such it exemplifies epigenetic regulation of metastatic breast cancer progression. These observations highlight SDPR as a potential prognostic biomarker and a target for future therapeutic applications.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Metastatic dissemination of breast cancer cells represents a significant clinical obstacle to curative therapy.", "The loss of function of metastasis suppressor genes is a major rate-limiting step in breast cancer progression that prevents the formation of new colonies at distal sites.", "However, the discovery of new metastasis suppressor genes in breast cancer using genomic efforts has been slow, potentially due to their primary regulation by epigenetic mechanisms.", "Here, we report the use of model cell lines with the same genetic lineage for the identification of a novel metastasis suppressor gene, serum deprivation response (SDPR), localized to 2q32-33, a region reported to be associated with significant loss of heterozygosity in breast cancer.", "In silico metaanalysis of publicly available gene expression datasets suggests that the loss of expression of SDPR correlates with significantly reduced distant-metastasis-free and relapse-free survival of breast cancer patients who underwent therapy.", "Furthermore, we found that stable SDPR overexpression in highly metastatic breast cancer model cell lines inhibited prosurvival pathways, shifted the balance of Bcl-2 family proteins in favor of apoptosis, and decreased migration and intravasation/extravasation potential, with a corresponding drastic suppression of metastatic nodule formation in the lungs of NOD/SCID mice.", "Moreover, SDPR expression is silenced by promoter DNA methylation, and as such it exemplifies epigenetic regulation of metastatic breast cancer progression.", "These observations highlight SDPR as a potential prognostic biomarker and a target for future therapeutic applications."], "title": "SDPR functions as a metastasis suppressor in breast cancer by promoting apoptosis."}
{"paper_id": 23596255, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The transcription factor Sox2 has been shown to play essential roles during embryonic development as well as in cancer. To more precisely understand tumor biology and to identify potential therapeutical targets, we thoroughly investigated the expression and function of Sox2 in medulloblastoma, a malignant embryonic brain tumor that initiates in the posterior fossa and eventually spreads throughout the entire cerebrospinal axis. We examined a large series of tumor samples (n = 188) to show that SOX2 is specifically expressed in Sonic hedgehog (SHH)-associated medulloblastoma with an interesting preponderance in adolescent and adult cases. We further show that cerebellar granule neuron precursors (CGNP), which are believed to serve as the cell of origin for this medulloblastoma subgroup, express Sox2 in early stages. Also, Shh-associated medulloblastoma can be initiated from such Sox2-positive CGNPs in mice. Independent of their endogenous Sox2 expression, constitutive activation of Shh signaling in CGNPs resulted in significantly enhanced proliferation and ectopic expression of Sox2 in vitro and Sox2-positive medulloblastoma in vivo. Genetic ablation of Sox2 from murine medulloblastoma did not affect survival, most likely due to a compensatory overexpression of Sox3. However, acute deletion of Sox2 from primary cultures of CGNPs with constitutive Shh signaling significantly decreased proliferation, whereas overexpression of Sox2 enhanced proliferation of murine medulloblastoma cells. We conclude that Sox2 is a marker for Shh-dependent medulloblastomas where it is required and sufficient to drive tumor cell proliferation.", "journal": "Cancer research", "sentences": ["The transcription factor Sox2 has been shown to play essential roles during embryonic development as well as in cancer.", "To more precisely understand tumor biology and to identify potential therapeutical targets, we thoroughly investigated the expression and function of Sox2 in medulloblastoma, a malignant embryonic brain tumor that initiates in the posterior fossa and eventually spreads throughout the entire cerebrospinal axis.", "We examined a large series of tumor samples (n = 188) to show that SOX2 is specifically expressed in Sonic hedgehog (SHH)-associated medulloblastoma with an interesting preponderance in adolescent and adult cases.", "We further show that cerebellar granule neuron precursors (CGNP), which are believed to serve as the cell of origin for this medulloblastoma subgroup, express Sox2 in early stages.", "Also, Shh-associated medulloblastoma can be initiated from such Sox2-positive CGNPs in mice.", "Independent of their endogenous Sox2 expression, constitutive activation of Shh signaling in CGNPs resulted in significantly enhanced proliferation and ectopic expression of Sox2 in vitro and Sox2-positive medulloblastoma in vivo.", "Genetic ablation of Sox2 from murine medulloblastoma did not affect survival, most likely due to a compensatory overexpression of Sox3.", "However, acute deletion of Sox2 from primary cultures of CGNPs with constitutive Shh signaling significantly decreased proliferation, whereas overexpression of Sox2 enhanced proliferation of murine medulloblastoma cells.", "We conclude that Sox2 is a marker for Shh-dependent medulloblastomas where it is required and sufficient to drive tumor cell proliferation."], "title": "Sox2 requirement in sonic hedgehog-associated medulloblastoma."}
{"paper_id": 27003208, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Abnormal aggregation of Tau in glial cells has been reported in Alzheimer's disease (AD) and other tauopathies; however, the pathological significance of these aggregates remains unsolved to date. In this study, we evaluated whether full-length Tau (Tau441) and its aspartic acid421-truncated Tau variant (Tau421) produce alterations in the normal organization of the cytoskeleton and plasma membrane (PM) when transiently expressed in cultured C6-glial cells. Forty-eight hours post-transfection, abnormal microtubule bundling was observed in the majority of the cells, which expressed either Tau441 or Tau421. Moreover, both variants of Tau produced extensive PM blebbing associated with cortical redistribution of filamentous actin (F-Actin). These effects were reverted when Tau-expressing cells were incubated with drugs that depolymerize F-Actin. In addition, when glial cells showing Tau-induced PM blebbing were incubated with inhibitors of the Rho-associated protein kinase (ROCK) signaling pathway, both formation of abnormal PM blebs and F-Actin remodeling were avoided. All of these effects were initiated upstream by abnormal Tau-induced microtubule bundling, which may release the microtubule-bound guanine nucleotide exchange factor-H1 (GEF-H1) into the cytoplasm in order to activate its major effector RhoA-GTPase. These results may represent a new mechanism of Tau toxicity in which Tau-induced microtubule bundling produces activation of the Rho-GTPase-ROCK pathway that in turn mediates the remodeling of cortical Actin and PM blebbing. In AD and other tauopathies, these Tau-induced abnormalities may occur and contribute to the impairment of glial activity.", "journal": "Journal of Alzheimer's disease : JAD", "sentences": ["Abnormal aggregation of Tau in glial cells has been reported in Alzheimer's disease (AD) and other tauopathies; however, the pathological significance of these aggregates remains unsolved to date.", "In this study, we evaluated whether full-length Tau (Tau441) and its aspartic acid421-truncated Tau variant (Tau421) produce alterations in the normal organization of the cytoskeleton and plasma membrane (PM) when transiently expressed in cultured C6-glial cells.", "Forty-eight hours post-transfection, abnormal microtubule bundling was observed in the majority of the cells, which expressed either Tau441 or Tau421.", "Moreover, both variants of Tau produced extensive PM blebbing associated with cortical redistribution of filamentous actin (F-Actin).", "These effects were reverted when Tau-expressing cells were incubated with drugs that depolymerize F-Actin.", "In addition, when glial cells showing Tau-induced PM blebbing were incubated with inhibitors of the Rho-associated protein kinase (ROCK) signaling pathway, both formation of abnormal PM blebs and F-Actin remodeling were avoided.", "All of these effects were initiated upstream by abnormal Tau-induced microtubule bundling, which may release the microtubule-bound guanine nucleotide exchange factor-H1 (GEF-H1) into the cytoplasm in order to activate its major effector RhoA-GTPase.", "These results may represent a new mechanism of Tau toxicity in which Tau-induced microtubule bundling produces activation of the Rho-GTPase-ROCK pathway that in turn mediates the remodeling of cortical Actin and PM blebbing.", "In AD and other tauopathies, these Tau-induced abnormalities may occur and contribute to the impairment of glial activity."], "title": "Expression of Tau Produces Aberrant Plasma Membrane Blebbing in Glial Cells Through RhoA-ROCK-Dependent F-Actin Remodeling."}
{"paper_id": 25880832, "labels": ["0", "0", "0", "1", "0", "1"], "abstract": "Dopamine (DA) is a neurotransmitter which plays a key role in the life science. Self-assembled Au@Ag nanorod dimers based on aptamers were developed for ultrasensitive dopamine detection. The electronic field was significantly enhanced by the addition of silver shell coating on the surface of Au NR dimer. The results displayed that Au@Ag NR dimers were ideal building blocks for constructing the SERS substrates with prominent Raman enhancement effects. It was found that with using this Surface-enhanced Raman scattering (SERS)-encoded this sensing system, a limit of detection of 0.006 pM and a wide linear range of 0.01-10 pM for dopamine detection were obtained. Our work open up a new avenue for the diagnosis and drug-discovery programs.", "journal": "Biosensors & bioelectronics", "sentences": ["Dopamine (DA) is a neurotransmitter which plays a key role in the life science.", "Self-assembled Au@Ag nanorod dimers based on aptamers were developed for ultrasensitive dopamine detection.", "The electronic field was significantly enhanced by the addition of silver shell coating on the surface of Au NR dimer.", "The results displayed that Au@Ag NR dimers were ideal building blocks for constructing the SERS substrates with prominent Raman enhancement effects.", "It was found that with using this Surface-enhanced Raman scattering (SERS)-encoded this sensing system, a limit of detection of 0.006 pM and a wide linear range of 0.01-10 pM for dopamine detection were obtained.", "Our work open up a new avenue for the diagnosis and drug-discovery programs."], "title": "SERS-active Au@Ag nanorod dimers for ultrasensitive dopamine detection."}
{"paper_id": 26264005, "labels": ["0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "This cross-sectional study examined differences in children's health behaviors during school term (ST) versus school holiday (SH: June-July) and how associations changed when weather characteristics were considered. Children aged 5-18 years (n = 406) from a subtropical climate reported behaviors over 20 months. Multivariable regression models controlling for age, sex, race and body mass index z-score (BMIz) were used to examine associations between SH and each behavior. A second model included heat index, precipitation and daylight hours. Strenuous activity, moderate activity, total activity and TV viewing were significantly higher during SH than ST. After adjusting for weather characteristics, total activity remained significantly higher during SH, but the association with TV viewing was attenuated. Youth surveyed during high precipitation were significantly less likely to meet physical activity guidelines. There were no significant associations between SH and meeting sleep, physical activity or screen-time guidelines. Weather characteristics influenced associations between SH and youth's physical activity and TV viewing.", "journal": "International journal of environmental research and public health", "sentences": ["This cross-sectional study examined differences in children's health behaviors during school term (ST) versus school holiday (SH: June-July) and how associations changed when weather characteristics were considered.", "Children aged 5-18 years (n = 406) from a subtropical climate reported behaviors over 20 months.", "Multivariable regression models controlling for age, sex, race and body mass index z-score (BMIz) were used to examine associations between SH and each behavior.", "A second model included heat index, precipitation and daylight hours.", "Strenuous activity, moderate activity, total activity and TV viewing were significantly higher during SH than ST. After adjusting for weather characteristics, total activity remained significantly higher during SH, but the association with TV viewing was attenuated.", "Youth surveyed during high precipitation were significantly less likely to meet physical activity guidelines.", "There were no significant associations between SH and meeting sleep, physical activity or screen-time guidelines.", "Weather characteristics influenced associations between SH and youth's physical activity and TV viewing."], "title": "School Term vs. School Holiday: Associations with Children's Physical Activity, Screen-Time, Diet and Sleep."}
{"paper_id": 25003710, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Previous studies found that prostaglandins in skeletal muscle play a role in evoking the exercise pressor reflex; however the role played by prostaglandins in the spinal transmission of the reflex is not known. We determined, therefore, whether or not spinal blockade of cyclooxygenase (COX) activity and/or spinal blockade of endoperoxide (EP) 2 or 4 receptors attenuated the exercise pressor reflex in decerebrated rats. We first established that intrathecal doses of a non-specific COX inhibitor Ketorolac (100 \u03bcg in 10 \u03bcl), a COX-2-specific inhibitor Celecoxib (100 \u03bcg in 10 \u03bcl), an EP2 antagonist PF-04418948 (10 \u03bcg in 10 \u03bcl), and an EP4 antagonist L-161,982 (4 \u03bcg in 10 \u03bcl) effectively attenuated the pressor responses to intrathecal injections of arachidonic acid (100 \u03bcg in 10 \u03bcl), EP2 agonist Butaprost (4 ng in 10 \u03bcl), and EP4 agonist TCS 2510 (6.25 \u03bcg in 2.5 \u03bcl), respectively. Once effective doses were established, we statically contracted the hind limb before and after intrathecal injections of Ketorolac, Celecoxib, the EP2 antagonist and the EP4 antagonist. We found that Ketorolac significantly attenuated the pressor response to static contraction (before Ketorolac: 23 \u00b1 5 mmHg, after Ketorolac 14 \u00b1 5 mmHg; p<0.05) whereas Celecoxib had no effect. We also found that 8 \u03bcg of L-161,982, but not 4 \u03bcg of L-161,982, significantly attenuated the pressor response to static contraction (before L-161,982: 21 \u00b1 4 mmHg, after L-161,982 12 \u00b1 3 mmHg; p<0.05), whereas PF-04418948 (10 \u03bcg) had no effect. We conclude that spinal COX-1, but not COX-2, plays a role in evoking the exercise pressor reflex, and that the spinal prostaglandins produced by this enzyme are most likely activating spinal EP4 receptors, but not EP2 receptors.", "journal": "Neuroscience", "sentences": ["Previous studies found that prostaglandins in skeletal muscle play a role in evoking the exercise pressor reflex; however the role played by prostaglandins in the spinal transmission of the reflex is not known.", "We determined, therefore, whether or not spinal blockade of cyclooxygenase (COX) activity and/or spinal blockade of endoperoxide (EP) 2 or 4 receptors attenuated the exercise pressor reflex in decerebrated rats.", "We first established that intrathecal doses of a non-specific COX inhibitor Ketorolac (100 \u03bcg in 10 \u03bcl), a COX-2-specific inhibitor Celecoxib (100 \u03bcg in 10 \u03bcl), an EP2 antagonist PF-04418948 (10 \u03bcg in 10 \u03bcl), and an EP4 antagonist L-161,982 (4 \u03bcg in 10 \u03bcl) effectively attenuated the pressor responses to intrathecal injections of arachidonic acid (100 \u03bcg in 10 \u03bcl), EP2 agonist Butaprost (4 ng in 10 \u03bcl), and EP4 agonist TCS 2510 (6.25 \u03bcg in 2.5 \u03bcl), respectively.", "Once effective doses were established, we statically contracted the hind limb before and after intrathecal injections of Ketorolac, Celecoxib, the EP2 antagonist and the EP4 antagonist.", "We found that Ketorolac significantly attenuated the pressor response to static contraction (before Ketorolac: 23 \u00b1 5 mmHg, after Ketorolac 14 \u00b1 5 mmHg; p<0.05) whereas Celecoxib had no effect.", "We also found that 8 \u03bcg of L-161,982, but not 4 \u03bcg of L-161,982, significantly attenuated the pressor response to static contraction (before L-161,982: 21 \u00b1 4 mmHg, after L-161,982 12 \u00b1 3 mmHg; p<0.05), whereas PF-04418948 (10 \u03bcg) had no effect.", "We conclude that spinal COX-1, but not COX-2, plays a role in evoking the exercise pressor reflex, and that the spinal prostaglandins produced by this enzyme are most likely activating spinal EP4 receptors, but not EP2 receptors."], "title": "Role of prostaglandins in spinal transmission of the exercise pressor reflex in decerebrated rats."}
{"paper_id": 25115387, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic malignancy characterized by dismal prognosis and overall poor therapeutic response. Since the biology of BPDCN is barely understood, our study aims to shed light on the genetic make-up of these highly malignant tumors. Using targeted high-coverage massive parallel sequencing, we investigated 50 common cancer genes in 33 BPDCN samples. We detected point mutations in NRAS (27.3% of cases), ATM (21.2%), MET, KRAS, IDH2, KIT (9.1% each), APC and RB1 (6.1%), as well as in VHL, BRAF, MLH1, TP53 and RET1 (3% each). Moreover, NRAS-, KRAS- and ATM-mutations were found to be mutually exclusive and we observed recurrent mutations in NRAS, IDH2, APC and ATM. CDKN2A deletions were detected in 27.3% of the cases followed by deletions of RB1 (9.1%), PTEN and TP53 (3% each). The mutual exclusive distribution of some mutations may point to different subgroups of BPDCN whose biological significance remains to be explored.", "journal": "Oncotarget", "sentences": ["Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic malignancy characterized by dismal prognosis and overall poor therapeutic response.", "Since the biology of BPDCN is barely understood, our study aims to shed light on the genetic make-up of these highly malignant tumors.", "Using targeted high-coverage massive parallel sequencing, we investigated 50 common cancer genes in 33 BPDCN samples.", "We detected point mutations in NRAS (27.3% of cases), ATM (21.2%), MET, KRAS, IDH2, KIT (9.1% each), APC and RB1 (6.1%), as well as in VHL, BRAF, MLH1, TP53 and RET1 (3% each).", "Moreover, NRAS-, KRAS- and ATM-mutations were found to be mutually exclusive and we observed recurrent mutations in NRAS, IDH2, APC and ATM.", "CDKN2A deletions were detected in 27.3% of the cases followed by deletions of RB1 (9.1%), PTEN and TP53 (3% each).", "The mutual exclusive distribution of some mutations may point to different subgroups of BPDCN whose biological significance remains to be explored."], "title": "Targeted ultra-deep sequencing reveals recurrent and mutually exclusive mutations of cancer genes in blastic plasmacytoid dendritic cell neoplasm."}
{"paper_id": 25912430, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "Aging represents a major risk factor for numerous illnesses that are of increasing importance to society, including two of the most prevalent: diabetes and Alzheimer's disease. Studies have shown that diabetes is a risk factor for spontaneous Alzheimer's disease. While these studies suggest that diabetes can contribute to Alzheimer's disease, the implications of AD on diabetes are practically unexplored. The major mediator of the pathophysiological effects, the A\u03b242 peptide, has been shown to enter neurons and lead to an alteration of the intracellular distribution of the molecular motor myosin Vb. Myosin Vb functions in memory and learning by participating in the strengthening of the long-term potentiation (LTP) of synaptic transmissions. It has also been implicated in the translocation of the glucose transporter, GLUT4, to the plasma membrane in response to insulin, a process that is defective in diabetes. Here, the effect on GLUT4 upon entry of the A\u03b242 peptide into cultured chick retinal neurons was explored. The results suggest an alteration in distribution and a reduced level at the cell surface, as well as an increased colocalization with myosin Vb, which can partially explain the changes in glucose metabolism associated with AD. It is also shown that the presence of the A\u03b240 peptide inhibits the internalization of the A\u03b242 peptide in cultured cells. Together, the results provide additional targets for the development of therapeutics against the progression and effects of Alzheimer's disease.", "journal": "Brain research", "sentences": ["Aging represents a major risk factor for numerous illnesses that are of increasing importance to society, including two of the most prevalent: diabetes and Alzheimer's disease.", "Studies have shown that diabetes is a risk factor for spontaneous Alzheimer's disease.", "While these studies suggest that diabetes can contribute to Alzheimer's disease, the implications of AD on diabetes are practically unexplored.", "The major mediator of the pathophysiological effects, the A\u03b242 peptide, has been shown to enter neurons and lead to an alteration of the intracellular distribution of the molecular motor myosin Vb.", "Myosin Vb functions in memory and learning by participating in the strengthening of the long-term potentiation (LTP) of synaptic transmissions.", "It has also been implicated in the translocation of the glucose transporter, GLUT4, to the plasma membrane in response to insulin, a process that is defective in diabetes.", "Here, the effect on GLUT4 upon entry of the A\u03b242 peptide into cultured chick retinal neurons was explored.", "The results suggest an alteration in distribution and a reduced level at the cell surface, as well as an increased colocalization with myosin Vb, which can partially explain the changes in glucose metabolism associated with AD.", "It is also shown that the presence of the A\u03b240 peptide inhibits the internalization of the A\u03b242 peptide in cultured cells.", "Together, the results provide additional targets for the development of therapeutics against the progression and effects of Alzheimer's disease."], "title": "Exogenous \u03b2-amyloid peptide interferes with GLUT4 localization in neurons."}
{"paper_id": 26239071, "labels": ["0", "0", "0", "0", "1", "0", "0"], "abstract": "We expressed a glucansucrase, DsrI, from Leuconostoc mesenteroides that catalyzes formation of water-insoluble glucans from sucrose using a nisin-controlled gene expression system in Lactococcus lactis. These polymers have potential for production of biodegradable gels, fibers, and films. We optimized production of DsrI using several different background vectors, signal peptides, strains, induction conditions, and bioreactor parameters to increase extracellular accumulation. Optimal production of the enzyme utilized a high-copy plasmid, pMSP3535H3, which contains a nisin immunity gene, L. lactis LM0230, and bioreactors maintained at pH 6.0 to stabilize the enzyme. We were able to significantly improve growth using the lactic acid inhibitor heme and by continuous removal of lactic acid with anion exchange resins, but enzyme production was less than the controls. The recombinant enzyme under optimized conditions accumulated in the culture medium to approximately 380\u00a0mg/L, which was over 150-fold higher compared to the native L. mesenteroides strain. Methods are also included for purification of DsrI utilizing the glucan-binding domain of the enzyme.", "journal": "Applied microbiology and biotechnology", "sentences": ["We expressed a glucansucrase, DsrI, from Leuconostoc mesenteroides that catalyzes formation of water-insoluble glucans from sucrose using a nisin-controlled gene expression system in Lactococcus lactis.", "These polymers have potential for production of biodegradable gels, fibers, and films.", "We optimized production of DsrI using several different background vectors, signal peptides, strains, induction conditions, and bioreactor parameters to increase extracellular accumulation.", "Optimal production of the enzyme utilized a high-copy plasmid, pMSP3535H3, which contains a nisin immunity gene, L. lactis LM0230, and bioreactors maintained at pH 6.0 to stabilize the enzyme.", "We were able to significantly improve growth using the lactic acid inhibitor heme and by continuous removal of lactic acid with anion exchange resins, but enzyme production was less than the controls.", "The recombinant enzyme under optimized conditions accumulated in the culture medium to approximately 380\u00a0mg/L, which was over 150-fold higher compared to the native L. mesenteroides strain.", "Methods are also included for purification of DsrI utilizing the glucan-binding domain of the enzyme."], "title": "Secreted expression of Leuconostoc mesenteroides glucansucrase in Lactococcus lactis for the production of insoluble glucans."}
{"paper_id": 26578595, "labels": ["0", "0", "0", "1", "1"], "abstract": "Oxidation of a DNA thymine to 5-hydroxymethyluracil is one of several recently discovered epigenetic modifications. Here, we report the results of nanopore translocation experiments and molecular dynamics simulations that provide insight into the impact of this modification on the structure and dynamics of DNA. When transported through ultrathin solid-state nanopores, short DNA fragments containing thymine modifications were found to exhibit distinct, reproducible features in their transport characteristics that differentiate them from unmodified molecules. Molecular dynamics simulations suggest that 5-hydroxymethyluracil alters the flexibility and hydrophilicity of the DNA molecules, which may account for the differences observed in our nanopore translocation experiments. The altered physico-chemical properties of DNA produced by the thymine modifications may have implications for recognition and processing of such modifications by regulatory DNA-binding proteins.", "journal": "Nucleic acids research", "sentences": ["Oxidation of a DNA thymine to 5-hydroxymethyluracil is one of several recently discovered epigenetic modifications.", "Here, we report the results of nanopore translocation experiments and molecular dynamics simulations that provide insight into the impact of this modification on the structure and dynamics of DNA.", "When transported through ultrathin solid-state nanopores, short DNA fragments containing thymine modifications were found to exhibit distinct, reproducible features in their transport characteristics that differentiate them from unmodified molecules.", "Molecular dynamics simulations suggest that 5-hydroxymethyluracil alters the flexibility and hydrophilicity of the DNA molecules, which may account for the differences observed in our nanopore translocation experiments.", "The altered physico-chemical properties of DNA produced by the thymine modifications may have implications for recognition and processing of such modifications by regulatory DNA-binding proteins."], "title": "Hydroxymethyluracil modifications enhance the flexibility and hydrophilicity of double-stranded DNA."}
{"paper_id": 26266386, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "Both dexmedetomidine and sufentanil modulate spinal analgesia by different mechanisms, and yet no human studies are available on their combination for analgesia during the first 72 hours after abdominal hysterectomy.This CONSORT-prospective, randomized, double-blinded, controlled trial sought to evaluate the safety and efficacy of the combination of dexmedetomidine and sufentanil in intravenous patient-controlled analgesia (PCA) for 72 hours after abdominal hysterectomy.Ninety women undergoing total abdominal hysterectomy were divided into 3 equal groups that received sufentanil (Group C; 0.02\u200a\u03bcg/kg/h), sufentanil plus dexmedetomidine (Group D1; 0.02\u200a\u03bcg/kg/h, each), or sufentanil (0.02\u200a\u03bcg/kg/h) plus dexmedetomidine (0.05\u200a\u03bcg/kg/h) (Group D2) for 72 hours after surgery in this double-blinded, randomized study. The primary outcome measure was the postoperative sufentanil consumption, whereas the secondary outcome measures were pain intensity (visual analogue scale), requirement of narcotic drugs during the operation, level of sedation, Bruggrmann comfort scale, and concerning adverse effects.The postoperative sufentanil consumption was significantly lower in Groups D1 and D2 than in Group C during the observation period (P\u200a<\u200a0.05), but lower in Group D2 than in Group D1 at 24, 48, and 72 hours after surgery (P\u200a<\u200a0.05). The heart rate after intubation and incision was lower in Groups D1 and D2 than in Group C (P\u200a<\u200a0.05). On arrival at the recovery room, Groups D1 and D2 had lower mean blood pressure than Group C (P\u200a<\u200a0.05). The intraoperative requirement of sevoflurane was 30% lesser in Groups D1 and D2 than in Group C. The sedation levels were greater in Groups D1 and D2 during the first hour (P\u200a<\u200a0.05). Compared with Groups C and D1, Group D2 showed lower levels of the overall incidence of nausea and vomiting (P\u200a<\u200a0.05).Among the tested PCA options, the addition of dexmedetomidine (0.05\u200a\u03bcg/kg/h) and sufentanil (0.02\u200a\u03bcg/kg/h) showed better analgesic effect and greater patient satisfaction without other clinically relevant side effects for patients undergoing hysterectomy during the first 72 hours after abdominal hysterectomy.", "journal": "Medicine", "sentences": ["Both dexmedetomidine and sufentanil modulate spinal analgesia by different mechanisms, and yet no human studies are available on their combination for analgesia during the first 72 hours after abdominal hysterectomy.This CONSORT-prospective, randomized, double-blinded, controlled trial sought to evaluate the safety and efficacy of the combination of dexmedetomidine and sufentanil in intravenous patient-controlled analgesia (PCA) for 72 hours after abdominal hysterectomy.Ninety women undergoing total abdominal hysterectomy were divided into 3 equal groups that received sufentanil (Group C; 0.02\u200a\u03bcg/kg/h), sufentanil plus dexmedetomidine (Group D1; 0.02\u200a\u03bcg/kg/h, each), or sufentanil (0.02\u200a\u03bcg/kg/h) plus dexmedetomidine (0.05\u200a\u03bcg/kg/h) (Group D2) for 72 hours after surgery in this double-blinded, randomized study.", "The primary outcome measure was the postoperative sufentanil consumption, whereas the secondary outcome measures were pain intensity (visual analogue scale), requirement of narcotic drugs during the operation, level of sedation, Bruggrmann comfort scale, and concerning adverse effects.The postoperative sufentanil consumption was significantly lower in Groups D1 and D2 than in Group C during the observation period (P\u200a<\u200a0.05), but lower in Group D2 than in Group D1 at 24, 48, and 72 hours after surgery (P\u200a<\u200a0.05).", "The heart rate after intubation and incision was lower in Groups D1 and D2 than in Group C (P\u200a<\u200a0.05).", "On arrival at the recovery room, Groups D1 and D2 had lower mean blood pressure than Group C (P\u200a<\u200a0.05).", "The intraoperative requirement of sevoflurane was 30% lesser in Groups D1 and D2 than in Group C. The sedation levels were greater in Groups D1 and D2 during the first hour (P\u200a<\u200a0.05).", "Compared with Groups C and D1, Group D2 showed lower levels of the overall incidence of nausea and vomiting (P\u200a<\u200a0.05).Among the tested PCA options, the addition of dexmedetomidine (0.05\u200a\u03bcg/kg/h) and sufentanil (0.02\u200a\u03bcg/kg/h) showed better analgesic effect and greater patient satisfaction without other clinically relevant side effects for patients undergoing hysterectomy during the first 72 hours after abdominal hysterectomy."], "title": "Dexmedetomidine in Postoperative Analgesia in Patients Undergoing Hysterectomy: A CONSORT-Prospective, Randomized, Controlled Trial."}
{"paper_id": 22174948, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "New non-invasive technologies allow direct measurement of heart rates (and thus, developmental rates) of embryos. We applied these methods to a diverse array of oviparous reptiles (24 species of lizards, 18 snakes, 11 turtles, 1 crocodilian), to identify general influences on cardiac rates during embryogenesis. Heart rates increased with ambient temperature in all lineages, but (at the same temperature) were faster in lizards and turtles than in snakes and crocodilians. We analysed these data within a phylogenetic framework. Embryonic heart rates were faster in species with smaller adult sizes, smaller egg sizes, and shorter incubation periods. Phylogenetic changes in heart rates were negatively correlated with concurrent changes in adult body mass and residual incubation period among the lizards, snakes (especially within pythons) and crocodilians. The total number of embryonic heart beats between oviposition and hatching was lower in squamates than in turtles or the crocodilian. Within squamates, embryonic iguanians and gekkonids required more heartbeats to complete development than did embryos of the other squamate families that we tested. These differences plausibly reflect phylogenetic divergence in the proportion of embryogenesis completed before versus after laying.", "journal": "PloS one", "sentences": ["New non-invasive technologies allow direct measurement of heart rates (and thus, developmental rates) of embryos.", "We applied these methods to a diverse array of oviparous reptiles (24 species of lizards, 18 snakes, 11 turtles, 1 crocodilian), to identify general influences on cardiac rates during embryogenesis.", "Heart rates increased with ambient temperature in all lineages, but (at the same temperature) were faster in lizards and turtles than in snakes and crocodilians.", "We analysed these data within a phylogenetic framework.", "Embryonic heart rates were faster in species with smaller adult sizes, smaller egg sizes, and shorter incubation periods.", "Phylogenetic changes in heart rates were negatively correlated with concurrent changes in adult body mass and residual incubation period among the lizards, snakes (especially within pythons) and crocodilians.", "The total number of embryonic heart beats between oviposition and hatching was lower in squamates than in turtles or the crocodilian.", "Within squamates, embryonic iguanians and gekkonids required more heartbeats to complete development than did embryos of the other squamate families that we tested.", "These differences plausibly reflect phylogenetic divergence in the proportion of embryogenesis completed before versus after laying."], "title": "Patterns of interspecific variation in the heart rates of embryonic reptiles."}
{"paper_id": 25423171, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Beneficial or adverse effects of Static Magnetic Fields (SMFs) are a large concern for the scientific community. In particular, the effect of SMF exposure during anticancer therapies still needs to be fully elucidated. Here, we evaluate the effects of SMF at induction levels that cisPt-treated cancer patients experience during the imaging process conducted in Low field (200-500 mT), Open field (300-700 mT) and/or inhomogeneous High field (1.5-3 T) Magnetic Resonance Imaging (MRI) machines. Human adrenergic neuroblastoma SH-SY5Y cells treated with 0.1 \u00b5M cisPt (i.e. the lowest concentration capable of inducing apoptosis) were exposed to SMF and their response was studied in vitro. Exposure of 0.1 \u00b5M cisPt-treated cells to SMF for 2 h decreased cell viability (30%) and caused overexpression of the apoptosis-related cleaved caspase-3 protein (46%). Furthermore, increase in ROS (Reactive Oxygen Species) production (23%) and reduction in the number of mitochondria vs controls were seen. The sole exposure of SMF for up to 24 h had no effect on cell viability but increased ROS production and modified cellular shape. On the other hand, the toxicity of cisPt was significantly prevented during 24 h exposure to SMF as shown by the levels of cell viability, cleaved caspase-3 and ROS production. In conclusion, due to the cytoprotective effect of 31.7-232.0 mT SMF on low-cisPt-concentration-treated SH-SY5Y cells, our data suggest that exposure to various sources of SMF in cancer patients under a cisPt regimen should be strictly controlled.", "journal": "PloS one", "sentences": ["Beneficial or adverse effects of Static Magnetic Fields (SMFs) are a large concern for the scientific community.", "In particular, the effect of SMF exposure during anticancer therapies still needs to be fully elucidated.", "Here, we evaluate the effects of SMF at induction levels that cisPt-treated cancer patients experience during the imaging process conducted in Low field (200-500 mT), Open field (300-700 mT) and/or inhomogeneous High field (1.5-3 T) Magnetic Resonance Imaging (MRI) machines.", "Human adrenergic neuroblastoma SH-SY5Y cells treated with 0.1 \u00b5M cisPt (i.e.", "the lowest concentration capable of inducing apoptosis) were exposed to SMF and their response was studied in vitro.", "Exposure of 0.1 \u00b5M cisPt-treated cells to SMF for 2 h decreased cell viability (30%) and caused overexpression of the apoptosis-related cleaved caspase-3 protein (46%).", "Furthermore, increase in ROS (Reactive Oxygen Species) production (23%) and reduction in the number of mitochondria vs controls were seen.", "The sole exposure of SMF for up to 24 h had no effect on cell viability but increased ROS production and modified cellular shape.", "On the other hand, the toxicity of cisPt was significantly prevented during 24 h exposure to SMF as shown by the levels of cell viability, cleaved caspase-3 and ROS production.", "In conclusion, due to the cytoprotective effect of 31.7-232.0 mT SMF on low-cisPt-concentration-treated SH-SY5Y cells, our data suggest that exposure to various sources of SMF in cancer patients under a cisPt regimen should be strictly controlled."], "title": "Impact of inhomogeneous static magnetic field (31.7-232.0 mT) exposure on human neuroblastoma SH-SY5Y cells during cisplatin administration."}
{"paper_id": 23922378, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Low reticulocytosis, indicating reduced red blood cell (RBC) output, is an important feature of severe malarial anemia. Evidence supports a role for Plasmodium products, especially hemozoin (Hz), in suppressed erythropoiesis during malaria, but the mechanism(s) involved remains unclear. Here, we demonstrated that low reticulocytosis and suppressed erythropoietin (Epo)-induced erythropoiesis are features of malarial anemia in Plasmodium yoelii- and Plasmodium berghei ANKA-infected mice, similar to our previous observations in Plasmodium chabaudi AS-infected mice. The magnitude of decreases in RBC was a reflection of parasitemia level, but low reticulocytosis was evident despite differences in parasitemia, clinical manifestation, and infection outcome. Schizont extracts and Hz from P. falciparum and P. yoelii and synthetic Hz suppressed Epo-induced proliferation of erythroid precursors in vitro but did not inhibit RBC maturation. To determine whether Hz contributes to malarial anemia, P. yoelii-derived or synthetic Hz was administered to naive mice, and the development of anemia, reticulocytosis, and RBC turnover was determined. Parasite-derived Hz induced significant decreases in RBC and increased RBC turnover with compensatory reticulocytosis, but anemia was not as severe as that in infected mice. Our findings suggest that parasite factors, including Hz, contribute to severe malarial anemia by suppressing Epo-induced proliferation of erythroid precursors.", "journal": "The Journal of infectious diseases", "sentences": ["Low reticulocytosis, indicating reduced red blood cell (RBC) output, is an important feature of severe malarial anemia.", "Evidence supports a role for Plasmodium products, especially hemozoin (Hz), in suppressed erythropoiesis during malaria, but the mechanism(s) involved remains unclear.", "Here, we demonstrated that low reticulocytosis and suppressed erythropoietin (Epo)-induced erythropoiesis are features of malarial anemia in Plasmodium yoelii- and Plasmodium berghei ANKA-infected mice, similar to our previous observations in Plasmodium chabaudi AS-infected mice.", "The magnitude of decreases in RBC was a reflection of parasitemia level, but low reticulocytosis was evident despite differences in parasitemia, clinical manifestation, and infection outcome.", "Schizont extracts and Hz from P. falciparum and P. yoelii and synthetic Hz suppressed Epo-induced proliferation of erythroid precursors in vitro but did not inhibit RBC maturation.", "To determine whether Hz contributes to malarial anemia, P. yoelii-derived or synthetic Hz was administered to naive mice, and the development of anemia, reticulocytosis, and RBC turnover was determined.", "Parasite-derived Hz induced significant decreases in RBC and increased RBC turnover with compensatory reticulocytosis, but anemia was not as severe as that in infected mice.", "Our findings suggest that parasite factors, including Hz, contribute to severe malarial anemia by suppressing Epo-induced proliferation of erythroid precursors."], "title": "Plasmodium products contribute to severe malarial anemia by inhibiting erythropoietin-induced proliferation of erythroid precursors."}
{"paper_id": 26802899, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "An estimated 1.5 billion people worldwide are deficient in the skeletal muscle protein \u03b1-actinin-3 due to homozygosity for the common ACTN3 R577X polymorphism. \u03b1-Actinin-3 deficiency influences muscle performance in elite athletes and the general population. The sarcomeric \u03b1-actinins were originally characterised as scaffold proteins at the muscle Z-line. Through studying the Actn3 knockout mouse and \u03b1-actinin-3 deficient humans, significant progress has been made in understanding how ACTN3 genotype alters muscle function, leading to an appreciation of the diverse roles that \u03b1-actinins play in muscle. The \u03b1-actinins interact with a number of partner proteins, which broadly fall into three biological pathways-structural, metabolic and signalling. Differences in functioning of these pathways have been identified in \u03b1-actinin-3 deficient muscle that together contributes to altered muscle performance in mice and humans. Here we discuss new insights that have been made in understanding the molecular mechanisms that underlie the consequences of \u03b1-actinin-3 deficiency.", "journal": "Biochimica et biophysica acta", "sentences": ["An estimated 1.5 billion people worldwide are deficient in the skeletal muscle protein \u03b1-actinin-3 due to homozygosity for the common ACTN3 R577X polymorphism.", "\u03b1-Actinin-3 deficiency influences muscle performance in elite athletes and the general population.", "The sarcomeric \u03b1-actinins were originally characterised as scaffold proteins at the muscle Z-line.", "Through studying the Actn3 knockout mouse and \u03b1-actinin-3 deficient humans, significant progress has been made in understanding how ACTN3 genotype alters muscle function, leading to an appreciation of the diverse roles that \u03b1-actinins play in muscle.", "The \u03b1-actinins interact with a number of partner proteins, which broadly fall into three biological pathways-structural, metabolic and signalling.", "Differences in functioning of these pathways have been identified in \u03b1-actinin-3 deficient muscle that together contributes to altered muscle performance in mice and humans.", "Here we discuss new insights that have been made in understanding the molecular mechanisms that underlie the consequences of \u03b1-actinin-3 deficiency."], "title": "How does \u03b1-actinin-3 deficiency alter muscle function? Mechanistic insights into ACTN3, the 'gene for speed'."}
{"paper_id": 25656414, "labels": ["0", "0", "0", "1", "0", "0", "1"], "abstract": "Single-atom/molecule manipulation for fabricating an atomic-scale switching device is a promising technology for nanoelectronics. So far, scanning probe microscopy studies have demonstrated several atomic-scale switches, mostly in cryogenic environments. Although a high-performance switch at room temperature is essential for practical applications, this remains a challenging obstacle to overcome. Here we report a room-temperature switch composed of a binary atom cluster on the semiconductor surface. Distinctly different types of manipulation techniques enable the construction of an atomically defined binary cluster and the electronic switching of the conformations, either unidirectionally or bidirectionally. The switching process involves a complex rearrangement of multiple atoms in concerted manner. Such a feature is strikingly different from any switches mediated by single-atom/molecule processes that have been previously reported.", "journal": "Nature communications", "sentences": ["Single-atom/molecule manipulation for fabricating an atomic-scale switching device is a promising technology for nanoelectronics.", "So far, scanning probe microscopy studies have demonstrated several atomic-scale switches, mostly in cryogenic environments.", "Although a high-performance switch at room temperature is essential for practical applications, this remains a challenging obstacle to overcome.", "Here we report a room-temperature switch composed of a binary atom cluster on the semiconductor surface.", "Distinctly different types of manipulation techniques enable the construction of an atomically defined binary cluster and the electronic switching of the conformations, either unidirectionally or bidirectionally.", "The switching process involves a complex rearrangement of multiple atoms in concerted manner.", "Such a feature is strikingly different from any switches mediated by single-atom/molecule processes that have been previously reported."], "title": "Room-temperature-concerted switch made of a binary atom cluster."}
{"paper_id": 26448650, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The East Continental Shelf (ECS) of Brazil is a hotspot of endemism and biodiversity of reef biota in the South Atlantic, hosting a number of Marine Protected Areas (MPAs). Connectivity of MPAs through larval dispersal influences recruitment, population dynamics, genetic structure and biogeography in coral reef ecosystems. Connectivity of protected reef ecosystem in the ECS was investigated with a hydrodynamic model (ROMS) forcing an Individual Based Model (IBM-Ichthyop), and used groupers (genus Mycteroperca) as functional group. The hydrodynamic output from ROMS was compared with satellite data and showed good agreement with observed surface fields. Eggs were released, in IBM experiments, from April to September along six years (2002-2007) in five MPAs along the ECS. Intrannual variability in recruitment and self-recruitment of grouper larvae was observed, as well as a negative correlation of these population parameters with total Kinetic Energy (KE) used as a metric of the physical environment. Higher KE leads to increased offshore advection of larvae, reduced total recruitment and connectivity of MPAs. Our results indicate high and uni-directional connectivity between MPAs from north to south influenced by the Brazil Current flowing in the same direction. Results also showed that some MPAs act predominantly as \"sink\" while others are mainly \"source\" areas.", "journal": "PloS one", "sentences": ["The East Continental Shelf (ECS) of Brazil is a hotspot of endemism and biodiversity of reef biota in the South Atlantic, hosting a number of Marine Protected Areas (MPAs).", "Connectivity of MPAs through larval dispersal influences recruitment, population dynamics, genetic structure and biogeography in coral reef ecosystems.", "Connectivity of protected reef ecosystem in the ECS was investigated with a hydrodynamic model (ROMS) forcing an Individual Based Model (IBM-Ichthyop), and used groupers (genus Mycteroperca) as functional group.", "The hydrodynamic output from ROMS was compared with satellite data and showed good agreement with observed surface fields.", "Eggs were released, in IBM experiments, from April to September along six years (2002-2007) in five MPAs along the ECS.", "Intrannual variability in recruitment and self-recruitment of grouper larvae was observed, as well as a negative correlation of these population parameters with total Kinetic Energy (KE) used as a metric of the physical environment.", "Higher KE leads to increased offshore advection of larvae, reduced total recruitment and connectivity of MPAs.", "Our results indicate high and uni-directional connectivity between MPAs from north to south influenced by the Brazil Current flowing in the same direction.", "Results also showed that some MPAs act predominantly as \"sink\" while others are mainly \"source\" areas."], "title": "Connectivity of Marine Protected Areas and Its Relation with Total Kinetic Energy."}
{"paper_id": 24050404, "labels": ["0", "0", "0", "1", "1", "1"], "abstract": "The CYFIP1/SRA1 gene is located in a chromosomal region linked to various neurological disorders, including intellectual disability, autism, and schizophrenia. CYFIP1 plays a dual role in two apparently unrelated processes, inhibiting local protein synthesis and favoring actin remodeling. Here, we show that brain-derived neurotrophic factor (BDNF)-driven synaptic signaling releases CYFIP1 from the translational inhibitory complex, triggering translation of target mRNAs and shifting CYFIP1 into the WAVE regulatory complex. Active Rac1 alters the CYFIP1 conformation, as demonstrated by intramolecular FRET, and is key in changing the equilibrium of the two complexes. CYFIP1 thus orchestrates the two molecular cascades, protein translation and actin polymerization, each of which is necessary for correct spine morphology in neurons. The CYFIP1 interactome reveals many interactors associated with brain disorders, opening new perspectives to define regulatory pathways shared by neurological disabilities characterized by spine dysmorphogenesis.", "journal": "Neuron", "sentences": ["The CYFIP1/SRA1 gene is located in a chromosomal region linked to various neurological disorders, including intellectual disability, autism, and schizophrenia.", "CYFIP1 plays a dual role in two apparently unrelated processes, inhibiting local protein synthesis and favoring actin remodeling.", "Here, we show that brain-derived neurotrophic factor (BDNF)-driven synaptic signaling releases CYFIP1 from the translational inhibitory complex, triggering translation of target mRNAs and shifting CYFIP1 into the WAVE regulatory complex.", "Active Rac1 alters the CYFIP1 conformation, as demonstrated by intramolecular FRET, and is key in changing the equilibrium of the two complexes.", "CYFIP1 thus orchestrates the two molecular cascades, protein translation and actin polymerization, each of which is necessary for correct spine morphology in neurons.", "The CYFIP1 interactome reveals many interactors associated with brain disorders, opening new perspectives to define regulatory pathways shared by neurological disabilities characterized by spine dysmorphogenesis."], "title": "CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic spine formation."}
{"paper_id": 21224412, "labels": ["0", "0", "0", "0", "1"], "abstract": "RA-inducible gene I (RIG-I/DDX58) has been shown to activate IFN-\u03b2 promoter stimulator 1 (IPS-1) on recognizing cytoplasmic viral RNAs. It is unclear how RIG-I functions within the IFN and/or RA signaling process in acute myeloid leukemia (AML) cells, however, where obvious RIG-I induction is observed. Here, we show that the RIG-I induction functionally contributes to IFN-\u03b1 plus RA-triggered growth inhibition of AML cells. Interestingly, although RIG-I induction itself is under the regulation of STAT1, a major IFN intracellular signal mediator, under circumstances in which it does not stimulate IPS-1, it conversely augments STAT1 activation to induce IFN-stimulatory gene expression and inhibit leukemia cell proliferation. Thus, our results unveil a previously undescribed RIG-I activity in regulating the cellular proliferation of leukemia cells via STAT1, which is independent of its classic role of sensing viral invasion to trigger type I IFN transcription.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["RA-inducible gene I (RIG-I/DDX58) has been shown to activate IFN-\u03b2 promoter stimulator 1 (IPS-1) on recognizing cytoplasmic viral RNAs.", "It is unclear how RIG-I functions within the IFN and/or RA signaling process in acute myeloid leukemia (AML) cells, however, where obvious RIG-I induction is observed.", "Here, we show that the RIG-I induction functionally contributes to IFN-\u03b1 plus RA-triggered growth inhibition of AML cells.", "Interestingly, although RIG-I induction itself is under the regulation of STAT1, a major IFN intracellular signal mediator, under circumstances in which it does not stimulate IPS-1, it conversely augments STAT1 activation to induce IFN-stimulatory gene expression and inhibit leukemia cell proliferation.", "Thus, our results unveil a previously undescribed RIG-I activity in regulating the cellular proliferation of leukemia cells via STAT1, which is independent of its classic role of sensing viral invasion to trigger type I IFN transcription."], "title": "RA-inducible gene-I induction augments STAT1 activation to inhibit leukemia cell proliferation."}
{"paper_id": 23576790, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The effects of selectively different experience of eye contact and gaze behaviour on the early development of five sighted infants of blind parents were investigated. Infants were assessed longitudinally at 6-10, 12-15 and 24-47 months. Face scanning and gaze following were assessed using eye tracking. In addition, established measures of autistic-like behaviours and standardized tests of cognitive, motor and linguistic development, as well as observations of naturalistic parent-child interaction were collected. These data were compared with those obtained from a larger group of sighted infants of sighted parents. Infants with blind parents did not show an overall decrease in eye contact or gaze following when they observed sighted adults on video or in live interactions, nor did they show any autistic-like behaviours. However, they directed their own eye gaze somewhat less frequently towards their blind mothers and also showed improved performance in visual memory and attention at younger ages. Being reared with significantly reduced experience of eye contact and gaze behaviour does not preclude sighted infants from developing typical gaze processing and other social-communication skills. Indeed, the need to switch between different types of communication strategy may actually enhance other skills during development.", "journal": "Proceedings. Biological sciences / The Royal Society", "sentences": ["The effects of selectively different experience of eye contact and gaze behaviour on the early development of five sighted infants of blind parents were investigated.", "Infants were assessed longitudinally at 6-10, 12-15 and 24-47 months.", "Face scanning and gaze following were assessed using eye tracking.", "In addition, established measures of autistic-like behaviours and standardized tests of cognitive, motor and linguistic development, as well as observations of naturalistic parent-child interaction were collected.", "These data were compared with those obtained from a larger group of sighted infants of sighted parents.", "Infants with blind parents did not show an overall decrease in eye contact or gaze following when they observed sighted adults on video or in live interactions, nor did they show any autistic-like behaviours.", "However, they directed their own eye gaze somewhat less frequently towards their blind mothers and also showed improved performance in visual memory and attention at younger ages.", "Being reared with significantly reduced experience of eye contact and gaze behaviour does not preclude sighted infants from developing typical gaze processing and other social-communication skills.", "Indeed, the need to switch between different types of communication strategy may actually enhance other skills during development."], "title": "The importance of the eyes: communication skills in infants of blind parents."}
{"paper_id": 26271045, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Current molecular methods to characterize microalgae are time-intensive and expensive. Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) may represent a rapid and economical alternative approach. The objectives of this study were to determine whether MALDI-TOF MS can be used to: 1) differentiate microalgae at the species and strain levels and 2) characterize simple microalgal mixtures. A common protein extraction sample preparation method was used to facilitate rapid mass spectrometry-based analysis of 31 microalgae. Each yielded spectra containing between 6 and 56 peaks in the m/z 2,000 to 20,000 range. The taxonomic resolution of this approach appeared higher than that of 18S rDNA sequence analysis. For example, two strains of Scenedesmus acutus differed only by two 18S rDNA nucleotides, but yielded distinct MALDI-TOF mass spectra. Mixtures of two and three microalgae yielded relatively complex spectra that contained peaks associated with members of each mixture. Interestingly, though, mixture-specific peaks were observed at m/z 11,048 and 11,230. Our results suggest that MALDI-TOF MS affords rapid characterization of individual microalgae and simple microalgal mixtures.", "journal": "PloS one", "sentences": ["Current molecular methods to characterize microalgae are time-intensive and expensive.", "Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) may represent a rapid and economical alternative approach.", "The objectives of this study were to determine whether MALDI-TOF MS can be used to: 1) differentiate microalgae at the species and strain levels and 2) characterize simple microalgal mixtures.", "A common protein extraction sample preparation method was used to facilitate rapid mass spectrometry-based analysis of 31 microalgae.", "Each yielded spectra containing between 6 and 56 peaks in the m/z 2,000 to 20,000 range.", "The taxonomic resolution of this approach appeared higher than that of 18S rDNA sequence analysis.", "For example, two strains of Scenedesmus acutus differed only by two 18S rDNA nucleotides, but yielded distinct MALDI-TOF mass spectra.", "Mixtures of two and three microalgae yielded relatively complex spectra that contained peaks associated with members of each mixture.", "Interestingly, though, mixture-specific peaks were observed at m/z 11,048 and 11,230.", "Our results suggest that MALDI-TOF MS affords rapid characterization of individual microalgae and simple microalgal mixtures."], "title": "Rapid Characterization of Microalgae and Microalgae Mixtures Using Matrix-Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS)."}
{"paper_id": 25504045, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "We report siblings of consanguineous parents with an infantile-onset neurodegenerative disorder manifesting a predominant sensorimotor axonal neuropathy, optic atrophy and cognitive deficit. We used homozygosity mapping to identify an \u223c12-Mbp interval identical by descent (IBD) between the affected individuals on chromosome 3q13.13-21.1 with an LOD score of 2.31. We combined family-based whole-exome and whole-genome sequencing of parents and affected siblings and, after filtering of likely non-pathogenic variants, identified a unique missense variant in syntaxin-binding protein 5-like (STXBP5L c.3127G>A, p.Val1043Ile [CCDS43137.1]) in the IBD interval. Considering other modes of inheritance, we also found compound heterozygous variants in FMNL3 (c.114G>C, p.Phe38Leu and c.1372T>G, p.Ile458Leu [CCDS44874.1]) located on chromosome 12. STXBP5L (or Tomosyn-2) is expressed in the central and peripheral nervous system and is known to inhibit neurotransmitter release through inhibition of the formation of the SNARE complexes between synaptic vesicles and the plasma membrane. FMNL3 is expressed more widely and is a formin family protein that is involved in the regulation of cell morphology and cytoskeletal organization. The STXBP5L p.Val1043Ile variant enhanced inhibition of exocytosis in comparison with wild-type (WT) STXBP5L. Furthermore, WT STXBP5L, but not variant STXBP5L, promoted axonal outgrowth in manipulated mouse primary hippocampal neurons. However, the FMNL3 p.Phe38Leu and p.Ile458Leu variants showed minimal effects in these cells. Collectively, our clinical, genetic and molecular data suggest that the IBD variant in STXBP5L is the likely cause of the disorder.", "journal": "Human molecular genetics", "sentences": ["We report siblings of consanguineous parents with an infantile-onset neurodegenerative disorder manifesting a predominant sensorimotor axonal neuropathy, optic atrophy and cognitive deficit.", "We used homozygosity mapping to identify an \u223c12-Mbp interval identical by descent (IBD) between the affected individuals on chromosome 3q13.13-21.1 with an LOD score of 2.31.", "We combined family-based whole-exome and whole-genome sequencing of parents and affected siblings and, after filtering of likely non-pathogenic variants, identified a unique missense variant in syntaxin-binding protein 5-like (STXBP5L c.3127G>A, p.Val1043Ile [CCDS43137.1]) in the IBD interval.", "Considering other modes of inheritance, we also found compound heterozygous variants in FMNL3 (c.114G>C, p.Phe38Leu and c.1372T>G, p.Ile458Leu [CCDS44874.1]) located on chromosome 12.", "STXBP5L (or Tomosyn-2) is expressed in the central and peripheral nervous system and is known to inhibit neurotransmitter release through inhibition of the formation of the SNARE complexes between synaptic vesicles and the plasma membrane.", "FMNL3 is expressed more widely and is a formin family protein that is involved in the regulation of cell morphology and cytoskeletal organization.", "The STXBP5L p.Val1043Ile variant enhanced inhibition of exocytosis in comparison with wild-type (WT) STXBP5L.", "Furthermore, WT STXBP5L, but not variant STXBP5L, promoted axonal outgrowth in manipulated mouse primary hippocampal neurons.", "However, the FMNL3 p.Phe38Leu and p.Ile458Leu variants showed minimal effects in these cells.", "Collectively, our clinical, genetic and molecular data suggest that the IBD variant in STXBP5L is the likely cause of the disorder."], "title": "Homozygous mutation of STXBP5L explains an autosomal recessive infantile-onset neurodegenerative disorder."}
{"paper_id": 26059866, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Takotsubo cardiomyopathy (TC) is generally recognized to have a good prognosis, but it can be rarely aggravated. We sought to investigate the clinical characteristics of TC and to evaluate the effects of clinical parameters on predicting delayed recovery. We enrolled consecutive patients with TC admitted to our hospital from January 1991 to January 2014. We defined delayed recovery as sustained left ventricular (LV) systolic dysfunction requiring \u226510\u00a0days for LV contraction to normalize. We screened 9,630 patients suspected of having acute coronary syndrome, and 60 patients (0.6%; men/women: 20/38; mean age: 69.7 \u00b1 11.9\u00a0years) were diagnosed as having TC. With the exception of 2 patients who died before LV systolic function improved, all patients recovered from LV systolic dysfunction within 6\u00a0months; the mean recovery period was 9.1 \u00b1 11.5\u00a0days. Twenty-eight patients met the criteria for delayed recovery. Univariate logistic regression analyses showed that male gender, LV end-diastolic diameter, brain natriuretic peptide (BNP) level, body mass index (BMI), and nonuse of calcium channel blockers (CCBs) at baseline were associated with delayed recovery. Among these factors, multiple logistic regression analysis identified BNP \u2265238 pg/ml (relative risk [RR] 11.6, p\u00a0= 0.002) and nonuse of CCBs (RR 22.2, p\u00a0= 0.0014) as independent risk factors for delayed recovery and leptosomic build (BMI <20\u00a0kg/m(2)) as an independent predictor of rapid recovery (RR 0.11, p\u00a0= 0.02). In conclusion, BNP level, BMI, and use of CCBs are associated with recovery speed of LV systolic function in patients with TC.", "journal": "The American journal of cardiology", "sentences": ["Takotsubo cardiomyopathy (TC) is generally recognized to have a good prognosis, but it can be rarely aggravated.", "We sought to investigate the clinical characteristics of TC and to evaluate the effects of clinical parameters on predicting delayed recovery.", "We enrolled consecutive patients with TC admitted to our hospital from January 1991 to January 2014.", "We defined delayed recovery as sustained left ventricular (LV) systolic dysfunction requiring \u226510\u00a0days for LV contraction to normalize.", "We screened 9,630 patients suspected of having acute coronary syndrome, and 60 patients (0.6%; men/women: 20/38; mean age: 69.7 \u00b1 11.9\u00a0years) were diagnosed as having TC.", "With the exception of 2 patients who died before LV systolic function improved, all patients recovered from LV systolic dysfunction within 6\u00a0months; the mean recovery period was 9.1 \u00b1 11.5\u00a0days.", "Twenty-eight patients met the criteria for delayed recovery.", "Univariate logistic regression analyses showed that male gender, LV end-diastolic diameter, brain natriuretic peptide (BNP) level, body mass index (BMI), and nonuse of calcium channel blockers (CCBs) at baseline were associated with delayed recovery.", "Among these factors, multiple logistic regression analysis identified BNP \u2265238 pg/ml (relative risk [RR] 11.6, p\u00a0= 0.002) and nonuse of CCBs (RR 22.2, p\u00a0= 0.0014) as independent risk factors for delayed recovery and leptosomic build (BMI <20\u00a0kg/m(2)) as an independent predictor of rapid recovery (RR 0.11, p\u00a0= 0.02).", "In conclusion, BNP level, BMI, and use of CCBs are associated with recovery speed of LV systolic function in patients with TC."], "title": "Impact of Brain Natriuretic Peptide, Calcium Channel Blockers, and Body Mass Index on Recovery Time from Left Ventricular Systolic Dysfunction in Patients With Takotsubo Cardiomyopathy."}
{"paper_id": 21636790, "labels": ["0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "During the past several decades, numerous reports from disparate geographical areas have documented an increased frequency of \"bleaching\" in reef-forming corals. The phenomenon, triggered by increased sea surface temperatures, occurs when the cnidarian hosts digest and/or expel their intracellular, photosynthetic dinoflagellate symbionts (\"zooxanthellae\" in the genus Symbiodinium). Although coral bleaching is often followed by the death of the animal hosts, in some cases, the animal survives and can be repopulated with viable zooxanthellae. The physiological factors determining the ability of the coral to survive bleaching events are poorly understood. In this study, we experimentally established that bleaching and death of the host animal involve a caspase-mediated apoptotic cascade induced by reactive oxygen species produced primarily by the algal symbionts. In addition, we demonstrate that, although some corals naturally suppress caspase activity and significantly reduce caspase concentration under high temperatures as a mechanism to prevent colony death from apoptosis, even sensitive corals can be prevented from dying by application of exogenous inhibitors of caspases. Our results indicate that variability in response to thermal stress in corals is determined by a four-element, combinatorial genetic matrix intrinsic to the specific symbiotic association. Based on our experimental data, we present a working model in which the phenotypic expression of this symbiont/host relationship places a selective pressure on the symbiotic association. The model predicts the survival of the host animals in which the caspase-mediated apoptotic cascade is down-regulated.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["During the past several decades, numerous reports from disparate geographical areas have documented an increased frequency of \"bleaching\" in reef-forming corals.", "The phenomenon, triggered by increased sea surface temperatures, occurs when the cnidarian hosts digest and/or expel their intracellular, photosynthetic dinoflagellate symbionts (\"zooxanthellae\" in the genus Symbiodinium).", "Although coral bleaching is often followed by the death of the animal hosts, in some cases, the animal survives and can be repopulated with viable zooxanthellae.", "The physiological factors determining the ability of the coral to survive bleaching events are poorly understood.", "In this study, we experimentally established that bleaching and death of the host animal involve a caspase-mediated apoptotic cascade induced by reactive oxygen species produced primarily by the algal symbionts.", "In addition, we demonstrate that, although some corals naturally suppress caspase activity and significantly reduce caspase concentration under high temperatures as a mechanism to prevent colony death from apoptosis, even sensitive corals can be prevented from dying by application of exogenous inhibitors of caspases.", "Our results indicate that variability in response to thermal stress in corals is determined by a four-element, combinatorial genetic matrix intrinsic to the specific symbiotic association.", "Based on our experimental data, we present a working model in which the phenotypic expression of this symbiont/host relationship places a selective pressure on the symbiotic association.", "The model predicts the survival of the host animals in which the caspase-mediated apoptotic cascade is down-regulated."], "title": "Apoptosis and the selective survival of host animals following thermal bleaching in zooxanthellate corals."}
{"paper_id": 24045342, "labels": ["0", "0", "0", "1", "0", "0", "1"], "abstract": "Facial length is one of the best known examples of heterochrony. Changes in the timing of facial growth have been invoked as a mechanism for the origin of our short human face from our long-faced extinct relatives. Such heterochronic changes arguably permit great evolutionary flexibility, allowing the mammalian face to be remodelled simply by modifying postnatal growth. Here we present new data that show that this mechanism is significantly constrained by adult size. Small mammals are more brachycephalic (short faced) than large ones, despite the putative independence between adult size and facial length. This pattern holds across four phenotypic lineages: antelopes, fruit bats, tree squirrels and mongooses. Despite the apparent flexibility of facial heterochrony, growth of the face is linked to absolute size and introduces what seems to be a loose but clade-wide mammalian constraint on head shape.", "journal": "Nature communications", "sentences": ["Facial length is one of the best known examples of heterochrony.", "Changes in the timing of facial growth have been invoked as a mechanism for the origin of our short human face from our long-faced extinct relatives.", "Such heterochronic changes arguably permit great evolutionary flexibility, allowing the mammalian face to be remodelled simply by modifying postnatal growth.", "Here we present new data that show that this mechanism is significantly constrained by adult size.", "Small mammals are more brachycephalic (short faced) than large ones, despite the putative independence between adult size and facial length.", "This pattern holds across four phenotypic lineages: antelopes, fruit bats, tree squirrels and mongooses.", "Despite the apparent flexibility of facial heterochrony, growth of the face is linked to absolute size and introduces what seems to be a loose but clade-wide mammalian constraint on head shape."], "title": "Larger mammals have longer faces because of size-related constraints on skull form."}
{"paper_id": 24657971, "labels": ["0", "1", "1", "0", "0", "1"], "abstract": "Loss of secreted phospholipase A2 receptor (PLA2R1) has recently been found to render human primary cells more resistant to senescence whereas increased PLA2R1 expression is able to induce cell cycle arrest, cancer cell death or blockage of cancer cell transformation in vitro, suggesting that PLA2R1 displays tumor suppressive activities. Here we report that PLA2R1 expression strongly decreases in samples of human renal cell carcinoma (RCC). Knockdown of PLA2R1 increases renal cancer cell tumorigenicity supporting a role of PLA2R1 loss to promote in vivo RCC growth. Most RCC result from Von Hippel-Lindau (VHL) tumor suppressor loss-of-function and subsequent gain-of-function of the oncogenic HIF-2alpha/c-MYC pathway. Here, by genetically manipulating VHL, HIF-2alpha and c-MYC, we demonstrate that loss of VHL, stabilization of HIF-2alpha and subsequent increased c-MYC activity, binding and transcriptional repression, through induction of PLA2R1 DNA methylation closed to PLA2R1 transcriptional start site, results in decreased PLA2R1 transcription. Our results describe for the first time an oncogenic pathway leading to PLA2R1 transcriptional repression and the importance of this repression for tumor growth.", "journal": "Oncotarget", "sentences": ["Loss of secreted phospholipase A2 receptor (PLA2R1) has recently been found to render human primary cells more resistant to senescence whereas increased PLA2R1 expression is able to induce cell cycle arrest, cancer cell death or blockage of cancer cell transformation in vitro, suggesting that PLA2R1 displays tumor suppressive activities.", "Here we report that PLA2R1 expression strongly decreases in samples of human renal cell carcinoma (RCC).", "Knockdown of PLA2R1 increases renal cancer cell tumorigenicity supporting a role of PLA2R1 loss to promote in vivo RCC growth.", "Most RCC result from Von Hippel-Lindau (VHL) tumor suppressor loss-of-function and subsequent gain-of-function of the oncogenic HIF-2alpha/c-MYC pathway.", "Here, by genetically manipulating VHL, HIF-2alpha and c-MYC, we demonstrate that loss of VHL, stabilization of HIF-2alpha and subsequent increased c-MYC activity, binding and transcriptional repression, through induction of PLA2R1 DNA methylation closed to PLA2R1 transcriptional start site, results in decreased PLA2R1 transcription.", "Our results describe for the first time an oncogenic pathway leading to PLA2R1 transcriptional repression and the importance of this repression for tumor growth."], "title": "Repression of PLA2R1 by c-MYC and HIF-2alpha promotes cancer growth."}
{"paper_id": 27538720, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "The widespread use of fuel cells is currently limited by the lack of efficient and cost-effective catalysts for the oxygen reduction reaction. Iron-based non-precious metal catalysts exhibit promising activity and stability, as an alternative to state-of-the-art platinum catalysts. However, the identity of the active species in non-precious metal catalysts remains elusive, impeding the development of new catalysts. Here we demonstrate the reversible deactivation and reactivation of an iron-based non-precious metal oxygen reduction catalyst achieved using high-temperature gas-phase chlorine and hydrogen treatments. In addition, we observe a decrease in catalyst heterogeneity following treatment with chlorine and hydrogen, using M\u00f6ssbauer and X-ray absorption spectroscopy. Our study reveals that protected sites adjacent to iron nanoparticles are responsible for the observed activity and stability of the catalyst. These findings may allow for the design and synthesis of enhanced non-precious metal oxygen reduction catalysts with a higher density of active sites.", "journal": "Nature communications", "sentences": ["The widespread use of fuel cells is currently limited by the lack of efficient and cost-effective catalysts for the oxygen reduction reaction.", "Iron-based non-precious metal catalysts exhibit promising activity and stability, as an alternative to state-of-the-art platinum catalysts.", "However, the identity of the active species in non-precious metal catalysts remains elusive, impeding the development of new catalysts.", "Here we demonstrate the reversible deactivation and reactivation of an iron-based non-precious metal oxygen reduction catalyst achieved using high-temperature gas-phase chlorine and hydrogen treatments.", "In addition, we observe a decrease in catalyst heterogeneity following treatment with chlorine and hydrogen, using M\u00f6ssbauer and X-ray absorption spectroscopy.", "Our study reveals that protected sites adjacent to iron nanoparticles are responsible for the observed activity and stability of the catalyst.", "These findings may allow for the design and synthesis of enhanced non-precious metal oxygen reduction catalysts with a higher density of active sites."], "title": "Identification of carbon-encapsulated iron nanoparticles as active species in non-precious metal oxygen reduction catalysts."}
{"paper_id": 25801118, "labels": ["0", "0", "0", "0", "1", "0"], "abstract": "Growth factors, long studied for their involvement in neuronal development and plasticity, also regulate responses to drugs of abuse, including alcohol. This review details the intricate interaction between the Brain-Derived Neurotrophic Factor (BDNF) and alcohol, and provides evidence to suggest that corticostriatal BDNF signaling acts to keep alcohol drinking in moderation. Specifically, we describe studies in rodent models suggesting that moderate consumption of alcohol increases BDNF levels in the dorsal striatum, which in turn act to suppress alcohol intake by activating a Mitogen-Activated Protein Kinase (MAPK)-dependent genomic mechanism. We further provide data to suggest that alcohol intake levels escalate when the endogenous corticostriatal BDNF pathway becomes dysregulated. Finally, we summarize recent studies suggesting that specific microRNAs targeting BDNF mRNA in the medial prefrontal cortex (mPFC) regulate the breakdown of the protective corticostriatal BDNF pathway. This article is part of a Special Issue entitled SI:Addiction circuits.", "journal": "Brain research", "sentences": ["Growth factors, long studied for their involvement in neuronal development and plasticity, also regulate responses to drugs of abuse, including alcohol.", "This review details the intricate interaction between the Brain-Derived Neurotrophic Factor (BDNF) and alcohol, and provides evidence to suggest that corticostriatal BDNF signaling acts to keep alcohol drinking in moderation.", "Specifically, we describe studies in rodent models suggesting that moderate consumption of alcohol increases BDNF levels in the dorsal striatum, which in turn act to suppress alcohol intake by activating a Mitogen-Activated Protein Kinase (MAPK)-dependent genomic mechanism.", "We further provide data to suggest that alcohol intake levels escalate when the endogenous corticostriatal BDNF pathway becomes dysregulated.", "Finally, we summarize recent studies suggesting that specific microRNAs targeting BDNF mRNA in the medial prefrontal cortex (mPFC) regulate the breakdown of the protective corticostriatal BDNF pathway.", "This article is part of a Special Issue entitled SI:Addiction circuits."], "title": "Corticostriatal BDNF and alcohol addiction."}
{"paper_id": 25953561, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "A novel nonenzymatic sensor was developed for glucose detection by the use of ionic liquid derived fibrillated mesoporous carbon (IFMC) decorated with palladium nanoparticles (PdNPs). PdNPs were uniformly decorated on IFMC and then the prepared nano-hybrid material (Pd@IFMC) was drop cast on the surface of a glassy carbon electrode to fabricate a glucose sensor. The prepared Pd@IFMC showed excellent electrocatalytic activity towards glucose oxidation. An oxidation peak at about +0.40 V vs. Ag|AgCl|KClsat was observed for glucose on the fabricated sensor in alkaline solution. The oxidation peak current intensity was linear towards glucose in the concentration range between 1 and 55 mM (R(2) = 0.9958) with a detection limit of 0.2 mM. The relative standard deviation (RSD) for repetitive measurements (n = 6) of 5 mM of glucose was of 5.3%. The fabricated sensor showed a number of great features such as ease of fabrication, wide linear range, excellent reproducibility, satisfactory operational stability and outstanding resistance towards interfering species such as ascorbic acid, uric acid, dopamine, fructose and chloride.", "journal": "Materials science & engineering. C, Materials for biological applications", "sentences": ["A novel nonenzymatic sensor was developed for glucose detection by the use of ionic liquid derived fibrillated mesoporous carbon (IFMC) decorated with palladium nanoparticles (PdNPs).", "PdNPs were uniformly decorated on IFMC and then the prepared nano-hybrid material (Pd@IFMC) was drop cast on the surface of a glassy carbon electrode to fabricate a glucose sensor.", "The prepared Pd@IFMC showed excellent electrocatalytic activity towards glucose oxidation.", "An oxidation peak at about +0.40 V vs. Ag|AgCl|KClsat was observed for glucose on the fabricated sensor in alkaline solution.", "The oxidation peak current intensity was linear towards glucose in the concentration range between 1 and 55 mM (R(2) = 0.9958) with a detection limit of 0.2 mM.", "The relative standard deviation (RSD) for repetitive measurements (n = 6) of 5 mM of glucose was of 5.3%.", "The fabricated sensor showed a number of great features such as ease of fabrication, wide linear range, excellent reproducibility, satisfactory operational stability and outstanding resistance towards interfering species such as ascorbic acid, uric acid, dopamine, fructose and chloride."], "title": "Fabrication of a nonenzymatic glucose sensor using Pd-nanoparticles decorated ionic liquid derived fibrillated mesoporous carbon."}
{"paper_id": 26523099, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "Since their discovery two decades ago, CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) have become the subject of intense investigation by immunologists. Unlike other T cells, which promote an immune response, Tregs actively inhibit inflammation when activated by their cognate antigen, thus raising hope that these cells could be engineered into a highly targeted, antigen-specific, immunosuppressant therapy. Although Tregs represent less than 10% of circulating CD4(+)T cells, they have been shown to play an essential role in preventing or limiting inflammation in a variety of animal models and human diseases. In particular, spontaneous intestinal inflammation has been shown to occur in the absence of Tregs, suggesting that there may be a Treg defect central to the pathogenesis of human inflammatory bowel disease (IBD). However, over the past decade, multiple groups have reported no qualitative or quantitative deficits in Tregs from the intestines and blood of IBD patients to explain why these cells fail to regulate inflammation in Crohn's disease and ulcerative colitis. In this review, we will discuss the history of Tregs, what is known about them in IBD, and what progress and obstacles have been seen with efforts to employ them for therapeutic benefit.", "journal": "World journal of gastroenterology", "sentences": ["Since their discovery two decades ago, CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) have become the subject of intense investigation by immunologists.", "Unlike other T cells, which promote an immune response, Tregs actively inhibit inflammation when activated by their cognate antigen, thus raising hope that these cells could be engineered into a highly targeted, antigen-specific, immunosuppressant therapy.", "Although Tregs represent less than 10% of circulating CD4(+)T cells, they have been shown to play an essential role in preventing or limiting inflammation in a variety of animal models and human diseases.", "In particular, spontaneous intestinal inflammation has been shown to occur in the absence of Tregs, suggesting that there may be a Treg defect central to the pathogenesis of human inflammatory bowel disease (IBD).", "However, over the past decade, multiple groups have reported no qualitative or quantitative deficits in Tregs from the intestines and blood of IBD patients to explain why these cells fail to regulate inflammation in Crohn's disease and ulcerative colitis.", "In this review, we will discuss the history of Tregs, what is known about them in IBD, and what progress and obstacles have been seen with efforts to employ them for therapeutic benefit."], "title": "Promises and paradoxes of regulatory T cells in inflammatory bowel disease."}
{"paper_id": 24376746, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are progressive multisystemic disorders caused by similar mutations at two different genetic loci. The common key feature of DM pathogenesis is nuclear accumulation of mutant RNA which causes aberrant alternative splicing of specific pre-mRNAs by altering the functions of two RNA binding proteins, MBNL1 and CUGBP1. However, DM1 and DM2 show disease-specific features that make them clearly separate diseases suggesting that other cellular and molecular pathways may be involved. In this study we have analysed the histopathological, and biomolecular features of skeletal muscle biopsies from DM1 and DM2 patients in relation to presenting phenotypes to better define the molecular pathogenesis. Particularly, the expression of CUGBP1 protein has been examined to clarify if this factor may act as modifier of disease-specific manifestations in DM. The results indicate that the splicing and muscle pathological alterations observed are related to the clinical phenotype both in DM1 and in DM2 and that CUGBP1 seems to play a role in classic DM1 but not in DM2. In conclusion, our results indicate that multisystemic disease spectrum of DM pathologies may not be explained only by spliceopathy thus confirming that the molecular pathomechanism of DM is more complex than that actually suggested.", "journal": "PloS one", "sentences": ["Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are progressive multisystemic disorders caused by similar mutations at two different genetic loci.", "The common key feature of DM pathogenesis is nuclear accumulation of mutant RNA which causes aberrant alternative splicing of specific pre-mRNAs by altering the functions of two RNA binding proteins, MBNL1 and CUGBP1.", "However, DM1 and DM2 show disease-specific features that make them clearly separate diseases suggesting that other cellular and molecular pathways may be involved.", "In this study we have analysed the histopathological, and biomolecular features of skeletal muscle biopsies from DM1 and DM2 patients in relation to presenting phenotypes to better define the molecular pathogenesis.", "Particularly, the expression of CUGBP1 protein has been examined to clarify if this factor may act as modifier of disease-specific manifestations in DM.", "The results indicate that the splicing and muscle pathological alterations observed are related to the clinical phenotype both in DM1 and in DM2 and that CUGBP1 seems to play a role in classic DM1 but not in DM2.", "In conclusion, our results indicate that multisystemic disease spectrum of DM pathologies may not be explained only by spliceopathy thus confirming that the molecular pathomechanism of DM is more complex than that actually suggested."], "title": "Overexpression of CUGBP1 in skeletal muscle from adult classic myotonic dystrophy type 1 but not from myotonic dystrophy type 2."}
{"paper_id": 26886917, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "At old age, humans generally have declining muscle mass and increased fat deposition, which can increase the risk of developing cardiometabolic diseases. While regular physical activity postpones these age-related derangements, this is not always possible in the elderly because of disabilities or risk of injury. Whole-body vibration (WBV) training may be considered as an alternative to physical activity particularly in the frail population. To explore this possibility, we characterized whole-body and organ-specific metabolic processes in 6-month and 25-month old mice, over a period of 14 weeks of WBV versus sham training. WBV training tended to increase blood glucose turnover rates and stimulated hepatic glycogen utilization during fasting irrespective of age. WBV was effective in reducing white fat mass and hepatic triglyceride content only in old but not in young mice and these reductions were related to upregulation of hepatic mitochondrial uncoupling of metabolism (assessed by high-resolution respirometry) and increased expression of uncoupling protein 2. Because these changes occurred independent of changes in food intake and whole-body metabolic rate (assessed by indirect calorimetry), the liver-specific effects of WBV may be a primary mechanism to improve metabolic health during aging, rather than that it is a consequence of alterations in energy balance.", "journal": "PloS one", "sentences": ["At old age, humans generally have declining muscle mass and increased fat deposition, which can increase the risk of developing cardiometabolic diseases.", "While regular physical activity postpones these age-related derangements, this is not always possible in the elderly because of disabilities or risk of injury.", "Whole-body vibration (WBV) training may be considered as an alternative to physical activity particularly in the frail population.", "To explore this possibility, we characterized whole-body and organ-specific metabolic processes in 6-month and 25-month old mice, over a period of 14 weeks of WBV versus sham training.", "WBV training tended to increase blood glucose turnover rates and stimulated hepatic glycogen utilization during fasting irrespective of age.", "WBV was effective in reducing white fat mass and hepatic triglyceride content only in old but not in young mice and these reductions were related to upregulation of hepatic mitochondrial uncoupling of metabolism (assessed by high-resolution respirometry) and increased expression of uncoupling protein 2.", "Because these changes occurred independent of changes in food intake and whole-body metabolic rate (assessed by indirect calorimetry), the liver-specific effects of WBV may be a primary mechanism to improve metabolic health during aging, rather than that it is a consequence of alterations in energy balance."], "title": "Whole-Body Vibration Partially Reverses Aging-Induced Increases in Visceral Adiposity and Hepatic Lipid Storage in Mice."}
{"paper_id": 26870991, "labels": ["0", "0", "0", "0", "0", "1", "1", "1", "0", "1"], "abstract": "Cancer stem cells (CSCs) play an important role in tumor initiation, progression, therapeutic failure and tumor relapse. In this study, we evaluated the efficacy of the thiazole derivative 3-methylcyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl]hydrazone (CPTH6), a novel pCAF and Gcn5 histone acetyltransferase inhibitor, as a small molecule that preferentially targets lung cancer stem-like cells (LCSCs) derived from non-small cell lung cancer (NSCLC) patients. Notably, although CPTH6 inhibits the growth of both LCSC and NSCLC cell lines, LCSCs exhibit greater growth inhibition than established NSCLC cells. Growth inhibitory effect of CPTH6 in LCSC lines is primarily due to apoptosis induction. Of note, differentiated progeny of LCSC lines is more resistant to CPTH6 in terms of loss of cell viability and reduction of protein acetylation, when compared to their undifferentiated counterparts. Interestingly, in LCSC lines CPTH6 treatment is also associated with a reduction of stemness markers. By using different HAT inhibitors we provide clear evidence that inhibition of HAT confers a strong preferential inhibitory effect on cell viability of undifferentiated LCSC lines when compared to their differentiated progeny. In vivo, CPTH6 is able to inhibit the growth of LCSC-derived xenografts and to reduce cancer stem cell content in treated tumors, as evidenced by marked reduction of tumor-initiating capacity in limiting dilution assays. Strikingly, the ability of CPTH6 to inhibit tubulin acetylation is also confirmed in vivo. Overall, our studies propose histone acetyltransferase inhibition as an attractive target for cancer therapy of NSCLC.", "journal": "Oncotarget", "sentences": ["Cancer stem cells (CSCs) play an important role in tumor initiation, progression, therapeutic failure and tumor relapse.", "In this study, we evaluated the efficacy of the thiazole derivative 3-methylcyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl]hydrazone (CPTH6), a novel pCAF and Gcn5 histone acetyltransferase inhibitor, as a small molecule that preferentially targets lung cancer stem-like cells (LCSCs) derived from non-small cell lung cancer (NSCLC) patients.", "Notably, although CPTH6 inhibits the growth of both LCSC and NSCLC cell lines, LCSCs exhibit greater growth inhibition than established NSCLC cells.", "Growth inhibitory effect of CPTH6 in LCSC lines is primarily due to apoptosis induction.", "Of note, differentiated progeny of LCSC lines is more resistant to CPTH6 in terms of loss of cell viability and reduction of protein acetylation, when compared to their undifferentiated counterparts.", "Interestingly, in LCSC lines CPTH6 treatment is also associated with a reduction of stemness markers.", "By using different HAT inhibitors we provide clear evidence that inhibition of HAT confers a strong preferential inhibitory effect on cell viability of undifferentiated LCSC lines when compared to their differentiated progeny.", "In vivo, CPTH6 is able to inhibit the growth of LCSC-derived xenografts and to reduce cancer stem cell content in treated tumors, as evidenced by marked reduction of tumor-initiating capacity in limiting dilution assays.", "Strikingly, the ability of CPTH6 to inhibit tubulin acetylation is also confirmed in vivo.", "Overall, our studies propose histone acetyltransferase inhibition as an attractive target for cancer therapy of NSCLC."], "title": "Histone acetyltransferase inhibitor CPTH6 preferentially targets lung cancer stem-like cells."}
{"paper_id": 26719277, "labels": ["0", "0", "0", "1", "0", "0", "1", "1", "1"], "abstract": "UNLABELLED\nImpairment of Nef function, including reduced CD4 downregulation, was described in a subset of HIV-1-infected individuals that control viral replication without antiretroviral treatment (elite controllers [EC]). Elimination of HIV-1-infected cells by antibody-dependent cellular cytotoxicity (ADCC) requires the presence of envelope glycoproteins (Env) in the CD4-bound conformation, raising the possibility that accumulating CD4 at the surface of virus-infected cells in EC could interact with Env and thereby sensitize these cells to ADCC. We observed a significant increase in the exposure of Env epitopes targeted by ADCC-mediating antibodies at the surface of cells expressing Nef isolates from EC; this correlated with enhanced susceptibility to ADCC. Altogether, our results suggest that enhanced susceptibility of HIV-1-infected cells to ADCC may contribute to the EC phenotype.\n\n\nIMPORTANCE\nNef clones derived from elite controllers (EC) have been shown to be attenuated for CD4 downregulation; how this contributes to the nonprogressor phenotype of these infected individuals remains uncertain. Increasing evidence supports a role for HIV-specific antibody-dependent cellular cytotoxicity (ADCC) in controlling viral infection and replication. Here, we show that residual CD4 left at the surface of cells expressing Nef proteins isolated from ECs are sufficient to allow Env-CD4 interaction, leading to increased exposure of Env CD4-induced epitopes and increased susceptibility of infected cells to ADCC. Our results suggest that ADCC might be an active immune mechanism in EC that helps to maintain durable suppression of viral replication and low plasma viremia level in this rare subset of infected individuals. Therefore, targeting Nef's ability to downregulate CD4 could render HIV-1-infected cells susceptible to ADCC and thus have therapeutic utility.", "journal": "Journal of virology", "sentences": ["UNLABELLED\nImpairment of Nef function, including reduced CD4 downregulation, was described in a subset of HIV-1-infected individuals that control viral replication without antiretroviral treatment (elite controllers [EC]).", "Elimination of HIV-1-infected cells by antibody-dependent cellular cytotoxicity (ADCC) requires the presence of envelope glycoproteins (Env) in the CD4-bound conformation, raising the possibility that accumulating CD4 at the surface of virus-infected cells in EC could interact with Env and thereby sensitize these cells to ADCC.", "We observed a significant increase in the exposure of Env epitopes targeted by ADCC-mediating antibodies at the surface of cells expressing Nef isolates from EC; this correlated with enhanced susceptibility to ADCC.", "Altogether, our results suggest that enhanced susceptibility of HIV-1-infected cells to ADCC may contribute to the EC phenotype.", "IMPORTANCE\nNef clones derived from elite controllers (EC) have been shown to be attenuated for CD4 downregulation; how this contributes to the nonprogressor phenotype of these infected individuals remains uncertain.", "Increasing evidence supports a role for HIV-specific antibody-dependent cellular cytotoxicity (ADCC) in controlling viral infection and replication.", "Here, we show that residual CD4 left at the surface of cells expressing Nef proteins isolated from ECs are sufficient to allow Env-CD4 interaction, leading to increased exposure of Env CD4-induced epitopes and increased susceptibility of infected cells to ADCC.", "Our results suggest that ADCC might be an active immune mechanism in EC that helps to maintain durable suppression of viral replication and low plasma viremia level in this rare subset of infected individuals.", "Therefore, targeting Nef's ability to downregulate CD4 could render HIV-1-infected cells susceptible to ADCC and thus have therapeutic utility."], "title": "Nef Proteins from HIV-1 Elite Controllers Are Inefficient at Preventing Antibody-Dependent Cellular Cytotoxicity."}
{"paper_id": 24227997, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Seabed sediments of commercial ports are often characterized by high pollution levels. Differences in number and distribution of bacteria in such areas can be related to distribution of pollutants in the port and to sediment conditions. In this study, the bacterial communities of five sites from Leghorn Harbor seabed were characterized, and the main bacterial groups were identified. T-RFLP was used for all samples; two 16S rRNA libraries and in silico digestion of clones were used to identify fingerprint profiles. Library data, phylogenetic analysis, and T-RFLP coupled with in silico digestion of the obtained sequences evidenced the dominance of Proteobacteria and the high percentage of Bacteroidetes in all sites. The approach highlighted similar bacterial communities between samples coming from the five sites, suggesting a modest differentiation among bacterial communities of different harbor seabed sediments and hence the capacity of bacterial communities to adapt to different levels and types of pollution.", "journal": "TheScientificWorldJournal", "sentences": ["Seabed sediments of commercial ports are often characterized by high pollution levels.", "Differences in number and distribution of bacteria in such areas can be related to distribution of pollutants in the port and to sediment conditions.", "In this study, the bacterial communities of five sites from Leghorn Harbor seabed were characterized, and the main bacterial groups were identified.", "T-RFLP was used for all samples; two 16S rRNA libraries and in silico digestion of clones were used to identify fingerprint profiles.", "Library data, phylogenetic analysis, and T-RFLP coupled with in silico digestion of the obtained sequences evidenced the dominance of Proteobacteria and the high percentage of Bacteroidetes in all sites.", "The approach highlighted similar bacterial communities between samples coming from the five sites, suggesting a modest differentiation among bacterial communities of different harbor seabed sediments and hence the capacity of bacterial communities to adapt to different levels and types of pollution."], "title": "Bacterial communities in polluted seabed sediments: a molecular biology assay in Leghorn Harbor."}
{"paper_id": 24782211, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Tea is the second most popular non-alcoholic beverage in the world. In recent years, several molecular markers have been used in genetic studies of the tea plant. Yet, only a few single nucleotide polymorphisms (SNPs) have been reported. Here, we identified 818 putative SNPs from expressed sequence tag (EST) databases for the tea plant, which produced a frequency of 1 SNP/170 bp. A direct sequencing method was then used to verify 253 putative SNPs in genome DNA of 17 tea varieties. Fifty (20%) candidate and 299 new SNPs were identified. The haplotype polymorphism and nucleotide diversity of these markers ranged from 0 to 0.960 and 0 to 1.797%, respectively. Using these SNPs, the 17 varieties were classified into 2 groups by cluster analysis. The results indicate that Camellia sinensis-derived ESTs provide a valuable resource for SNP discovery. Furthermore, the abundance of SNPs in tea varieties is anticipated to generate the development of associated genetic studies, in addition to enhancing tea plant-breeding programs.", "journal": "Genetics and molecular research : GMR", "sentences": ["Tea is the second most popular non-alcoholic beverage in the world.", "In recent years, several molecular markers have been used in genetic studies of the tea plant.", "Yet, only a few single nucleotide polymorphisms (SNPs) have been reported.", "Here, we identified 818 putative SNPs from expressed sequence tag (EST) databases for the tea plant, which produced a frequency of 1 SNP/170 bp.", "A direct sequencing method was then used to verify 253 putative SNPs in genome DNA of 17 tea varieties.", "Fifty (20%) candidate and 299 new SNPs were identified.", "The haplotype polymorphism and nucleotide diversity of these markers ranged from 0 to 0.960 and 0 to 1.797%, respectively.", "Using these SNPs, the 17 varieties were classified into 2 groups by cluster analysis.", "The results indicate that Camellia sinensis-derived ESTs provide a valuable resource for SNP discovery.", "Furthermore, the abundance of SNPs in tea varieties is anticipated to generate the development of associated genetic studies, in addition to enhancing tea plant-breeding programs."], "title": "Development and characterization of single nucleotide polymorphism markers in Camellia sinensis (Theaceae)."}
{"paper_id": 24787137, "labels": ["0", "0", "1", "0", "0", "1", "1", "1", "1"], "abstract": "Friedreich ataxia (FRDA) and Fragile X syndrome (FXS) are among 40 diseases associated with expansion of repeated sequences (TREDs). Although their molecular pathology is not well understood, formation of repressive chromatin and unusual DNA structures over repeat regions were proposed to play a role. Our study now shows that RNA/DNA hybrids (R-loops) form in patient cells on expanded repeats of endogenous FXN and FMR1 genes, associated with FRDA and FXS. These transcription-dependent R-loops are stable, co-localise with repressive H3K9me2 chromatin mark and impede RNA Polymerase II transcription in patient cells. We investigated the interplay between repressive chromatin marks and R-loops on the FXN gene. We show that decrease in repressive H3K9me2 chromatin mark has no effect on R-loop levels. Importantly, increasing R-loop levels by treatment with DNA topoisomerase inhibitor camptothecin leads to up-regulation of repressive chromatin marks, resulting in FXN transcriptional silencing. This provides a direct molecular link between R-loops and the pathology of TREDs, suggesting that R-loops act as an initial trigger to promote FXN and FMR1 silencing. Thus R-loops represent a common feature of nucleotide expansion disorders and provide a new target for therapeutic interventions.", "journal": "PLoS genetics", "sentences": ["Friedreich ataxia (FRDA) and Fragile X syndrome (FXS) are among 40 diseases associated with expansion of repeated sequences (TREDs).", "Although their molecular pathology is not well understood, formation of repressive chromatin and unusual DNA structures over repeat regions were proposed to play a role.", "Our study now shows that RNA/DNA hybrids (R-loops) form in patient cells on expanded repeats of endogenous FXN and FMR1 genes, associated with FRDA and FXS.", "These transcription-dependent R-loops are stable, co-localise with repressive H3K9me2 chromatin mark and impede RNA Polymerase II transcription in patient cells.", "We investigated the interplay between repressive chromatin marks and R-loops on the FXN gene.", "We show that decrease in repressive H3K9me2 chromatin mark has no effect on R-loop levels.", "Importantly, increasing R-loop levels by treatment with DNA topoisomerase inhibitor camptothecin leads to up-regulation of repressive chromatin marks, resulting in FXN transcriptional silencing.", "This provides a direct molecular link between R-loops and the pathology of TREDs, suggesting that R-loops act as an initial trigger to promote FXN and FMR1 silencing.", "Thus R-loops represent a common feature of nucleotide expansion disorders and provide a new target for therapeutic interventions."], "title": "R-loops associated with triplet repeat expansions promote gene silencing in Friedreich ataxia and fragile X syndrome."}
{"paper_id": 24403137, "labels": ["0", "0", "0", "0", "0", "1", "1", "1", "1"], "abstract": "Ongoing neuronal activity in the CNS waxes and wanes continuously across widespread spatial and temporal scales. In the human brain, these spontaneous fluctuations are salient in blood oxygenation level-dependent (BOLD) signals and correlated within specific brain systems or \"intrinsic-connectivity networks.\" In electrophysiological recordings, both the amplitude dynamics of fast (1-100 Hz) oscillations and the scalp potentials per se exhibit fluctuations in the same infra-slow (0.01-0.1 Hz) frequency range where the BOLD fluctuations are conspicuous. While several lines of evidence show that the BOLD fluctuations are correlated with fast-amplitude dynamics, it has remained unclear whether the infra-slow scalp potential fluctuations in full-band electroencephalography (fbEEG) are related to the resting-state BOLD signals. We used concurrent fbEEG and functional magnetic resonance imaging (fMRI) recordings to address the relationship of infra-slow fluctuations (ISFs) in scalp potentials and BOLD signals. We show here that independent components of fbEEG recordings are selectively correlated with subsets of cortical BOLD signals in specific task-positive and task-negative, fMRI-defined resting-state networks. This brain system-specific association indicates that infra-slow scalp potentials are directly associated with the endogenous fluctuations in neuronal activity levels. fbEEG thus yields a noninvasive, high-temporal resolution window into the dynamics of intrinsic connectivity networks. These results support the view that the slow potentials reflect changes in cortical excitability and shed light on neuronal substrates underlying both electrophysiological and behavioral ISFs.", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "sentences": ["Ongoing neuronal activity in the CNS waxes and wanes continuously across widespread spatial and temporal scales.", "In the human brain, these spontaneous fluctuations are salient in blood oxygenation level-dependent (BOLD) signals and correlated within specific brain systems or \"intrinsic-connectivity networks.\"", "In electrophysiological recordings, both the amplitude dynamics of fast (1-100 Hz) oscillations and the scalp potentials per se exhibit fluctuations in the same infra-slow (0.01-0.1 Hz) frequency range where the BOLD fluctuations are conspicuous.", "While several lines of evidence show that the BOLD fluctuations are correlated with fast-amplitude dynamics, it has remained unclear whether the infra-slow scalp potential fluctuations in full-band electroencephalography (fbEEG) are related to the resting-state BOLD signals.", "We used concurrent fbEEG and functional magnetic resonance imaging (fMRI) recordings to address the relationship of infra-slow fluctuations (ISFs) in scalp potentials and BOLD signals.", "We show here that independent components of fbEEG recordings are selectively correlated with subsets of cortical BOLD signals in specific task-positive and task-negative, fMRI-defined resting-state networks.", "This brain system-specific association indicates that infra-slow scalp potentials are directly associated with the endogenous fluctuations in neuronal activity levels.", "fbEEG thus yields a noninvasive, high-temporal resolution window into the dynamics of intrinsic connectivity networks.", "These results support the view that the slow potentials reflect changes in cortical excitability and shed light on neuronal substrates underlying both electrophysiological and behavioral ISFs."], "title": "Infra-slow EEG fluctuations are correlated with resting-state network dynamics in fMRI."}
{"paper_id": 25555219, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Bacterial infections represent a rapidly growing challenge to human health. Aminoglycosides are widely used broad-spectrum antibiotics, but they inflict permanent hearing loss in up to ~50% of patients by causing selective sensory hair cell loss. Here, we hypothesized that reducing aminoglycoside entry into hair cells via mechanotransducer channels would reduce ototoxicity, and therefore we synthesized 9 aminoglycosides with modifications based on biophysical properties of the hair cell mechanotransducer channel and interactions between aminoglycosides and the bacterial ribosome. Compared with the parent aminoglycoside sisomicin, all 9 derivatives displayed no or reduced ototoxicity, with the lead compound N1MS 17 times less ototoxic and with reduced penetration of hair cell mechanotransducer channels in rat cochlear cultures. Both N1MS and sisomicin suppressed growth of E. coli and K. pneumoniae, with N1MS exhibiting superior activity against extended spectrum \u03b2 lactamase producers, despite diminished activity against P. aeruginosa and S. aureus. Moreover, systemic sisomicin treatment of mice resulted in 75% to 85% hair cell loss and profound hearing loss, whereas N1MS treatment preserved both hair cells and hearing. Finally, in mice with E. coli-infected bladders, systemic N1MS treatment eliminated bacteria from urinary tract tissues and serially collected urine samples, without compromising auditory and kidney functions. Together, our findings establish N1MS as a nonototoxic aminoglycoside and support targeted modification as a promising approach to generating nonototoxic antibiotics.", "journal": "The Journal of clinical investigation", "sentences": ["Bacterial infections represent a rapidly growing challenge to human health.", "Aminoglycosides are widely used broad-spectrum antibiotics, but they inflict permanent hearing loss in up to ~50% of patients by causing selective sensory hair cell loss.", "Here, we hypothesized that reducing aminoglycoside entry into hair cells via mechanotransducer channels would reduce ototoxicity, and therefore we synthesized 9 aminoglycosides with modifications based on biophysical properties of the hair cell mechanotransducer channel and interactions between aminoglycosides and the bacterial ribosome.", "Compared with the parent aminoglycoside sisomicin, all 9 derivatives displayed no or reduced ototoxicity, with the lead compound N1MS 17 times less ototoxic and with reduced penetration of hair cell mechanotransducer channels in rat cochlear cultures.", "Both N1MS and sisomicin suppressed growth of E. coli and K. pneumoniae, with N1MS exhibiting superior activity against extended spectrum \u03b2 lactamase producers, despite diminished activity against P. aeruginosa and S. aureus.", "Moreover, systemic sisomicin treatment of mice resulted in 75% to 85% hair cell loss and profound hearing loss, whereas N1MS treatment preserved both hair cells and hearing.", "Finally, in mice with E. coli-infected bladders, systemic N1MS treatment eliminated bacteria from urinary tract tissues and serially collected urine samples, without compromising auditory and kidney functions.", "Together, our findings establish N1MS as a nonototoxic aminoglycoside and support targeted modification as a promising approach to generating nonototoxic antibiotics."], "title": "Designer aminoglycosides prevent cochlear hair cell loss and hearing loss."}
{"paper_id": 23185043, "labels": ["0", "0", "0", "0", "0"], "abstract": "This article introduces DoBISCUIT (Database of BIoSynthesis clusters CUrated and InTegrated, http://www.bio.nite.go.jp/pks/), a literature-based, manually curated database of gene clusters for secondary metabolite biosynthesis. Bacterial secondary metabolites often show pharmacologically important activities and can serve as lead compounds and/or candidates for drug development. Biosynthesis of each secondary metabolite is catalyzed by a number of enzymes, usually encoded by a gene cluster. Although many scientific papers describe such gene clusters, the gene information is not always described in a comprehensive manner and the related information is rarely integrated. DoBISCUIT integrates the latest literature information and provides standardized gene/module/domain descriptions related to the gene clusters.", "journal": "Nucleic acids research", "sentences": ["This article introduces DoBISCUIT (Database of BIoSynthesis clusters CUrated and InTegrated, http://www.bio.nite.go.jp/pks/), a literature-based, manually curated database of gene clusters for secondary metabolite biosynthesis.", "Bacterial secondary metabolites often show pharmacologically important activities and can serve as lead compounds and/or candidates for drug development.", "Biosynthesis of each secondary metabolite is catalyzed by a number of enzymes, usually encoded by a gene cluster.", "Although many scientific papers describe such gene clusters, the gene information is not always described in a comprehensive manner and the related information is rarely integrated.", "DoBISCUIT integrates the latest literature information and provides standardized gene/module/domain descriptions related to the gene clusters."], "title": "DoBISCUIT: a database of secondary metabolite biosynthetic gene clusters."}
{"paper_id": 26785351, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The relationship between body size and vocalization parameters has been studied in many animal species. In insect species, however, the effect of body size on song frequency has remained unclear. Here we analyzed the effect of body size on the frequency spectra of mating songs produced by the two-spotted cricket, Gryllus bimaculatus. We recorded the calling songs and courtship songs of male crickets of different body sizes. The calling songs contained a frequency component that peaked at 5.7 kHz. On the other hand, courtship songs contained two frequency components that peaked at 5.8 and 14.7 kHz. The dominant frequency of each component in both the calling and courtship songs was constant regardless of body size. The size of the harp and mirror regions in the cricket forewings, which are the acoustic sources of the songs, correlated positively with body size. These findings suggest that the frequency contents of both the calling and courtship songs of the cricket are unaffected by whole body, harp, or mirror size.", "journal": "PloS one", "sentences": ["The relationship between body size and vocalization parameters has been studied in many animal species.", "In insect species, however, the effect of body size on song frequency has remained unclear.", "Here we analyzed the effect of body size on the frequency spectra of mating songs produced by the two-spotted cricket, Gryllus bimaculatus.", "We recorded the calling songs and courtship songs of male crickets of different body sizes.", "The calling songs contained a frequency component that peaked at 5.7 kHz.", "On the other hand, courtship songs contained two frequency components that peaked at 5.8 and 14.7 kHz.", "The dominant frequency of each component in both the calling and courtship songs was constant regardless of body size.", "The size of the harp and mirror regions in the cricket forewings, which are the acoustic sources of the songs, correlated positively with body size.", "These findings suggest that the frequency contents of both the calling and courtship songs of the cricket are unaffected by whole body, harp, or mirror size."], "title": "No Effect of Body Size on the Frequency of Calling and Courtship Song in the Two-Spotted Cricket, Gryllus bimaculatus."}
{"paper_id": 21637786, "labels": ["0", "0", "0", "1", "0", "1", "1", "1", "1"], "abstract": "Vertebrate mesendoderm specification requires the Nodal signaling pathway and its transcriptional effector FoxH1. However, loss of FoxH1 in several species does not reliably cause the full range of loss-of-Nodal phenotypes, indicating that Nodal signals through additional transcription factors during early development. We investigated the FoxH1-dependent and -independent roles of Nodal signaling during mesendoderm patterning using a novel recessive zebrafish FoxH1 mutation called midway, which produces a C-terminally truncated FoxH1 protein lacking the Smad-interaction domain but retaining DNA-binding capability. Using a combination of gel shift assays, Nodal overexpression experiments, and genetic epistasis analyses, we demonstrate that midway more accurately represents a complete loss of FoxH1-dependent Nodal signaling than the existing zebrafish FoxH1 mutant schmalspur. Maternal-zygotic midway mutants lack notochords, in agreement with FoxH1 loss in other organisms, but retain near wild-type expression of markers of endoderm and various nonaxial mesoderm fates, including paraxial and intermediate mesoderm and blood precursors. We found that the activity of the T-box transcription factor Eomesodermin accounts for specification of these tissues in midway embryos. Inhibition of Eomesodermin in midway mutants severely reduces the specification of these tissues and effectively phenocopies the defects seen upon complete loss of Nodal signaling. Our results indicate that the specific combinations of transcription factors available for signal transduction play critical and separable roles in determining Nodal pathway output during mesendoderm patterning. Our findings also offer novel insights into the co-evolution of the Nodal signaling pathway, the notochord specification program, and the chordate branch of the deuterostome family of animals.", "journal": "PLoS genetics", "sentences": ["Vertebrate mesendoderm specification requires the Nodal signaling pathway and its transcriptional effector FoxH1.", "However, loss of FoxH1 in several species does not reliably cause the full range of loss-of-Nodal phenotypes, indicating that Nodal signals through additional transcription factors during early development.", "We investigated the FoxH1-dependent and -independent roles of Nodal signaling during mesendoderm patterning using a novel recessive zebrafish FoxH1 mutation called midway, which produces a C-terminally truncated FoxH1 protein lacking the Smad-interaction domain but retaining DNA-binding capability.", "Using a combination of gel shift assays, Nodal overexpression experiments, and genetic epistasis analyses, we demonstrate that midway more accurately represents a complete loss of FoxH1-dependent Nodal signaling than the existing zebrafish FoxH1 mutant schmalspur.", "Maternal-zygotic midway mutants lack notochords, in agreement with FoxH1 loss in other organisms, but retain near wild-type expression of markers of endoderm and various nonaxial mesoderm fates, including paraxial and intermediate mesoderm and blood precursors.", "We found that the activity of the T-box transcription factor Eomesodermin accounts for specification of these tissues in midway embryos.", "Inhibition of Eomesodermin in midway mutants severely reduces the specification of these tissues and effectively phenocopies the defects seen upon complete loss of Nodal signaling.", "Our results indicate that the specific combinations of transcription factors available for signal transduction play critical and separable roles in determining Nodal pathway output during mesendoderm patterning.", "Our findings also offer novel insights into the co-evolution of the Nodal signaling pathway, the notochord specification program, and the chordate branch of the deuterostome family of animals."], "title": "Nodal-dependent mesendoderm specification requires the combinatorial activities of FoxH1 and Eomesodermin."}
{"paper_id": 22719072, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Epithelial-to-mesenchymal transition (EMT), a crucial developmental program, contributes to cancer invasion and metastasis. In this study, we show that death-effector domain-containing DNA-binding protein (DEDD) attenuates EMT and acts as an endogenous suppressor of tumor growth and metastasis. We found that expression levels of DEDD were conversely correlated with poor prognosis in patients with breast and colon cancer. Both in vitro and in vivo, overexpression of DEDD attenuated the invasive phenotype of highly metastatic cells, whereas silencing of DEDD promoted the invasion of nonmetastatic cells. Via direct interaction with the class III PI-3-kinase (PI3KC3)/Beclin1, DEDD activated autophagy and induced the degradation of Snail and Twist, two master regulators of EMT. The DEDD-PI3KC3 interaction led to stabilization of PI3KC3, which further contributed to autophagy and the degradation of Snail and Twist. Together, our findings highlight a novel mechanism in which the intracellular signaling protein DEDD functions as an endogenous tumor suppressor. DEDD expression therefore may represent a prognostic marker and potential therapeutic target for the prevention and treatment of cancer metastasis.", "journal": "Cancer research", "sentences": ["Epithelial-to-mesenchymal transition (EMT), a crucial developmental program, contributes to cancer invasion and metastasis.", "In this study, we show that death-effector domain-containing DNA-binding protein (DEDD) attenuates EMT and acts as an endogenous suppressor of tumor growth and metastasis.", "We found that expression levels of DEDD were conversely correlated with poor prognosis in patients with breast and colon cancer.", "Both in vitro and in vivo, overexpression of DEDD attenuated the invasive phenotype of highly metastatic cells, whereas silencing of DEDD promoted the invasion of nonmetastatic cells.", "Via direct interaction with the class III PI-3-kinase (PI3KC3)/Beclin1, DEDD activated autophagy and induced the degradation of Snail and Twist, two master regulators of EMT.", "The DEDD-PI3KC3 interaction led to stabilization of PI3KC3, which further contributed to autophagy and the degradation of Snail and Twist.", "Together, our findings highlight a novel mechanism in which the intracellular signaling protein DEDD functions as an endogenous tumor suppressor.", "DEDD expression therefore may represent a prognostic marker and potential therapeutic target for the prevention and treatment of cancer metastasis."], "title": "DEDD interacts with PI3KC3 to activate autophagy and attenuate epithelial-mesenchymal transition in human breast cancer."}
{"paper_id": 21752923, "labels": ["0", "0", "1", "1", "1", "1"], "abstract": "High-mobility group box 1 (HMGB1), an abundant nuclear protein that triggers host immune responses, is an endogenous danger signal involved in the pathogenesis of various infectious agents. However, its role in hepatitis C virus (HCV) infection is not known. Here, we show that HMGB1 protein is translocated from the nucleus to cytoplasm and subsequently is released into the extracellular milieu by HCV infection. Secreted HMGB1 triggers antiviral responses and blocks HCV infection, a mechanism that may limit HCV propagation in HCV patients. Secreted HMGB1 also may have a role in liver cirrhosis, which is a common comorbidity in HCV patients. Further investigations into the roles of HMGB1 in the diseases caused by HCV infection will shed light on and potentially help prevent these serious and prevalent HCV-related diseases.", "journal": "Journal of virology", "sentences": ["High-mobility group box 1 (HMGB1), an abundant nuclear protein that triggers host immune responses, is an endogenous danger signal involved in the pathogenesis of various infectious agents.", "However, its role in hepatitis C virus (HCV) infection is not known.", "Here, we show that HMGB1 protein is translocated from the nucleus to cytoplasm and subsequently is released into the extracellular milieu by HCV infection.", "Secreted HMGB1 triggers antiviral responses and blocks HCV infection, a mechanism that may limit HCV propagation in HCV patients.", "Secreted HMGB1 also may have a role in liver cirrhosis, which is a common comorbidity in HCV patients.", "Further investigations into the roles of HMGB1 in the diseases caused by HCV infection will shed light on and potentially help prevent these serious and prevalent HCV-related diseases."], "title": "Hepatitis C virus infection is blocked by HMGB1 released from virus-infected cells."}
{"paper_id": 24459530, "labels": ["0", "0", "0", "0", "1"], "abstract": "The bioassay-guided isolation of the active extract of Salvinia auriculata Aubl. led to the separation of three main compounds, characterized as stigmasterone, stigmasterol, and friedelinol. The pure form of diketosteroid presented a potential antibacterial activity with a minimum inhibitory concentration (MIC) value of 0.01\u2009mg\u2009mL(-1) against Staphylococcus aureus isolated from animals with mastitis infections. The active extract also showed a similar result to that previously obtained with pure diketosteroid when tested with the same isolates. The present study's results demonstrate the potential of this plant as an excipient for the production of antibacterial soaps aimed at controlling bovine mastitis infections, especially on small farms.", "journal": "Evidence-based complementary and alternative medicine : eCAM", "sentences": ["The bioassay-guided isolation of the active extract of Salvinia auriculata Aubl.", "led to the separation of three main compounds, characterized as stigmasterone, stigmasterol, and friedelinol.", "The pure form of diketosteroid presented a potential antibacterial activity with a minimum inhibitory concentration (MIC) value of 0.01\u2009mg\u2009mL(-1) against Staphylococcus aureus isolated from animals with mastitis infections.", "The active extract also showed a similar result to that previously obtained with pure diketosteroid when tested with the same isolates.", "The present study's results demonstrate the potential of this plant as an excipient for the production of antibacterial soaps aimed at controlling bovine mastitis infections, especially on small farms."], "title": "Antibacterial Chemical Constituent and Antiseptic Herbal Soap from Salvinia auriculata Aubl."}
{"paper_id": 27467658, "labels": ["0", "0", "0", "0", "0", "1", "0", "1", "1", "1"], "abstract": "Shikonin is a highly lipophilic naphtoquinone found in the roots of Lithospermum erythrorhizon used for its pleiotropic effects in traditional Chinese medicine. Based on its reported antipyretic and anti-inflammatory properties, we investigated whether shikonin suppresses the activation of NLRP3 inflammasome. Inflammasomes are cytosolic protein complexes that serve as scaffolds for recruitment and activation of caspase-1, which, in turn, results in cleavage and secretion of proinflammatory cytokines IL-1\u03b2 and IL-18. NLRP3 inflammasome activation involves two steps: priming, i.e. the activation of NF-\u03baB pathway, and inflammasome assembly. While shikonin has previously been reported to suppress the priming step, we demonstrated that shikonin also inhibits the second step of inflammasome activation induced by soluble and particulate NLRP3 instigators in primed immortalized murine bone marrow-derived macrophages. Shikonin decreased NLRP3 inflammasome activation in response to nigericin more potently than acetylshikonin. Our results showed that shikonin also inhibits AIM2 inflammasome activation by double stranded DNA. Shikonin inhibited ASC speck formation and caspase-1 activation in murine macrophages and suppressed the activity of isolated caspase-1, demonstrating that it directly targets caspase-1. Complexing shikonin with \u03b2-lactoglobulin reduced its toxicity while preserving the inhibitory effect on NLRP3 inflammasome activation, suggesting that shikonin with improved bioavailability might be interesting for therapeutic applications in inflammasome-mediated conditions.", "journal": "PloS one", "sentences": ["Shikonin is a highly lipophilic naphtoquinone found in the roots of Lithospermum erythrorhizon used for its pleiotropic effects in traditional Chinese medicine.", "Based on its reported antipyretic and anti-inflammatory properties, we investigated whether shikonin suppresses the activation of NLRP3 inflammasome.", "Inflammasomes are cytosolic protein complexes that serve as scaffolds for recruitment and activation of caspase-1, which, in turn, results in cleavage and secretion of proinflammatory cytokines IL-1\u03b2 and IL-18.", "NLRP3 inflammasome activation involves two steps: priming, i.e.", "the activation of NF-\u03baB pathway, and inflammasome assembly.", "While shikonin has previously been reported to suppress the priming step, we demonstrated that shikonin also inhibits the second step of inflammasome activation induced by soluble and particulate NLRP3 instigators in primed immortalized murine bone marrow-derived macrophages.", "Shikonin decreased NLRP3 inflammasome activation in response to nigericin more potently than acetylshikonin.", "Our results showed that shikonin also inhibits AIM2 inflammasome activation by double stranded DNA.", "Shikonin inhibited ASC speck formation and caspase-1 activation in murine macrophages and suppressed the activity of isolated caspase-1, demonstrating that it directly targets caspase-1.", "Complexing shikonin with \u03b2-lactoglobulin reduced its toxicity while preserving the inhibitory effect on NLRP3 inflammasome activation, suggesting that shikonin with improved bioavailability might be interesting for therapeutic applications in inflammasome-mediated conditions."], "title": "Shikonin Suppresses NLRP3 and AIM2 Inflammasomes by Direct Inhibition of Caspase-1."}
{"paper_id": 22271448, "labels": ["0", "0", "0", "0", "1", "1"], "abstract": "We describe the use of novel bispecific hexavalent Abs (HexAbs) to enhance anticancer immunotherapy. Two bispecific HexAbs [IgG-(Fab)(4) constructed from veltuzumab (anti-CD20 IgG) and milatuzumab (anti-CD74 IgG)] show enhanced cytotoxicity in mantle cell lymphoma (MCL) and other lymphoma/leukemia cell lines, as well as patient tumor samples, without a crosslinking Ab, compared with their parental mAb counterparts, alone or in combination. The bispecific HexAbs have different properties from and are more potent than their parental mAbs in vitro. The juxtaposition of CD20 and CD74 on MCL cells by the HexAbs resulted in homotypic adhesion and triggered intracellular changes that include loss of mitochondrial transmembrane potential, production of reactive oxygen species, rapid and sustained phosphorylation of ERKs and JNK, down-regulation of pAkt and Bcl-xL, actin reorganization, and lysosomal membrane permeabilization, culminating in cell death. They also displayed different potencies in depleting lymphoma cells and normal B cells from whole blood ex vivo and significantly extended the survival of nude mice bearing MCL xenografts in a dose-dependent manner, thus indicating stability and antitumor activity in vivo. Such bispecific HexAbs may constitute a new class of therapeutic agents for improved cancer immunotherapy, as shown here for MCL and other CD20(+)/CD74(+) malignancies.", "journal": "Blood", "sentences": ["We describe the use of novel bispecific hexavalent Abs (HexAbs) to enhance anticancer immunotherapy.", "Two bispecific HexAbs [IgG-(Fab)(4) constructed from veltuzumab (anti-CD20 IgG) and milatuzumab (anti-CD74 IgG)] show enhanced cytotoxicity in mantle cell lymphoma (MCL) and other lymphoma/leukemia cell lines, as well as patient tumor samples, without a crosslinking Ab, compared with their parental mAb counterparts, alone or in combination.", "The bispecific HexAbs have different properties from and are more potent than their parental mAbs in vitro.", "The juxtaposition of CD20 and CD74 on MCL cells by the HexAbs resulted in homotypic adhesion and triggered intracellular changes that include loss of mitochondrial transmembrane potential, production of reactive oxygen species, rapid and sustained phosphorylation of ERKs and JNK, down-regulation of pAkt and Bcl-xL, actin reorganization, and lysosomal membrane permeabilization, culminating in cell death.", "They also displayed different potencies in depleting lymphoma cells and normal B cells from whole blood ex vivo and significantly extended the survival of nude mice bearing MCL xenografts in a dose-dependent manner, thus indicating stability and antitumor activity in vivo.", "Such bispecific HexAbs may constitute a new class of therapeutic agents for improved cancer immunotherapy, as shown here for MCL and other CD20(+)/CD74(+) malignancies."], "title": "Dual-targeting immunotherapy of lymphoma: potent cytotoxicity of anti-CD20/CD74 bispecific antibodies in mantle cell and other lymphomas."}
{"paper_id": 26289598, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "Our understanding of the internal dynamics of the Earth is largely based on images of seismic velocity variations in the mantle obtained with global tomography. However, our ability to image the mantle is severely hampered by a lack of seismic data collected in marine areas. Here we report observations made under different noise conditions (in the Mediterranean Sea, the Indian and Pacific Oceans) by a submarine floating seismograph, and show that such floats are able to fill the oceanic data gap. Depending on the ambient noise level, the floats can record between 35 and 63% of distant earthquakes with a moment magnitude M\u22656.5. Even magnitudes <6.0 can be successfully observed under favourable noise conditions. The serendipitous recording of an earthquake swarm near the Indian Ocean triple junction enabled us to establish a threshold magnitude between 2.7 and 3.4 for local earthquakes in the noisiest of the three environments.", "journal": "Nature communications", "sentences": ["Our understanding of the internal dynamics of the Earth is largely based on images of seismic velocity variations in the mantle obtained with global tomography.", "However, our ability to image the mantle is severely hampered by a lack of seismic data collected in marine areas.", "Here we report observations made under different noise conditions (in the Mediterranean Sea, the Indian and Pacific Oceans) by a submarine floating seismograph, and show that such floats are able to fill the oceanic data gap.", "Depending on the ambient noise level, the floats can record between 35 and 63% of distant earthquakes with a moment magnitude M\u22656.5.", "Even magnitudes <6.0 can be successfully observed under favourable noise conditions.", "The serendipitous recording of an earthquake swarm near the Indian Ocean triple junction enabled us to establish a threshold magnitude between 2.7 and 3.4 for local earthquakes in the noisiest of the three environments."], "title": "Seismic monitoring in the oceans by autonomous floats."}
{"paper_id": 26575745, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "The \u03c0 bond shifting (automerization) by carbon tunneling of cyclopropenyl anions was computationally analyzed by the small curvature tunneling methodology. Similar to other antiaromatic cases, the process is hindered by substituents departing from planarity, since these groups must be realigned along with the \u03c0 bond shifting. With hydrogens as substituents the tunneling is extremely fast, in a case of both heavy and light atom tunneling. But, with more massive substituents (such as Me and F), and especially with longer groups (such as CN), the tunneling probability is reduced or even virtually canceled. The automerization of triphenylcyclopropyl anion by tunneling was supposed to be impossible due to the high mass of the phenyl groups. However, it was found that the ground state of this species is actually a D3h aromatic triplet, a single-well system that cannot undergo automerization. For this and other systems with \u03c0 acceptor groups, the superposition of states that generates the second-order Jahn-Teller distortion is diminished, and by Hund's rule, the triplet results in the ground state.", "journal": "Journal of chemical theory and computation", "sentences": ["The \u03c0 bond shifting (automerization) by carbon tunneling of cyclopropenyl anions was computationally analyzed by the small curvature tunneling methodology.", "Similar to other antiaromatic cases, the process is hindered by substituents departing from planarity, since these groups must be realigned along with the \u03c0 bond shifting.", "With hydrogens as substituents the tunneling is extremely fast, in a case of both heavy and light atom tunneling.", "But, with more massive substituents (such as Me and F), and especially with longer groups (such as CN), the tunneling probability is reduced or even virtually canceled.", "The automerization of triphenylcyclopropyl anion by tunneling was supposed to be impossible due to the high mass of the phenyl groups.", "However, it was found that the ground state of this species is actually a D3h aromatic triplet, a single-well system that cannot undergo automerization.", "For this and other systems with \u03c0 acceptor groups, the superposition of states that generates the second-order Jahn-Teller distortion is diminished, and by Hund's rule, the triplet results in the ground state."], "title": "Cyclopropenyl Anions: Carbon Tunneling or Diradical Formation? A Contest between Jahn-Teller and Hund."}
{"paper_id": 25761712, "labels": ["0", "0", "0", "1", "0", "1", "1", "1"], "abstract": "Ecological traps occur when environmental changes cause maladaptive habitat selection. Despite their relevance to metapopulations, ecological traps have been studied predominantly at local scales. How these local impacts scale up to affect the dynamics of spatially structured metapopulations in heterogeneous landscapes remains unexplored. We propose that assessing the metapopulation consequences of traps depends on a variety of factors that can be grouped into four categories: the probability of encounter, the likelihood of selection, the fitness costs of selection and species-specific vulnerability to these costs. We evaluate six hypotheses using a network-based metapopulation model to explore the relative importance of factors across these categories within a spatial context. Our model suggests (i) traps are most severe when they represent a large proportion of habitats, severely reduce fitness and are highly attractive, and (ii) species with high intrinsic fitness will be most susceptible. We provide the first evidence that (iii) traps may be beneficial for metapopulations in rare instances, and (iv) preferences for natal-like habitats can magnify the effects of traps. Our study provides important insight into the effects of traps at landscape scales, and highlights the need to explicitly consider spatial context to better understand and manage traps within metapopulations.", "journal": "Proceedings. Biological sciences / The Royal Society", "sentences": ["Ecological traps occur when environmental changes cause maladaptive habitat selection.", "Despite their relevance to metapopulations, ecological traps have been studied predominantly at local scales.", "How these local impacts scale up to affect the dynamics of spatially structured metapopulations in heterogeneous landscapes remains unexplored.", "We propose that assessing the metapopulation consequences of traps depends on a variety of factors that can be grouped into four categories: the probability of encounter, the likelihood of selection, the fitness costs of selection and species-specific vulnerability to these costs.", "We evaluate six hypotheses using a network-based metapopulation model to explore the relative importance of factors across these categories within a spatial context.", "Our model suggests (i) traps are most severe when they represent a large proportion of habitats, severely reduce fitness and are highly attractive, and (ii) species with high intrinsic fitness will be most susceptible.", "We provide the first evidence that (iii) traps may be beneficial for metapopulations in rare instances, and (iv) preferences for natal-like habitats can magnify the effects of traps.", "Our study provides important insight into the effects of traps at landscape scales, and highlights the need to explicitly consider spatial context to better understand and manage traps within metapopulations."], "title": "Evaluating the metapopulation consequences of ecological traps."}
{"paper_id": 26673710, "labels": ["0", "0", "0", "0", "1", "1", "0", "1", "1"], "abstract": "Genome engineering of human cells plays an important role in biotechnology and molecular medicine. In particular, insertions of functional multi-transgene cassettes into suitable endogenous sequences will lead to novel applications. Although several tools have been exploited in this context, safety issues such as cytotoxicity, insertional mutagenesis and off-target cleavage together with limitations in cargo size/expression often compromise utility. Phage \u03bb integrase (Int) is a transgenesis tool that mediates conservative site-specific integration of 48 kb DNA into a safe harbor site of the bacterial genome. Here, we show that an Int variant precisely recombines large episomes into a sequence, termedattH4X, found in 1000 human Long INterspersed Elements-1 (LINE-1). We demonstrate single-copy transgenesis throughattH4X-targeting in various cell lines including hESCs, with the flexibility of selecting clones according to transgene performance and downstream applications. This is exemplified with pluripotency reporter cassettes and constitutively expressed payloads that remain functional inLINE1-targeted hESCs and differentiated progenies. Furthermore,LINE-1targeting does not induce DNA damage-response or chromosomal aberrations, and neither global nor localized endogenous gene expression is substantially affected. Hence, this simple transgene addition tool should become particularly useful for applications that require engineering of the human genome with multi-transgenes.", "journal": "Nucleic acids research", "sentences": ["Genome engineering of human cells plays an important role in biotechnology and molecular medicine.", "In particular, insertions of functional multi-transgene cassettes into suitable endogenous sequences will lead to novel applications.", "Although several tools have been exploited in this context, safety issues such as cytotoxicity, insertional mutagenesis and off-target cleavage together with limitations in cargo size/expression often compromise utility.", "Phage \u03bb integrase (Int) is a transgenesis tool that mediates conservative site-specific integration of 48 kb DNA into a safe harbor site of the bacterial genome.", "Here, we show that an Int variant precisely recombines large episomes into a sequence, termedattH4X, found in 1000 human Long INterspersed Elements-1 (LINE-1).", "We demonstrate single-copy transgenesis throughattH4X-targeting in various cell lines including hESCs, with the flexibility of selecting clones according to transgene performance and downstream applications.", "This is exemplified with pluripotency reporter cassettes and constitutively expressed payloads that remain functional inLINE1-targeted hESCs and differentiated progenies.", "Furthermore,LINE-1targeting does not induce DNA damage-response or chromosomal aberrations, and neither global nor localized endogenous gene expression is substantially affected.", "Hence, this simple transgene addition tool should become particularly useful for applications that require engineering of the human genome with multi-transgenes."], "title": "Conservative site-specific and single-copy transgenesis in human LINE-1 elements."}
{"paper_id": 26422475, "labels": ["1", "0", "0", "0", "0", "0", "1"], "abstract": "A novel enzyme-linked receptor assay (ELRA) based on \u03b22-adrenergic receptor (\u03b22-AR) has been developed for rapid and high-throughput detection of \u03b2-adrenergic agonists (\u03b2-agonists) in urine. Human embryonic kidney cells (HEK293) were introduced as the expression system to enhance the functionality of the recombinant \u03b22-AR, and the attempt to detect \u03b2-agonists in swine urine using such approaches was accomplished unprecedentedly. In this article, a recombinant porcine \u03b22-AR was produced in the inner membrane of HEK293 cells and purified from crude membrane protein by nickel-nitrilotriacetic acid affinity chromatography. After activity identification, the recombinant receptor was used in the development of direct competitive ELRA. Several parameters such as blocking buffer and blocking process were optimized and the performance of the system was determined. The IC50 concentrations of clenbuterol, salbutamol, and ractopamine were 34, 53 and 63 \u03bcg/L, and the average recovery rates were 68.2%, 60.3% and 65.5%, respectively. ELRA based on \u03b22-AR shows a series of advantages such as safety, easy operation, and high efficiency, making it promising for the rapid screening of \u03b2-agonists in animal urine.", "journal": "PloS one", "sentences": ["A novel enzyme-linked receptor assay (ELRA) based on \u03b22-adrenergic receptor (\u03b22-AR) has been developed for rapid and high-throughput detection of \u03b2-adrenergic agonists (\u03b2-agonists) in urine.", "Human embryonic kidney cells (HEK293) were introduced as the expression system to enhance the functionality of the recombinant \u03b22-AR, and the attempt to detect \u03b2-agonists in swine urine using such approaches was accomplished unprecedentedly.", "In this article, a recombinant porcine \u03b22-AR was produced in the inner membrane of HEK293 cells and purified from crude membrane protein by nickel-nitrilotriacetic acid affinity chromatography.", "After activity identification, the recombinant receptor was used in the development of direct competitive ELRA.", "Several parameters such as blocking buffer and blocking process were optimized and the performance of the system was determined.", "The IC50 concentrations of clenbuterol, salbutamol, and ractopamine were 34, 53 and 63 \u03bcg/L, and the average recovery rates were 68.2%, 60.3% and 65.5%, respectively.", "ELRA based on \u03b22-AR shows a series of advantages such as safety, easy operation, and high efficiency, making it promising for the rapid screening of \u03b2-agonists in animal urine."], "title": "Multiresidue Method for Analysis of \u03b2 Agonists in Swine Urine by Enzyme Linked Receptor Assay Based on \u03b22 Adrenergic Receptor Expressed in HEK293 Cells."}
{"paper_id": 24101477, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Phenotypic polarization of macrophages is regulated by a milieu of cues in the local tissue microenvironment. Although much is known about how soluble factors influence macrophage polarization, relatively little is known about how physical cues present in the extracellular environment might modulate proinflammatory (M1) vs. prohealing (M2) activation. Specifically, the role of cell shape has not been explored, even though it has been observed that macrophages adopt different geometries in vivo. We and others observed that macrophages polarized toward different phenotypes in vitro exhibit dramatic changes in cell shape: M2 cells exhibit an elongated shape compared with M1 cells. Using a micropatterning approach to control macrophage cell shape directly, we demonstrate here that elongation itself, without exogenous cytokines, leads to the expression of M2 phenotype markers and reduces the secretion of inflammatory cytokines. Moreover, elongation enhances the effects of M2-inducing cytokines IL-4 and IL-13 and protects cells from M1-inducing stimuli LPS and IFN-\u03b3. In addition shape- but not cytokine-induced polarization is abrogated when actin and actin/myosin contractility are inhibited by pharmacological agents, suggesting a role for the cytoskeleton in the control of macrophage polarization by cell geometry. Our studies demonstrate that alterations in cell shape associated with changes in ECM architecture may provide integral cues to modulate macrophage phenotype polarization.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Phenotypic polarization of macrophages is regulated by a milieu of cues in the local tissue microenvironment.", "Although much is known about how soluble factors influence macrophage polarization, relatively little is known about how physical cues present in the extracellular environment might modulate proinflammatory (M1) vs. prohealing (M2) activation.", "Specifically, the role of cell shape has not been explored, even though it has been observed that macrophages adopt different geometries in vivo.", "We and others observed that macrophages polarized toward different phenotypes in vitro exhibit dramatic changes in cell shape: M2 cells exhibit an elongated shape compared with M1 cells.", "Using a micropatterning approach to control macrophage cell shape directly, we demonstrate here that elongation itself, without exogenous cytokines, leads to the expression of M2 phenotype markers and reduces the secretion of inflammatory cytokines.", "Moreover, elongation enhances the effects of M2-inducing cytokines IL-4 and IL-13 and protects cells from M1-inducing stimuli LPS and IFN-\u03b3.", "In addition shape- but not cytokine-induced polarization is abrogated when actin and actin/myosin contractility are inhibited by pharmacological agents, suggesting a role for the cytoskeleton in the control of macrophage polarization by cell geometry.", "Our studies demonstrate that alterations in cell shape associated with changes in ECM architecture may provide integral cues to modulate macrophage phenotype polarization."], "title": "Modulation of macrophage phenotype by cell shape."}
{"paper_id": 21880957, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "The prevailing model of bacterial membrane function predicts that the outer membrane is permeable to most small solutes because of pores with limited selectivity based primarily on size. Here, we identified mnoP in the Gram-negative bacterium Bradyrhizobium japonicum as a gene coregulated with the inner membrane Mn(2+) transporter gene mntH. MnoP is an outer membrane protein expressed specifically under manganese limitation. MnoP acts as a channel to facilitate the tranlocation of Mn(2+), but not Co(2+) or Cu(2+), into reconstituted proteoliposomes. An mnoP mutant is defective in high-affinity Mn(2+) transport into cells and has a severe growth phenotype under manganese limitation. We suggest that the outer membrane is a barrier to divalent metal ions that requires a selective channel to meet the nutritional needs of the cell.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["The prevailing model of bacterial membrane function predicts that the outer membrane is permeable to most small solutes because of pores with limited selectivity based primarily on size.", "Here, we identified mnoP in the Gram-negative bacterium Bradyrhizobium japonicum as a gene coregulated with the inner membrane Mn(2+) transporter gene mntH.", "MnoP is an outer membrane protein expressed specifically under manganese limitation.", "MnoP acts as a channel to facilitate the tranlocation of Mn(2+), but not Co(2+) or Cu(2+), into reconstituted proteoliposomes.", "An mnoP mutant is defective in high-affinity Mn(2+) transport into cells and has a severe growth phenotype under manganese limitation.", "We suggest that the outer membrane is a barrier to divalent metal ions that requires a selective channel to meet the nutritional needs of the cell."], "title": "Bacterial outer membrane channel for divalent metal ion acquisition."}
{"paper_id": 26759810, "labels": ["0", "0", "0", "0", "1"], "abstract": "D-Ribose is a five-carbon sugar and generally used as an energy source to improve athletic performance and the ability. The culture conditions for maximum D-ribose production performance from cheap raw material corn starch hydrolysate were improved by using one-factor-at-a-time experiments and a three-level Box-Behnken factorial design. The optimal fermentation parameters were obtained as 36\u00b0C culture temperature, 10% inoculum volume, and 7.0 initial pH. The mathematical model was then developed to show the effect of each medium composition and their interactions on the production of D-ribose and estimated that the optimized D-ribose production performance with the concentration of 62.13\u2009g/L, yield of 0.40\u2009g/g, and volumetric productivity of 0.86\u2009g/L\u00b7h could be obtained when the medium compositions were set as 157\u2009g/L glucose, 21\u2009g/L corn steep liquor, 3.2\u2009g/L (NH4)2SO4, 1\u2009g/L yeast extract, 0.05\u2009g/L MnSO4\u00b7H2O, and 20\u2009g/L CaCO3. These findings indicated the D-ribose production performance was significantly improved compared to that under original conditions.", "journal": "BioMed research international", "sentences": ["D-Ribose is a five-carbon sugar and generally used as an energy source to improve athletic performance and the ability.", "The culture conditions for maximum D-ribose production performance from cheap raw material corn starch hydrolysate were improved by using one-factor-at-a-time experiments and a three-level Box-Behnken factorial design.", "The optimal fermentation parameters were obtained as 36\u00b0C culture temperature, 10% inoculum volume, and 7.0 initial pH.", "The mathematical model was then developed to show the effect of each medium composition and their interactions on the production of D-ribose and estimated that the optimized D-ribose production performance with the concentration of 62.13\u2009g/L, yield of 0.40\u2009g/g, and volumetric productivity of 0.86\u2009g/L\u00b7h could be obtained when the medium compositions were set as 157\u2009g/L glucose, 21\u2009g/L corn steep liquor, 3.2\u2009g/L (NH4)2SO4, 1\u2009g/L yeast extract, 0.05\u2009g/L MnSO4\u00b7H2O, and 20\u2009g/L CaCO3.", "These findings indicated the D-ribose production performance was significantly improved compared to that under original conditions."], "title": "Improvement of D-Ribose Production from Corn Starch Hydrolysate by a Transketolase-Deficient Strain Bacillus subtilis UJS0717."}
{"paper_id": 25835002, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Elevated nighttime blood pressure (BP) and heart rate (HR), increased BP and HR variability, and altered diurnal variations of BP and HR (nighttime dipping and morning surge) in patients with systemic hypertension are each associated with increased adverse cardiovascular events. However, there are no reports on the effect of hypertension treatment on these important hemodynamic parameters in the growing population of hypertensive patients with atherosclerotic coronary artery disease (CAD). This was a pre-specified subgroup analysis of the INternational VErapamil SR-Trandolapril STudy (INVEST), which involved 22,576 clinically stable patients aged \u2265 50 years with hypertension and CAD randomized to either verapamil SR- or atenolol-based hypertension treatment strategies. The subgroup consisted of 117 patients undergoing 24-hour ambulatory monitoring at baseline and after 1 year of treatment. Hourly systolic and diastolic BP (SBP and DBP) decreased after 1 year for both verapamil SR- and atenolol-based treatment strategies compared with baseline (P<0.0001). Atenolol also decreased hourly HR (P<0.0001). Both treatment strategies decreased SBP variability (weighted standard deviation: P = 0.012 and 0.021, respectively). Compared with verapamil SR, atenolol also increased the prevalence of BP and HR nighttime dipping among prior non-dippers (BP: OR = 3.37; 95% CI: 1.26-8.97 P = 0.015; HR: OR = 4.06; 95% CI: 1.35-12.17; P = 0.012) and blunted HR morning surge (+2.8 vs. +4.5 beats/min/hr; P = 0.019). Both verapamil SR- and especially atenolol-based strategies resulted in favorable changes in ambulatory monitoring parameters that have been previously associated with increased adverse cardiovascular events.", "journal": "PloS one", "sentences": ["Elevated nighttime blood pressure (BP) and heart rate (HR), increased BP and HR variability, and altered diurnal variations of BP and HR (nighttime dipping and morning surge) in patients with systemic hypertension are each associated with increased adverse cardiovascular events.", "However, there are no reports on the effect of hypertension treatment on these important hemodynamic parameters in the growing population of hypertensive patients with atherosclerotic coronary artery disease (CAD).", "This was a pre-specified subgroup analysis of the INternational VErapamil SR-Trandolapril STudy (INVEST), which involved 22,576 clinically stable patients aged \u2265 50 years with hypertension and CAD randomized to either verapamil SR- or atenolol-based hypertension treatment strategies.", "The subgroup consisted of 117 patients undergoing 24-hour ambulatory monitoring at baseline and after 1 year of treatment.", "Hourly systolic and diastolic BP (SBP and DBP) decreased after 1 year for both verapamil SR- and atenolol-based treatment strategies compared with baseline (P<0.0001).", "Atenolol also decreased hourly HR (P<0.0001).", "Both treatment strategies decreased SBP variability (weighted standard deviation: P = 0.012 and 0.021, respectively).", "Compared with verapamil SR, atenolol also increased the prevalence of BP and HR nighttime dipping among prior non-dippers (BP: OR = 3.37; 95% CI: 1.26-8.97 P = 0.015; HR: OR = 4.06; 95% CI: 1.35-12.17; P = 0.012) and blunted HR morning surge (+2.8 vs. +4.5 beats/min/hr; P = 0.019).", "Both verapamil SR- and especially atenolol-based strategies resulted in favorable changes in ambulatory monitoring parameters that have been previously associated with increased adverse cardiovascular events."], "title": "Effects of verapamil SR and atenolol on 24-hour blood pressure and heart rate in hypertension patients with coronary artery disease: an international verapamil SR-trandolapril ambulatory monitoring substudy."}
{"paper_id": 23349854, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Two surface glycoproteins of influenza virus, haemagglutinin (HA) and neuraminidase (NA), play opposite roles in terms of their interaction with host sialic acid receptors. HA attaches to sialic acid on host cell surface receptors to initiate virus infection while NA removes these sialic acids to facilitate release of progeny virions. This functional opposition requires a balance. To explore what might happen when NA of an influenza virus was replaced by one from another isolate or subtype, in this study, we generated three recombinant influenza A viruses in the background of A/PR/8/34 (PR8) (H1N1) and with NA genes obtained respectively from the 2009 pandemic H1N1 virus, a highly pathogenic avian H5N1 virus, and a lowly pathogenic avian H9N2 virus. These recombinant viruses, rPR8-H1N1NA, rPR8-H5N1NA, and rPR8-H9N2NA, were shown to have similar growth kinetics in cells and pathogenicity in mice. However, much more rPR8-H5N1NA and PR8-wt virions were released from chicken erythrocytes than virions of rPR8-H1N1NA and rPR8-H9N2NA after 1 h. In addition, in MDCK cells, rPR8-H5N1NA and rPR8-H9N2NA infected a higher percentage of cells, and induced cell-cell fusion faster and more extensively than PR8-wt and rPR8-H1N1NA did in the early phase of infection. In conclusion, NA replacement in this study did not affect virus replication kinetics but had different effects on infection initiation, virus release and fusion of infected cells. These phenomena might be partially due to NA proteins' different specificity to \u03b12-3/2-6-sialylated carbohydrate chains, but the exact mechanism remains to be explored.", "journal": "PloS one", "sentences": ["Two surface glycoproteins of influenza virus, haemagglutinin (HA) and neuraminidase (NA), play opposite roles in terms of their interaction with host sialic acid receptors.", "HA attaches to sialic acid on host cell surface receptors to initiate virus infection while NA removes these sialic acids to facilitate release of progeny virions.", "This functional opposition requires a balance.", "To explore what might happen when NA of an influenza virus was replaced by one from another isolate or subtype, in this study, we generated three recombinant influenza A viruses in the background of A/PR/8/34 (PR8) (H1N1) and with NA genes obtained respectively from the 2009 pandemic H1N1 virus, a highly pathogenic avian H5N1 virus, and a lowly pathogenic avian H9N2 virus.", "These recombinant viruses, rPR8-H1N1NA, rPR8-H5N1NA, and rPR8-H9N2NA, were shown to have similar growth kinetics in cells and pathogenicity in mice.", "However, much more rPR8-H5N1NA and PR8-wt virions were released from chicken erythrocytes than virions of rPR8-H1N1NA and rPR8-H9N2NA after 1 h. In addition, in MDCK cells, rPR8-H5N1NA and rPR8-H9N2NA infected a higher percentage of cells, and induced cell-cell fusion faster and more extensively than PR8-wt and rPR8-H1N1NA did in the early phase of infection.", "In conclusion, NA replacement in this study did not affect virus replication kinetics but had different effects on infection initiation, virus release and fusion of infected cells.", "These phenomena might be partially due to NA proteins' different specificity to \u03b12-3/2-6-sialylated carbohydrate chains, but the exact mechanism remains to be explored."], "title": "NA proteins of influenza A viruses H1N1/2009, H5N1, and H9N2 show differential effects on infection initiation, virus release, and cell-cell fusion."}
{"paper_id": 23285100, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Combinations of proteasome inhibitors and histone deacetylases (HDAC) inhibitors appear to be the most potent to produce synergistic cytotoxicity in preclinical trials. We have recently confirmed that L-carnitine (LC) is an endogenous HDAC inhibitor. In the current study, the anti-tumor effect of LC plus proteasome inhibitor bortezomib (velcade, Vel) was investigated both in cultured hepatoma cancer cells and in Balb/c mice bearing HepG2 tumor. Cell death and cell viability were assayed by flow cytometry and MTS, respectively. Gene, mRNA expression and protein levels were detected by gene microarray, quantitative real-time PCR and Western blot, respectively. The effect of Vel on the acetylation of histone H3 associated with the p21(cip1) gene promoter was examined by using ChIP assay and proteasome peptidase activity was detected by cell-based chymotrypsin-like (CT-like) activity assay. Here we report that (i) the combination of LC and Vel synergistically induces cytotoxicity in vitro; (ii) the combination also synergistically inhibits tumor growth in vivo; (iii) two major pathways are involved in the synergistical effects of the combinational treatment: increased p21(cip1) expression and histone acetylation in vitro and in vivo and enhanced Vel-induced proteasome inhibition by LC. The synergistic effect of LC and Vel in cancer therapy should have great potential in the future clinical trials.", "journal": "PloS one", "sentences": ["Combinations of proteasome inhibitors and histone deacetylases (HDAC) inhibitors appear to be the most potent to produce synergistic cytotoxicity in preclinical trials.", "We have recently confirmed that L-carnitine (LC) is an endogenous HDAC inhibitor.", "In the current study, the anti-tumor effect of LC plus proteasome inhibitor bortezomib (velcade, Vel) was investigated both in cultured hepatoma cancer cells and in Balb/c mice bearing HepG2 tumor.", "Cell death and cell viability were assayed by flow cytometry and MTS, respectively.", "Gene, mRNA expression and protein levels were detected by gene microarray, quantitative real-time PCR and Western blot, respectively.", "The effect of Vel on the acetylation of histone H3 associated with the p21(cip1) gene promoter was examined by using ChIP assay and proteasome peptidase activity was detected by cell-based chymotrypsin-like (CT-like) activity assay.", "Here we report that (i) the combination of LC and Vel synergistically induces cytotoxicity in vitro; (ii) the combination also synergistically inhibits tumor growth in vivo; (iii) two major pathways are involved in the synergistical effects of the combinational treatment: increased p21(cip1) expression and histone acetylation in vitro and in vivo and enhanced Vel-induced proteasome inhibition by LC.", "The synergistic effect of LC and Vel in cancer therapy should have great potential in the future clinical trials."], "title": "HDAC inhibitor L-carnitine and proteasome inhibitor bortezomib synergistically exert anti-tumor activity in vitro and in vivo."}
{"paper_id": 26503169, "labels": ["0", "0", "0", "0", "1", "1"], "abstract": "Regeneration relies on coordinated action of multiple cell types to reconstitute the damaged tissue. Here we inactivate the endocytic adaptor protein Numb in skeletal muscle stem cells prior to chronic or severe muscle injury in mice. We observe two types of senescence in regenerating muscle; a transient senescence in non-myogenic cells of control and Numb mutant mice that partly depends on INK4a/ARF activity, and a persistent senescence in myogenic cells lacking Numb. The senescence levels of Numb-deficient muscle is reduced to wild type levels by an anti-oxidant treatment or p53 ablation, resulting in functional rescue of the regenerative potential in Numb mutants. Ex vivo experiments suggest that Numb-deficient senescent cells recruit macrophages to sustain inflammation and drive fibrosis, two hallmarks of the impaired muscle regeneration in Numb mutants. These findings provide insights into previously reported developmental and oncogenic senescence that are also differentially regulated by p53.", "journal": "Nature communications", "sentences": ["Regeneration relies on coordinated action of multiple cell types to reconstitute the damaged tissue.", "Here we inactivate the endocytic adaptor protein Numb in skeletal muscle stem cells prior to chronic or severe muscle injury in mice.", "We observe two types of senescence in regenerating muscle; a transient senescence in non-myogenic cells of control and Numb mutant mice that partly depends on INK4a/ARF activity, and a persistent senescence in myogenic cells lacking Numb.", "The senescence levels of Numb-deficient muscle is reduced to wild type levels by an anti-oxidant treatment or p53 ablation, resulting in functional rescue of the regenerative potential in Numb mutants.", "Ex vivo experiments suggest that Numb-deficient senescent cells recruit macrophages to sustain inflammation and drive fibrosis, two hallmarks of the impaired muscle regeneration in Numb mutants.", "These findings provide insights into previously reported developmental and oncogenic senescence that are also differentially regulated by p53."], "title": "Numb is required to prevent p53-dependent senescence following skeletal muscle injury."}
{"paper_id": 25725465, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "A green method for phenol spectrophotometric determination was developed based on the color reaction of phenol with 4-aminoantipyrine catalyzed by addition of Bacillus amyloliquefaciens endospores in the presence of O2. The catalytic activity of the endospores may be attributed to the presence of coat protein A on the cell surfaces. This deduction was confirmed by cotA gene knock-out from B. amyloliquefaciens using the homologous double-exchange method. Under optimal conditions, linear responses were obtained over phenol concentrations ranging from 5.0\u00d710(-5)gL(-1) to 1.0\u00d710(-2)gL(-1) (r=0.9984) with a detection limit of 2.1\u00d710(-5)gL(-1) (3\u03c3). Repeatability measurements of 1.0mgL(-1) phenol provided reproducible results with a relative standard deviation of 5.3% (n=11). Standard addition tests indicated recoveries ranging from 92.78% to 107.60%. The proposed whole-cell method was successfully used to detect total phenol in synthetic samples. Results confirmed the potential use of the developed method in practical applications.", "journal": "Biosensors & bioelectronics", "sentences": ["A green method for phenol spectrophotometric determination was developed based on the color reaction of phenol with 4-aminoantipyrine catalyzed by addition of Bacillus amyloliquefaciens endospores in the presence of O2.", "The catalytic activity of the endospores may be attributed to the presence of coat protein A on the cell surfaces.", "This deduction was confirmed by cotA gene knock-out from B. amyloliquefaciens using the homologous double-exchange method.", "Under optimal conditions, linear responses were obtained over phenol concentrations ranging from 5.0\u00d710(-5)gL(-1) to 1.0\u00d710(-2)gL(-1) (r=0.9984) with a detection limit of 2.1\u00d710(-5)gL(-1) (3\u03c3).", "Repeatability measurements of 1.0mgL(-1) phenol provided reproducible results with a relative standard deviation of 5.3% (n=11).", "Standard addition tests indicated recoveries ranging from 92.78% to 107.60%.", "The proposed whole-cell method was successfully used to detect total phenol in synthetic samples.", "Results confirmed the potential use of the developed method in practical applications."], "title": "Whole-cell method for phenol detection based on the color reaction of phenol with 4-aminoantipyrine catalyzed by CotA laccase on endospore surfaces."}
{"paper_id": 21386968, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Acinetobacter baumannii is an important nosocomial pathogen that causes a high morbidity and mortality rate in infected patients, but pathogenic mechanisms of this microorganism regarding the secretion and delivery of virulence factors to host cells have not been characterized. Gram-negative bacteria naturally secrete outer membrane vesicles (OMVs) that play a role in the delivery of virulence factors to host cells. A. baumannii has been shown to secrete OMVs when cultured in vitro, but the role of OMVs in A. baumannii pathogenesis is not well elucidated. In the present study, we evaluated the secretion and delivery of virulence factors of A. baumannii to host cells via the OMVs and assessed the cytotoxic activity of outer membrane protein A (AbOmpA) packaged in the OMVs. A. baumannii ATCC 19606(T) secreted OMVs during in vivo infection as well as in vitro cultures. Potential virulence factors, including AbOmpA and tissue-degrading enzymes, were associated with A. baumannii OMVs. A. baumannii OMVs interacted with lipid rafts in the plasma membranes and then delivered virulence factors to host cells. The OMVs from A. baumannii ATCC 19606(T) induced apoptosis of host cells, whereas this effect was not detected in the OMVs from the \u0394ompA mutant, thereby reflecting AbOmpA-dependent host cell death. The N-terminal region of AbOmpA(22-170) was responsible for host cell death. In conclusion, the OMV-mediated delivery of virulence factors to host cells may well contribute to pathogenesis during A. baumannii infection.", "journal": "PloS one", "sentences": ["Acinetobacter baumannii is an important nosocomial pathogen that causes a high morbidity and mortality rate in infected patients, but pathogenic mechanisms of this microorganism regarding the secretion and delivery of virulence factors to host cells have not been characterized.", "Gram-negative bacteria naturally secrete outer membrane vesicles (OMVs) that play a role in the delivery of virulence factors to host cells.", "A. baumannii has been shown to secrete OMVs when cultured in vitro, but the role of OMVs in A. baumannii pathogenesis is not well elucidated.", "In the present study, we evaluated the secretion and delivery of virulence factors of A. baumannii to host cells via the OMVs and assessed the cytotoxic activity of outer membrane protein A (AbOmpA) packaged in the OMVs.", "A. baumannii ATCC 19606(T) secreted OMVs during in vivo infection as well as in vitro cultures.", "Potential virulence factors, including AbOmpA and tissue-degrading enzymes, were associated with A. baumannii OMVs.", "A. baumannii OMVs interacted with lipid rafts in the plasma membranes and then delivered virulence factors to host cells.", "The OMVs from A. baumannii ATCC 19606(T) induced apoptosis of host cells, whereas this effect was not detected in the OMVs from the \u0394ompA mutant, thereby reflecting AbOmpA-dependent host cell death.", "The N-terminal region of AbOmpA(22-170) was responsible for host cell death.", "In conclusion, the OMV-mediated delivery of virulence factors to host cells may well contribute to pathogenesis during A. baumannii infection."], "title": "Acinetobacter baumannii secretes cytotoxic outer membrane protein A via outer membrane vesicles."}
{"paper_id": 20431432, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "This is not a prospective randomized clinical trial or a consecutive case series, but rather the description of a technique developed years ago, but still applicable. As spine surgeons, we wish to know the true correctability of a curvature before determining the best method of treatment. Do we need to do a posterior surgery only? Do we need to do a combined anterior and posterior surgery? Do we need to place the patient in preoperative skeletal traction? Although many different techniques have been described for the determination of true curve flexibility, the Moe Maximal Correction Test has never before been described.", "journal": "Spine", "sentences": ["This is not a prospective randomized clinical trial or a consecutive case series, but rather the description of a technique developed years ago, but still applicable.", "As spine surgeons, we wish to know the true correctability of a curvature before determining the best method of treatment.", "Do we need to do a posterior surgery only?", "Do we need to do a combined anterior and posterior surgery?", "Do we need to place the patient in preoperative skeletal traction?", "Although many different techniques have been described for the determination of true curve flexibility, the Moe Maximal Correction Test has never before been described."], "title": "The Moe Maximal Correction Test to determine true curve flexibility: a historical note with current application."}
{"paper_id": 24639514, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "The mammalian gut is a dynamic community of symbiotic microbes that interact with the host to impact health, disease, and metabolism. We constructed engineered bacteria that survive in the mammalian gut and sense, remember, and report on their experiences. Based on previous genetic memory systems, we constructed a two-part system with a \"trigger element\" in which the lambda Cro gene is transcribed from a tetracycline-inducible promoter, and a \"memory element\" derived from the cI/Cro region of phage lambda. The memory element has an extremely stable cI state and a Cro state that is stable for many cell divisions. When Escherichia coli bearing the memory system are administered to mice treated with anhydrotetracycline, the recovered bacteria all have switched to the Cro state, whereas those administered to untreated mice remain in the cI state. The trigger and memory elements were transferred from E. coli K12 to a newly isolated murine E. coli strain; the stability and switching properties of the memory element were essentially identical in vitro and during passage through mice, but the engineered murine E. coli was more stably established in the mouse gut. This work lays a foundation for the use of synthetic genetic circuits as monitoring systems in complex, ill-defined environments, and may lead to the development of living diagnostics and therapeutics.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["The mammalian gut is a dynamic community of symbiotic microbes that interact with the host to impact health, disease, and metabolism.", "We constructed engineered bacteria that survive in the mammalian gut and sense, remember, and report on their experiences.", "Based on previous genetic memory systems, we constructed a two-part system with a \"trigger element\" in which the lambda Cro gene is transcribed from a tetracycline-inducible promoter, and a \"memory element\" derived from the cI/Cro region of phage lambda.", "The memory element has an extremely stable cI state and a Cro state that is stable for many cell divisions.", "When Escherichia coli bearing the memory system are administered to mice treated with anhydrotetracycline, the recovered bacteria all have switched to the Cro state, whereas those administered to untreated mice remain in the cI state.", "The trigger and memory elements were transferred from E. coli K12 to a newly isolated murine E. coli strain; the stability and switching properties of the memory element were essentially identical in vitro and during passage through mice, but the engineered murine E. coli was more stably established in the mouse gut.", "This work lays a foundation for the use of synthetic genetic circuits as monitoring systems in complex, ill-defined environments, and may lead to the development of living diagnostics and therapeutics."], "title": "Programmable bacteria detect and record an environmental signal in the mammalian gut."}
{"paper_id": 27535914, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "UNLABELLED\nThe bed nuclei of the stria terminalis (BST) are critically important for integrating stress-related signals between the limbic forebrain and hypothalamo-pituitary-adrenal (HPA) effector neurons in the paraventricular hypothalamus (PVH). Nevertheless, the circuitry underlying BST control over the stress axis and its role in depression-related behaviors has remained obscure. Utilizing optogenetic approaches in rats, we have identified a novel role for the anteroventral subdivision of BST in the coordinated inhibition of both HPA output and passive coping behaviors during acute inescapable (tail suspension, TS) stress. Follow-up experiments probed axonal pathways emanating from the anteroventral BST which accounted for separable endocrine and behavioral functions subserved by this cell group. The PVH and ventrolateral periaqueductal gray were recipients of GABAergic outputs from the anteroventral BST that were necessary to restrain stress-induced HPA activation and passive coping behavior, respectively, during TS and forced swim tests. In contrast to other BST subdivisions implicated in anxiety-like responses, these results direct attention to the anteroventral BST as a nodal point in a stress-modulatory network for coordinating neuroendocrine and behavioral coping responses, wherein impairment could account for core features of stress-related mood disorders.\n\n\nSIGNIFICANCE STATEMENT\nDysregulation of the neural pathways modulating stress-adaptive behaviors is implicated in stress-related psychiatric illness. While aversive situations activate a network of limbic forebrain regions thought to mediate such changes, little is known about how this information is integrated to orchestrate complex stress responses. Here we identify novel roles for the anteroventral bed nuclei of the stria terminalis in inhibiting both stress hormone output and passive coping behavior via divergent projections to regions of the hypothalamus and midbrain. Inhibition of these projections produced features observed with rodent models of depression, namely stress hormone hypersecretion and increased passive coping behavior, suggesting that dysfunction in these networks may contribute to expression of pathological changes in stress-related disorders.", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "sentences": ["UNLABELLED\nThe bed nuclei of the stria terminalis (BST) are critically important for integrating stress-related signals between the limbic forebrain and hypothalamo-pituitary-adrenal (HPA) effector neurons in the paraventricular hypothalamus (PVH).", "Nevertheless, the circuitry underlying BST control over the stress axis and its role in depression-related behaviors has remained obscure.", "Utilizing optogenetic approaches in rats, we have identified a novel role for the anteroventral subdivision of BST in the coordinated inhibition of both HPA output and passive coping behaviors during acute inescapable (tail suspension, TS) stress.", "Follow-up experiments probed axonal pathways emanating from the anteroventral BST which accounted for separable endocrine and behavioral functions subserved by this cell group.", "The PVH and ventrolateral periaqueductal gray were recipients of GABAergic outputs from the anteroventral BST that were necessary to restrain stress-induced HPA activation and passive coping behavior, respectively, during TS and forced swim tests.", "In contrast to other BST subdivisions implicated in anxiety-like responses, these results direct attention to the anteroventral BST as a nodal point in a stress-modulatory network for coordinating neuroendocrine and behavioral coping responses, wherein impairment could account for core features of stress-related mood disorders.", "SIGNIFICANCE STATEMENT\nDysregulation of the neural pathways modulating stress-adaptive behaviors is implicated in stress-related psychiatric illness.", "While aversive situations activate a network of limbic forebrain regions thought to mediate such changes, little is known about how this information is integrated to orchestrate complex stress responses.", "Here we identify novel roles for the anteroventral bed nuclei of the stria terminalis in inhibiting both stress hormone output and passive coping behavior via divergent projections to regions of the hypothalamus and midbrain.", "Inhibition of these projections produced features observed with rodent models of depression, namely stress hormone hypersecretion and increased passive coping behavior, suggesting that dysfunction in these networks may contribute to expression of pathological changes in stress-related disorders."], "title": "A Basal Forebrain Site Coordinates the Modulation of Endocrine and Behavioral Stress Responses via Divergent Neural Pathways."}
{"paper_id": 25632387, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Phosphate solubilizing bacteria (PSB) can convert insoluble form of phosphorous to an available form. Applications of PSB as inoculants increase the phosphorus uptake by plant in the field. In this study, isolation and precise identification of PSB were carried out in Malaysian (Serdang) oil palm field (University Putra Malaysia). Identification and phylogenetic analysis of 8 better isolates were carried out by 16S rRNA gene sequencing in which as a result five isolates belong to the Beta subdivision of Proteobacteria, one isolate was related to the Gama subdivision of Proteobacteria, and two isolates were related to the Firmicutes. Bacterial isolates of 6upmr, 2upmr, 19upmnr, 10upmr, and 24upmr were identified as Alcaligenes faecalis. Also, bacterial isolates of 20upmnr and 17upmnr were identified as Bacillus cereus and Vagococcus carniphilus, respectively, and bacterial isolates of 31upmr were identified as Serratia plymuthica. Molecular identification and characterization of oil palm strains as the specific phosphate solubilizer can reduce the time and cost of producing effective inoculate (biofertilizer) in an oil palm field.", "journal": "BioMed research international", "sentences": ["Phosphate solubilizing bacteria (PSB) can convert insoluble form of phosphorous to an available form.", "Applications of PSB as inoculants increase the phosphorus uptake by plant in the field.", "In this study, isolation and precise identification of PSB were carried out in Malaysian (Serdang) oil palm field (University Putra Malaysia).", "Identification and phylogenetic analysis of 8 better isolates were carried out by 16S rRNA gene sequencing in which as a result five isolates belong to the Beta subdivision of Proteobacteria, one isolate was related to the Gama subdivision of Proteobacteria, and two isolates were related to the Firmicutes.", "Bacterial isolates of 6upmr, 2upmr, 19upmnr, 10upmr, and 24upmr were identified as Alcaligenes faecalis.", "Also, bacterial isolates of 20upmnr and 17upmnr were identified as Bacillus cereus and Vagococcus carniphilus, respectively, and bacterial isolates of 31upmr were identified as Serratia plymuthica.", "Molecular identification and characterization of oil palm strains as the specific phosphate solubilizer can reduce the time and cost of producing effective inoculate (biofertilizer) in an oil palm field."], "title": "Phylogenetic relationship of phosphate solubilizing bacteria according to 16S rRNA genes."}
{"paper_id": 26627125, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "The advent of autonomous self-propulsion has instigated research towards making colloidal machines that can deliver mechanical work in the form of transport, and other functions such as sensing and cleaning. While much progress has been made in the last 10 years on various mechanisms to generate self-propulsion, the ability to steer self-propelled colloidal devices has so far been much more limited. A critical barrier in increasing the impact of such motors is in directing their motion against the Brownian rotation, which randomizes particle orientations. In this context, here we report directed motion of a specific class of catalytic motors when moving in close proximity to solid surfaces. This is achieved through active quenching of their Brownian rotation by constraining it in a rotational well, caused not by equilibrium, but by hydrodynamic effects. We demonstrate how combining these geometric constraints can be utilized to steer these active colloids along arbitrary trajectories.", "journal": "Nature communications", "sentences": ["The advent of autonomous self-propulsion has instigated research towards making colloidal machines that can deliver mechanical work in the form of transport, and other functions such as sensing and cleaning.", "While much progress has been made in the last 10 years on various mechanisms to generate self-propulsion, the ability to steer self-propelled colloidal devices has so far been much more limited.", "A critical barrier in increasing the impact of such motors is in directing their motion against the Brownian rotation, which randomizes particle orientations.", "In this context, here we report directed motion of a specific class of catalytic motors when moving in close proximity to solid surfaces.", "This is achieved through active quenching of their Brownian rotation by constraining it in a rotational well, caused not by equilibrium, but by hydrodynamic effects.", "We demonstrate how combining these geometric constraints can be utilized to steer these active colloids along arbitrary trajectories."], "title": "Boundaries can steer active Janus spheres."}
{"paper_id": 21425879, "labels": ["0", "0", "0", "0", "0", "0", "1", "0"], "abstract": "The fraudulent treatment of cattle with growth promoting agents (GPAs) is a matter of great concern for the European Union (EU) authorities and consumers. It has been estimated that 10% of animals are being illegally treated in the EU. In contrast, only a much lower percentage of animals (<0.5%) are actually found as being noncompliant by conventional analytical methods. Thus, it has been proposed that methods should be developed that can detect the use of the substances via the biological effects of these substances on target organs, such as the alteration of protein expression profiles. Here we present a study aimed at evaluating if a correlation exists between the treatment with GPAs and alterations in the two-dimensional electrophoresis (2DE) protein pattern obtained from the biceps brachii skeletal muscle from mixed-bred cattle. After image analysis and statistical evaluation, protein spots that differentiate between treated and control groups were selected for analysis by mass spectrometry. A set of proteins could be defined that accurately detect the use of glucocorticoids and \u03b2(2)-agonists as growth promoters through the changes caused in muscle differentiation. As a further validation, we repeated the analysis using an independent set of samples from a strain of pure-bred cattle and verified these proteins by Western blot analysis.", "journal": "Journal of proteome research", "sentences": ["The fraudulent treatment of cattle with growth promoting agents (GPAs) is a matter of great concern for the European Union (EU) authorities and consumers.", "It has been estimated that 10% of animals are being illegally treated in the EU.", "In contrast, only a much lower percentage of animals (<0.5%) are actually found as being noncompliant by conventional analytical methods.", "Thus, it has been proposed that methods should be developed that can detect the use of the substances via the biological effects of these substances on target organs, such as the alteration of protein expression profiles.", "Here we present a study aimed at evaluating if a correlation exists between the treatment with GPAs and alterations in the two-dimensional electrophoresis (2DE) protein pattern obtained from the biceps brachii skeletal muscle from mixed-bred cattle.", "After image analysis and statistical evaluation, protein spots that differentiate between treated and control groups were selected for analysis by mass spectrometry.", "A set of proteins could be defined that accurately detect the use of glucocorticoids and \u03b2(2)-agonists as growth promoters through the changes caused in muscle differentiation.", "As a further validation, we repeated the analysis using an independent set of samples from a strain of pure-bred cattle and verified these proteins by Western blot analysis."], "title": "Protein expression changes in skeletal muscle in response to growth promoter abuse in beef cattle."}
{"paper_id": 26505352, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "APETALA2 plays critical roles in establishing meristem and organ identity during plant floral development. In this study, we obtained a CeAP2-like gene by using the mRNA differential display technique to analyze the wild type and a multitepal mutant of the orchid Cymbidium ensifolium. The full-length cDNA encoding the CeAP2-like transcription factor shows significant similarity to the cDNA of AP2 from Erycina pusilla and contains nucleotides complementary to miR172. Using a transient gene expression system of Arabidopsis protoplasts, we found that the accumulation of CeAP2-like protein and transcripts was negatively regulated by miR172, indicating this gene as a putative target of miR172. Northern blotting revealed that CeAP2-like is dominantly expressed in the sepals and petals of the wild-type flower, and shows low expression in the gynostemium. In contrast, the accumulation of CeAP2-like transcripts decreased significantly, especially in the central part of the mutant flower, corresponding to its abnormal petals and the absence of the gynostemium. Furthermore, we found an antagonistic expression pattern between CeAP2-like and AGAMOUS in the wild type, representing A- and C-class genes that specify floral organ fate. However, this antagonistic distribution was modified in the multitepal mutant, and both genes showed lower expression than that in the wild type. This result suggested that the balance between CeAP2-like and AGAMOUS activity was important for the regulation of floral patterning in C. ensifolium. This study represents the first report on a class A gene and its regulatory role for floral development in the orchid C. ensifolium.", "journal": "Genetics and molecular research : GMR", "sentences": ["APETALA2 plays critical roles in establishing meristem and organ identity during plant floral development.", "In this study, we obtained a CeAP2-like gene by using the mRNA differential display technique to analyze the wild type and a multitepal mutant of the orchid Cymbidium ensifolium.", "The full-length cDNA encoding the CeAP2-like transcription factor shows significant similarity to the cDNA of AP2 from Erycina pusilla and contains nucleotides complementary to miR172.", "Using a transient gene expression system of Arabidopsis protoplasts, we found that the accumulation of CeAP2-like protein and transcripts was negatively regulated by miR172, indicating this gene as a putative target of miR172.", "Northern blotting revealed that CeAP2-like is dominantly expressed in the sepals and petals of the wild-type flower, and shows low expression in the gynostemium.", "In contrast, the accumulation of CeAP2-like transcripts decreased significantly, especially in the central part of the mutant flower, corresponding to its abnormal petals and the absence of the gynostemium.", "Furthermore, we found an antagonistic expression pattern between CeAP2-like and AGAMOUS in the wild type, representing A- and C-class genes that specify floral organ fate.", "However, this antagonistic distribution was modified in the multitepal mutant, and both genes showed lower expression than that in the wild type.", "This result suggested that the balance between CeAP2-like and AGAMOUS activity was important for the regulation of floral patterning in C. ensifolium.", "This study represents the first report on a class A gene and its regulatory role for floral development in the orchid C. ensifolium."], "title": "A putative miR172-targeted CeAPETALA2-like gene is involved in floral patterning regulation of the orchid Cymbidium ensifolium."}
{"paper_id": 26812621, "labels": ["0", "0", "1", "0", "0", "0", "0", "1"], "abstract": "Nuclear hormone receptors have important roles in the regulation of metabolic and inflammatory pathways. The retinoid-related orphan receptor alpha (Ror\u03b1)-deficient staggerer (sg/sg) mice display several phenotypes indicative of aberrant lipid metabolism, including dyslipidemia, and increased susceptibility to atherosclerosis. In this study we demonstrate that macrophages from sg/sg mice have increased ability to accumulate lipids and accordingly exhibit larger lipid droplets (LD). We have previously shown that BMMs from sg/sg mice have significantly decreased expression of cholesterol 25-hydroxylase (Ch25h) mRNA, the enzyme that produces the oxysterol, 25-hydroxycholesterol (25HC), and now confirm this at the protein level. 25HC functions as an inverse agonist for ROR\u03b1. siRNA knockdown of Ch25h in macrophages up-regulates Vldlr mRNA expression and causes increased accumulation of LDs. Treatment with physiological concentrations of 25HC in sg/sg macrophages restored lipid accumulation back to normal levels. Thus, 25HC and ROR\u03b1 signify a new pathway involved in the regulation of lipid homeostasis in macrophages, potentially via increased uptake of lipid which is suggested by mRNA expression changes in Vldlr and other related genes.", "journal": "PloS one", "sentences": ["Nuclear hormone receptors have important roles in the regulation of metabolic and inflammatory pathways.", "The retinoid-related orphan receptor alpha (Ror\u03b1)-deficient staggerer (sg/sg) mice display several phenotypes indicative of aberrant lipid metabolism, including dyslipidemia, and increased susceptibility to atherosclerosis.", "In this study we demonstrate that macrophages from sg/sg mice have increased ability to accumulate lipids and accordingly exhibit larger lipid droplets (LD).", "We have previously shown that BMMs from sg/sg mice have significantly decreased expression of cholesterol 25-hydroxylase (Ch25h) mRNA, the enzyme that produces the oxysterol, 25-hydroxycholesterol (25HC), and now confirm this at the protein level.", "25HC functions as an inverse agonist for ROR\u03b1.", "siRNA knockdown of Ch25h in macrophages up-regulates Vldlr mRNA expression and causes increased accumulation of LDs.", "Treatment with physiological concentrations of 25HC in sg/sg macrophages restored lipid accumulation back to normal levels.", "Thus, 25HC and ROR\u03b1 signify a new pathway involved in the regulation of lipid homeostasis in macrophages, potentially via increased uptake of lipid which is suggested by mRNA expression changes in Vldlr and other related genes."], "title": "ROR\u03b1 and 25-Hydroxycholesterol Crosstalk Regulates Lipid Droplet Homeostasis in Macrophages."}
{"paper_id": 26808689, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Improvement of cognitive impairments represents a high medical need in the development of new antipsychotics. Aberrant EEG gamma oscillations and reductions in the P1/N1 complex peak amplitude of the auditory evoked potential (AEP) are neurophysiological biomarkers for schizophrenia that indicate disruption in sensory information processing. Inhibition of phosphodiesterase (i.e. PDE10A) and activation of metabotropic glutamate receptor (mGluR2) signaling are believed to provide antipsychotic efficacy in schizophrenia, but it is unclear whether this occurs with cognition-enhancing potential. The present study used the auditory paired click paradigm in passive awake Sprague Dawley rats to 1) model disruption of AEP waveforms and oscillations as observed in schizophrenia by peripheral administration of amphetamine and the N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP); 2) confirm the potential of the antipsychotics risperidone and olanzapine to attenuate these disruptions; 3) evaluate the potential of mGluR2 agonist LY404039 and PDE10 inhibitor PQ-10 to improve AEP deficits in both the amphetamine and PCP models. PCP and amphetamine disrupted auditory information processing to the first click, associated with suppression of the P1/N1 complex peak amplitude, and increased cortical gamma oscillations. Risperidone and olanzapine normalized PCP and amphetamine-induced abnormalities in AEP waveforms and aberrant gamma/alpha oscillations, respectively. LY404039 increased P1/N1 complex peak amplitudes and potently attenuated the disruptive effects of both PCP and amphetamine on AEPs amplitudes and oscillations. However, PQ-10 failed to show such effect in either models. These outcomes indicate that modulation of the mGluR2 results in effective restoration of abnormalities in AEP components in two widely used animal models of psychosis, whereas PDE10A inhibition does not.", "journal": "PloS one", "sentences": ["Improvement of cognitive impairments represents a high medical need in the development of new antipsychotics.", "Aberrant EEG gamma oscillations and reductions in the P1/N1 complex peak amplitude of the auditory evoked potential (AEP) are neurophysiological biomarkers for schizophrenia that indicate disruption in sensory information processing.", "Inhibition of phosphodiesterase (i.e.", "PDE10A) and activation of metabotropic glutamate receptor (mGluR2) signaling are believed to provide antipsychotic efficacy in schizophrenia, but it is unclear whether this occurs with cognition-enhancing potential.", "The present study used the auditory paired click paradigm in passive awake Sprague Dawley rats to 1) model disruption of AEP waveforms and oscillations as observed in schizophrenia by peripheral administration of amphetamine and the N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP); 2) confirm the potential of the antipsychotics risperidone and olanzapine to attenuate these disruptions; 3) evaluate the potential of mGluR2 agonist LY404039 and PDE10 inhibitor PQ-10 to improve AEP deficits in both the amphetamine and PCP models.", "PCP and amphetamine disrupted auditory information processing to the first click, associated with suppression of the P1/N1 complex peak amplitude, and increased cortical gamma oscillations.", "Risperidone and olanzapine normalized PCP and amphetamine-induced abnormalities in AEP waveforms and aberrant gamma/alpha oscillations, respectively.", "LY404039 increased P1/N1 complex peak amplitudes and potently attenuated the disruptive effects of both PCP and amphetamine on AEPs amplitudes and oscillations.", "However, PQ-10 failed to show such effect in either models.", "These outcomes indicate that modulation of the mGluR2 results in effective restoration of abnormalities in AEP components in two widely used animal models of psychosis, whereas PDE10A inhibition does not."], "title": "Modulation of mGlu2 Receptors, but Not PDE10A Inhibition Normalizes Pharmacologically-Induced Deviance in Auditory Evoked Potentials and Oscillations in Conscious Rats."}
{"paper_id": 25023666, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "More than 33,000 glycosyltransferases have been identified. Structural studies, however, have only revealed two distinct glycosyltransferase (GT) folds, GT-A and GT-B. Here we report a 1.34-\u00c5 resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. DUF1792 homologues from both Gram-positive and Gram-negative bacteria also exhibit the activity. Thus, DUF1792 represents a new family of glycosyltransferases; therefore, we designate it as a GT-D glycosyltransferase fold. As the domain is highly conserved in bacteria and not found in eukaryotes, it can be explored as a new antibacterial target.", "journal": "Nature communications", "sentences": ["More than 33,000 glycosyltransferases have been identified.", "Structural studies, however, have only revealed two distinct glycosyltransferase (GT) folds, GT-A and GT-B.", "Here we report a 1.34-\u00c5 resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins.", "Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis.", "DUF1792 homologues from both Gram-positive and Gram-negative bacteria also exhibit the activity.", "Thus, DUF1792 represents a new family of glycosyltransferases; therefore, we designate it as a GT-D glycosyltransferase fold.", "As the domain is highly conserved in bacteria and not found in eukaryotes, it can be explored as a new antibacterial target."], "title": "The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold."}
{"paper_id": 27488197, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Arsenic is a ubiquitous element which may be found in surface water, groundwater, and drinking water. In higher concentrations, this element is considered genotoxic and carcinogenic; thus, its level must be strictly controlled. We investigated the concentration of total arsenic and arsenic species: As(III), As(V), MMA, DMA, and AsB in drinking water, surface water, wastewater, and snow collected from the provinces of Wielkopolska, Kujawy-Pomerania, and Lower Silesia (Poland). The total arsenic was analyzed by inductively coupled plasma mass spectrometry (ICP-MS), and arsenic species were analyzed with use of high-performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC/ICP-MS). Obtained results revealed that maximum total arsenic concentration determined in drinking water samples was equal to 1.01\u00a0\u03bcg\u00a0L(-1). The highest concentration of total arsenic in surface water, equal to 3778\u00a0\u03bcg\u00a0L(-1) was determined in Truj\u0105ca Stream situated in the area affected by geogenic arsenic contamination. Total arsenic concentration in wastewater samples was comparable to those determined in drinking water samples. However, significantly higher arsenic concentration, equal to 83.1\u00a0\u00b1\u00a05.9\u00a0\u03bcg\u00a0L(-1), was found in a snow sample collected in Legnica. As(V) was present in all of the investigated samples, and in most of them, it was the sole species observed. However, in snow sample collected in Legnica, more than 97\u00a0% of the determined concentration, amounting to 81\u00a0\u00b1\u00a011\u00a0\u03bcg\u00a0L(-1), was in the form of As(III), the most toxic arsenic species.", "journal": "Environmental monitoring and assessment", "sentences": ["Arsenic is a ubiquitous element which may be found in surface water, groundwater, and drinking water.", "In higher concentrations, this element is considered genotoxic and carcinogenic; thus, its level must be strictly controlled.", "We investigated the concentration of total arsenic and arsenic species: As(III), As(V), MMA, DMA, and AsB in drinking water, surface water, wastewater, and snow collected from the provinces of Wielkopolska, Kujawy-Pomerania, and Lower Silesia (Poland).", "The total arsenic was analyzed by inductively coupled plasma mass spectrometry (ICP-MS), and arsenic species were analyzed with use of high-performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC/ICP-MS).", "Obtained results revealed that maximum total arsenic concentration determined in drinking water samples was equal to 1.01\u00a0\u03bcg\u00a0L(-1).", "The highest concentration of total arsenic in surface water, equal to 3778\u00a0\u03bcg\u00a0L(-1) was determined in Truj\u0105ca Stream situated in the area affected by geogenic arsenic contamination.", "Total arsenic concentration in wastewater samples was comparable to those determined in drinking water samples.", "However, significantly higher arsenic concentration, equal to 83.1\u00a0\u00b1\u00a05.9\u00a0\u03bcg\u00a0L(-1), was found in a snow sample collected in Legnica.", "As(V) was present in all of the investigated samples, and in most of them, it was the sole species observed.", "However, in snow sample collected in Legnica, more than 97\u00a0% of the determined concentration, amounting to 81\u00a0\u00b1\u00a011\u00a0\u03bcg\u00a0L(-1), was in the form of As(III), the most toxic arsenic species."], "title": "Determination of total arsenic and arsenic species in drinking water, surface water, wastewater, and snow from Wielkopolska, Kujawy-Pomerania, and Lower Silesia provinces, Poland."}
{"paper_id": 24642514, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Rett syndrome is a severe pediatric neurological disorder caused by loss of function mutations within the gene encoding methyl CpG-binding protein 2 (MeCP2). Although MeCP2 is expressed near ubiquitously, the primary pathophysiology of Rett syndrome stems from impairments of nervous system function. One alteration within different regions of the MeCP2-deficient brain is the presence of hyper-excitable network responses. In the hippocampus, such responses exist despite there being an overall decrease in spontaneous excitatory drive within the network. In this study, we generated and used mathematical, neuronal network models to resolve this apparent paradox. We did this by taking advantage of previous mathematical modelling insights that indicated that decreased excitatory fluctuations, but not mean excitatory drive, more critically explain observed changes in hippocampal network oscillations from MeCP2-null mouse slices. Importantly, reduced excitatory fluctuations could also bring about hyper-excitable responses in our network models. Therefore, these results indicate that diminished excitatory fluctuations may be responsible for the hyper-excitable state of MeCP2-deficient hippocampal circuitry.", "journal": "PloS one", "sentences": ["Rett syndrome is a severe pediatric neurological disorder caused by loss of function mutations within the gene encoding methyl CpG-binding protein 2 (MeCP2).", "Although MeCP2 is expressed near ubiquitously, the primary pathophysiology of Rett syndrome stems from impairments of nervous system function.", "One alteration within different regions of the MeCP2-deficient brain is the presence of hyper-excitable network responses.", "In the hippocampus, such responses exist despite there being an overall decrease in spontaneous excitatory drive within the network.", "In this study, we generated and used mathematical, neuronal network models to resolve this apparent paradox.", "We did this by taking advantage of previous mathematical modelling insights that indicated that decreased excitatory fluctuations, but not mean excitatory drive, more critically explain observed changes in hippocampal network oscillations from MeCP2-null mouse slices.", "Importantly, reduced excitatory fluctuations could also bring about hyper-excitable responses in our network models.", "Therefore, these results indicate that diminished excitatory fluctuations may be responsible for the hyper-excitable state of MeCP2-deficient hippocampal circuitry."], "title": "Network models predict that reduced excitatory fluctuations can give rise to hippocampal network hyper-excitability in MeCP2-null mice."}
{"paper_id": 24713927, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "The function and survival of normal and malignant plasma cells depends on the elaborately regulated ubiquitin proteasome system. Proteasome inhibitors such as bortezomib have proved to be highly effective in the treatment of multiple myeloma (MM), and their effects are related to normal protein homeostasis which is critical for plasma cell survival. Many ubiquitin ligases are regulated by conjugation with NEDD8. Therefore, neddylation may also impact survival and proliferation of malignant plasma cells. Here, we show that MLN4924, a potent NEDD8 activating enzyme (NAE) inhibitor, induced cytotoxicity in MM cell lines, and its antitumor effect is associated with suppression of the AKT and mammalian target of rapamycin (mTOR) signaling pathways through increased expression of REDD1. Combining MLN4924 with the proteasome inhibitor bortezomib induces synergistic apoptosis in MM cell lines which can overcome the prosurvival effects of growth factors such as interleukin-6 and insulin-like growth factor-1. Altogether, our findings demonstrate an important function for REDD1 in MLN4924-induced cytotoxicity in MM and also provide a promising therapeutic combination strategy for myeloma.", "journal": "Blood", "sentences": ["The function and survival of normal and malignant plasma cells depends on the elaborately regulated ubiquitin proteasome system.", "Proteasome inhibitors such as bortezomib have proved to be highly effective in the treatment of multiple myeloma (MM), and their effects are related to normal protein homeostasis which is critical for plasma cell survival.", "Many ubiquitin ligases are regulated by conjugation with NEDD8.", "Therefore, neddylation may also impact survival and proliferation of malignant plasma cells.", "Here, we show that MLN4924, a potent NEDD8 activating enzyme (NAE) inhibitor, induced cytotoxicity in MM cell lines, and its antitumor effect is associated with suppression of the AKT and mammalian target of rapamycin (mTOR) signaling pathways through increased expression of REDD1.", "Combining MLN4924 with the proteasome inhibitor bortezomib induces synergistic apoptosis in MM cell lines which can overcome the prosurvival effects of growth factors such as interleukin-6 and insulin-like growth factor-1.", "Altogether, our findings demonstrate an important function for REDD1 in MLN4924-induced cytotoxicity in MM and also provide a promising therapeutic combination strategy for myeloma."], "title": "MLN4924, an NAE inhibitor, suppresses AKT and mTOR signaling via upregulation of REDD1 in human myeloma cells."}
{"paper_id": 19795445, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The primary objective of this study is to identify prognostic site-specific epigenetic changes in surgically treated Stage I and II nonsmall cell lung cancer (NSCLC) patients by quantifying methylation levels at multiple CpG sites within each gene promoter. Paraffin-embedded tumors from stage Ib, IIa and IIb in training and validation groups of 75 and 57 surgically treated NSCLC patients, respectively, were analyzed for p16, MGMT, RASSF1, RASSF5, CDH1, LET7, DAPK and PTEN promoter hypermethylation. Hypermethylation status was quantified individually at multiple CpG sites within each promoter by pyrosequencing. Molecular and clinical characteristics with time to recurrence (TTR) and overall survival (OS) were evaluated. Overall average promoter methylation levels of MGMT and RASSF1 were significantly higher in smokers than in nonsmokers (p = 0.006 and p = 0.029, respectively). Methylation levels of the p16 promoter were significantly higher in squamous cell carcinoma than in adenocarcinoma (p = 0.020). In univariate analysis, hypermethylation of RASSF1 at CpG sites -53 and -48 and PTEN at CpG site -1310 were the significantly associated with shorter TTR (p = 0.002 and p < 0.000, respectively). Hypermethylation of PTEN at -1310 and DAPK at -1482 were most significantly associated with outcome in multivariate analysis. These results show that methylation of specific promoter CpG sites in PTEN, RASSF1 and DAPK is associated with outcome in early stage surgically treated NSCLC.", "journal": "International journal of cancer", "sentences": ["The primary objective of this study is to identify prognostic site-specific epigenetic changes in surgically treated Stage I and II nonsmall cell lung cancer (NSCLC) patients by quantifying methylation levels at multiple CpG sites within each gene promoter.", "Paraffin-embedded tumors from stage Ib, IIa and IIb in training and validation groups of 75 and 57 surgically treated NSCLC patients, respectively, were analyzed for p16, MGMT, RASSF1, RASSF5, CDH1, LET7, DAPK and PTEN promoter hypermethylation.", "Hypermethylation status was quantified individually at multiple CpG sites within each promoter by pyrosequencing.", "Molecular and clinical characteristics with time to recurrence (TTR) and overall survival (OS) were evaluated.", "Overall average promoter methylation levels of MGMT and RASSF1 were significantly higher in smokers than in nonsmokers (p = 0.006 and p = 0.029, respectively).", "Methylation levels of the p16 promoter were significantly higher in squamous cell carcinoma than in adenocarcinoma (p = 0.020).", "In univariate analysis, hypermethylation of RASSF1 at CpG sites -53 and -48 and PTEN at CpG site -1310 were the significantly associated with shorter TTR (p = 0.002 and p < 0.000, respectively).", "Hypermethylation of PTEN at -1310 and DAPK at -1482 were most significantly associated with outcome in multivariate analysis.", "These results show that methylation of specific promoter CpG sites in PTEN, RASSF1 and DAPK is associated with outcome in early stage surgically treated NSCLC."], "title": "PTEN, RASSF1 and DAPK site-specific hypermethylation and outcome in surgically treated stage I and II nonsmall cell lung cancer patients."}
{"paper_id": 26325666, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Cellulose, the main chemical polymer of wood, is the most abundant polysaccharide in nature.1 The ability to perturb the abundance and structure of cellulose microfibrils is of critical importance to the pulp and paper industry as well as for the textile, wood products, and liquid biofuels industries. Although much has been learned at the transcript level about the biosynthesis of cellulose, a quantitative understanding at the proteome level has yet to be established. The study described herein sought to identify the proteins directly involved in cellulose biosynthesis during wood formation in Populus trichocarpa along with known xylem-specific transcription factors involved in regulating these key proteins. Development of an effective discovery proteomic strategy through a combination of subcellular fractionation of stem differentiating xylem tissue (SDX) with recently optimized FASP digestion protocols, StageTip fractionation, as well as optimized instrument parameters for global proteomic analysis using the quadrupole-orbitrap mass spectrometer resulted in the deepest proteomic coverage of SDX protein from P. trichocarpa with 9,146 protein groups being identified (1% FDR). Of these, 20 cellulosic/hemicellulosic enzymes and 43 xylem-specific transcription factor groups were identified. Finally, selection of surrogate peptides led to an assay for absolute quantification of 14 cellulosic proteins in SDX of P. trichocarpa.", "journal": "Journal of proteome research", "sentences": ["Cellulose, the main chemical polymer of wood, is the most abundant polysaccharide in nature.1 The ability to perturb the abundance and structure of cellulose microfibrils is of critical importance to the pulp and paper industry as well as for the textile, wood products, and liquid biofuels industries.", "Although much has been learned at the transcript level about the biosynthesis of cellulose, a quantitative understanding at the proteome level has yet to be established.", "The study described herein sought to identify the proteins directly involved in cellulose biosynthesis during wood formation in Populus trichocarpa along with known xylem-specific transcription factors involved in regulating these key proteins.", "Development of an effective discovery proteomic strategy through a combination of subcellular fractionation of stem differentiating xylem tissue (SDX) with recently optimized FASP digestion protocols, StageTip fractionation, as well as optimized instrument parameters for global proteomic analysis using the quadrupole-orbitrap mass spectrometer resulted in the deepest proteomic coverage of SDX protein from P. trichocarpa with 9,146 protein groups being identified (1% FDR).", "Of these, 20 cellulosic/hemicellulosic enzymes and 43 xylem-specific transcription factor groups were identified.", "Finally, selection of surrogate peptides led to an assay for absolute quantification of 14 cellulosic proteins in SDX of P. trichocarpa."], "title": "Elucidation of Xylem-Specific Transcription Factors and Absolute Quantification of Enzymes Regulating Cellulose Biosynthesis in Populus trichocarpa."}
{"paper_id": 22981839, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The recession of the late 2000s has increased interest in the consequences of housing instability. Previous research has shown poorer health among those experiencing housing instability, but extant studies generally have focused on selected populations (e.g., homeowners or renters) or studied only one type of housing instability (e.g. homelessness). Using new data from the Michigan Recession and Recovery Study, a population-based sample of working-aged adults from Southeastern Michigan, U.S.A., in late 2009-early 2010, we found that about one-third of respondents recently experienced some type of housing instability. Many, but not all, types of instability were associated with health. Even after adjustment for sociodemographic characteristics and earlier health, individuals who had moved for cost reasons in the past three years were more likely than those with no housing instability to report a recent anxiety attack, while those who experienced homelessness in the past year had a higher likelihood of reporting fair/poor self-rated health and of meeting criteria for major or minor depression. Renters behind on rental payments were more likely to meet criteria for depression, while mortgage-holders behind on their mortgage or in foreclosure had a higher likelihood of reporting fair/poor self-rated health or a recent anxiety attack. Among respondents who had ever owned a home, those who completed a foreclosure recently were more likely to report major or minor depression or an anxiety attack. However, frequent moves were not associated with poorer health, and doubling up and eviction were not associated with poorer health after adjustment for characteristics that sort people into different housing instability experiences. Our findings suggest the importance of considering multiple types of housing instability and using appropriate risk groups and comparison categories.", "journal": "Social science & medicine (1982)", "sentences": ["The recession of the late 2000s has increased interest in the consequences of housing instability.", "Previous research has shown poorer health among those experiencing housing instability, but extant studies generally have focused on selected populations (e.g., homeowners or renters) or studied only one type of housing instability (e.g.", "homelessness).", "Using new data from the Michigan Recession and Recovery Study, a population-based sample of working-aged adults from Southeastern Michigan, U.S.A., in late 2009-early 2010, we found that about one-third of respondents recently experienced some type of housing instability.", "Many, but not all, types of instability were associated with health.", "Even after adjustment for sociodemographic characteristics and earlier health, individuals who had moved for cost reasons in the past three years were more likely than those with no housing instability to report a recent anxiety attack, while those who experienced homelessness in the past year had a higher likelihood of reporting fair/poor self-rated health and of meeting criteria for major or minor depression.", "Renters behind on rental payments were more likely to meet criteria for depression, while mortgage-holders behind on their mortgage or in foreclosure had a higher likelihood of reporting fair/poor self-rated health or a recent anxiety attack.", "Among respondents who had ever owned a home, those who completed a foreclosure recently were more likely to report major or minor depression or an anxiety attack.", "However, frequent moves were not associated with poorer health, and doubling up and eviction were not associated with poorer health after adjustment for characteristics that sort people into different housing instability experiences.", "Our findings suggest the importance of considering multiple types of housing instability and using appropriate risk groups and comparison categories."], "title": "Housing instability and health: findings from the Michigan Recession and Recovery Study."}
{"paper_id": 27419873, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "The epigenome orchestrates genome accessibility,\u00a0functionality, and three-dimensional structure. Because epigenetic variation can impact transcription and thus phenotypes, it may contribute to adaptation. Here, we report 1,107 high-quality single-base resolution methylomes and 1,203 transcriptomes from the 1001 Genomes collection of Arabidopsis thaliana. Although the genetic basis of methylation variation is highly complex, geographic origin is a major predictor of genome-wide DNA methylation levels and of altered gene expression caused by epialleles. Comparison to cistrome and epicistrome datasets identifies associations between transcription factor binding sites, methylation, nucleotide variation, and co-expression modules. Physical maps for nine of the most diverse genomes reveal how transposons and other structural variants shape the epigenome, with dramatic effects on immunity genes. The 1001 Epigenomes Project provides a comprehensive resource for understanding how variation in DNA methylation contributes to molecular and non-molecular phenotypes in natural populations of the most studied model plant.", "journal": "Cell", "sentences": ["The epigenome orchestrates genome accessibility,\u00a0functionality, and three-dimensional structure.", "Because epigenetic variation can impact transcription and thus phenotypes, it may contribute to adaptation.", "Here, we report 1,107 high-quality single-base resolution methylomes and 1,203 transcriptomes from the 1001 Genomes collection of Arabidopsis thaliana.", "Although the genetic basis of methylation variation is highly complex, geographic origin is a major predictor of genome-wide DNA methylation levels and of altered gene expression caused by epialleles.", "Comparison to cistrome and epicistrome datasets identifies associations between transcription factor binding sites, methylation, nucleotide variation, and co-expression modules.", "Physical maps for nine of the most diverse genomes reveal how transposons and other structural variants shape the epigenome, with dramatic effects on immunity genes.", "The 1001 Epigenomes Project provides a comprehensive resource for understanding how variation in DNA methylation contributes to molecular and non-molecular phenotypes in natural populations of the most studied model plant."], "title": "Epigenomic Diversity in a Global Collection of Arabidopsis thaliana Accessions."}
{"paper_id": 26512615, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Immunologic checkpoint marker B7 homolog 1 (B7-H1) plays a fundamental role in the initiation and progression of gastric cancer (GC); however, the clinicopathologic significance and prognostic value of B7-H1 in GC remains controversial. In this study, we aimed to assess their relationship through a meta-analysis.Medline/PubMed, EMBASE, the Cochrane Library databases, and Grey literature were searched up to August 10, 2015, for eligible studies of the association between B7-H1 expression and overall survival in GC. The hazard ratio and its 95% confidence interval (CI) were calculated from the included studies. Moreover, the odds ratio (OR) was also extracted to evaluate the association between the clinicopathologic parameters of participants and B7-H1 expression.Five studies involving 481 patients were included in the meta-analysis. The pooled results showed that positive B7-H1 expression was a negative predictor for overall survival with hazard ratio of 1.74 (95% CI: 1.40-2.17; Pheterogeneity\u200a=\u200a0.146) in GC. Additionally, increased B7-H1 was found to be significantly associated with positive lymph node metastasis (OR\u200a=\u200a2.61, 95% CI: 1.78-3.84; Pheterogeneity\u200a=\u200a0.004) and poorer tumor stage (OR\u200a=\u200a2.28, 95% CI: 1.39-3.74; Pheterogeneity\u200a=\u200a0.006); however, higher B7-H1 expression was not significantly correlated with poorer tumor differentiation (OR\u200a=\u200a1.29, 95% CI: 0.90-1.86; Pheterogeneity\u200a=\u200a0.013) and bigger tumor size (OR\u200a=\u200a1.18, 95% CI: 0.81-1.73; Pheterogeneity\u200a=\u200a0.104).The meta-analysis suggested that B7-H1 could act as a significant biomarker in the poor prognosis of gastric carcinoma.", "journal": "Medicine", "sentences": ["Immunologic checkpoint marker B7 homolog 1 (B7-H1) plays a fundamental role in the initiation and progression of gastric cancer (GC); however, the clinicopathologic significance and prognostic value of B7-H1 in GC remains controversial.", "In this study, we aimed to assess their relationship through a meta-analysis.Medline/PubMed, EMBASE, the Cochrane Library databases, and Grey literature were searched up to August 10, 2015, for eligible studies of the association between B7-H1 expression and overall survival in GC.", "The hazard ratio and its 95% confidence interval (CI) were calculated from the included studies.", "Moreover, the odds ratio (OR) was also extracted to evaluate the association between the clinicopathologic parameters of participants and B7-H1 expression.Five studies involving 481 patients were included in the meta-analysis.", "The pooled results showed that positive B7-H1 expression was a negative predictor for overall survival with hazard ratio of 1.74 (95% CI: 1.40-2.17; Pheterogeneity\u200a=\u200a0.146) in GC.", "Additionally, increased B7-H1 was found to be significantly associated with positive lymph node metastasis (OR\u200a=\u200a2.61, 95% CI: 1.78-3.84; Pheterogeneity\u200a=\u200a0.004) and poorer tumor stage (OR\u200a=\u200a2.28, 95% CI: 1.39-3.74; Pheterogeneity\u200a=\u200a0.006); however, higher B7-H1 expression was not significantly correlated with poorer tumor differentiation (OR\u200a=\u200a1.29, 95% CI: 0.90-1.86; Pheterogeneity\u200a=\u200a0.013) and bigger tumor size (OR\u200a=\u200a1.18, 95% CI: 0.81-1.73; Pheterogeneity\u200a=\u200a0.104).The meta-analysis suggested that B7-H1 could act as a significant biomarker in the poor prognosis of gastric carcinoma."], "title": "Clinicopathologic Significance and Prognostic Value of B7 Homolog 1 in Gastric Cancer: A Systematic Review and Meta-Analysis."}
{"paper_id": 26979754, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "High-throughput sequencing of the antibody repertoire provides a large number of antibody variable region sequences that can be used to generate human monoclonal antibodies. However, current screening methods for identifying antigen-specific antibodies are inefficient. In the present study, we developed an antibody clone screening strategy based on clone dynamics and relative frequency, and used it to identify antigen-specific human monoclonal antibodies. Enzyme-linked immunosorbent assay showed that at least 52% of putative positive immunoglobulin heavy chains composed antigen-specific antibodies. Combining information on dynamics and relative frequency improved identification of positive clones and elimination of negative clones. and increase the credibility of putative positive clones. Therefore the screening strategy could simplify the subsequent experimental screening and may facilitate the generation of antigen-specific antibodies.", "journal": "Biochemical and biophysical research communications", "sentences": ["High-throughput sequencing of the antibody repertoire provides a large number of antibody variable region sequences that can be used to generate human monoclonal antibodies.", "However, current screening methods for identifying antigen-specific antibodies are inefficient.", "In the present study, we developed an antibody clone screening strategy based on clone dynamics and relative frequency, and used it to identify antigen-specific human monoclonal antibodies.", "Enzyme-linked immunosorbent assay showed that at least 52% of putative positive immunoglobulin heavy chains composed antigen-specific antibodies.", "Combining information on dynamics and relative frequency improved identification of positive clones and elimination of negative clones.", "and increase the credibility of putative positive clones.", "Therefore the screening strategy could simplify the subsequent experimental screening and may facilitate the generation of antigen-specific antibodies."], "title": "Identification of antigen-specific human monoclonal antibodies using high-throughput sequencing of the antibody repertoire."}
{"paper_id": 26933631, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Renal cell carcinoma represents 3\u00a0% of all cancers. Around 4-10\u00a0% of cases present with inferior vena cava involvement, generally with tumor thrombus. Clinical and preoperative stage will be classified depending of the thrombus extension. A high quality preoperative workup is essential to properly plan surgical approach. Complete surgical resection of the tumor is potentially the only curative treatment, although it supposes a real challenge due to operative difficulty, potential for massive bleeding or tumor pulmonary thromboembolism. Surgery includes techniques derived from transplantation surgery and, in some cases, cardiovascular intervention with cardiopulmonary bypass. Long-term oncological outcomes after complete removal of the entire tumor burden are acceptable. In this report we describe step-by-step surgical maneuvers depending on the thrombus lever, and focusing in complete abdominal approach for the complete excision of the tumor. Moreover, a recent literature review about oncological results is reported.", "journal": "SpringerPlus", "sentences": ["Renal cell carcinoma represents 3\u00a0% of all cancers.", "Around 4-10\u00a0% of cases present with inferior vena cava involvement, generally with tumor thrombus.", "Clinical and preoperative stage will be classified depending of the thrombus extension.", "A high quality preoperative workup is essential to properly plan surgical approach.", "Complete surgical resection of the tumor is potentially the only curative treatment, although it supposes a real challenge due to operative difficulty, potential for massive bleeding or tumor pulmonary thromboembolism.", "Surgery includes techniques derived from transplantation surgery and, in some cases, cardiovascular intervention with cardiopulmonary bypass.", "Long-term oncological outcomes after complete removal of the entire tumor burden are acceptable.", "In this report we describe step-by-step surgical maneuvers depending on the thrombus lever, and focusing in complete abdominal approach for the complete excision of the tumor.", "Moreover, a recent literature review about oncological results is reported."], "title": "Surgical technique for the treatment of renal cell carcinoma with inferior vena cava tumor thrombus: tips, tricks and oncological results."}
{"paper_id": 26258879, "labels": ["0", "0", "0", "0", "1"], "abstract": "The production of high affinity, class switched antibodies produced by B cells hinges on the effective differentiation of T follicular helper (Tfh) cells. Here we define conditions specifically enhancing Tfh differentiation and providing protection in a model of influenza infection. Tfh responses were associated with prolonged antigen presentation by dendritic cells (DCs), which maintained T cell/DC interactions into stage 3 (&gt;72 hr) of activation. Blocking stage 3 interactions ablated Tfh generation, demonstrating a causal link between T cell-DC behaviour and functional outcomes. The current data therefore explain how duration of antigen presentation affects the dynamics of T cell-DC interactions and consequently determine Tfh cell differentiation in the developing immune response.", "journal": "eLife", "sentences": ["The production of high affinity, class switched antibodies produced by B cells hinges on the effective differentiation of T follicular helper (Tfh) cells.", "Here we define conditions specifically enhancing Tfh differentiation and providing protection in a model of influenza infection.", "Tfh responses were associated with prolonged antigen presentation by dendritic cells (DCs), which maintained T cell/DC interactions into stage 3 (&gt;72 hr) of activation.", "Blocking stage 3 interactions ablated Tfh generation, demonstrating a causal link between T cell-DC behaviour and functional outcomes.", "The current data therefore explain how duration of antigen presentation affects the dynamics of T cell-DC interactions and consequently determine Tfh cell differentiation in the developing immune response."], "title": "Antigen presentation kinetics control T cell/dendritic cell interactions and follicular helper T cell generation in vivo."}
{"paper_id": 26805818, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Photodynamic therapy has a role in the management of early and late thoracic malignancies. It can be used to facilitate minimally-invasive treatment of early endobronchial tumours and also to palliate obstructive and bleeding effects of advanced endobronchial tumours. Photodynamic therapy has been used as a means of downsizing tumours to allow for resection, as well as reducing the extent of resection necessary. It has also been used successfully for minimally-invasive management of local recurrences, which is especially valuable for patients who are not eligible for radiation therapy. Photodynamic therapy has also shown promising results in mesothelioma and pleural-based metastatic disease. As new generation photosensitizers are being developed and tested and methodological issues continue to be addressed, the role of photodynamic therapy in thoracic malignancies continues to evolve.", "journal": "International journal of molecular sciences", "sentences": ["Photodynamic therapy has a role in the management of early and late thoracic malignancies.", "It can be used to facilitate minimally-invasive treatment of early endobronchial tumours and also to palliate obstructive and bleeding effects of advanced endobronchial tumours.", "Photodynamic therapy has been used as a means of downsizing tumours to allow for resection, as well as reducing the extent of resection necessary.", "It has also been used successfully for minimally-invasive management of local recurrences, which is especially valuable for patients who are not eligible for radiation therapy.", "Photodynamic therapy has also shown promising results in mesothelioma and pleural-based metastatic disease.", "As new generation photosensitizers are being developed and tested and methodological issues continue to be addressed, the role of photodynamic therapy in thoracic malignancies continues to evolve."], "title": "Photodynamic Therapy in Non-Gastrointestinal Thoracic Malignancies."}
{"paper_id": 23671651, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The concentrations of mineral nutrients in seeds are critical to both the life cycle of plants as well as human nutrition. These concentrations are strongly influenced by soil conditions, as shown here by quantifying the concentration of 14 elements in seeds from Arabidopsis thaliana plants grown under four different soil conditions: standard, or modified with NaCl, heavy metals, or alkali. Each of the modified soils resulted in a unique change to the seed ionome (the mineral nutrient content of the seeds). To help identify the genetic networks regulating the seed ionome, changes in elemental concentrations were evaluated using mutants corresponding to 760 genes as well as 10 naturally occurring accessions. The frequency of ionomic phenotypes supports an estimate that as much as 11% of the A. thaliana genome encodes proteins of functional relevance to ion homeostasis in seeds. A subset of mutants were analyzed with two independent alleles, providing five examples of genes important for regulation of the seed ionome: SOS2, ABH1, CCC, At3g14280 and CNGC2. In a comparison of nine different accessions to a Col-0 reference, eight accessions were observed to have reproducible differences in elemental concentrations, seven of which were dependent on specific soil conditions. These results indicate that the A. thaliana seed ionome is distinct from the vegetative ionome, and that elemental analysis is a sensitive approach to identify genes controlling ion homeostasis, including those that regulate gene expression, phospho-regulation, and ion transport.", "journal": "PloS one", "sentences": ["The concentrations of mineral nutrients in seeds are critical to both the life cycle of plants as well as human nutrition.", "These concentrations are strongly influenced by soil conditions, as shown here by quantifying the concentration of 14 elements in seeds from Arabidopsis thaliana plants grown under four different soil conditions: standard, or modified with NaCl, heavy metals, or alkali.", "Each of the modified soils resulted in a unique change to the seed ionome (the mineral nutrient content of the seeds).", "To help identify the genetic networks regulating the seed ionome, changes in elemental concentrations were evaluated using mutants corresponding to 760 genes as well as 10 naturally occurring accessions.", "The frequency of ionomic phenotypes supports an estimate that as much as 11% of the A. thaliana genome encodes proteins of functional relevance to ion homeostasis in seeds.", "A subset of mutants were analyzed with two independent alleles, providing five examples of genes important for regulation of the seed ionome: SOS2, ABH1, CCC, At3g14280 and CNGC2.", "In a comparison of nine different accessions to a Col-0 reference, eight accessions were observed to have reproducible differences in elemental concentrations, seven of which were dependent on specific soil conditions.", "These results indicate that the A. thaliana seed ionome is distinct from the vegetative ionome, and that elemental analysis is a sensitive approach to identify genes controlling ion homeostasis, including those that regulate gene expression, phospho-regulation, and ion transport."], "title": "Elemental concentrations in the seed of mutants and natural variants of Arabidopsis thaliana grown under varying soil conditions."}
{"paper_id": 24135488, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "The introduction of anti-angiogenic drugs especially tyrosine kinase inhibitors (TKIs) was a breakthrough in the treatment of renal cell carcinoma (RCC). Although TKIs have significantly improved outcome in patients with metastatic disease, the majority still develop resistance over time. Because different combinations and sequences of TKIs are tested in clinical trials, resistance patterns and mechanisms underlying this phenomenon should be thoroughly investigated. From a clinical point of view, resistance occurs either as a primary phenomenon (intrinsic) or as a secondary phenomenon related to various escape/evasive mechanisms that the tumor develops in response to vascular endothelial growth factor (VEGF) inhibition. Intrinsic resistance is less common, and related to the primary redundancy of available angiogenic signals from the tumor, causing unresponsiveness to VEGF-targeted therapies. Acquired resistance in tumors is associated with activation of an angiogenic switch which leads to either upregulation of the existing VEGF pathway or recruitment of alternative factors responsible for tumor revascularization. Multiple mechanisms can be involved in different tumor settings that contribute both to evasive and intrinsic resistance, and current endeavor aims to identify these processes and assess their importance in clinical settings and design of pharmacological strategies that lead to enduring anti-angiogenic therapies.", "journal": "Biochimica et biophysica acta", "sentences": ["The introduction of anti-angiogenic drugs especially tyrosine kinase inhibitors (TKIs) was a breakthrough in the treatment of renal cell carcinoma (RCC).", "Although TKIs have significantly improved outcome in patients with metastatic disease, the majority still develop resistance over time.", "Because different combinations and sequences of TKIs are tested in clinical trials, resistance patterns and mechanisms underlying this phenomenon should be thoroughly investigated.", "From a clinical point of view, resistance occurs either as a primary phenomenon (intrinsic) or as a secondary phenomenon related to various escape/evasive mechanisms that the tumor develops in response to vascular endothelial growth factor (VEGF) inhibition.", "Intrinsic resistance is less common, and related to the primary redundancy of available angiogenic signals from the tumor, causing unresponsiveness to VEGF-targeted therapies.", "Acquired resistance in tumors is associated with activation of an angiogenic switch which leads to either upregulation of the existing VEGF pathway or recruitment of alternative factors responsible for tumor revascularization.", "Multiple mechanisms can be involved in different tumor settings that contribute both to evasive and intrinsic resistance, and current endeavor aims to identify these processes and assess their importance in clinical settings and design of pharmacological strategies that lead to enduring anti-angiogenic therapies."], "title": "Resistance to tyrosine kinase inhibitors in clear cell renal cell carcinoma: from the patient's bed to molecular mechanisms."}
{"paper_id": 25639486, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Aberrant activation of \u03b2-catenin in the nucleus has been implicated in a variety of human cancers, but the fate of nuclear \u03b2-catenin is unknown. Here we demonstrate that the tripartite motif-containing protein 33 (TRIM33), acting as an E3 ubiquitin ligase, reduces the abundance of nuclear \u03b2-catenin protein. TRIM33-mediated \u03b2-catenin is destabilized and is GSK-3\u03b2 or \u03b2-TrCP independent. TRIM33 interacts with and ubiquitylates nuclear \u03b2-catenin. Moreover, protein kinase C\u03b4, which directly phosphorylates \u03b2-catenin at Ser715, is required for the TRIM33-\u03b2-catenin interaction. The function of TRIM33 in suppressing tumour cell proliferation and brain tumour development depends on TRIM33-promoted \u03b2-catenin degradation. In human glioblastoma specimens, endogenous TRIM33 levels are inversely correlated with \u03b2-catenin. In summary, our findings identify TRIM33 as a tumour suppressor that can abolish tumour cell proliferation and tumorigenesis by degrading nuclear \u03b2-catenin. This work suggests a new therapeutic strategy against human cancers caused by aberrant activation of \u03b2-catenin.", "journal": "Nature communications", "sentences": ["Aberrant activation of \u03b2-catenin in the nucleus has been implicated in a variety of human cancers, but the fate of nuclear \u03b2-catenin is unknown.", "Here we demonstrate that the tripartite motif-containing protein 33 (TRIM33), acting as an E3 ubiquitin ligase, reduces the abundance of nuclear \u03b2-catenin protein.", "TRIM33-mediated \u03b2-catenin is destabilized and is GSK-3\u03b2 or \u03b2-TrCP independent.", "TRIM33 interacts with and ubiquitylates nuclear \u03b2-catenin.", "Moreover, protein kinase C\u03b4, which directly phosphorylates \u03b2-catenin at Ser715, is required for the TRIM33-\u03b2-catenin interaction.", "The function of TRIM33 in suppressing tumour cell proliferation and brain tumour development depends on TRIM33-promoted \u03b2-catenin degradation.", "In human glioblastoma specimens, endogenous TRIM33 levels are inversely correlated with \u03b2-catenin.", "In summary, our findings identify TRIM33 as a tumour suppressor that can abolish tumour cell proliferation and tumorigenesis by degrading nuclear \u03b2-catenin.", "This work suggests a new therapeutic strategy against human cancers caused by aberrant activation of \u03b2-catenin."], "title": "Tumour suppressor TRIM33 targets nuclear \u03b2-catenin degradation."}
{"paper_id": 24583084, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "The conformational dynamics of the histidine ABC transporter HisQMP2 from Salmonella enterica serovar Typhimurium, reconstituted into liposomes, is studied by site-directed spin labeling and double electron-electron resonance spectroscopy in the absence of nucleotides, in the ATP-bound, and in the post-hydrolysis state. The results show that the inter-dimer distances as measured between the Q-loops of HisP2 in the intact transporter resemble those determined for the maltose transporter in all three states of the hydrolysis cycle. Only in the presence of liganded HisJ the closed conformation of the nucleotide binding sites is achieved revealing the transmembrane communication of the presence of substrate. Two conformational states can be distinguished for the periplasmic moiety of HisQMP2 as detected by differences in distributions of interspin distances between positions 86 and 96 or 104 and 197. The observed conformational changes are correlated to proposed open, semi-open and closed conformations of the nucleotide binding domains HisP2. Our results are in line with a rearrangement of transmembrane helices 4 and 4' of HisQM during the closed to the semi-open transition of HisP2 driven by the reorientation of the coupled helices 3a and 3b to occur upon hydrolysis.", "journal": "Biochimica et biophysica acta", "sentences": ["The conformational dynamics of the histidine ABC transporter HisQMP2 from Salmonella enterica serovar Typhimurium, reconstituted into liposomes, is studied by site-directed spin labeling and double electron-electron resonance spectroscopy in the absence of nucleotides, in the ATP-bound, and in the post-hydrolysis state.", "The results show that the inter-dimer distances as measured between the Q-loops of HisP2 in the intact transporter resemble those determined for the maltose transporter in all three states of the hydrolysis cycle.", "Only in the presence of liganded HisJ the closed conformation of the nucleotide binding sites is achieved revealing the transmembrane communication of the presence of substrate.", "Two conformational states can be distinguished for the periplasmic moiety of HisQMP2 as detected by differences in distributions of interspin distances between positions 86 and 96 or 104 and 197.", "The observed conformational changes are correlated to proposed open, semi-open and closed conformations of the nucleotide binding domains HisP2.", "Our results are in line with a rearrangement of transmembrane helices 4 and 4' of HisQM during the closed to the semi-open transition of HisP2 driven by the reorientation of the coupled helices 3a and 3b to occur upon hydrolysis."], "title": "Conformational changes of the histidine ATP-binding cassette transporter studied by double electron-electron resonance spectroscopy."}
{"paper_id": 20552355, "labels": ["0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Thermoanaerobacter mathranii can produce ethanol from lignocellulosic biomass at high temperatures, but its biotechnological exploitation will require metabolic engineering to increase its ethanol yield. With a cofactor-dependent ethanol production pathway in T. mathranii, it may become crucial to regenerate cofactor to increase the ethanol yield. Feeding the cells with a more reduced carbon source, such as mannitol, was shown to increase ethanol yield beyond that obtained with glucose and xylose. The ldh gene coding for lactate dehydrogenase was previously deleted from T. mathranii to eliminate an NADH oxidation pathway. To further facilitate NADH regeneration used for ethanol formation, a heterologous gene gldA encoding an NAD(+)-dependent glycerol dehydrogenase was expressed in T. mathranii. One of the resulting recombinant strains, T. mathranii BG1G1 (Deltaldh, P(xyl)GldA), showed increased ethanol yield in the presence of glycerol using xylose as a substrate. With an inactivated lactate pathway and expressed glycerol dehydrogenase activity, the metabolism of the cells was shifted toward the production of ethanol over acetate, hence restoring the redox balance. It was also shown that strain BG1G1 acquired the capability to utilize glycerol as an extra carbon source in the presence of xylose, and utilization of the more reduced substrate glycerol resulted in a higher ethanol yield.", "journal": "Applied microbiology and biotechnology", "sentences": ["Thermoanaerobacter mathranii can produce ethanol from lignocellulosic biomass at high temperatures, but its biotechnological exploitation will require metabolic engineering to increase its ethanol yield.", "With a cofactor-dependent ethanol production pathway in T. mathranii, it may become crucial to regenerate cofactor to increase the ethanol yield.", "Feeding the cells with a more reduced carbon source, such as mannitol, was shown to increase ethanol yield beyond that obtained with glucose and xylose.", "The ldh gene coding for lactate dehydrogenase was previously deleted from T. mathranii to eliminate an NADH oxidation pathway.", "To further facilitate NADH regeneration used for ethanol formation, a heterologous gene gldA encoding an NAD(+)-dependent glycerol dehydrogenase was expressed in T. mathranii.", "One of the resulting recombinant strains, T. mathranii BG1G1 (Deltaldh, P(xyl)GldA), showed increased ethanol yield in the presence of glycerol using xylose as a substrate.", "With an inactivated lactate pathway and expressed glycerol dehydrogenase activity, the metabolism of the cells was shifted toward the production of ethanol over acetate, hence restoring the redox balance.", "It was also shown that strain BG1G1 acquired the capability to utilize glycerol as an extra carbon source in the presence of xylose, and utilization of the more reduced substrate glycerol resulted in a higher ethanol yield."], "title": "Metabolic engineering to improve ethanol production in Thermoanaerobacter mathranii."}
{"paper_id": 21656140, "labels": ["0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "In this work, the production of 1,3-propanediol from glucose and molasses was studied in a two-step process using two recombinant microorganisms. The first step of the process is the conversion of glucose or other sugar into glycerol by the metabolic engineered Saccharomyces cerevisiae strain HC42 adapted to high (>200 g l(-1)) glucose concentrations. The second step, carried out in the same bioreactor, was performed by the engineered strain Clostridium acetobutylicum DG1 (pSPD5) that converts glycerol to 1,3-propanediol. This two-step strategy led to a flexible process, resulting in a 1,3-propanediol production and yield that depended on the initial sugar concentration. Below 56.2 g l(-1) of sugar concentration, cultivation on molasses or glucose showed no significant differences. However, at higher molasses concentrations, glycerol initially produced by yeast could not be totally converted into 1,3-propanediol by C. acetobutylicum and a lower 1,3-propanediol overall yield was observed. In our hand, the best results were obtained with an initial glucose concentration of 103 g l(-1), leading to a final 1,3-propanediol concentration of 25.5 g l(-1), a productivity of 0.16 g l(-1) h(-1) and 1,3-propanediol yields of 0.56 g g(-1) glycerol and 0.24 g g(-1) sugar, which is the highest value reported for a two-step process. For an initial sugar concentration (from molasses) of 56.2 g l(-1), 27.4 g l(-1) of glycerol were produced, leading to 14.6 g l(-1) of 1.3-propanediol and similar values of productivity, 0.15 g l(-1) h(-1), and overall yield, 0.26 g g(-1) sugar.", "journal": "Applied microbiology and biotechnology", "sentences": ["In this work, the production of 1,3-propanediol from glucose and molasses was studied in a two-step process using two recombinant microorganisms.", "The first step of the process is the conversion of glucose or other sugar into glycerol by the metabolic engineered Saccharomyces cerevisiae strain HC42 adapted to high (>200 g l(-1)) glucose concentrations.", "The second step, carried out in the same bioreactor, was performed by the engineered strain Clostridium acetobutylicum DG1 (pSPD5) that converts glycerol to 1,3-propanediol.", "This two-step strategy led to a flexible process, resulting in a 1,3-propanediol production and yield that depended on the initial sugar concentration.", "Below 56.2 g l(-1) of sugar concentration, cultivation on molasses or glucose showed no significant differences.", "However, at higher molasses concentrations, glycerol initially produced by yeast could not be totally converted into 1,3-propanediol by C. acetobutylicum and a lower 1,3-propanediol overall yield was observed.", "In our hand, the best results were obtained with an initial glucose concentration of 103 g l(-1), leading to a final 1,3-propanediol concentration of 25.5 g l(-1), a productivity of 0.16 g l(-1) h(-1) and 1,3-propanediol yields of 0.56 g g(-1) glycerol and 0.24 g g(-1) sugar, which is the highest value reported for a two-step process.", "For an initial sugar concentration (from molasses) of 56.2 g l(-1), 27.4 g l(-1) of glycerol were produced, leading to 14.6 g l(-1) of 1.3-propanediol and similar values of productivity, 0.15 g l(-1) h(-1), and overall yield, 0.26 g g(-1) sugar."], "title": "1,3-Propanediol production in a two-step process fermentation from renewable feedstock."}
{"paper_id": 24520379, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Senescence of vascular endothelial cells is an important contributor to the pathogenesis of age-associated vascular disorders such as atherosclerosis. We investigated the effects of antihypertensive agents on high glucose-induced cellular senescence in human umbilical venous endothelial cells (HUVECs). Exposure of HUVECs to high glucose (22 mM) for 3 days increased senescence-associated- \u03b2-galactosidase (SA-\u03b2-gal) activity, a senescence marker, and decreased telomerase activity, a replicative senescence marker. The calcium channel blocker nifedipine, but not the \u03b21-adrenergic blocking agent atenolol or the angiotensin-converting enzyme inhibitor perindopril, reduced SA-\u03b2-gal positive cells and prevented a decrease in telomerase activity in a high-glucose environment. This beneficial effect of nifedipine was associated with reduced reactive oxygen species (ROS) and increased endothelial nitric oxide synthase (eNOS) activity. Thus, nifedipine prevented high glucose-induced ROS generation and increased basal eNOS phosphorylation level at Ser-1177. Treatment with N (G)-nitro-L-arginine (L-NAME) and transfection of small interfering RNA (siRNA) targeting eNOS eliminated the anti-senscence effect of nifedipine. These results demonstrate that nifedipine can prevent endothelial cell senescence in an eNOS-dependent manner. The anti-senescence action of nifedipine may represent a novel mechanism by which it protects against atherosclerosis.", "journal": "PloS one", "sentences": ["Senescence of vascular endothelial cells is an important contributor to the pathogenesis of age-associated vascular disorders such as atherosclerosis.", "We investigated the effects of antihypertensive agents on high glucose-induced cellular senescence in human umbilical venous endothelial cells (HUVECs).", "Exposure of HUVECs to high glucose (22 mM) for 3 days increased senescence-associated- \u03b2-galactosidase (SA-\u03b2-gal) activity, a senescence marker, and decreased telomerase activity, a replicative senescence marker.", "The calcium channel blocker nifedipine, but not the \u03b21-adrenergic blocking agent atenolol or the angiotensin-converting enzyme inhibitor perindopril, reduced SA-\u03b2-gal positive cells and prevented a decrease in telomerase activity in a high-glucose environment.", "This beneficial effect of nifedipine was associated with reduced reactive oxygen species (ROS) and increased endothelial nitric oxide synthase (eNOS) activity.", "Thus, nifedipine prevented high glucose-induced ROS generation and increased basal eNOS phosphorylation level at Ser-1177.", "Treatment with N (G)-nitro-L-arginine (L-NAME) and transfection of small interfering RNA (siRNA) targeting eNOS eliminated the anti-senscence effect of nifedipine.", "These results demonstrate that nifedipine can prevent endothelial cell senescence in an eNOS-dependent manner.", "The anti-senescence action of nifedipine may represent a novel mechanism by which it protects against atherosclerosis."], "title": "eNOS-dependent antisenscence effect of a calcium channel blocker in human endothelial cells."}
{"paper_id": 23691133, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The terminology used to describe neuropathic pain appears to be conserved across languages, which facilitates the translation of validated neuropathic pain screening tools into other languages. However, this assumption has not been assessed in an African language. Therefore we investigated the terminology used by 54 patients whose native language was isiZulu, a major Bantu language of Africa, when describing their symptomatic HIV-associated sensory neuropathy. Also, because English is a commonly spoken second-language in the region, we assessed these patients' knowledge and understanding of 21 English terms commonly used to describe neuropathic pain. English translations of the most commonly used isiZulu symptom descriptors included: \"hot/burning\" (50%), \"cramping\" (35%), \"painful/sore/aching\" (32%), \"itching\" (22%), \"numb\" (22%), \"cold/freezing\" (17%), and \"stabbing/pricking/pins-and-needles\" (13%). Thus, the isiZulu terminology to describe neuropathic pain was very similar to that used in non-African languages. However, knowledge and understanding of English neuropathic pain descriptors by these non-native English speakers was highly variable. For example, knowledge of English terms ranged from >98% (\"hot\", \"cold/freezing\", \"cramping\") to <25% (\"pricking\", \"radiating\", \"throbbing\"), and true understanding of English terms ranged from >90% (\"hot\", \"burning\", \"cramping\") to <35% (\"tingling\", \"jumping\", \"shooting\", \"radiating\"). In conclusion, we show significant similarity in the terms used to describe neuropathic pain in isiZulu compared to non-African languages, thus indicating that translation of existing neuropathic pain screening tools into this, and possibly other Bantu languages, is a viable option. However, the usefulness of English-language screening tools in this non-native English speaking population may be limited.", "journal": "PloS one", "sentences": ["The terminology used to describe neuropathic pain appears to be conserved across languages, which facilitates the translation of validated neuropathic pain screening tools into other languages.", "However, this assumption has not been assessed in an African language.", "Therefore we investigated the terminology used by 54 patients whose native language was isiZulu, a major Bantu language of Africa, when describing their symptomatic HIV-associated sensory neuropathy.", "Also, because English is a commonly spoken second-language in the region, we assessed these patients' knowledge and understanding of 21 English terms commonly used to describe neuropathic pain.", "English translations of the most commonly used isiZulu symptom descriptors included: \"hot/burning\" (50%), \"cramping\" (35%), \"painful/sore/aching\" (32%), \"itching\" (22%), \"numb\" (22%), \"cold/freezing\" (17%), and \"stabbing/pricking/pins-and-needles\" (13%).", "Thus, the isiZulu terminology to describe neuropathic pain was very similar to that used in non-African languages.", "However, knowledge and understanding of English neuropathic pain descriptors by these non-native English speakers was highly variable.", "For example, knowledge of English terms ranged from >98% (\"hot\", \"cold/freezing\", \"cramping\") to <25% (\"pricking\", \"radiating\", \"throbbing\"), and true understanding of English terms ranged from >90% (\"hot\", \"burning\", \"cramping\") to <35% (\"tingling\", \"jumping\", \"shooting\", \"radiating\").", "In conclusion, we show significant similarity in the terms used to describe neuropathic pain in isiZulu compared to non-African languages, thus indicating that translation of existing neuropathic pain screening tools into this, and possibly other Bantu languages, is a viable option.", "However, the usefulness of English-language screening tools in this non-native English speaking population may be limited."], "title": "Symptomatology of peripheral neuropathy in an African language."}
{"paper_id": 26848659, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "The giant freshwater prawn, Macrobrachium rosenbergii, is an economically important crustacean and is farmed in many countries. Since 2009, a larval mortality syndrome of M. rosenbergii has broken out and spread widely in the main breeding area, including Zhejiang, Jiangsu, Guangxi, and Guangdong Provinces in mainland China. A novel virus, named Macrobrachium rosenbergii Taihu virus (MrTV), was isolated from the moribund larvae and was determined to be the causative agent of the M. rosenbergii larval mortality syndrome by experimental infection. Further genomic sequencing suggested that the MrTV genome is monopartite, 10,303 nt in length, and dicistronic with two non-overlapping open reading frames (ORFs) separated by an intergenic region (IGR) and flanked by untranslated regions (UTRs). Phylogenetic analysis using the full-length genomic sequence and the putative amino acid sequences of the capsid protein revealed that MrTV was more closely related to the taura syndrome virus (TSV) than to any other viruses. According to these molecular features, we proposed that MrTV is a new species in the genus Aparavirus, family Dicistroviridae. These results may shed light on controlling larval mortality syndrome in M. rosenbergii.", "journal": "International journal of molecular sciences", "sentences": ["The giant freshwater prawn, Macrobrachium rosenbergii, is an economically important crustacean and is farmed in many countries.", "Since 2009, a larval mortality syndrome of M. rosenbergii has broken out and spread widely in the main breeding area, including Zhejiang, Jiangsu, Guangxi, and Guangdong Provinces in mainland China.", "A novel virus, named Macrobrachium rosenbergii Taihu virus (MrTV), was isolated from the moribund larvae and was determined to be the causative agent of the M. rosenbergii larval mortality syndrome by experimental infection.", "Further genomic sequencing suggested that the MrTV genome is monopartite, 10,303 nt in length, and dicistronic with two non-overlapping open reading frames (ORFs) separated by an intergenic region (IGR) and flanked by untranslated regions (UTRs).", "Phylogenetic analysis using the full-length genomic sequence and the putative amino acid sequences of the capsid protein revealed that MrTV was more closely related to the taura syndrome virus (TSV) than to any other viruses.", "According to these molecular features, we proposed that MrTV is a new species in the genus Aparavirus, family Dicistroviridae.", "These results may shed light on controlling larval mortality syndrome in M. rosenbergii."], "title": "Isolation and Characterization of a Novel Dicistrovirus Associated with Moralities of the Great Freshwater Prawn, Macrobrachium rosenbergii."}
{"paper_id": 26839879, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "The Community Pharmacy of the Department of Ambulatory Care and Community Medicine (Policlinique M\u00e9dicale Universitaire, PMU), University of Lausanne, developed and implemented an interdisciplinary medication adherence program. The program aims to support and reinforce medication adherence through a multifactorial and interdisciplinary intervention. Motivational interviewing is combined with medication adherence electronic monitors (MEMS, Aardex MWV) and a report to patient, physician, nurse, and other pharmacists. This program has become a routine activity and was extended for use with all chronic diseases. From 2004 to 2014, there were 819 patient inclusions, and 268 patients were in follow-up in 2014. This paper aims to present the organization and program's context, statistical data, published research, and future perspectives.", "journal": "BioMed research international", "sentences": ["The Community Pharmacy of the Department of Ambulatory Care and Community Medicine (Policlinique M\u00e9dicale Universitaire, PMU), University of Lausanne, developed and implemented an interdisciplinary medication adherence program.", "The program aims to support and reinforce medication adherence through a multifactorial and interdisciplinary intervention.", "Motivational interviewing is combined with medication adherence electronic monitors (MEMS, Aardex MWV) and a report to patient, physician, nurse, and other pharmacists.", "This program has become a routine activity and was extended for use with all chronic diseases.", "From 2004 to 2014, there were 819 patient inclusions, and 268 patients were in follow-up in 2014.", "This paper aims to present the organization and program's context, statistical data, published research, and future perspectives."], "title": "Interdisciplinary Medication Adherence Program: The Example of a University Community Pharmacy in Switzerland."}
{"paper_id": 25620895, "labels": ["0", "0", "1", "0", "0", "0", "1"], "abstract": "Given the demonstrated utility of coarse-grained modeling and simulations approaches in studying protein structure and dynamics, developing methods that allow experimental observables to be directly recovered from coarse-grained models is of great importance. In this work, we develop one such method that enables protein backbone chemical shifts (1HN, 1H\u03b1, 13C\u03b1, 13C, 13C\u03b2, and 15N) to be predicted from C\u03b1 coordinates. We show that our C\u03b1-based method, LARMORC\u03b1, predicts backbone chemical shifts with comparable accuracy to some all-atom approaches. More importantly, we demonstrate that LARMORC\u03b1 predicted chemical shifts are able to resolve native structure from decoy pools that contain both native and non-native models, and so it is sensitive to protein structure. As an application, we use LARMORC\u03b1 to characterize the transient state of the fast-folding protein gpW using recently published NMR relaxation dispersion derived backbone chemical shifts. The model we obtain is consistent with the previously proposed model based on independent analysis of the chemical shift dispersion pattern of the transient state. We anticipate that LARMORC\u03b1 will find utility as a tool that enables important protein conformational substates to be identified by \u201cparsing\u201d trajectories and ensembles generated using coarse-grained modeling and simulations.", "journal": "Journal of chemical theory and computation", "sentences": ["Given the demonstrated utility of coarse-grained modeling and simulations approaches in studying protein structure and dynamics, developing methods that allow experimental observables to be directly recovered from coarse-grained models is of great importance.", "In this work, we develop one such method that enables protein backbone chemical shifts (1HN, 1H\u03b1, 13C\u03b1, 13C, 13C\u03b2, and 15N) to be predicted from C\u03b1 coordinates.", "We show that our C\u03b1-based method, LARMORC\u03b1, predicts backbone chemical shifts with comparable accuracy to some all-atom approaches.", "More importantly, we demonstrate that LARMORC\u03b1 predicted chemical shifts are able to resolve native structure from decoy pools that contain both native and non-native models, and so it is sensitive to protein structure.", "As an application, we use LARMORC\u03b1 to characterize the transient state of the fast-folding protein gpW using recently published NMR relaxation dispersion derived backbone chemical shifts.", "The model we obtain is consistent with the previously proposed model based on independent analysis of the chemical shift dispersion pattern of the transient state.", "We anticipate that LARMORC\u03b1 will find utility as a tool that enables important protein conformational substates to be identified by \u201cparsing\u201d trajectories and ensembles generated using coarse-grained modeling and simulations."], "title": "Predicting protein backbone chemical shifts from C\u03b1 coordinates: extracting high resolution experimental observables from low resolution models."}
{"paper_id": 25996888, "labels": ["0", "0", "0", "0", "0", "0", "1", "1", "0", "1"], "abstract": "Higher levels of nearby traffic increase exposure to air pollution and adversely affect health outcomes. Populations with lower socio-economic status (SES) are particularly vulnerable to stressors like air pollution. We investigated cumulative exposures and risks from traffic and from MNRiskS-modeled air pollution in multiple source categories across demographic groups. Exposures and risks, especially from on-road sources, were higher than the mean for minorities and low SES populations and lower than the mean for white and high SES populations. Owning multiple vehicles and driving alone were linked to lower household exposures and risks. Those not owning a vehicle and walking or using transit had higher household exposures and risks. These results confirm for our study location that populations on the lower end of the socio-economic spectrum and minorities are disproportionately exposed to traffic and air pollution and at higher risk for adverse health outcomes. A major source of disparities appears to be the transportation infrastructure. Those outside the urban core had lower risks but drove more, while those living nearer the urban core tended to drive less but had higher exposures and risks from on-road sources. We suggest policy considerations for addressing these inequities.", "journal": "International journal of environmental research and public health", "sentences": ["Higher levels of nearby traffic increase exposure to air pollution and adversely affect health outcomes.", "Populations with lower socio-economic status (SES) are particularly vulnerable to stressors like air pollution.", "We investigated cumulative exposures and risks from traffic and from MNRiskS-modeled air pollution in multiple source categories across demographic groups.", "Exposures and risks, especially from on-road sources, were higher than the mean for minorities and low SES populations and lower than the mean for white and high SES populations.", "Owning multiple vehicles and driving alone were linked to lower household exposures and risks.", "Those not owning a vehicle and walking or using transit had higher household exposures and risks.", "These results confirm for our study location that populations on the lower end of the socio-economic spectrum and minorities are disproportionately exposed to traffic and air pollution and at higher risk for adverse health outcomes.", "A major source of disparities appears to be the transportation infrastructure.", "Those outside the urban core had lower risks but drove more, while those living nearer the urban core tended to drive less but had higher exposures and risks from on-road sources.", "We suggest policy considerations for addressing these inequities."], "title": "Traffic, air pollution, minority and socio-economic status: addressing inequities in exposure and risk."}
{"paper_id": 22403181, "labels": ["0", "0", "0", "0", "1"], "abstract": "We have identified tens of thousands of short extrachromosomal circular DNAs (microDNA) in mouse tissues as well as mouse and human cell lines. These microDNAs are 200 to 400 base pairs long, are derived from unique nonrepetitive sequence, and are enriched in the 5'-untranslated regions of genes, exons, and CpG islands. Chromosomal loci that are enriched sources of microDNA in the adult brain are somatically mosaic for microdeletions that appear to arise from the excision of microDNAs. Germline microdeletions identified by the \"Thousand Genomes\" project may also arise from the excision of microDNAs in the germline lineage. We have thus identified a previously unknown DNA entity in mammalian cells and provide evidence that their generation leaves behind deletions in different genomic loci.", "journal": "Science (New York, N.Y.)", "sentences": ["We have identified tens of thousands of short extrachromosomal circular DNAs (microDNA) in mouse tissues as well as mouse and human cell lines.", "These microDNAs are 200 to 400 base pairs long, are derived from unique nonrepetitive sequence, and are enriched in the 5'-untranslated regions of genes, exons, and CpG islands.", "Chromosomal loci that are enriched sources of microDNA in the adult brain are somatically mosaic for microdeletions that appear to arise from the excision of microDNAs.", "Germline microdeletions identified by the \"Thousand Genomes\" project may also arise from the excision of microDNAs in the germline lineage.", "We have thus identified a previously unknown DNA entity in mammalian cells and provide evidence that their generation leaves behind deletions in different genomic loci."], "title": "Extrachromosomal microDNAs and chromosomal microdeletions in normal tissues."}
{"paper_id": 26469898, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Early detection of hypertensive end-organ damage and secondary diseases are key determinants of cardiovascular prognosis in patients suffering from arterial hypertension. Presently, there are no biomarkers for the detection of hypertensive target organ damage, most outstandingly including blood vessels, the heart, and the kidneys.We aimed to validate the usefulness of the urinary excretion of the serine protease kallikrein-related peptidase 9 (KLK9) as a biomarker of hypertension-induced target organ damage.Urinary, plasma, and renal tissue levels of KLK9 were measured by the Western blot in different rat models of hypertension, including angiotensin-II infusion, DOCA-salt, L-NAME administration, and spontaneous hypertension. Urinary levels were associated to cardiovascular and renal injury, assessed by histopathology. The origin of urinary KLK9 was investigated through in situ renal perfusion experiments.The urinary excretion of KLK9 is increased in different experimental models of hypertension in rats. The ACE inhibitor trandolapril significantly reduced arterial pressure and the urinary level of KLK9. Hypertension did not increase kidney, heart, liver, lung, or plasma KLK9 levels. Hypertension-induced increased urinary excretion of KLK9 results from specific alterations in its tubular reabsorption, even in the absence of overt nephropathy. KLK9 urinary excretion strongly correlates with cardiac hypertrophy and aortic wall thickening.KLK9 appears in the urine in the presence of hypertension as a result of subtle renal handling alterations. Urinary KLK9 might be potentially used as an indicator of hypertensive cardiac and vascular damage.", "journal": "Medicine", "sentences": ["Early detection of hypertensive end-organ damage and secondary diseases are key determinants of cardiovascular prognosis in patients suffering from arterial hypertension.", "Presently, there are no biomarkers for the detection of hypertensive target organ damage, most outstandingly including blood vessels, the heart, and the kidneys.We aimed to validate the usefulness of the urinary excretion of the serine protease kallikrein-related peptidase 9 (KLK9) as a biomarker of hypertension-induced target organ damage.Urinary, plasma, and renal tissue levels of KLK9 were measured by the Western blot in different rat models of hypertension, including angiotensin-II infusion, DOCA-salt, L-NAME administration, and spontaneous hypertension.", "Urinary levels were associated to cardiovascular and renal injury, assessed by histopathology.", "The origin of urinary KLK9 was investigated through in situ renal perfusion experiments.The urinary excretion of KLK9 is increased in different experimental models of hypertension in rats.", "The ACE inhibitor trandolapril significantly reduced arterial pressure and the urinary level of KLK9.", "Hypertension did not increase kidney, heart, liver, lung, or plasma KLK9 levels.", "Hypertension-induced increased urinary excretion of KLK9 results from specific alterations in its tubular reabsorption, even in the absence of overt nephropathy.", "KLK9 urinary excretion strongly correlates with cardiac hypertrophy and aortic wall thickening.KLK9 appears in the urine in the presence of hypertension as a result of subtle renal handling alterations.", "Urinary KLK9 might be potentially used as an indicator of hypertensive cardiac and vascular damage."], "title": "Increased Klk9 Urinary Excretion Is Associated to Hypertension-Induced Cardiovascular Damage and Renal Alterations."}
{"paper_id": 21771857, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "A tetramer of HIV-1 integrase (IN) stably associates with the viral DNA ends to form a fully functional concerted integration intermediate. LEDGF/p75, a key cellular binding partner of the lentiviral enzyme, also stabilizes a tetrameric form of IN. However, functional assays have indicated the importance of the order of viral DNA and LEDGF/p75 addition to IN for productive concerted integration. Here, we employed F\u00f6rster Resonance Energy Transfer (FRET) to monitor assembly of individual IN subunits into tetramers in the presence of viral DNA and LEDGF/p75. The IN-viral DNA and IN-LEDGF/p75 complexes yielded significantly different FRET values suggesting two distinct IN conformations in these complexes. Furthermore, the order of addition experiments indicated that FRET for the preformed IN-viral DNA complex remained unchanged upon its subsequent binding to LEDGF/p75, whereas pre-incubation of LEDGF/p75 and IN followed by addition of viral DNA yielded FRET very similar to the IN-LEDGF/p75 complex. These findings provide new insights into the structural organization of IN subunits in functional concerted integration intermediates and suggest that differential multimerization of IN in the presence of various ligands could be exploited as a plausible therapeutic target for development of allosteric inhibitors.", "journal": "Nucleic acids research", "sentences": ["A tetramer of HIV-1 integrase (IN) stably associates with the viral DNA ends to form a fully functional concerted integration intermediate.", "LEDGF/p75, a key cellular binding partner of the lentiviral enzyme, also stabilizes a tetrameric form of IN.", "However, functional assays have indicated the importance of the order of viral DNA and LEDGF/p75 addition to IN for productive concerted integration.", "Here, we employed F\u00f6rster Resonance Energy Transfer (FRET) to monitor assembly of individual IN subunits into tetramers in the presence of viral DNA and LEDGF/p75.", "The IN-viral DNA and IN-LEDGF/p75 complexes yielded significantly different FRET values suggesting two distinct IN conformations in these complexes.", "Furthermore, the order of addition experiments indicated that FRET for the preformed IN-viral DNA complex remained unchanged upon its subsequent binding to LEDGF/p75, whereas pre-incubation of LEDGF/p75 and IN followed by addition of viral DNA yielded FRET very similar to the IN-LEDGF/p75 complex.", "These findings provide new insights into the structural organization of IN subunits in functional concerted integration intermediates and suggest that differential multimerization of IN in the presence of various ligands could be exploited as a plausible therapeutic target for development of allosteric inhibitors."], "title": "FRET analysis reveals distinct conformations of IN tetramers in the presence of viral DNA or LEDGF/p75."}
{"paper_id": 22723794, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Viruses are the major causative agents of central nervous system (CNS) infection worldwide. RNA and DNA viruses trigger broad activation of glial cells including microglia and astrocytes, eliciting the release of an array of mediators that can promote innate and adaptive immune responses. Such responses can limit viral replication and dissemination leading to infection resolution. However, a defining feature of viral CNS infection is the rapid onset of severe neuroinflammation and overzealous glial responses are associated with significant neurological damage or even death. The mechanisms by which microglia and astrocytes perceive neurotropic RNA and DNA viruses are only now becoming apparent with the discovery of a variety of cell surface and cytosolic molecules that serve as sensors for viral components. In this review we discuss the role played by members of the Toll-like family of pattern recognition receptors (PRRs) in the inflammatory responses of glial cells to the principle causative agents of viral encephalitis. Importantly, we also describe the evidence for the involvement of a number of newly described intracellular PRRs, including retinoic acid-inducible gene I and DNA-dependent activator of IFN regulatory factors, that are thought to function as intracellular sensors of RNA and DNA viruses, respectively. Finally, we explore the possibility that cross-talk exists between these disparate viral sensors and their signaling pathways, and describe how glial cytosolic and cell surface/endosomal PRRs could act in a cooperative manner to promote the fulminant inflammation associated with acute neurotropic viral infection.", "journal": "Frontiers in microbiology", "sentences": ["Viruses are the major causative agents of central nervous system (CNS) infection worldwide.", "RNA and DNA viruses trigger broad activation of glial cells including microglia and astrocytes, eliciting the release of an array of mediators that can promote innate and adaptive immune responses.", "Such responses can limit viral replication and dissemination leading to infection resolution.", "However, a defining feature of viral CNS infection is the rapid onset of severe neuroinflammation and overzealous glial responses are associated with significant neurological damage or even death.", "The mechanisms by which microglia and astrocytes perceive neurotropic RNA and DNA viruses are only now becoming apparent with the discovery of a variety of cell surface and cytosolic molecules that serve as sensors for viral components.", "In this review we discuss the role played by members of the Toll-like family of pattern recognition receptors (PRRs) in the inflammatory responses of glial cells to the principle causative agents of viral encephalitis.", "Importantly, we also describe the evidence for the involvement of a number of newly described intracellular PRRs, including retinoic acid-inducible gene I and DNA-dependent activator of IFN regulatory factors, that are thought to function as intracellular sensors of RNA and DNA viruses, respectively.", "Finally, we explore the possibility that cross-talk exists between these disparate viral sensors and their signaling pathways, and describe how glial cytosolic and cell surface/endosomal PRRs could act in a cooperative manner to promote the fulminant inflammation associated with acute neurotropic viral infection."], "title": "Viral CNS infections: role of glial pattern recognition receptors in neuroinflammation."}
{"paper_id": 26441073, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "0"], "abstract": "We examined whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]; 60 \u03bcg/kg/day) can prevent the negative effects of titanium (Ti) particles on implant fixation and periprosthetic osteolysis in a rat model. Eighteen adult male rats (12 weeks old, bones still growing) received intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group received vehicle injections, and 12 rats from the control group and PTH treatment group received Ti particle injections at the time of operation and intra-articular injections 2 and 4 weeks postoperatively. Six of the rats that received Ti particles from the PTH group also received PTH[1-34] treatment. Six weeks postoperatively, all specimens were collected for assessment by X-ray, micro-CT, biomechanical, scanning electron microscopy (SEM), and dynamic histomorphometry. A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate were observed in the control group compared to the blank group, demonstrating that a periprosthetic osteolysis model had been successfully established. Administration of PTH[1-34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group. SEM revealed higher bone-implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group. A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups. These findings imply that intermittent administration of PTH[1-34] prevents periprosthetic osteolysis by promoting bone formation. The effects of PTH[1-34] were evaluated at a suprapharmacological dosage to the human equivalent in rats; therefore, additional studies are required to demonstrate its therapeutic potential in periprosthetic osteolysis.", "journal": "PloS one", "sentences": ["We examined whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]; 60 \u03bcg/kg/day) can prevent the negative effects of titanium (Ti) particles on implant fixation and periprosthetic osteolysis in a rat model.", "Eighteen adult male rats (12 weeks old, bones still growing) received intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group received vehicle injections, and 12 rats from the control group and PTH treatment group received Ti particle injections at the time of operation and intra-articular injections 2 and 4 weeks postoperatively.", "Six of the rats that received Ti particles from the PTH group also received PTH[1-34] treatment.", "Six weeks postoperatively, all specimens were collected for assessment by X-ray, micro-CT, biomechanical, scanning electron microscopy (SEM), and dynamic histomorphometry.", "A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate were observed in the control group compared to the blank group, demonstrating that a periprosthetic osteolysis model had been successfully established.", "Administration of PTH[1-34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group.", "SEM revealed higher bone-implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group.", "A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups.", "These findings imply that intermittent administration of PTH[1-34] prevents periprosthetic osteolysis by promoting bone formation.", "The effects of PTH[1-34] were evaluated at a suprapharmacological dosage to the human equivalent in rats; therefore, additional studies are required to demonstrate its therapeutic potential in periprosthetic osteolysis."], "title": "Intermittent Administration of Parathyroid Hormone [1-34] Prevents Particle-Induced Periprosthetic Osteolysis in a Rat Model."}
{"paper_id": 20197604, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "In this paper 1D transient elastography was employed in fresh bovine skeletal muscle samples to assess the shear elastic modulus mu while the tissue was locally heated by means of an electrical resistance. The investigation is based on the study of the time shift of the shear wave propagation produced by the local temperature variation. The experiments show that the thermal expansion contribution to the time shift is negligible when compared with the shear wave speed variation. In such a case, the quantification of mu as a function of temperature becomes possible. Repeated experiments in different samples lead to a reproducible behavior of mu as a function of temperature. Irreversible elasticity changes are produced when the temperature exceeds a certain critical value T(c). The proposed method allows estimating this value as well as the spatial extension of the resulting thermal lesion. This point is important when considering applications in monitoring focused ultrasound surgery (FUS) because the surrounding normal tissue should remain unaffected.", "journal": "Physics in medicine and biology", "sentences": ["In this paper 1D transient elastography was employed in fresh bovine skeletal muscle samples to assess the shear elastic modulus mu while the tissue was locally heated by means of an electrical resistance.", "The investigation is based on the study of the time shift of the shear wave propagation produced by the local temperature variation.", "The experiments show that the thermal expansion contribution to the time shift is negligible when compared with the shear wave speed variation.", "In such a case, the quantification of mu as a function of temperature becomes possible.", "Repeated experiments in different samples lead to a reproducible behavior of mu as a function of temperature.", "Irreversible elasticity changes are produced when the temperature exceeds a certain critical value T(c).", "The proposed method allows estimating this value as well as the spatial extension of the resulting thermal lesion.", "This point is important when considering applications in monitoring focused ultrasound surgery (FUS) because the surrounding normal tissue should remain unaffected."], "title": "Monitoring heat-induced changes in soft tissues with 1D transient elastography."}
{"paper_id": 26819514, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "In addition to causing cirrhosis and hepatocellular carcinoma, hepatitis C virus (HCV) is thought to cause hypolipidemia, hepatic steatosis, insulin resistance, metabolic syndrome, and diabetes. The viral life cycle of HCV depends on cholesterol metabolism in host cells. HCV core protein and nonstructural protein 5A perturb crucial lipid and glucose pathways, such as the sterol regulatory element-binding protein pathway and the protein kinase B/mammalian target of rapamycin/S6 kinase 1 pathway. Although several lines of transgenic mice expressing core or full HCV proteins exhibit hepatic steatosis and/or dyslipidemia, whether they completely reflect the metabolic alterations in humans with HCV infection remains unknown. Many cross-sectional studies have demonstrated increased prevalences of metabolic alterations and cardiovascular events in patients with chronic hepatitis C (CHC); however, conflicting results exist, primarily due to unavoidable individual variations. Utilizing anti-HCV therapy, most longitudinal cohort studies of CHC patients have demonstrated the favorable effects of viral clearance in attenuating metabolic alterations and cardiovascular risks. To determine the risks of HCV-associated metabolic alterations and associated complications in patients with CHC, it is necessary to adjust for crucial confounders, such as HCV genotype and host baseline glucose metabolism, for a long follow-up period after anti-HCV treatment. Adipose tissue is an important endocrine organ due to its release of adipocytokines, which regulate lipid and glucose metabolism. However, most data on HCV infection and adipocytokine alteration are inconclusive. A comprehensive overview of HCV-associated metabolic and adipocytokine alterations, from bench to bedside, is presented in this topic highlight.", "journal": "World journal of gastroenterology", "sentences": ["In addition to causing cirrhosis and hepatocellular carcinoma, hepatitis C virus (HCV) is thought to cause hypolipidemia, hepatic steatosis, insulin resistance, metabolic syndrome, and diabetes.", "The viral life cycle of HCV depends on cholesterol metabolism in host cells.", "HCV core protein and nonstructural protein 5A perturb crucial lipid and glucose pathways, such as the sterol regulatory element-binding protein pathway and the protein kinase B/mammalian target of rapamycin/S6 kinase 1 pathway.", "Although several lines of transgenic mice expressing core or full HCV proteins exhibit hepatic steatosis and/or dyslipidemia, whether they completely reflect the metabolic alterations in humans with HCV infection remains unknown.", "Many cross-sectional studies have demonstrated increased prevalences of metabolic alterations and cardiovascular events in patients with chronic hepatitis C (CHC); however, conflicting results exist, primarily due to unavoidable individual variations.", "Utilizing anti-HCV therapy, most longitudinal cohort studies of CHC patients have demonstrated the favorable effects of viral clearance in attenuating metabolic alterations and cardiovascular risks.", "To determine the risks of HCV-associated metabolic alterations and associated complications in patients with CHC, it is necessary to adjust for crucial confounders, such as HCV genotype and host baseline glucose metabolism, for a long follow-up period after anti-HCV treatment.", "Adipose tissue is an important endocrine organ due to its release of adipocytokines, which regulate lipid and glucose metabolism.", "However, most data on HCV infection and adipocytokine alteration are inconclusive.", "A comprehensive overview of HCV-associated metabolic and adipocytokine alterations, from bench to bedside, is presented in this topic highlight."], "title": "Metabolic alterations and hepatitis C: From bench to bedside."}
{"paper_id": 21412410, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Aspergillus fumigatus is the most commonly encountered mold pathogen of humans, predominantly infecting the respiratory system. Colonization and penetration of the lung alveolar epithelium is a key but poorly understood step in the infection process. This study focused on identifying the transcriptional and cell-signaling responses activated in A549 alveolar carcinoma cells incubated in the presence of A. fumigatus wild-type and \u0394PrtT protease-deficient germinating conidia and culture filtrates (CF). Microarray analysis of exposed A549 cells identified distinct classes of genes whose expression is altered in the presence of germinating conidia and CF and suggested the involvement of both NFkB and MAPK signaling pathways in mediating the cellular response. Phosphoprotein analysis of A549 cells confirmed that JNK and ERK1/2 are phosphorylated in response to CF from wild-type A. fumigatus and not phosphorylated in response to CF from the \u0394PrtT protease-deficient strain. Inhibition of JNK or ERK1/2 kinase activity substantially decreased CF-induced cell damage, including cell peeling, actin-cytoskeleton damage, and reduction in metabolic activity and necrotic death. These results suggest that inhibition of MAPK-mediated host responses to treatment with A. fumigatus CF decreases cellular damage, a finding with possible clinical implications.", "journal": "PloS one", "sentences": ["Aspergillus fumigatus is the most commonly encountered mold pathogen of humans, predominantly infecting the respiratory system.", "Colonization and penetration of the lung alveolar epithelium is a key but poorly understood step in the infection process.", "This study focused on identifying the transcriptional and cell-signaling responses activated in A549 alveolar carcinoma cells incubated in the presence of A. fumigatus wild-type and \u0394PrtT protease-deficient germinating conidia and culture filtrates (CF).", "Microarray analysis of exposed A549 cells identified distinct classes of genes whose expression is altered in the presence of germinating conidia and CF and suggested the involvement of both NFkB and MAPK signaling pathways in mediating the cellular response.", "Phosphoprotein analysis of A549 cells confirmed that JNK and ERK1/2 are phosphorylated in response to CF from wild-type A. fumigatus and not phosphorylated in response to CF from the \u0394PrtT protease-deficient strain.", "Inhibition of JNK or ERK1/2 kinase activity substantially decreased CF-induced cell damage, including cell peeling, actin-cytoskeleton damage, and reduction in metabolic activity and necrotic death.", "These results suggest that inhibition of MAPK-mediated host responses to treatment with A. fumigatus CF decreases cellular damage, a finding with possible clinical implications."], "title": "PrtT-regulated proteins secreted by Aspergillus fumigatus activate MAPK signaling in exposed A549 lung cells leading to necrotic cell death."}
{"paper_id": 24465221, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "In natural environments, bacteria often adhere to surfaces where they form complex multicellular communities. Surface adherence is determined by the biochemical composition of the cell envelope. We describe a novel regulatory mechanism by which the bacterium, Caulobacter crescentus, integrates cell cycle and nutritional signals to control development of an adhesive envelope structure known as the holdfast. Specifically, we have discovered a 68-residue protein inhibitor of holdfast development (HfiA) that directly targets a conserved glycolipid glycosyltransferase required for holdfast production (HfsJ). Multiple cell cycle regulators associate with the hfiA and hfsJ promoters and control their expression, temporally constraining holdfast development to the late stages of G1. HfiA further functions as part of a 'nutritional override' system that decouples holdfast development from the cell cycle in response to nutritional cues. This control mechanism can limit surface adhesion in nutritionally sub-optimal environments without affecting cell cycle progression. We conclude that post-translational regulation of cell envelope enzymes by small proteins like HfiA may provide a general means to modulate the surface properties of bacterial cells.", "journal": "PLoS genetics", "sentences": ["In natural environments, bacteria often adhere to surfaces where they form complex multicellular communities.", "Surface adherence is determined by the biochemical composition of the cell envelope.", "We describe a novel regulatory mechanism by which the bacterium, Caulobacter crescentus, integrates cell cycle and nutritional signals to control development of an adhesive envelope structure known as the holdfast.", "Specifically, we have discovered a 68-residue protein inhibitor of holdfast development (HfiA) that directly targets a conserved glycolipid glycosyltransferase required for holdfast production (HfsJ).", "Multiple cell cycle regulators associate with the hfiA and hfsJ promoters and control their expression, temporally constraining holdfast development to the late stages of G1.", "HfiA further functions as part of a 'nutritional override' system that decouples holdfast development from the cell cycle in response to nutritional cues.", "This control mechanism can limit surface adhesion in nutritionally sub-optimal environments without affecting cell cycle progression.", "We conclude that post-translational regulation of cell envelope enzymes by small proteins like HfiA may provide a general means to modulate the surface properties of bacterial cells."], "title": "A cell cycle and nutritional checkpoint controlling bacterial surface adhesion."}
{"paper_id": 24349150, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The extent to which stray, hatchery-reared salmon affect wild populations is much debated. Although experiments show that artificial breeding and culture influence the genetics of hatchery salmon, little is known about the interaction between hatchery and wild salmon in a natural setting. Here, we estimated historical and contemporary genetic population structures of chum salmon (Oncorhynchus keta) in Prince William Sound (PWS), Alaska, with 135 single nucleotide polymorphism (SNP) markers. Historical population structure was inferred from the analysis of DNA from fish scales, which had been archived since the late 1960's for several populations in PWS. Parallel analyses with microsatellites and a test based on Hardy-Weinberg proportions showed that about 50% of the fish-scale DNA was cross-contaminated with DNA from other fish. These samples were removed from the analysis. We used a novel application of the classical source-sink model to compare SNP allele frequencies in these archived fish-scales (1964-1982) with frequencies in contemporary samples (2008-2010) and found a temporal shift toward hatchery allele frequencies in some wild populations. Other populations showed markedly less introgression, despite moderate amounts of hatchery straying. The extent of introgression may reflect similarities in spawning time and life-history traits between hatchery and wild fish, or the degree that hybrids return to a natal spawning area. The source-sink model is a powerful means of detecting low levels of introgression over several generations.", "journal": "PloS one", "sentences": ["The extent to which stray, hatchery-reared salmon affect wild populations is much debated.", "Although experiments show that artificial breeding and culture influence the genetics of hatchery salmon, little is known about the interaction between hatchery and wild salmon in a natural setting.", "Here, we estimated historical and contemporary genetic population structures of chum salmon (Oncorhynchus keta) in Prince William Sound (PWS), Alaska, with 135 single nucleotide polymorphism (SNP) markers.", "Historical population structure was inferred from the analysis of DNA from fish scales, which had been archived since the late 1960's for several populations in PWS.", "Parallel analyses with microsatellites and a test based on Hardy-Weinberg proportions showed that about 50% of the fish-scale DNA was cross-contaminated with DNA from other fish.", "These samples were removed from the analysis.", "We used a novel application of the classical source-sink model to compare SNP allele frequencies in these archived fish-scales (1964-1982) with frequencies in contemporary samples (2008-2010) and found a temporal shift toward hatchery allele frequencies in some wild populations.", "Other populations showed markedly less introgression, despite moderate amounts of hatchery straying.", "The extent of introgression may reflect similarities in spawning time and life-history traits between hatchery and wild fish, or the degree that hybrids return to a natal spawning area.", "The source-sink model is a powerful means of detecting low levels of introgression over several generations."], "title": "Source-sink estimates of genetic introgression show influence of hatchery strays on wild chum salmon populations in Prince William Sound, Alaska."}
{"paper_id": 25948814, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The TNF-\u03b1-induced protein 8 (TNFAIP8 or TIPE) is a risk factor for cancer and bacterial infection, and its expression is upregulated in a number of human cancers. However, its physiologic and pathologic functions are unclear. In this study, we describe the generation of TIPE-deficient mice and their increased sensitivity to colonic inflammation. TIPE-deficient mice were generated by germ line gene targeting and were born without noticeable developmental abnormalities. Their major organs, including lymphoid organs and intestines, were macroscopically and microscopically normal. However, after drinking dextran sodium sulfate-containing water, TIPE-deficient mice developed more severe colitis than wild type mice did, as demonstrated by decreased survival rates, increased body weight loss, and enhanced leukocyte infiltration, bacterial invasion, and inflammatory cytokine production in the colon. Bone marrow chimeric experiments revealed that TIPE deficiency in nonhematopoietic cells was responsible for the exacerbated colitis in TIPE-deficient mice. Consistent with this result, TIPE-deficient intestinal epithelial cells had increased rate of cell death and decreased rate of proliferation as compared with wild type controls. These findings indicate that TIPE plays an important role in maintaining colon homeostasis and in protecting against colitis.", "journal": "Journal of immunology (Baltimore, Md. : 1950)", "sentences": ["The TNF-\u03b1-induced protein 8 (TNFAIP8 or TIPE) is a risk factor for cancer and bacterial infection, and its expression is upregulated in a number of human cancers.", "However, its physiologic and pathologic functions are unclear.", "In this study, we describe the generation of TIPE-deficient mice and their increased sensitivity to colonic inflammation.", "TIPE-deficient mice were generated by germ line gene targeting and were born without noticeable developmental abnormalities.", "Their major organs, including lymphoid organs and intestines, were macroscopically and microscopically normal.", "However, after drinking dextran sodium sulfate-containing water, TIPE-deficient mice developed more severe colitis than wild type mice did, as demonstrated by decreased survival rates, increased body weight loss, and enhanced leukocyte infiltration, bacterial invasion, and inflammatory cytokine production in the colon.", "Bone marrow chimeric experiments revealed that TIPE deficiency in nonhematopoietic cells was responsible for the exacerbated colitis in TIPE-deficient mice.", "Consistent with this result, TIPE-deficient intestinal epithelial cells had increased rate of cell death and decreased rate of proliferation as compared with wild type controls.", "These findings indicate that TIPE plays an important role in maintaining colon homeostasis and in protecting against colitis."], "title": "Exacerbated experimental colitis in TNFAIP8-deficient mice."}
{"paper_id": 20846510, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Astaxanthin (AST) is a powerful antioxidant that occurs naturally in a wide variety of living organisms. Much experimental evidence has proved that AST has the function of eliminating oxygen free radicals and can protect organisms from oxidative damage. The present study was carried out to further investigate the neuroprotective effect of AST on oxidative stress induced toxicity in primary culture of cortical neurons and on focal cerebral ischemia-reperfusion induced brain damage in rats. AST, over a concentration range of 250-1000nM, attenuated 50\u03bcM H(2)O(2)-induced cell viability loss. 500nM AST pretreatment significantly inhibited H(2)O(2)-induced apoptosis measured by Hoechst 33342 staining and restored the mitochondrial membrane potential (MMP) measured by a fluorescent dye, Rhodamine 123. In vivo, AST prevented cerebral ischemic injury induced by 2h middle cerebral artery occlusion (MCAO) and 24h reperfusion in rats. Pretreatment of AST intragastrically twice at 5h and 1h prior to ischemia dramatically diminished infarct volume and improved neurological deficit in a dose-dependent manner. Nissl staining showed that the neuronal injury was significantly improved by pretreatment of AST at 80mg/kg. Taken together, these results suggest that pretreatment with AST exhibits noticeable neuroprotection against brain damage induced by ischemia-reperfusion and the antioxidant activity of AST maybe partly responsible for it.", "journal": "Brain research", "sentences": ["Astaxanthin (AST) is a powerful antioxidant that occurs naturally in a wide variety of living organisms.", "Much experimental evidence has proved that AST has the function of eliminating oxygen free radicals and can protect organisms from oxidative damage.", "The present study was carried out to further investigate the neuroprotective effect of AST on oxidative stress induced toxicity in primary culture of cortical neurons and on focal cerebral ischemia-reperfusion induced brain damage in rats.", "AST, over a concentration range of 250-1000nM, attenuated 50\u03bcM H(2)O(2)-induced cell viability loss.", "500nM AST pretreatment significantly inhibited H(2)O(2)-induced apoptosis measured by Hoechst 33342 staining and restored the mitochondrial membrane potential (MMP) measured by a fluorescent dye, Rhodamine 123.", "In vivo, AST prevented cerebral ischemic injury induced by 2h middle cerebral artery occlusion (MCAO) and 24h reperfusion in rats.", "Pretreatment of AST intragastrically twice at 5h and 1h prior to ischemia dramatically diminished infarct volume and improved neurological deficit in a dose-dependent manner.", "Nissl staining showed that the neuronal injury was significantly improved by pretreatment of AST at 80mg/kg.", "Taken together, these results suggest that pretreatment with AST exhibits noticeable neuroprotection against brain damage induced by ischemia-reperfusion and the antioxidant activity of AST maybe partly responsible for it."], "title": "Neuroprotective effect of astaxanthin on H(2)O(2)-induced neurotoxicity in vitro and on focal cerebral ischemia in vivo."}
{"paper_id": 26891221, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Kaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma and certain lymphoproliferative malignancies. Latent infection is established in the majority of tumor cells, whereas lytic replication is reactivated in a small fraction of cells, which is important for both virus spread and disease progression. A siRNA screen for novel regulators of KSHV reactivation identified the E3 ubiquitin ligase MDM2 as a negative regulator of viral reactivation. Depletion of MDM2, a repressor of p53, favored efficient activation of the viral lytic transcription program and viral reactivation. During lytic replication cells activated a p53 response, accumulated DNA damage and arrested at G2-phase. Depletion of p21, a p53 target gene, restored cell cycle progression and thereby impaired the virus reactivation cascade delaying the onset of virus replication induced cytopathic effect. Herpesviruses are known to reactivate in response to different kinds of stress, and our study now highlights the molecular events in the stressed host cell that KSHV has evolved to utilize to ensure efficient viral lytic replication.", "journal": "PLoS pathogens", "sentences": ["Kaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma and certain lymphoproliferative malignancies.", "Latent infection is established in the majority of tumor cells, whereas lytic replication is reactivated in a small fraction of cells, which is important for both virus spread and disease progression.", "A siRNA screen for novel regulators of KSHV reactivation identified the E3 ubiquitin ligase MDM2 as a negative regulator of viral reactivation.", "Depletion of MDM2, a repressor of p53, favored efficient activation of the viral lytic transcription program and viral reactivation.", "During lytic replication cells activated a p53 response, accumulated DNA damage and arrested at G2-phase.", "Depletion of p21, a p53 target gene, restored cell cycle progression and thereby impaired the virus reactivation cascade delaying the onset of virus replication induced cytopathic effect.", "Herpesviruses are known to reactivate in response to different kinds of stress, and our study now highlights the molecular events in the stressed host cell that KSHV has evolved to utilize to ensure efficient viral lytic replication."], "title": "Oncogenic Herpesvirus Utilizes Stress-Induced Cell Cycle Checkpoints for Efficient Lytic Replication."}
{"paper_id": 26125027, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Recently, vibration training is considered as a novel strategy of weight loss; however, its mechanisms are still unclear. In this study, normal or high-fat diet-induced rats were trained by whole body vibration for 8 weeks. We observed that the body weight and fat metabolism index, blood glucose, triglyceride, cholesterol, and free fatty acid in obesity rats decreased significantly compared with nonvibration group (n = 6). Although intrascapular BAT weight did not change significantly, vibration enhanced ATP reduction and increased protein level of the key molecule of brown adipose tissue (BAT), PGC-1\u03b1, and UCP1 in BAT. Interestingly, the adipocytes in retroperitoneal white adipose tissue (WAT) became smaller due to vibration exercise and had higher protein level of the key molecule of brown adipose tissue (BAT), PGC-1\u03b1, and UCP1 and inflammatory relative proteins, IL-6 and TNF\u03b1. Simultaneously, ATP content and PPAR\u03b3 protein level in WAT became less in rats compared with nonvibration group. The results indicated that vibration training changed lipid metabolism in rats and promoted brown fat-like change in white adipose tissues through triggering BAT associated gene expression, inflammatory reflect, and reducing energy reserve.", "journal": "BioMed research international", "sentences": ["Recently, vibration training is considered as a novel strategy of weight loss; however, its mechanisms are still unclear.", "In this study, normal or high-fat diet-induced rats were trained by whole body vibration for 8 weeks.", "We observed that the body weight and fat metabolism index, blood glucose, triglyceride, cholesterol, and free fatty acid in obesity rats decreased significantly compared with nonvibration group (n = 6).", "Although intrascapular BAT weight did not change significantly, vibration enhanced ATP reduction and increased protein level of the key molecule of brown adipose tissue (BAT), PGC-1\u03b1, and UCP1 in BAT.", "Interestingly, the adipocytes in retroperitoneal white adipose tissue (WAT) became smaller due to vibration exercise and had higher protein level of the key molecule of brown adipose tissue (BAT), PGC-1\u03b1, and UCP1 and inflammatory relative proteins, IL-6 and TNF\u03b1.", "Simultaneously, ATP content and PPAR\u03b3 protein level in WAT became less in rats compared with nonvibration group.", "The results indicated that vibration training changed lipid metabolism in rats and promoted brown fat-like change in white adipose tissues through triggering BAT associated gene expression, inflammatory reflect, and reducing energy reserve."], "title": "Vibration Training Triggers Brown Adipocyte Relative Protein Expression in Rat White Adipose Tissue."}
{"paper_id": 26360059, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Pseudomonas aeruginosa is a Gram-negative bacterium known to cause opportunistic infections in immune-compromised or immunosuppressed individuals that often prove fatal. New drugs to combat this organism are therefore sought after. To this end, we subjected the gene products of predicted perturbative genes to structure-based druggability predictions using DrugPred. Making this approach suitable for large-scale predictions required the introduction of new methods for calculation of descriptors, development of a workflow to identify suitable pockets in homologous proteins and establishment of criteria to obtain valid druggability predictions based on homologs. We were able to identify 29 perturbative proteins of P. aeruginosa that may contain druggable pockets, including some of them with no or no drug-like inhibitors deposited in ChEMBL. These proteins form promising novel targets for drug discovery against P. aeruginosa.", "journal": "PloS one", "sentences": ["Pseudomonas aeruginosa is a Gram-negative bacterium known to cause opportunistic infections in immune-compromised or immunosuppressed individuals that often prove fatal.", "New drugs to combat this organism are therefore sought after.", "To this end, we subjected the gene products of predicted perturbative genes to structure-based druggability predictions using DrugPred.", "Making this approach suitable for large-scale predictions required the introduction of new methods for calculation of descriptors, development of a workflow to identify suitable pockets in homologous proteins and establishment of criteria to obtain valid druggability predictions based on homologs.", "We were able to identify 29 perturbative proteins of P. aeruginosa that may contain druggable pockets, including some of them with no or no drug-like inhibitors deposited in ChEMBL.", "These proteins form promising novel targets for drug discovery against P. aeruginosa."], "title": "To Hit or Not to Hit, That Is the Question - Genome-wide Structure-Based Druggability Predictions for Pseudomonas aeruginosa Proteins."}
{"paper_id": 27610013, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Approximately 350 million people are estimated to be persistently infected with hepatitis B virus (HBV) worldwide. HBV maintains persistent infection by employing covalently closed circular DNA (cccDNA), a template for all HBV RNAs. Chronic hepatitis B (CHB) patients are currently treated with nucleos(t)ide analogs such as lamivudine, adefovir, entecavir, and tenofovir. However, these treatments rarely cure CHB because they are unable to inhibit cccDNA transcription and inhibit only a late stage in the HBV life cycle (the reverse transcription step in the nucleocapsid). Therefore, an understanding of the factors regulating cccDNA transcription is required to stop this process. Among numerous factors, hepatocyte nuclear factors (HNFs) play the most important roles in cccDNA transcription, especially in the generation of viral genomic RNA, a template for HBV replication. Therefore, proper control of HNF function could lead to the inhibition of HBV replication. In this review, we summarize and discuss the current understanding of the roles of HNFs in the HBV life cycle and the upstream factors that regulate HNFs. This knowledge will enable the identification of new therapeutic targets to cure CHB.", "journal": "World journal of gastroenterology", "sentences": ["Approximately 350 million people are estimated to be persistently infected with hepatitis B virus (HBV) worldwide.", "HBV maintains persistent infection by employing covalently closed circular DNA (cccDNA), a template for all HBV RNAs.", "Chronic hepatitis B (CHB) patients are currently treated with nucleos(t)ide analogs such as lamivudine, adefovir, entecavir, and tenofovir.", "However, these treatments rarely cure CHB because they are unable to inhibit cccDNA transcription and inhibit only a late stage in the HBV life cycle (the reverse transcription step in the nucleocapsid).", "Therefore, an understanding of the factors regulating cccDNA transcription is required to stop this process.", "Among numerous factors, hepatocyte nuclear factors (HNFs) play the most important roles in cccDNA transcription, especially in the generation of viral genomic RNA, a template for HBV replication.", "Therefore, proper control of HNF function could lead to the inhibition of HBV replication.", "In this review, we summarize and discuss the current understanding of the roles of HNFs in the HBV life cycle and the upstream factors that regulate HNFs.", "This knowledge will enable the identification of new therapeutic targets to cure CHB."], "title": "Roles of hepatocyte nuclear factors in hepatitis B virus infection."}
{"paper_id": 25808890, "labels": ["0", "0", "0", "1", "0", "1"], "abstract": "Farming was established in Central Europe by the Linearbandkeramik culture (LBK), a well-investigated archaeological horizon, which emerged in the Carpathian Basin, in today's Hungary. However, the genetic background of the LBK genesis is yet unclear. Here we present 9 Y chromosomal and 84 mitochondrial DNA profiles from Mesolithic, Neolithic Star\u010devo and LBK sites (seventh/sixth millennia BC) from the Carpathian Basin and southeastern Europe. We detect genetic continuity of both maternal and paternal elements during the initial spread of agriculture, and confirm the substantial genetic impact of early southeastern European and Carpathian Basin farming cultures on Central European populations of the sixth-fourth millennia BC. Comprehensive Y chromosomal and mitochondrial DNA population genetic analyses demonstrate a clear affinity of the early farmers to the modern Near East and Caucasus, tracing the expansion from that region through southeastern Europe and the Carpathian Basin into Central Europe. However, our results also reveal contrasting patterns for male and female genetic diversity in the European Neolithic, suggesting a system of patrilineal descent and patrilocal residential rules among the early farmers.", "journal": "Proceedings. Biological sciences / The Royal Society", "sentences": ["Farming was established in Central Europe by the Linearbandkeramik culture (LBK), a well-investigated archaeological horizon, which emerged in the Carpathian Basin, in today's Hungary.", "However, the genetic background of the LBK genesis is yet unclear.", "Here we present 9 Y chromosomal and 84 mitochondrial DNA profiles from Mesolithic, Neolithic Star\u010devo and LBK sites (seventh/sixth millennia BC) from the Carpathian Basin and southeastern Europe.", "We detect genetic continuity of both maternal and paternal elements during the initial spread of agriculture, and confirm the substantial genetic impact of early southeastern European and Carpathian Basin farming cultures on Central European populations of the sixth-fourth millennia BC.", "Comprehensive Y chromosomal and mitochondrial DNA population genetic analyses demonstrate a clear affinity of the early farmers to the modern Near East and Caucasus, tracing the expansion from that region through southeastern Europe and the Carpathian Basin into Central Europe.", "However, our results also reveal contrasting patterns for male and female genetic diversity in the European Neolithic, suggesting a system of patrilineal descent and patrilocal residential rules among the early farmers."], "title": "Tracing the genetic origin of Europe's first farmers reveals insights into their social organization."}
{"paper_id": 23382239, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "We present a technique for in situ visualization of the biomechanics of DNA structural networks using 4D electron microscopy. Vibrational oscillations of the DNA structure are excited mechanically through a short burst of substrate vibrations triggered by a laser pulse. Subsequently, the motion is probed with electron pulses to observe the impulse response of the specimen in space and time. From the frequency and amplitude of the observed oscillations, we determine the normal modes and eigenfrequencies of the structures involved. Moreover, by selective \"nano-cutting\" at a given point in the network, it was possible to obtain Young's modulus, and hence the stiffness, of the DNA filament at that position. This experimental approach enables nanoscale mechanics studies of macromolecules and should find applications in other domains of biological networks such as origamis.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["We present a technique for in situ visualization of the biomechanics of DNA structural networks using 4D electron microscopy.", "Vibrational oscillations of the DNA structure are excited mechanically through a short burst of substrate vibrations triggered by a laser pulse.", "Subsequently, the motion is probed with electron pulses to observe the impulse response of the specimen in space and time.", "From the frequency and amplitude of the observed oscillations, we determine the normal modes and eigenfrequencies of the structures involved.", "Moreover, by selective \"nano-cutting\" at a given point in the network, it was possible to obtain Young's modulus, and hence the stiffness, of the DNA filament at that position.", "This experimental approach enables nanoscale mechanics studies of macromolecules and should find applications in other domains of biological networks such as origamis."], "title": "Biomechanics of DNA structures visualized by 4D electron microscopy."}
{"paper_id": 26636021, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The composite right/left-handed (CRLH) transmission line (TL) is presented as a general TL possessing both left-handed (LH) and right-handed (RH) natures. RH materials have both positive permittivity and positive permeability, and LH materials have both negative permittivity and negative permeability. This paper aims to design and analyze nonlinear CRLH-TL transmission line loaded with resonant tunneling diode (RTD). The main application of this design is a very wideband and compact filter that amplifies the travelling signal. We used OrCAD and ADS software to analyze the proposed circuit. CRLH-TL consists of a microstrip line which is loaded with complementary split-rings resonators (CSRRs), series gaps, and shunt inductor connected parallel to the RTD. The designed structure possess a wide band that ranges from 5 to 10.5\u00a0GHz and amplifies signal up to 50\u00a0%. The proposed design is of interest to microwave compact component designers.", "journal": "SpringerPlus", "sentences": ["The composite right/left-handed (CRLH) transmission line (TL) is presented as a general TL possessing both left-handed (LH) and right-handed (RH) natures.", "RH materials have both positive permittivity and positive permeability, and LH materials have both negative permittivity and negative permeability.", "This paper aims to design and analyze nonlinear CRLH-TL transmission line loaded with resonant tunneling diode (RTD).", "The main application of this design is a very wideband and compact filter that amplifies the travelling signal.", "We used OrCAD and ADS software to analyze the proposed circuit.", "CRLH-TL consists of a microstrip line which is loaded with complementary split-rings resonators (CSRRs), series gaps, and shunt inductor connected parallel to the RTD.", "The designed structure possess a wide band that ranges from 5 to 10.5\u00a0GHz and amplifies signal up to 50\u00a0%.", "The proposed design is of interest to microwave compact component designers."], "title": "A compact very wideband amplifying filter based on RTD loaded composite right/left-handed transmission lines."}
{"paper_id": 22982069, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Two experiments investigated the functional-anatomical correlates of cognition supporting untrained, emergent relational inference in a stimulus equivalence task. In Experiment 1, after learning a series of conditional relations involving words and pseudowords, participants performed a relatedness task during which EEG was recorded. Behavioural performance was faster and more accurate on untrained, indirectly related symmetry (i.e., learn AB and infer BA) and equivalence trials (i.e., learn AB and AC and infer CB) than on unrelated trials, regardless of whether or not a formal test for stimulus equivalence relations had been conducted. Consistent with previous results, event related potentials (ERPs) evoked by trained and emergent trials at parietal and occipital sites differed only for those participants who had not received a prior equivalence test. Experiment 2 further replicated and extended these behavioural and ERP findings using arbitrary symbols as stimuli and demonstrated time and frequency differences for trained and untrained relatedness trials. Overall, the findings demonstrate convincingly the ERP correlates of intra-experimentally established stimulus equivalence relations consisting entirely of arbitrary symbols and offer support for a contemporary cognitive-behavioural model of symbolic categorisation and relational inference.", "journal": "Behavioural brain research", "sentences": ["Two experiments investigated the functional-anatomical correlates of cognition supporting untrained, emergent relational inference in a stimulus equivalence task.", "In Experiment 1, after learning a series of conditional relations involving words and pseudowords, participants performed a relatedness task during which EEG was recorded.", "Behavioural performance was faster and more accurate on untrained, indirectly related symmetry (i.e., learn AB and infer BA) and equivalence trials (i.e., learn AB and AC and infer CB) than on unrelated trials, regardless of whether or not a formal test for stimulus equivalence relations had been conducted.", "Consistent with previous results, event related potentials (ERPs) evoked by trained and emergent trials at parietal and occipital sites differed only for those participants who had not received a prior equivalence test.", "Experiment 2 further replicated and extended these behavioural and ERP findings using arbitrary symbols as stimuli and demonstrated time and frequency differences for trained and untrained relatedness trials.", "Overall, the findings demonstrate convincingly the ERP correlates of intra-experimentally established stimulus equivalence relations consisting entirely of arbitrary symbols and offer support for a contemporary cognitive-behavioural model of symbolic categorisation and relational inference."], "title": "Event-related potential correlates of emergent inference in human arbitrary relational learning."}
{"paper_id": 27093053, "labels": ["0", "0", "0", "0", "1", "1"], "abstract": "Proteases are widely used to remove affinity and solubility tags from recombinant proteins to avoid potential interference of these tags with the structure and function of the fusion partner. In recent years, great interest has been seen in use of the human rhinovirus 3C protease owing to its stringent sequence specificity and enhanced activity. Like other proteases, activity of the human rhinovirus 3C protease can be affected in part by the buffer components and additives that are generally employed for purification and stabilization of proteins, hence, necessitate their removal by tedious and time-consuming procedures before proteolysis can occur. To address this issue, we examined the effect of elution buffers used for common affinity based purifications, salt ions, stability/solubility and reducing agents, and detergents on the activity of the human rhinovirus 3C protease using three different fusion proteins at 4\u00b0C, a temperature of choice for purification of many proteins. The results show that the human rhinovirus 3C protease performs better at 4\u00b0C than the frequently used tobacco etch virus protease and its activity was insensitive to most of the experimental conditions tested. Though number of fusion proteins tested is limited, we expect that these finding will facilitate the use of the human rhinovirus 3C protease in recombinant protein production for pharmaceutical and biotechnological applications.", "journal": "PloS one", "sentences": ["Proteases are widely used to remove affinity and solubility tags from recombinant proteins to avoid potential interference of these tags with the structure and function of the fusion partner.", "In recent years, great interest has been seen in use of the human rhinovirus 3C protease owing to its stringent sequence specificity and enhanced activity.", "Like other proteases, activity of the human rhinovirus 3C protease can be affected in part by the buffer components and additives that are generally employed for purification and stabilization of proteins, hence, necessitate their removal by tedious and time-consuming procedures before proteolysis can occur.", "To address this issue, we examined the effect of elution buffers used for common affinity based purifications, salt ions, stability/solubility and reducing agents, and detergents on the activity of the human rhinovirus 3C protease using three different fusion proteins at 4\u00b0C, a temperature of choice for purification of many proteins.", "The results show that the human rhinovirus 3C protease performs better at 4\u00b0C than the frequently used tobacco etch virus protease and its activity was insensitive to most of the experimental conditions tested.", "Though number of fusion proteins tested is limited, we expect that these finding will facilitate the use of the human rhinovirus 3C protease in recombinant protein production for pharmaceutical and biotechnological applications."], "title": "Activity of the Human Rhinovirus 3C Protease Studied in Various Buffers, Additives and Detergents Solutions for Recombinant Protein Production."}
{"paper_id": 27271290, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Hepatitis B virus (HBV) infections account for approximately 780,000 deaths per year, most of which occur in the developing world. Co-infection with HBV and hepatitis delta virus (HDV) may lead to the most severe form of viral hepatitis. In Ghana, knowledge on the prevalence of HBV and HDV in the general population is scanty and the few genetic analyses of the prevailing HBV genotypes are dating back more than a decade. In the present study, 1,323 serum samples from individuals living in a rural area (Offin river valley) of Ghana were analyzed for the presence of the hepatitis B surface antigen (HBsAg). Positive sera were subsequently tested for the presence of anti-HDV antibodies. A total of 107 (8%) sera were HBsAg positive with an 8.4% prevalence of anti-HDV antibodies among the HBsAg positives. Phylogenetic analysis based on HBV pre-S/S sequences, attributed all 52 typable samples to genotype E. All belonged to serotype ayw4. While 19 sequences clustered with those from a number of African countries, the other 33 formed a separate cluster distinguished by an intergroup mean distance of 1.5% from the pan-African HBV/E cluster. Successful implementation of HBV vaccination in the region was reflected by the low HBsAg carrier rate of 1.8% among children \u226411 years.", "journal": "PloS one", "sentences": ["Hepatitis B virus (HBV) infections account for approximately 780,000 deaths per year, most of which occur in the developing world.", "Co-infection with HBV and hepatitis delta virus (HDV) may lead to the most severe form of viral hepatitis.", "In Ghana, knowledge on the prevalence of HBV and HDV in the general population is scanty and the few genetic analyses of the prevailing HBV genotypes are dating back more than a decade.", "In the present study, 1,323 serum samples from individuals living in a rural area (Offin river valley) of Ghana were analyzed for the presence of the hepatitis B surface antigen (HBsAg).", "Positive sera were subsequently tested for the presence of anti-HDV antibodies.", "A total of 107 (8%) sera were HBsAg positive with an 8.4% prevalence of anti-HDV antibodies among the HBsAg positives.", "Phylogenetic analysis based on HBV pre-S/S sequences, attributed all 52 typable samples to genotype E. All belonged to serotype ayw4.", "While 19 sequences clustered with those from a number of African countries, the other 33 formed a separate cluster distinguished by an intergroup mean distance of 1.5% from the pan-African HBV/E cluster.", "Successful implementation of HBV vaccination in the region was reflected by the low HBsAg carrier rate of 1.8% among children \u226411 years."], "title": "Limited Genetic Diversity of Hepatitis B Virus in the General Population of the Offin River Valley in Ghana."}
{"paper_id": 26149610, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Stress resilience is mediated, in part, by our ability to predict and control threats within our environment. Therefore, determining the neural mechanisms that regulate the emotional response to predictable and controllable threats may provide important new insight into the processes that mediate resilience to emotional dysfunction and guide the future development of interventions for anxiety disorders. To better understand the effect of predictability and controllability on threat-related brain activity in humans, two groups of healthy volunteers participated in a yoked Pavlovian fear conditioning study during functional magnetic resonance imaging (fMRI). Threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or by presenting the UCS alone (i.e., unpredictable). Similar to animal model research that has employed yoked fear conditioning procedures, one group (controllable condition; CC), but not the other group (uncontrollable condition; UC) was able to terminate the UCS. The fMRI signal response within the dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and posterior cingulate was diminished during predictable compared to unpredictable threat (i.e., UCS). In addition, threat-related activity within the ventromedial PFC and bilateral hippocampus was diminished only to threats that were both predictable and controllable. These findings provide insight into how threat predictability and controllability affects the activity of brain regions (i.e., ventromedial PFC and hippocampus) involved in emotion regulation, and may have important implications for better understanding neural processes that mediate emotional resilience to stress.", "journal": "NeuroImage", "sentences": ["Stress resilience is mediated, in part, by our ability to predict and control threats within our environment.", "Therefore, determining the neural mechanisms that regulate the emotional response to predictable and controllable threats may provide important new insight into the processes that mediate resilience to emotional dysfunction and guide the future development of interventions for anxiety disorders.", "To better understand the effect of predictability and controllability on threat-related brain activity in humans, two groups of healthy volunteers participated in a yoked Pavlovian fear conditioning study during functional magnetic resonance imaging (fMRI).", "Threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or by presenting the UCS alone (i.e., unpredictable).", "Similar to animal model research that has employed yoked fear conditioning procedures, one group (controllable condition; CC), but not the other group (uncontrollable condition; UC) was able to terminate the UCS.", "The fMRI signal response within the dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and posterior cingulate was diminished during predictable compared to unpredictable threat (i.e., UCS).", "In addition, threat-related activity within the ventromedial PFC and bilateral hippocampus was diminished only to threats that were both predictable and controllable.", "These findings provide insight into how threat predictability and controllability affects the activity of brain regions (i.e., ventromedial PFC and hippocampus) involved in emotion regulation, and may have important implications for better understanding neural processes that mediate emotional resilience to stress."], "title": "Controllability modulates the neural response to predictable but not unpredictable threat in humans."}
{"paper_id": 26707221, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Neuraminidase-inhibition (NI) antibody titers can be used to evaluate the immunogenicity of inactivated influenza vaccines and have provided evidence of serologic cross-reactivity between seasonal and pandemic H1N1 viruses. The traditional thiobarbituric acid assay is impractical for large serologic analyses, and therefore many laboratories use an enzyme-linked lectin assay (ELLA) to determine serum NI antibody titers. The comparability of ELLA NI antibody titers when measured in different laboratories was unknown. Here we report a study conducted through the Consortium for the Standardisation of Influenza SeroEpidemiology (CONSISE) to evaluate the variability of the ELLA. NI antibody titers of a set of 12 samples were measured against both N1 and N2 neuraminidase antigens in 3 independent assays by each of 23 laboratories. For a sample repeated in the same assay, \u226596% of N1 and N2 assays had less than a 4-fold difference in titer. Comparison of the titers measured in assays conducted on 3 different days in the same laboratory showed that a four-fold difference in titer was uncommon. Titers of the same sera measured in different laboratories spanned 3 to 6 two-fold dilutions (i.e., 8-64 fold difference in titer), with an average percent geometric coefficient of variation (%GCV) of 112 and 82% against N1 and N2 antigens, respectively. The difference in titer as indicated by fold range and %GCV was improved by normalizing the NI titers to a standard that was included in each assay. This study identified background signal and the amount of antigen in the assay as critical factors that influence titer, providing important information toward development of a consensus ELLA protocol.", "journal": "Vaccine", "sentences": ["Neuraminidase-inhibition (NI) antibody titers can be used to evaluate the immunogenicity of inactivated influenza vaccines and have provided evidence of serologic cross-reactivity between seasonal and pandemic H1N1 viruses.", "The traditional thiobarbituric acid assay is impractical for large serologic analyses, and therefore many laboratories use an enzyme-linked lectin assay (ELLA) to determine serum NI antibody titers.", "The comparability of ELLA NI antibody titers when measured in different laboratories was unknown.", "Here we report a study conducted through the Consortium for the Standardisation of Influenza SeroEpidemiology (CONSISE) to evaluate the variability of the ELLA.", "NI antibody titers of a set of 12 samples were measured against both N1 and N2 neuraminidase antigens in 3 independent assays by each of 23 laboratories.", "For a sample repeated in the same assay, \u226596% of N1 and N2 assays had less than a 4-fold difference in titer.", "Comparison of the titers measured in assays conducted on 3 different days in the same laboratory showed that a four-fold difference in titer was uncommon.", "Titers of the same sera measured in different laboratories spanned 3 to 6 two-fold dilutions (i.e., 8-64 fold difference in titer), with an average percent geometric coefficient of variation (%GCV) of 112 and 82% against N1 and N2 antigens, respectively.", "The difference in titer as indicated by fold range and %GCV was improved by normalizing the NI titers to a standard that was included in each assay.", "This study identified background signal and the amount of antigen in the assay as critical factors that influence titer, providing important information toward development of a consensus ELLA protocol."], "title": "Comparability of neuraminidase inhibition antibody titers measured by enzyme-linked lectin assay (ELLA) for the analysis of influenza vaccine immunogenicity."}
{"paper_id": 26587537, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.", "journal": "BioMed research international", "sentences": ["Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers.", "In cancer treatment, development of acquired drug resistance phenotype is a serious issue.", "Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance.", "EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells.", "In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer.", "The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed.", "Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs."], "title": "The Emerging Role of Extracellular Vesicle-Mediated Drug Resistance in Cancers: Implications in Advanced Prostate Cancer."}
{"paper_id": 26632706, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Endoscopic interventional is a commonly used treatment method for idiopathic chronic pancreatitis. Serine protease inhibitor Kazal type 1 (SPINK1) 194+2T>C mutation is most frequently observed in Chinese pancreatitis patients and influences the clinical course of idiopathic chronic pancreatitis patients. We conducted this study to determine the impacts of this mutation on the outcome of endoscopic treatments.In this study, we enrolled 423 patients. Among them, 101 idiopathic chronic pancreatitis patients without other relevant mutations had a successful endoscopic procedure and completed follow-up. Clinical characteristics including Izbicki pain score, exocrine and endocrine function, were evaluated. Genetic sequencing was conducted to detect SPINK1 194+2T>C mutations.The c.194+2T>C mutation was found in 58 (57.43%) patients. Factors relevant to pain relief are c.194+2T>C mutation (P\u200a=\u200a0.011), severe pain before treatment (P\u200a=\u200a0.005), and necessary subsequent endoscopic treatments (P\u200a<\u200a0.001). More patients with the intronic mutation had deteriorated endocrine function (P\u200a=\u200a0.001) relative to those patients without the mutation.Patients carrying the c.194+2T>C mutation were less likely to achieve pain relief through endoscopic treatments. They also have a higher risk of endocrine function deterioration. SPINK1 c.194+2T>C mutation may be applied as a pretreatment predictor in idiopathic chronic pancreatitis patients.", "journal": "Medicine", "sentences": ["Endoscopic interventional is a commonly used treatment method for idiopathic chronic pancreatitis.", "Serine protease inhibitor Kazal type 1 (SPINK1) 194+2T>C mutation is most frequently observed in Chinese pancreatitis patients and influences the clinical course of idiopathic chronic pancreatitis patients.", "We conducted this study to determine the impacts of this mutation on the outcome of endoscopic treatments.In this study, we enrolled 423 patients.", "Among them, 101 idiopathic chronic pancreatitis patients without other relevant mutations had a successful endoscopic procedure and completed follow-up.", "Clinical characteristics including Izbicki pain score, exocrine and endocrine function, were evaluated.", "Genetic sequencing was conducted to detect SPINK1 194+2T>C mutations.The c.194+2T>C mutation was found in 58 (57.43%) patients.", "Factors relevant to pain relief are c.194+2T>C mutation (P\u200a=\u200a0.011), severe pain before treatment (P\u200a=\u200a0.005), and necessary subsequent endoscopic treatments (P\u200a<\u200a0.001).", "More patients with the intronic mutation had deteriorated endocrine function (P\u200a=\u200a0.001) relative to those patients without the mutation.Patients carrying the c.194+2T>C mutation were less likely to achieve pain relief through endoscopic treatments.", "They also have a higher risk of endocrine function deterioration.", "SPINK1 c.194+2T>C mutation may be applied as a pretreatment predictor in idiopathic chronic pancreatitis patients."], "title": "Serine Protease Inhibitor Kazal Type 1 (SPINK1) c.194+2T > C Mutation May Predict Long-term Outcome of Endoscopic Treatments in Idiopathic Chronic Pancreatitis."}
{"paper_id": 27136572, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The aim of the study was to evaluate the frequency of breakfast and other meal consumption by adolescents and to assess the relationship between the first and the last meal consumption and sex, body mass index (BMI), and middle school and high school students' education level. The study was conducted in 2013-2014 among 3009 students (1658 girls and 1351 boys) from middle s and high schools in Krakow and Silesia (Poland). The data was obtained from questionnaires that were analyzed with a logistic regression model for measurable and dichotomous variables. Breakfast consumers were seen to eat other meals (second breakfast, lunch, dessert, supper) significantly more often than breakfast skippers. The main meal consumption habits depend on sex and change as adolescents age. Being a girl and a high school student predisposed participants to skip breakfast and supper more often. The BMI of breakfast consumers does not differ significantly from the BMI of breakfast skippers, so BMI might thus not be a sufficient marker of breakfast consumption regularity and dietary habits in an adolescent group. The importance of regularly eaten meals, especially breakfast, together with adequate daily dietary energy intake are beneficial for physical and psychological development and cannot be overestimated in nutritional education and it is necessary to promote healthy eating behavior for well-being in later adult life.", "journal": "International journal of environmental research and public health", "sentences": ["The aim of the study was to evaluate the frequency of breakfast and other meal consumption by adolescents and to assess the relationship between the first and the last meal consumption and sex, body mass index (BMI), and middle school and high school students' education level.", "The study was conducted in 2013-2014 among 3009 students (1658 girls and 1351 boys) from middle s and high schools in Krakow and Silesia (Poland).", "The data was obtained from questionnaires that were analyzed with a logistic regression model for measurable and dichotomous variables.", "Breakfast consumers were seen to eat other meals (second breakfast, lunch, dessert, supper) significantly more often than breakfast skippers.", "The main meal consumption habits depend on sex and change as adolescents age.", "Being a girl and a high school student predisposed participants to skip breakfast and supper more often.", "The BMI of breakfast consumers does not differ significantly from the BMI of breakfast skippers, so BMI might thus not be a sufficient marker of breakfast consumption regularity and dietary habits in an adolescent group.", "The importance of regularly eaten meals, especially breakfast, together with adequate daily dietary energy intake are beneficial for physical and psychological development and cannot be overestimated in nutritional education and it is necessary to promote healthy eating behavior for well-being in later adult life."], "title": "Breakfast and Other Meal Consumption in Adolescents from Southern Poland."}
{"paper_id": 20138822, "labels": ["0", "0", "0", "0", "1", "0", "0", "0", "0", "1"], "abstract": "Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel that is present in a variety of epithelial cell types, and usually expressed in the luminal membrane. In contrast, prestin (SLC26A5) is a voltage-dependent motor protein, which is present in the basolateral membrane of cochlear outer hair cells (OHCs), and plays an important role in the frequency selectivity and sensitivity of mammalian hearing. By using in situ hybridization and immunofluorescence, we found that both mRNA and protein of CFTR are present in OHCs, and that CFTR localizes in both the apical and the lateral membranes. CFTR was not detected in the lateral membrane of inner hair cells (IHCs) or in that of OHCs derived from prestin-knockout mice, i.e., in instances where prestin is not expressed. These results suggest that prestin may interact physically with CFTR in the lateral membrane of OHCs. Immunoprecipitation experiments confirmed a prestin-CFTR interaction. Because chloride is important for prestin function and for the efferent-mediated inhibition of cochlear output, the prestin-directed localization of CFTR to the lateral membrane of OHCs has a potential physiological significance. Aside from its role as a chloride channel, CFTR is known as a regulator of multiple protein functions, including those of the solute carrier family 26 (SLC26). Because prestin is in the SLC26 family, several members of which interact with CFTR, we explored the potential modulatory relationship associated with a direct, physical interaction between prestin and CFTR. Electrophysiological experiments demonstrated that cAMP-activated CFTR is capable of enhancing voltage-dependent charge displacement, a signature of OHC motility, whereas prestin does not affect the chloride conductance of CFTR.", "journal": "Biochimica et biophysica acta", "sentences": ["Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel that is present in a variety of epithelial cell types, and usually expressed in the luminal membrane.", "In contrast, prestin (SLC26A5) is a voltage-dependent motor protein, which is present in the basolateral membrane of cochlear outer hair cells (OHCs), and plays an important role in the frequency selectivity and sensitivity of mammalian hearing.", "By using in situ hybridization and immunofluorescence, we found that both mRNA and protein of CFTR are present in OHCs, and that CFTR localizes in both the apical and the lateral membranes.", "CFTR was not detected in the lateral membrane of inner hair cells (IHCs) or in that of OHCs derived from prestin-knockout mice, i.e., in instances where prestin is not expressed.", "These results suggest that prestin may interact physically with CFTR in the lateral membrane of OHCs.", "Immunoprecipitation experiments confirmed a prestin-CFTR interaction.", "Because chloride is important for prestin function and for the efferent-mediated inhibition of cochlear output, the prestin-directed localization of CFTR to the lateral membrane of OHCs has a potential physiological significance.", "Aside from its role as a chloride channel, CFTR is known as a regulator of multiple protein functions, including those of the solute carrier family 26 (SLC26).", "Because prestin is in the SLC26 family, several members of which interact with CFTR, we explored the potential modulatory relationship associated with a direct, physical interaction between prestin and CFTR.", "Electrophysiological experiments demonstrated that cAMP-activated CFTR is capable of enhancing voltage-dependent charge displacement, a signature of OHC motility, whereas prestin does not affect the chloride conductance of CFTR."], "title": "Interaction between CFTR and prestin (SLC26A5)."}
{"paper_id": 27240341, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "Melasma is a commonly acquired hypermelanosis that affects sun-exposed areas of the skin, with frequent facial involvement. Its histologic manifestations are evident in the epidermis, extracellular matrix, and dermis. In addition to epidermal pigmentation, pathologic findings of melasma include extracellular matrix abnormality, especially solar elastosis. The disrupted basement membrane has been described in melasma with variable incidences. In the dermis, an increase in vascularity and an increase in the number of mast cells were observed, indicating that dermal factors have critical roles in the pathogenesis of melasma, despite the fact that melasma is characterized by epidermal hyperpigmentation. This review discusses such histologic characteristics of melasma, with consideration to their implications for melasma treatment.", "journal": "International journal of molecular sciences", "sentences": ["Melasma is a commonly acquired hypermelanosis that affects sun-exposed areas of the skin, with frequent facial involvement.", "Its histologic manifestations are evident in the epidermis, extracellular matrix, and dermis.", "In addition to epidermal pigmentation, pathologic findings of melasma include extracellular matrix abnormality, especially solar elastosis.", "The disrupted basement membrane has been described in melasma with variable incidences.", "In the dermis, an increase in vascularity and an increase in the number of mast cells were observed, indicating that dermal factors have critical roles in the pathogenesis of melasma, despite the fact that melasma is characterized by epidermal hyperpigmentation.", "This review discusses such histologic characteristics of melasma, with consideration to their implications for melasma treatment."], "title": "Heterogeneous Pathology of Melasma and Its Clinical Implications."}
{"paper_id": 26339381, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Retinoic acid is an important molecular taking part in the development and homeostasis of nervous system. Neural stem cells (NSCs) are pluripotent cells that can differentiate into three main neural cells including neuron, astrocyte and oligodendrocyte. However, whether retinoic acid can induce NSCs derived from embryonic spinal cord differentiating into functional neurons and its efficiency are not clear. In this experiment, NSCs were isolated from embryonic 14 d spinal cord of rats. The growth and neuronal differentiation of NSCs induced by 500 nM RA was examined in vitro. It was indicated that compared with the control group, there were more differentiated cells with longer cytodendrites in the medium treated with RA at different time. And more, there were more neuronal marker positive cells in 500 nM RA group than the control group seven days after differentiation. At the same time, the expression of \u03b2-tublin III protein in RA group was higher than those in control group, which was contrary to the expression of astrocyte marker GFAP protein at seven days after differentiation. However the differentiated neurons, whether treated with RA or not both exhibited biological electrical reactivity after stimulated by glutamine. Therefore, these findings indicated that RA could promote growth of cellular dendrites and neuronal differentiation of NSCs, which also induce functional maturation of differentiated neurons finally.", "journal": "International journal of clinical and experimental pathology", "sentences": ["Retinoic acid is an important molecular taking part in the development and homeostasis of nervous system.", "Neural stem cells (NSCs) are pluripotent cells that can differentiate into three main neural cells including neuron, astrocyte and oligodendrocyte.", "However, whether retinoic acid can induce NSCs derived from embryonic spinal cord differentiating into functional neurons and its efficiency are not clear.", "In this experiment, NSCs were isolated from embryonic 14 d spinal cord of rats.", "The growth and neuronal differentiation of NSCs induced by 500 nM RA was examined in vitro.", "It was indicated that compared with the control group, there were more differentiated cells with longer cytodendrites in the medium treated with RA at different time.", "And more, there were more neuronal marker positive cells in 500 nM RA group than the control group seven days after differentiation.", "At the same time, the expression of \u03b2-tublin III protein in RA group was higher than those in control group, which was contrary to the expression of astrocyte marker GFAP protein at seven days after differentiation.", "However the differentiated neurons, whether treated with RA or not both exhibited biological electrical reactivity after stimulated by glutamine.", "Therefore, these findings indicated that RA could promote growth of cellular dendrites and neuronal differentiation of NSCs, which also induce functional maturation of differentiated neurons finally."], "title": "Retinoic acid induced the differentiation of neural stem cells from embryonic spinal cord into functional neurons in vitro."}
{"paper_id": 23275546, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "RNA-dependent RNA polymerase (RdRp) is essential to viral replication and is therefore one of the primary targets of countermeasures against these dangerous infectious agents. Development of broad-spectrum therapeutics targeting polymerases has been hampered by the extreme sequence variability of these sequences. RdRps range in length from 400-800 residues, yet contain only \u223c20 residues that are conserved in most species. In this study, we made structure-based comparisons that are independent of sequence composition using a recently developed algorithm. We identified residue-to-residue correspondences of multiple protein structures and created (two-dimensional) structure-based alignment maps of 37 polymerase structures that provide both sequence and structure details. Using these maps, we determined that \u223c75% of each polymerase species consists of seven protein segments, each of which has high structural similarity to segments in other species, though they are widely divergent in sequence composition and order. We define each of these segments as a 'homomorph', and each includes (though most are much larger than) the well-known conserved polymerase motifs. All homomorphs contact the template tunnel or nucleoside triphosphate (NTP) entry tunnel and the exterior of the protein, suggesting they constitute a structural and functional skeleton common among the polymerases.", "journal": "Nucleic acids research", "sentences": ["RNA-dependent RNA polymerase (RdRp) is essential to viral replication and is therefore one of the primary targets of countermeasures against these dangerous infectious agents.", "Development of broad-spectrum therapeutics targeting polymerases has been hampered by the extreme sequence variability of these sequences.", "RdRps range in length from 400-800 residues, yet contain only \u223c20 residues that are conserved in most species.", "In this study, we made structure-based comparisons that are independent of sequence composition using a recently developed algorithm.", "We identified residue-to-residue correspondences of multiple protein structures and created (two-dimensional) structure-based alignment maps of 37 polymerase structures that provide both sequence and structure details.", "Using these maps, we determined that \u223c75% of each polymerase species consists of seven protein segments, each of which has high structural similarity to segments in other species, though they are widely divergent in sequence composition and order.", "We define each of these segments as a 'homomorph', and each includes (though most are much larger than) the well-known conserved polymerase motifs.", "All homomorphs contact the template tunnel or nucleoside triphosphate (NTP) entry tunnel and the exterior of the protein, suggesting they constitute a structural and functional skeleton common among the polymerases."], "title": "Highly similar structural frames link the template tunnel and NTP entry tunnel to the exterior surface in RNA-dependent RNA polymerases."}
{"paper_id": 26923390, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "This review covers the fundamentals of protein partitioning in aqueous two-phase systems (ATPS). Included is a review of advancements in the analytical application of solute partitioning in ATPS over the last two decades, with multiple examples of experimental data providing evidence that phase-forming polymers do not interact with solutes partitioned in ATPS. The partitioning of solutes is governed by the differences in solute interactions with aqueous media in the two phases. Solvent properties of the aqueous media in these two phases may be characterized and manipulated. The solvent interaction analysis (SIA) method, based on the solute partitioning in ATPS, may be used for characterization and analysis of individual proteins and their interactions with different partners. The current state of clinical proteomics regarding the discovery and monitoring of new protein biomarkers is discussed, and it is argued that the protein expression level in a biological fluid may be not the optimal focus of clinical proteomic research. Multiple examples of application of the SIA method for discovery of changes in protein structure and protein-partner interactions in biological fluids are described. The SIA method reveals new opportunities for discovery and monitoring structure-based protein biomarkers.", "journal": "Biochimica et biophysica acta", "sentences": ["This review covers the fundamentals of protein partitioning in aqueous two-phase systems (ATPS).", "Included is a review of advancements in the analytical application of solute partitioning in ATPS over the last two decades, with multiple examples of experimental data providing evidence that phase-forming polymers do not interact with solutes partitioned in ATPS.", "The partitioning of solutes is governed by the differences in solute interactions with aqueous media in the two phases.", "Solvent properties of the aqueous media in these two phases may be characterized and manipulated.", "The solvent interaction analysis (SIA) method, based on the solute partitioning in ATPS, may be used for characterization and analysis of individual proteins and their interactions with different partners.", "The current state of clinical proteomics regarding the discovery and monitoring of new protein biomarkers is discussed, and it is argued that the protein expression level in a biological fluid may be not the optimal focus of clinical proteomic research.", "Multiple examples of application of the SIA method for discovery of changes in protein structure and protein-partner interactions in biological fluids are described.", "The SIA method reveals new opportunities for discovery and monitoring structure-based protein biomarkers."], "title": "Analytical applications of partitioning in aqueous two-phase systems: Exploring protein structural changes and protein-partner interactions in vitro and in vivo by solvent interaction analysis method."}
{"paper_id": 20944009, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Activation of the canonical Notch pathways has been implicated in Th cell differentiation, but the role of specific Notch ligands in Th2-mediated allergic airway responses has not been completely elucidated. In this study, we show that delta-like ligand 4 (Dll4) was upregulated on dendritic cells in response to cockroach allergen. Blocking Dll4 in vivo during either the primary or secondary response enhanced allergen-induced pathogenic consequences including airway hyperresponsiveness and mucus production via increased Th2 cytokines. In vitro assays demonstrated that Dll4 regulates IL-2 in T cells from established Th2 responses as well as during primary stimulation. Notably, Dll4 blockade during the primary, but not the secondary, response increased IL-2 levels in lung and lymph node of allergic mice. The in vivo neutralization of Dll4 was associated with increased expansion and decreased apoptosis during the primary allergen sensitization. Moreover, Dll4-mediated Notch activation of T cells during primary stimulation in vitro increased apoptosis during the contraction/resting phase of the response, which could be rescued by exogenous IL-2. Consistent with the role for Dll4-mediated IL-2 regulation in overall T cell function, the frequency of IL-4-producing cells was also significantly altered by Dll4 both in vivo and in vitro. These data demonstrate a regulatory role of Dll4 both in initial Th2 differentiation and in Th2 cytokine production in established allergic responses.", "journal": "Journal of immunology (Baltimore, Md. : 1950)", "sentences": ["Activation of the canonical Notch pathways has been implicated in Th cell differentiation, but the role of specific Notch ligands in Th2-mediated allergic airway responses has not been completely elucidated.", "In this study, we show that delta-like ligand 4 (Dll4) was upregulated on dendritic cells in response to cockroach allergen.", "Blocking Dll4 in vivo during either the primary or secondary response enhanced allergen-induced pathogenic consequences including airway hyperresponsiveness and mucus production via increased Th2 cytokines.", "In vitro assays demonstrated that Dll4 regulates IL-2 in T cells from established Th2 responses as well as during primary stimulation.", "Notably, Dll4 blockade during the primary, but not the secondary, response increased IL-2 levels in lung and lymph node of allergic mice.", "The in vivo neutralization of Dll4 was associated with increased expansion and decreased apoptosis during the primary allergen sensitization.", "Moreover, Dll4-mediated Notch activation of T cells during primary stimulation in vitro increased apoptosis during the contraction/resting phase of the response, which could be rescued by exogenous IL-2.", "Consistent with the role for Dll4-mediated IL-2 regulation in overall T cell function, the frequency of IL-4-producing cells was also significantly altered by Dll4 both in vivo and in vitro.", "These data demonstrate a regulatory role of Dll4 both in initial Th2 differentiation and in Th2 cytokine production in established allergic responses."], "title": "Notch ligand delta-like 4 regulates development and pathogenesis of allergic airway responses by modulating IL-2 production and Th2 immunity."}
{"paper_id": 26548953, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Diverse repertoires of antigen-receptor genes that result from combinatorial splicing of coding segments by V(D)J recombination are hallmarks of vertebrate immunity. The (RAG1-RAG2)2 recombinase (RAG) recognizes recombination signal sequences (RSSs) containing a heptamer, a spacer of 12 or 23 base pairs, and a nonamer (12-RSS or 23-RSS) and introduces precise breaks at RSS-coding segment junctions. RAG forms synaptic complexes only with one 12-RSS and one 23-RSS, a dogma known as the 12/23 rule that governs the recombination fidelity. We report cryo-electron microscopy structures of synaptic RAG complexes at up to 3.4 \u00c5 resolution, which reveal a closed conformation with base flipping and base-specific recognition of RSSs. Distortion at RSS-coding segment junctions and base flipping in coding segments uncover the two-metal-ion catalytic mechanism. Induced asymmetry involving tilting of the nonamer-binding domain dimer of RAG1 upon binding of HMGB1-bent 12-RSS or 23-RSS underlies the molecular mechanism for the 12/23 rule.", "journal": "Cell", "sentences": ["Diverse repertoires of antigen-receptor genes that result from combinatorial splicing of coding segments by V(D)J recombination are hallmarks of vertebrate immunity.", "The (RAG1-RAG2)2 recombinase (RAG) recognizes recombination signal sequences (RSSs) containing a heptamer, a spacer of 12 or 23 base pairs, and a nonamer (12-RSS or 23-RSS) and introduces precise breaks at RSS-coding segment junctions.", "RAG forms synaptic complexes only with one 12-RSS and one 23-RSS, a dogma known as the 12/23 rule that governs the recombination fidelity.", "We report cryo-electron microscopy structures of synaptic RAG complexes at up to 3.4 \u00c5 resolution, which reveal a closed conformation with base flipping and base-specific recognition of RSSs.", "Distortion at RSS-coding segment junctions and base flipping in coding segments uncover the two-metal-ion catalytic mechanism.", "Induced asymmetry involving tilting of the nonamer-binding domain dimer of RAG1 upon binding of HMGB1-bent 12-RSS or 23-RSS underlies the molecular mechanism for the 12/23 rule."], "title": "Molecular Mechanism of V(D)J Recombination from Synaptic RAG1-RAG2 Complex Structures."}
{"paper_id": 20802531, "labels": ["1", "0", "0", "0", "0", "0", "0", "1"], "abstract": "We report here a novel role for Jun dimerization protein-2 (JDP2) as a regulator of the progression of normal cells through the cell cycle. To determine the role of JDP2 in vivo, we generated Jdp2-knockout (Jdp2KO) mice by targeting exon-1 to disrupt the site of initiation of transcription. The epidermal thickening of skin from the Jdp2KO mice after treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) proceeded more rapidly than that of control mice, and more proliferating cells were found at the epidermis. Fibroblasts derived from embryos of Jdp2KO mice proliferated faster and formed more colonies than fibroblasts from wild-type mice. JDP2 was recruited to the promoter of the gene for cyclin-A2 (ccna2) at the AP-1 site. Cells lacking Jdp2 had elevated levels of cyclin-A2 mRNA. Furthermore, reintroduction of JDP2 resulted in the repression of transcription of ccna2 and of cell-cycle progression. Thus, transcription of the gene for cyclin-A2 appears to be a direct target of JDP2 in the suppression of cell proliferation.", "journal": "Oncogene", "sentences": ["We report here a novel role for Jun dimerization protein-2 (JDP2) as a regulator of the progression of normal cells through the cell cycle.", "To determine the role of JDP2 in vivo, we generated Jdp2-knockout (Jdp2KO) mice by targeting exon-1 to disrupt the site of initiation of transcription.", "The epidermal thickening of skin from the Jdp2KO mice after treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) proceeded more rapidly than that of control mice, and more proliferating cells were found at the epidermis.", "Fibroblasts derived from embryos of Jdp2KO mice proliferated faster and formed more colonies than fibroblasts from wild-type mice.", "JDP2 was recruited to the promoter of the gene for cyclin-A2 (ccna2) at the AP-1 site.", "Cells lacking Jdp2 had elevated levels of cyclin-A2 mRNA.", "Furthermore, reintroduction of JDP2 resulted in the repression of transcription of ccna2 and of cell-cycle progression.", "Thus, transcription of the gene for cyclin-A2 appears to be a direct target of JDP2 in the suppression of cell proliferation."], "title": "Suppression of cell-cycle progression by Jun dimerization protein-2 (JDP2) involves downregulation of cyclin-A2."}
{"paper_id": 25350656, "labels": ["0", "0", "0", "0", "0", "1", "0"], "abstract": "In ion beam radiotherapy, PET-based treatment verification provides a consistency check of the delivered treatment with respect to a simulation based on the treatment planning. In this work the region-based MLEM reconstruction algorithm is proposed as a new evaluation strategy in PET-based treatment verification. The comparative evaluation is based on reconstructed PET images in selected regions, which are automatically identified on the expected PET images according to homogeneity in activity values. The strategy was tested on numerical and physical phantoms, simulating mismatches between the planned and measured \u03b2+ activity distributions. The region-based MLEM reconstruction was demonstrated to be robust against noise and the sensitivity of the strategy results were comparable to three voxel units, corresponding to 6\u2009mm in numerical phantoms. The robustness of the region-based MLEM evaluation outperformed the voxel-based strategies. The potential of the proposed strategy was also retrospectively assessed on patient data and further clinical validation is envisioned.", "journal": "Physics in medicine and biology", "sentences": ["In ion beam radiotherapy, PET-based treatment verification provides a consistency check of the delivered treatment with respect to a simulation based on the treatment planning.", "In this work the region-based MLEM reconstruction algorithm is proposed as a new evaluation strategy in PET-based treatment verification.", "The comparative evaluation is based on reconstructed PET images in selected regions, which are automatically identified on the expected PET images according to homogeneity in activity values.", "The strategy was tested on numerical and physical phantoms, simulating mismatches between the planned and measured \u03b2+ activity distributions.", "The region-based MLEM reconstruction was demonstrated to be robust against noise and the sensitivity of the strategy results were comparable to three voxel units, corresponding to 6\u2009mm in numerical phantoms.", "The robustness of the region-based MLEM evaluation outperformed the voxel-based strategies.", "The potential of the proposed strategy was also retrospectively assessed on patient data and further clinical validation is envisioned."], "title": "Regional MLEM reconstruction strategy for PET-based treatment verification in ion beam radiotherapy."}
{"paper_id": 25516683, "labels": ["0", "0", "0", "0", "1"], "abstract": "Twin to twin transfusion syndrome (TTTS) is caused by aberrant vascular connections between infant twins and results in high morbidity and mortality in the perinatal period. In donor infants with TTTS and symptoms of intestinal obstruction, small-bowel lesions have been reported in most cases. We report on a 33(+6) gestational wk donor infant with TTTS who had intermittent obstructive episodes, including delayed meconium passage and colonic dilatation on abdominal X-ray. The diagnosis of Hirschsprung's disease was based on a lateral pelvic film with a reversed rectosigmoid ratio. A subsequent barium colon study and rectal suction biopsy indicated a short segment aganglionosis of the colon.", "journal": "World journal of gastroenterology", "sentences": ["Twin to twin transfusion syndrome (TTTS) is caused by aberrant vascular connections between infant twins and results in high morbidity and mortality in the perinatal period.", "In donor infants with TTTS and symptoms of intestinal obstruction, small-bowel lesions have been reported in most cases.", "We report on a 33(+6) gestational wk donor infant with TTTS who had intermittent obstructive episodes, including delayed meconium passage and colonic dilatation on abdominal X-ray.", "The diagnosis of Hirschsprung's disease was based on a lateral pelvic film with a reversed rectosigmoid ratio.", "A subsequent barium colon study and rectal suction biopsy indicated a short segment aganglionosis of the colon."], "title": "Hirschsprung's disease in twin to twin transfusion syndrome: a case report."}
{"paper_id": 24722568, "labels": ["0", "0", "0", "1", "0", "0", "0", "1"], "abstract": "The role of LeuRS, an aminoacyl-tRNA synthetase, as an intracellular l-leucine sensor for the mTORC1 pathway has been the subject of much research recently. Despite this, the association between LeuRS and lactation in dairy cow mammary epithelial cells (DCMECs) remains unknown. In this study, we found that LeuRS expression in mammary gland tissue was significantly higher during lactation than pregnancy. Moreover, our data demonstrates that LeuRS is localized in the cytoplasm. Treatment with leucine increased DCMECs viability and proliferation, as well as mammalian target of rapamycin (mTOR), p-mTOR, ribosomal protein S6 kinase 1 (S6K1), p-S6K1, \u03b2-Casein, sterol regulatory element binding protein 1c (SREBP-1c), glucose transporter 1 (GLUT1), and Cyclin D1 mRNA and protein expression. Secretion of lactose and triglyceride were also increased. siRNA-mediated knockdown of LeuRS led to reduction in all of these processes. Based on these data, LeuRS up-regulates the mTOR pathway to promote proliferation and lactation of DCMECs in response to changes in the intracellular leucine concentration.", "journal": "International journal of molecular sciences", "sentences": ["The role of LeuRS, an aminoacyl-tRNA synthetase, as an intracellular l-leucine sensor for the mTORC1 pathway has been the subject of much research recently.", "Despite this, the association between LeuRS and lactation in dairy cow mammary epithelial cells (DCMECs) remains unknown.", "In this study, we found that LeuRS expression in mammary gland tissue was significantly higher during lactation than pregnancy.", "Moreover, our data demonstrates that LeuRS is localized in the cytoplasm.", "Treatment with leucine increased DCMECs viability and proliferation, as well as mammalian target of rapamycin (mTOR), p-mTOR, ribosomal protein S6 kinase 1 (S6K1), p-S6K1, \u03b2-Casein, sterol regulatory element binding protein 1c (SREBP-1c), glucose transporter 1 (GLUT1), and Cyclin D1 mRNA and protein expression.", "Secretion of lactose and triglyceride were also increased.", "siRNA-mediated knockdown of LeuRS led to reduction in all of these processes.", "Based on these data, LeuRS up-regulates the mTOR pathway to promote proliferation and lactation of DCMECs in response to changes in the intracellular leucine concentration."], "title": "Leucyl-tRNA synthetase regulates lactation and cell proliferation via mTOR signaling in dairy cow mammary epithelial cells."}
{"paper_id": 26971273, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Fluorescent siderophore pyoverdin (PVD) was produced from a soil isolate Pseudomonas monteilii strain MKP 213. The PVD was purified near to homogeneity and applied for the fluorescent chemosensing of various antibiotics in aqueous solution (pH=7.0). Upon addition of ciprofloxacin, PVD showed new UV-vis absorption bands at 252 and 321nm due to an internal charge transfer mechanism. Also, the addition of ciprofloxacin induced a highly selective fluorescence enhancement of PVD with a 13nm blue shift from 458 to 445nm. The combination of a long peptide chain along with the chromophore unit of PVD generates a converging cleft for ciprofloxacin recognition with LOD and LOQ of 7.13\u03bcM and 21.6\u03bcM, respectively without interference from other studied antibiotics. The association constant (Ka) of PVD with ciprofloxacin was calculated to be as low as 1.40\u00d710(5)M(-1) using Benesi-Hildebrand plot depicting its significance in detection. The pharmaceutical tablet analysis measures the sensing with negligible matrix effect and quantitative recovery.", "journal": "Biosensors & bioelectronics", "sentences": ["Fluorescent siderophore pyoverdin (PVD) was produced from a soil isolate Pseudomonas monteilii strain MKP 213.", "The PVD was purified near to homogeneity and applied for the fluorescent chemosensing of various antibiotics in aqueous solution (pH=7.0).", "Upon addition of ciprofloxacin, PVD showed new UV-vis absorption bands at 252 and 321nm due to an internal charge transfer mechanism.", "Also, the addition of ciprofloxacin induced a highly selective fluorescence enhancement of PVD with a 13nm blue shift from 458 to 445nm.", "The combination of a long peptide chain along with the chromophore unit of PVD generates a converging cleft for ciprofloxacin recognition with LOD and LOQ of 7.13\u03bcM and 21.6\u03bcM, respectively without interference from other studied antibiotics.", "The association constant (Ka) of PVD with ciprofloxacin was calculated to be as low as 1.40\u00d710(5)M(-1) using Benesi-Hildebrand plot depicting its significance in detection.", "The pharmaceutical tablet analysis measures the sensing with negligible matrix effect and quantitative recovery."], "title": "Selective ciprofloxacin antibiotic detection by fluorescent siderophore pyoverdin."}
{"paper_id": 25863070, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "G-protein-coupled receptors (GPCRs) are important membrane proteins that mediate cellular signaling and represent primary targets for about one-third of currently marketed drugs. Recent x-ray crystallographic studies identified distinct conformations of GPCRs in the active and inactive states. An allosteric sodium ion was found bound to a highly conserved D2.50 residue in inactive GPCRs, whereas the D2.50 allosteric pocket became collapsed in active GPCR structures. However, the dynamic mechanisms underlying these observations remain elusive. In this study, we aimed to understand the mechanistic effects of sodium ion binding on dynamic activation of the M3 muscarinic GPCR through long-timescale accelerated molecular dynamics (aMD) simulations. Results showed that with the D2.50 residue deprotonated, the M3 receptor is bound by an allosteric sodium ion and confined mostly in the inactive state with remarkably reduced flexibility. In contrast, the D2.50-protonated receptor does not exhibit sodium ion binding to the D2.50 allosteric site and samples a significantly larger conformational space. The receptor activation is captured and characterized by large-scale structural rearrangements of the transmembrane helices via dynamic hydrogen bond and salt bridge interactions. The residue motions are highly correlated during receptor activation. Further network analysis revealed that the allosteric signaling between residue D2.50 and key residues in the intracellular, extracellular, and orthosteric pockets is significantly weakened upon sodium ion binding.", "journal": "Biophysical journal", "sentences": ["G-protein-coupled receptors (GPCRs) are important membrane proteins that mediate cellular signaling and represent primary targets for about one-third of currently marketed drugs.", "Recent x-ray crystallographic studies identified distinct conformations of GPCRs in the active and inactive states.", "An allosteric sodium ion was found bound to a highly conserved D2.50 residue in inactive GPCRs, whereas the D2.50 allosteric pocket became collapsed in active GPCR structures.", "However, the dynamic mechanisms underlying these observations remain elusive.", "In this study, we aimed to understand the mechanistic effects of sodium ion binding on dynamic activation of the M3 muscarinic GPCR through long-timescale accelerated molecular dynamics (aMD) simulations.", "Results showed that with the D2.50 residue deprotonated, the M3 receptor is bound by an allosteric sodium ion and confined mostly in the inactive state with remarkably reduced flexibility.", "In contrast, the D2.50-protonated receptor does not exhibit sodium ion binding to the D2.50 allosteric site and samples a significantly larger conformational space.", "The receptor activation is captured and characterized by large-scale structural rearrangements of the transmembrane helices via dynamic hydrogen bond and salt bridge interactions.", "The residue motions are highly correlated during receptor activation.", "Further network analysis revealed that the allosteric signaling between residue D2.50 and key residues in the intracellular, extracellular, and orthosteric pockets is significantly weakened upon sodium ion binding."], "title": "Allosteric effects of sodium ion binding on activation of the m3 muscarinic g-protein-coupled receptor."}
{"paper_id": 21350172, "labels": ["0", "0", "0", "0", "0"], "abstract": "Despite being implicated as important intermediates, iron(V) compounds have proven very challenging to isolate and characterize. Here, we report the preparation of the iron(V) nitrido complex, [PhB((t)BuIm)(3)Fe(V)\u2261N]BAr(F24) (PhB((t)BuIm)(3)(-) = phenyltris(3-tert-butylimidazol-2-ylidene)borato, BAr(F24) = B(3,5-(CF(3))(2)C(6)H(3))(4)(-)), by one electron oxidation of the iron(IV) nitrido precursor. Single-crystal x-ray diffraction of the iron(V) complex reveals a four-coordinate metal ion with a terminal nitrido ligand. M\u00f6\u00dfbauer and electron paramagnetic resonance spectroscopic characterization, supported by electronic structure calculations, provide evidence for a d(3) iron(V) metal center in a low spin (S = 1/2) electron configuration. Low-temperature reaction of the iron(V) nitrido complex with water under reducing conditions leads to high yields of ammonia with concomitant formation of an iron(II) species.", "journal": "Science (New York, N.Y.)", "sentences": ["Despite being implicated as important intermediates, iron(V) compounds have proven very challenging to isolate and characterize.", "Here, we report the preparation of the iron(V) nitrido complex, [PhB((t)BuIm)(3)Fe(V)\u2261N]BAr(F24) (PhB((t)BuIm)(3)(-) = phenyltris(3-tert-butylimidazol-2-ylidene)borato, BAr(F24) = B(3,5-(CF(3))(2)C(6)H(3))(4)(-)), by one electron oxidation of the iron(IV) nitrido precursor.", "Single-crystal x-ray diffraction of the iron(V) complex reveals a four-coordinate metal ion with a terminal nitrido ligand.", "M\u00f6\u00dfbauer and electron paramagnetic resonance spectroscopic characterization, supported by electronic structure calculations, provide evidence for a d(3) iron(V) metal center in a low spin (S = 1/2) electron configuration.", "Low-temperature reaction of the iron(V) nitrido complex with water under reducing conditions leads to high yields of ammonia with concomitant formation of an iron(II) species."], "title": "Synthesis, structure, and reactivity of an iron(V) nitride."}
{"paper_id": 26598671, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Difficult search tasks are known to involve attentional resources, but the spatiotemporal behavior of attention remains unknown. Are multiple search targets processed in sequence or in parallel? We developed an innovative methodology to solve this notoriously difficult problem. Observers performed a difficult search task during which two probes were flashed at varying delays. Performance in reporting probes at each location was considered a measure of attentional deployment. By solving a second-degree equation, we determined the probability of probe report at the most and least attended probe locations on each trial. Because these values differed significantly, we conclude that attention was focused on one stimulus or subgroup of stimuli at a time, and not divided uniformly among all search stimuli. Furthermore, this deployment was modulated periodically over time at \u223c7 Hz. These results provide evidence for a nonuniform spatiotemporal deployment of attention during difficult search.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Difficult search tasks are known to involve attentional resources, but the spatiotemporal behavior of attention remains unknown.", "Are multiple search targets processed in sequence or in parallel?", "We developed an innovative methodology to solve this notoriously difficult problem.", "Observers performed a difficult search task during which two probes were flashed at varying delays.", "Performance in reporting probes at each location was considered a measure of attentional deployment.", "By solving a second-degree equation, we determined the probability of probe report at the most and least attended probe locations on each trial.", "Because these values differed significantly, we conclude that attention was focused on one stimulus or subgroup of stimuli at a time, and not divided uniformly among all search stimuli.", "Furthermore, this deployment was modulated periodically over time at \u223c7 Hz.", "These results provide evidence for a nonuniform spatiotemporal deployment of attention during difficult search."], "title": "Attention searches nonuniformly in space and in time."}
{"paper_id": 26243466, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Dysfunctional adipose tissue represents a hallmark of type 2 diabetes and systemic insulin resistance, characterized by fibrotic deposition of collagens and increased immune cell infiltration within the depots. Here we generate an inducible model of loss of function of the protein phosphatase and tensin homologue (PTEN), a phosphatase critically involved in turning off the insulin signal transduction cascade, to assess the role of enhanced insulin signalling specifically in mature adipocytes. These mice gain more weight on chow diet and short-term as well as long-term high-fat diet exposure. Despite the increase in weight, they retain enhanced insulin sensitivity, show improvements in oral glucose tolerance tests, display reduced adipose tissue inflammation and maintain elevated adiponectin levels. These improvements also lead to reduced hepatic steatosis and enhanced hepatic insulin sensitivity. Prolonging insulin action selectively in the mature adipocyte is therefore sufficient to maintain normal systemic metabolic homeostasis.", "journal": "Nature communications", "sentences": ["Dysfunctional adipose tissue represents a hallmark of type 2 diabetes and systemic insulin resistance, characterized by fibrotic deposition of collagens and increased immune cell infiltration within the depots.", "Here we generate an inducible model of loss of function of the protein phosphatase and tensin homologue (PTEN), a phosphatase critically involved in turning off the insulin signal transduction cascade, to assess the role of enhanced insulin signalling specifically in mature adipocytes.", "These mice gain more weight on chow diet and short-term as well as long-term high-fat diet exposure.", "Despite the increase in weight, they retain enhanced insulin sensitivity, show improvements in oral glucose tolerance tests, display reduced adipose tissue inflammation and maintain elevated adiponectin levels.", "These improvements also lead to reduced hepatic steatosis and enhanced hepatic insulin sensitivity.", "Prolonging insulin action selectively in the mature adipocyte is therefore sufficient to maintain normal systemic metabolic homeostasis."], "title": "Selective enhancement of insulin sensitivity in the mature adipocyte is sufficient for systemic metabolic improvements."}
{"paper_id": 23727534, "labels": ["0", "0", "0", "0", "0", "1", "0", "0"], "abstract": "The presence of physiological noise in functional MRI can greatly limit the sensitivity and accuracy of BOLD signal measurements, and produce significant false positives. There are two main types of physiological confounds: (1) high-variance signal in non-neuronal tissues of the brain including vascular tracts, sinuses and ventricles, and (2) physiological noise components which extend into gray matter tissue. These physiological effects may also be partially coupled with stimuli (and thus the BOLD response). To address these issues, we have developed PHYCAA+, a significantly improved version of the PHYCAA algorithm (Churchill et al., 2011) that (1) down-weights the variance of voxels in probable non-neuronal tissue, and (2) identifies the multivariate physiological noise subspace in gray matter that is linked to non-neuronal tissue. This model estimates physiological noise directly from EPI data, without requiring external measures of heartbeat and respiration, or manual selection of physiological components. The PHYCAA+ model significantly improves the prediction accuracy and reproducibility of single-subject analyses, compared to PHYCAA and a number of commonly-used physiological correction algorithms. Individual subject denoising with PHYCAA+ is independently validated by showing that it consistently increased between-subject activation overlap, and minimized false-positive signal in non gray-matter loci. The results are demonstrated for both block and fast single-event task designs, applied to standard univariate and adaptive multivariate analysis models.", "journal": "NeuroImage", "sentences": ["The presence of physiological noise in functional MRI can greatly limit the sensitivity and accuracy of BOLD signal measurements, and produce significant false positives.", "There are two main types of physiological confounds: (1) high-variance signal in non-neuronal tissues of the brain including vascular tracts, sinuses and ventricles, and (2) physiological noise components which extend into gray matter tissue.", "These physiological effects may also be partially coupled with stimuli (and thus the BOLD response).", "To address these issues, we have developed PHYCAA+, a significantly improved version of the PHYCAA algorithm (Churchill et al., 2011) that (1) down-weights the variance of voxels in probable non-neuronal tissue, and (2) identifies the multivariate physiological noise subspace in gray matter that is linked to non-neuronal tissue.", "This model estimates physiological noise directly from EPI data, without requiring external measures of heartbeat and respiration, or manual selection of physiological components.", "The PHYCAA+ model significantly improves the prediction accuracy and reproducibility of single-subject analyses, compared to PHYCAA and a number of commonly-used physiological correction algorithms.", "Individual subject denoising with PHYCAA+ is independently validated by showing that it consistently increased between-subject activation overlap, and minimized false-positive signal in non gray-matter loci.", "The results are demonstrated for both block and fast single-event task designs, applied to standard univariate and adaptive multivariate analysis models."], "title": "PHYCAA+: an optimized, adaptive procedure for measuring and controlling physiological noise in BOLD fMRI."}
{"paper_id": 27031231, "labels": ["0", "0", "0", "0", "0", "1", "0"], "abstract": "The adoption of Artemisinin based combination therapies (ACT) constitutes a basic strategy for malaria control in sub-Saharan Africa. Moreover, since cases of ACT resistance have been reported in South-East Asia, the need to understand P. falciparum resistance mechanism to ACT has become a global research goal. The selective pressure of ACT and the possibility that some specific Pfcrt and Pfmdr1 alleles are associated with treatment failures was assessed in a clinical trial comparing ASAQ to AL in Nanoro. Dried blood spots collected on Day 0 and on the day of recurrent parasitaemia during the 28-day follow-up were analyzed using the restriction fragments length polymorphism (PCR-RFLP) method to detect single nucleotide polymorphisms (SNPs) in Pfcrt (codon76) and Pfmdr1 (codons 86, 184, 1034, 1042, and 1246) genes. Multivariate analysis of the relationship between the presence of Pfcrt and Pfmdr1 alleles and treatment outcome was performed. AL and ASAQ exerted opposite trends in selecting Pfcrt K76T and Pfmdr1-N86Y alleles, raising the potential beneficial effect of using diverse ACT at the same time as first line treatments to reduce the selective pressure by each treatment regimen. No clear association between the presence of Pfcrt and Pfmdr1 alleles carried at baseline and treatment failure was observed.", "journal": "PloS one", "sentences": ["The adoption of Artemisinin based combination therapies (ACT) constitutes a basic strategy for malaria control in sub-Saharan Africa.", "Moreover, since cases of ACT resistance have been reported in South-East Asia, the need to understand P. falciparum resistance mechanism to ACT has become a global research goal.", "The selective pressure of ACT and the possibility that some specific Pfcrt and Pfmdr1 alleles are associated with treatment failures was assessed in a clinical trial comparing ASAQ to AL in Nanoro.", "Dried blood spots collected on Day 0 and on the day of recurrent parasitaemia during the 28-day follow-up were analyzed using the restriction fragments length polymorphism (PCR-RFLP) method to detect single nucleotide polymorphisms (SNPs) in Pfcrt (codon76) and Pfmdr1 (codons 86, 184, 1034, 1042, and 1246) genes.", "Multivariate analysis of the relationship between the presence of Pfcrt and Pfmdr1 alleles and treatment outcome was performed.", "AL and ASAQ exerted opposite trends in selecting Pfcrt K76T and Pfmdr1-N86Y alleles, raising the potential beneficial effect of using diverse ACT at the same time as first line treatments to reduce the selective pressure by each treatment regimen.", "No clear association between the presence of Pfcrt and Pfmdr1 alleles carried at baseline and treatment failure was observed."], "title": "Artesunate-Amodiaquine and Artemether-Lumefantrine Therapies and Selection of Pfcrt and Pfmdr1 Alleles in Nanoro, Burkina Faso."}
{"paper_id": 26881808, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The unprecedented rise in atmospheric CO2 concentration and injudicious fertilization or heterogeneous distribution of Mg in the soil warrant further research to understand the synergistic and holistic mechanisms involved in the plant growth regulation. This study investigated the influence of elevated CO2 (800 \u03bcL L-1) on physiological and transcriptomic profiles in Arabidopsis cultured in hydroponic media treated with 1 \u03bcM (low), 1000 \u03bcM (normal) and 10000 \u03bcM (high) Mg2+. Following 7-d treatment, elevated CO2 increased the shoot growth and chlorophyll content under both low and normal Mg supply, whereas root growth was improved exclusively under normal Mg nutrition. Notably, the effect of elevated CO2 on mineral homeostasis in both shoots and roots was less than that of Mg supply. Irrespective of CO2 treatment, high Mg increased number of young leaf but decreased root growth and absorption of P, K, Ca, Fe and Mn whereas low Mg increased the concentration of P, K, Ca and Fe in leaves. Transcriptomics results showed that elevated CO2 decreased the expression of genes related to cell redox homeostasis, cadmium response, and lipid localization, but enhanced signal transduction, protein phosphorylation, NBS-LRR disease resistance proteins and subsequently programmed cell death in low-Mg shoots. By comparison, elevated CO2 enhanced the response of lipid localization (mainly LTP transfer protein/protease inhibitor), endomembrane system, heme binding and cell wall modification in high-Mg roots. Some of these transcriptomic results are substantially in accordance with our physiological and/or biochemical analysis. The present findings broaden our current understanding on the interactive effect of elevated CO2 and Mg levels in the Arabidopsis, which may help to design the novel metabolic engineering strategies to cope with Mg deficiency/excess in crops under elevated CO2.", "journal": "PloS one", "sentences": ["The unprecedented rise in atmospheric CO2 concentration and injudicious fertilization or heterogeneous distribution of Mg in the soil warrant further research to understand the synergistic and holistic mechanisms involved in the plant growth regulation.", "This study investigated the influence of elevated CO2 (800 \u03bcL L-1) on physiological and transcriptomic profiles in Arabidopsis cultured in hydroponic media treated with 1 \u03bcM (low), 1000 \u03bcM (normal) and 10000 \u03bcM (high) Mg2+.", "Following 7-d treatment, elevated CO2 increased the shoot growth and chlorophyll content under both low and normal Mg supply, whereas root growth was improved exclusively under normal Mg nutrition.", "Notably, the effect of elevated CO2 on mineral homeostasis in both shoots and roots was less than that of Mg supply.", "Irrespective of CO2 treatment, high Mg increased number of young leaf but decreased root growth and absorption of P, K, Ca, Fe and Mn whereas low Mg increased the concentration of P, K, Ca and Fe in leaves.", "Transcriptomics results showed that elevated CO2 decreased the expression of genes related to cell redox homeostasis, cadmium response, and lipid localization, but enhanced signal transduction, protein phosphorylation, NBS-LRR disease resistance proteins and subsequently programmed cell death in low-Mg shoots.", "By comparison, elevated CO2 enhanced the response of lipid localization (mainly LTP transfer protein/protease inhibitor), endomembrane system, heme binding and cell wall modification in high-Mg roots.", "Some of these transcriptomic results are substantially in accordance with our physiological and/or biochemical analysis.", "The present findings broaden our current understanding on the interactive effect of elevated CO2 and Mg levels in the Arabidopsis, which may help to design the novel metabolic engineering strategies to cope with Mg deficiency/excess in crops under elevated CO2."], "title": "Physiological and Transcriptome Responses to Combinations of Elevated CO2 and Magnesium in Arabidopsis thaliana."}
{"paper_id": 26370960, "labels": ["0", "0", "0", "0", "0", "0", "1", "0", "1"], "abstract": "Despite intense research, few treatments are available for most neurological disorders. Demyelinating diseases are no exception. This is perhaps not surprising considering the multifactorial nature of these diseases, which involve complex interactions between immune system cells, glia and neurons. In the case of multiple sclerosis, for example, there is no unanimity among researchers about the cause or even which system or cell type could be ground zero. This situation precludes the development and strategic application of mechanism-based therapies. We will discuss how computational modeling applied to questions at different biological levels can help link together disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism. By making testable predictions and revealing critical gaps in existing knowledge, such models can help direct research and will provide a rigorous framework in which to integrate new data as they are collected. Nowadays, there is no shortage of data; the challenge is to make sense of it all. In that respect, computational modeling is an invaluable tool that could, ultimately, transform how we understand, diagnose, and treat demyelinating diseases.", "journal": "International journal of molecular sciences", "sentences": ["Despite intense research, few treatments are available for most neurological disorders.", "Demyelinating diseases are no exception.", "This is perhaps not surprising considering the multifactorial nature of these diseases, which involve complex interactions between immune system cells, glia and neurons.", "In the case of multiple sclerosis, for example, there is no unanimity among researchers about the cause or even which system or cell type could be ground zero.", "This situation precludes the development and strategic application of mechanism-based therapies.", "We will discuss how computational modeling applied to questions at different biological levels can help link together disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism.", "By making testable predictions and revealing critical gaps in existing knowledge, such models can help direct research and will provide a rigorous framework in which to integrate new data as they are collected.", "Nowadays, there is no shortage of data; the challenge is to make sense of it all.", "In that respect, computational modeling is an invaluable tool that could, ultimately, transform how we understand, diagnose, and treat demyelinating diseases."], "title": "Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling."}
{"paper_id": 23896410, "labels": ["0", "0", "0", "0", "1", "1", "1"], "abstract": "The SRC family kinases (SFKs) and the receptor tyrosine kinase c-Kit are activated in human acute myeloid leukemia (AML) cells. We show here that the SFKs LYN, HCK, or FGR are overexpressed and activated in AML progenitor cells. Treatment with the SFK and c-KIT inhibitor dasatinib selectively inhibits human AML stem/progenitor cell growth in vitro. Importantly, dasatinib markedly increases the elimination of AML stem cells capable of engrafting immunodeficient mice by chemotherapeutic agents. In vivo dasatinib treatment enhances chemotherapy-induced targeting of primary murine AML stem cells capable of regenerating leukemia in secondary recipients. Our studies suggest that enhanced targeting of AML cells by the combination of dasatinib with daunorubicin may be related to inhibition of AKT-mediated human mouse double minute 2 homolog phosphorylation, resulting in enhanced p53 activity in AML cells. Combined treatment using dasatinib and chemotherapy provides a novel approach to increasing p53 activity and enhancing targeting of AML stem cells.", "journal": "Blood", "sentences": ["The SRC family kinases (SFKs) and the receptor tyrosine kinase c-Kit are activated in human acute myeloid leukemia (AML) cells.", "We show here that the SFKs LYN, HCK, or FGR are overexpressed and activated in AML progenitor cells.", "Treatment with the SFK and c-KIT inhibitor dasatinib selectively inhibits human AML stem/progenitor cell growth in vitro.", "Importantly, dasatinib markedly increases the elimination of AML stem cells capable of engrafting immunodeficient mice by chemotherapeutic agents.", "In vivo dasatinib treatment enhances chemotherapy-induced targeting of primary murine AML stem cells capable of regenerating leukemia in secondary recipients.", "Our studies suggest that enhanced targeting of AML cells by the combination of dasatinib with daunorubicin may be related to inhibition of AKT-mediated human mouse double minute 2 homolog phosphorylation, resulting in enhanced p53 activity in AML cells.", "Combined treatment using dasatinib and chemotherapy provides a novel approach to increasing p53 activity and enhancing targeting of AML stem cells."], "title": "The Src and c-Kit kinase inhibitor dasatinib enhances p53-mediated targeting of human acute myeloid leukemia stem cells by chemotherapeutic agents."}
{"paper_id": 20712048, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Although the prevalence of chronic hepatitis B virus (HBV) infection has declined in renal transplant recipients (RTRs), it remains a relevant clinical problem with high morbidity and mortality in long-term follow up. A thorough evaluation, including liver biopsy as well as assessment of HBV replication in serum (i.e. hepatitis B e antigen and/or HBV DNA) is required before transplantation. Interferon should not be used in this setting because of low efficacy and precipitation on acute allograft rejection. The advent of effective antiviral therapies offers the opportunity to prevent the progression of liver disease after renal transplantation. However, as far as we are aware, no studies have compared prophylactic and preemptive strategies. To date, the majority of RTRs with HBV-related liver disease have had a high virological and biochemical response to lamivudine use. However, lamivudine resistance is frequent with a prolonged course of therapy. Considering long-term treatment, antiviral agents with a high genetic barrier to resistance and lack of nephrotoxicity are suggested. The optimal strategy in RTRs with HBV infection remains to be established in the near future.", "journal": "World journal of gastroenterology", "sentences": ["Although the prevalence of chronic hepatitis B virus (HBV) infection has declined in renal transplant recipients (RTRs), it remains a relevant clinical problem with high morbidity and mortality in long-term follow up.", "A thorough evaluation, including liver biopsy as well as assessment of HBV replication in serum (i.e.", "hepatitis B e antigen and/or HBV DNA) is required before transplantation.", "Interferon should not be used in this setting because of low efficacy and precipitation on acute allograft rejection.", "The advent of effective antiviral therapies offers the opportunity to prevent the progression of liver disease after renal transplantation.", "However, as far as we are aware, no studies have compared prophylactic and preemptive strategies.", "To date, the majority of RTRs with HBV-related liver disease have had a high virological and biochemical response to lamivudine use.", "However, lamivudine resistance is frequent with a prolonged course of therapy.", "Considering long-term treatment, antiviral agents with a high genetic barrier to resistance and lack of nephrotoxicity are suggested.", "The optimal strategy in RTRs with HBV infection remains to be established in the near future."], "title": "Hepatitis B virus infection and renal transplantation."}
{"paper_id": 23345332, "labels": ["0", "0", "0", "0", "1", "0", "0", "1"], "abstract": "The innate immune system is important for control of infections, including herpesvirus infections. Intracellular DNA potently stimulates antiviral IFN responses. It is known that plasmacytoid dendritic cells sense herpesvirus DNA in endosomes via TLR9 and that nonimmune tissue cells can sense herpesvirus DNA in the nucleus. However, it remains unknown how and where myeloid cells, such as macrophages and conventional dendritic cells, detect infections with herpesviruses. In this study, we demonstrate that the HSV-1 capsid was ubiquitinated in the cytosol and degraded by the proteasome, hence releasing genomic DNA into the cytoplasm for detection by DNA sensors. In this context, the DNA sensor IFN-\u03b3-inducible 16 is important for induction of IFN-\u03b2 in human macrophages postinfection with HSV-1 and CMV. Viral DNA localized to the same cytoplasmic regions as did IFN-\u03b3-inducible 16, with DNA sensing being independent of viral nuclear entry. Thus, proteasomal degradation of herpesvirus capsids releases DNA to the cytoplasm for recognition by DNA sensors.", "journal": "Journal of immunology (Baltimore, Md. : 1950)", "sentences": ["The innate immune system is important for control of infections, including herpesvirus infections.", "Intracellular DNA potently stimulates antiviral IFN responses.", "It is known that plasmacytoid dendritic cells sense herpesvirus DNA in endosomes via TLR9 and that nonimmune tissue cells can sense herpesvirus DNA in the nucleus.", "However, it remains unknown how and where myeloid cells, such as macrophages and conventional dendritic cells, detect infections with herpesviruses.", "In this study, we demonstrate that the HSV-1 capsid was ubiquitinated in the cytosol and degraded by the proteasome, hence releasing genomic DNA into the cytoplasm for detection by DNA sensors.", "In this context, the DNA sensor IFN-\u03b3-inducible 16 is important for induction of IFN-\u03b2 in human macrophages postinfection with HSV-1 and CMV.", "Viral DNA localized to the same cytoplasmic regions as did IFN-\u03b3-inducible 16, with DNA sensing being independent of viral nuclear entry.", "Thus, proteasomal degradation of herpesvirus capsids releases DNA to the cytoplasm for recognition by DNA sensors."], "title": "Proteasomal degradation of herpes simplex virus capsids in macrophages releases DNA to the cytosol for recognition by DNA sensors."}
{"paper_id": 22232736, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "Like many solid tumors, sarcomas are heterogeneous and include a small fraction of the so-called side population (SP) cells with stem-like tumor-initiating potential. Here, we report that SP cells from a soft tissue tumor of enigmatic origin termed undifferentiated pleomorphic sarcoma (also known as malignant fibrous histiocytoma or MFH sarcoma) display activation of both the Hedgehog and Notch pathways. Blockade to these pathways in murine xenograft models, this human cancer decreased the proportion of SP cells present and suppressed tumor self-renewal, as illustrated by the striking inability of xenograft tumors subjected to pathway blockade to be serially transplanted to new hosts. In contrast, conventional chemotherapies increased the proportion of SP cells present in tumor xenografts and did not affect their ability to be serially transplanted. SP cells from these tumors displayed an unexpectedly high proliferation rate which was selectively inhibited by Hedgehog and Notch blockade compared with conventional chemotherapies. Together, our findings deepen the concept that Hedgehog and Notch signaling are fundamental drivers of tumor self-renewal, acting in a small population of tumor-initiating cells present in tumors. Furthermore, our results suggest not only novel treatment strategies for deadly recurrent unresectable forms of this soft tumor subtype, but also potential insights into its etiology which has been historically controversial.", "journal": "Cancer research", "sentences": ["Like many solid tumors, sarcomas are heterogeneous and include a small fraction of the so-called side population (SP) cells with stem-like tumor-initiating potential.", "Here, we report that SP cells from a soft tissue tumor of enigmatic origin termed undifferentiated pleomorphic sarcoma (also known as malignant fibrous histiocytoma or MFH sarcoma) display activation of both the Hedgehog and Notch pathways.", "Blockade to these pathways in murine xenograft models, this human cancer decreased the proportion of SP cells present and suppressed tumor self-renewal, as illustrated by the striking inability of xenograft tumors subjected to pathway blockade to be serially transplanted to new hosts.", "In contrast, conventional chemotherapies increased the proportion of SP cells present in tumor xenografts and did not affect their ability to be serially transplanted.", "SP cells from these tumors displayed an unexpectedly high proliferation rate which was selectively inhibited by Hedgehog and Notch blockade compared with conventional chemotherapies.", "Together, our findings deepen the concept that Hedgehog and Notch signaling are fundamental drivers of tumor self-renewal, acting in a small population of tumor-initiating cells present in tumors.", "Furthermore, our results suggest not only novel treatment strategies for deadly recurrent unresectable forms of this soft tumor subtype, but also potential insights into its etiology which has been historically controversial."], "title": "Hedgehog and Notch signaling regulate self-renewal of undifferentiated pleomorphic sarcomas."}
{"paper_id": 26927887, "labels": ["0", "0", "1", "0", "0", "1"], "abstract": "Extracellular traps (ETs) from neutrophils are reticulated nets of DNA decorated with anti-microbial granules, and are capable of trapping and killing extracellular pathogens. Various phagocytes of mammals and invertebrates produce ETs, however, the evolutionary history of this DNA-based host defence strategy is unclear. Here we report that Sentinel (S) cells of the multicellular slug stage of the social amoeba Dictyostelium discoideum produce ETs upon stimulation with bacteria or lipopolysaccharide in a reactive oxygen species-dependent manner. The production of ETs by S cells requires a Toll/Interleukin-1 receptor domain-containing protein TirA and reactive oxygen species-generating NADPH oxidases. Disruption of these genes results in decreased clearance of bacterial infections. Our results demonstrate that D. discoideum is a powerful model organism to study the evolution and conservation of mechanisms of cell-intrinsic immunity, and suggest that the origin of DNA-based ETs as an innate immune defence predates the emergence of metazoans.", "journal": "Nature communications", "sentences": ["Extracellular traps (ETs) from neutrophils are reticulated nets of DNA decorated with anti-microbial granules, and are capable of trapping and killing extracellular pathogens.", "Various phagocytes of mammals and invertebrates produce ETs, however, the evolutionary history of this DNA-based host defence strategy is unclear.", "Here we report that Sentinel (S) cells of the multicellular slug stage of the social amoeba Dictyostelium discoideum produce ETs upon stimulation with bacteria or lipopolysaccharide in a reactive oxygen species-dependent manner.", "The production of ETs by S cells requires a Toll/Interleukin-1 receptor domain-containing protein TirA and reactive oxygen species-generating NADPH oxidases.", "Disruption of these genes results in decreased clearance of bacterial infections.", "Our results demonstrate that D. discoideum is a powerful model organism to study the evolution and conservation of mechanisms of cell-intrinsic immunity, and suggest that the origin of DNA-based ETs as an innate immune defence predates the emergence of metazoans."], "title": "Social amoebae trap and kill bacteria by casting DNA nets."}
{"paper_id": 25856549, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "The gas phase pyrolysis of trichlorfon was investigated by the on-line gas chromatography - mass spectrometry (GC-MS) pyrolysis and theoretical calculations. Two reaction channels were proposed in the pyrolytic reaction, by analyzing the detected pyrolytic products in the total ion chromatography, including 2,2,2-trichloroacetaldehyde, dimethyl phosphite, and dichlorvos. Theoretical calculations showed that there is an intramolecular hydrogen bond between the hydroxyl group and the phosphate O atom in trichlorfon, through which the hydroxyl H atom can be easily transferred to phosphate O atom to trigger two pyrolytic channels. In path-a, migration of H atom results in direct decomposition of trichlorfon to give 2,2,2-trichloroacetaldehyde and dimethyl phosphite in one step. In path-b, migration of H atom in trichlorfon is combined with formation of the O-P bond to give an intermediate, followed by HCl elimination to afford dichlorvos. Path-a is kinetically more favorable than path-b, which is consistent with the GC-MS results.", "journal": "PloS one", "sentences": ["The gas phase pyrolysis of trichlorfon was investigated by the on-line gas chromatography - mass spectrometry (GC-MS) pyrolysis and theoretical calculations.", "Two reaction channels were proposed in the pyrolytic reaction, by analyzing the detected pyrolytic products in the total ion chromatography, including 2,2,2-trichloroacetaldehyde, dimethyl phosphite, and dichlorvos.", "Theoretical calculations showed that there is an intramolecular hydrogen bond between the hydroxyl group and the phosphate O atom in trichlorfon, through which the hydroxyl H atom can be easily transferred to phosphate O atom to trigger two pyrolytic channels.", "In path-a, migration of H atom results in direct decomposition of trichlorfon to give 2,2,2-trichloroacetaldehyde and dimethyl phosphite in one step.", "In path-b, migration of H atom in trichlorfon is combined with formation of the O-P bond to give an intermediate, followed by HCl elimination to afford dichlorvos.", "Path-a is kinetically more favorable than path-b, which is consistent with the GC-MS results."], "title": "Investigation on the Gas-phase decomposition of trichlorfon by GC-MS and theoretical calculation."}
{"paper_id": 21944923, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "A multiplexing electrochemical immunosensor was developed for ultrasensitive detection of cancer related protein biomarkers. We employed disposable screen-printed carbon electrode (SPCE) array as the detection platform. A universal multi-labeled nanoprobe was developed by loading HRP and goat-anti-rabbit IgG (secondary antibody, Ab(2)) onto multiwalled carbon nanotube (MWNT). This universal nanoprobe was available for virtually any sandwich-based antigen detection and showed superiority in several areas. By using the SPCE array and the universal nanoprobe, we could detect as low as 5 pg mL(-1) of prostate specific antigen (PSA) and 8 pg mL(-1) of Interleukin 8 (IL-8) with the electrochemical immunosensor. We also demonstrated simultaneous detection of two protein biomarkers with this platform. With these attracted features, our immunoassay system shows promising applications for in-field and point-of-care test in clinical diagnostics.", "journal": "Biosensors & bioelectronics", "sentences": ["A multiplexing electrochemical immunosensor was developed for ultrasensitive detection of cancer related protein biomarkers.", "We employed disposable screen-printed carbon electrode (SPCE) array as the detection platform.", "A universal multi-labeled nanoprobe was developed by loading HRP and goat-anti-rabbit IgG (secondary antibody, Ab(2)) onto multiwalled carbon nanotube (MWNT).", "This universal nanoprobe was available for virtually any sandwich-based antigen detection and showed superiority in several areas.", "By using the SPCE array and the universal nanoprobe, we could detect as low as 5 pg mL(-1) of prostate specific antigen (PSA) and 8 pg mL(-1) of Interleukin 8 (IL-8) with the electrochemical immunosensor.", "We also demonstrated simultaneous detection of two protein biomarkers with this platform.", "With these attracted features, our immunoassay system shows promising applications for in-field and point-of-care test in clinical diagnostics."], "title": "Carbon nanotube-based ultrasensitive multiplexing electrochemical immunosensor for cancer biomarkers."}
{"paper_id": 23706214, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Mechanical properties of single cells are of increasing interest both from a fundamental cell biological perspective and in the context of disease diagnostics. In this respect, atomic force microscopy (AFM) has become a powerful tool for imaging and assessing mechanical properties of biological samples. However, while these tests are typically carried out on chemically fixed cells, the most important data is that on living cells. The present study applies AFM technique to assess the Young's modulus of two cell lines: mouse embryonic fibroblasts (NIH/3T3) and human epithelial cancer cells (SW-13). Both living cells and those fixed with paraformaldehyde were investigated. This analysis quantifies the difference between Young's modulus for these two conditions and provides a coefficient to relate them. Knowing the relation between Young's modulus of living and fixed cells, allows carrying out and comparing data obtained during steady-state measurements on fixed cells that are more frequently available in the clinical and research settings and simpler to maintain and probe.", "journal": "Materials science & engineering. C, Materials for biological applications", "sentences": ["Mechanical properties of single cells are of increasing interest both from a fundamental cell biological perspective and in the context of disease diagnostics.", "In this respect, atomic force microscopy (AFM) has become a powerful tool for imaging and assessing mechanical properties of biological samples.", "However, while these tests are typically carried out on chemically fixed cells, the most important data is that on living cells.", "The present study applies AFM technique to assess the Young's modulus of two cell lines: mouse embryonic fibroblasts (NIH/3T3) and human epithelial cancer cells (SW-13).", "Both living cells and those fixed with paraformaldehyde were investigated.", "This analysis quantifies the difference between Young's modulus for these two conditions and provides a coefficient to relate them.", "Knowing the relation between Young's modulus of living and fixed cells, allows carrying out and comparing data obtained during steady-state measurements on fixed cells that are more frequently available in the clinical and research settings and simpler to maintain and probe."], "title": "Atomic force microscopy of 3T3 and SW-13 cell lines: an investigation of cell elasticity changes due to fixation."}
{"paper_id": 27057906, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "The aim of the study was to examine how well aggregate data meta-analyses (ADMAs) and individual patient data meta-analyses (IPDMAs) agree in their overall results and how frequently interactions are detected in IPDMAs and ADMAs.ADMA articles immediately published before the IPDMA and matching the research topic were identified. Agreement in the overall result was achieved if the estimate was in the same direction. The number of subgroup analyses, in particular that of significant interactions, was compared between the 2 types of meta-analyses.A total of 829 IPDMA articles were identified; 129 (15.6%) were found to have a matched ADMA article and 204 paired meta-analyses were identified. Agreement in the overall effect was observed in 187 (91.7%) of the 204 paired meta-analyses. Fifty-three (26.0%) ADMAs and 121 (59.3%) IPDMAs conducted subgroup analyses and presented 150 and 634 subgroup analyses, respectively. The IPDMAs conducted 7 times more subgroup analyses on interaction (544 in IPDMAs vs 68 in ADMAs) and identified 14 times more potential interactions (44 in IPDMAs vs 3 in ADMAs).ADMAs will almost always agree with their corresponding IPDMAs in the overall result if greater efforts are made to improve the methodology in conducting ADMAs. The IPDMA is required mostly if interactions are suspected.", "journal": "Medicine", "sentences": ["The aim of the study was to examine how well aggregate data meta-analyses (ADMAs) and individual patient data meta-analyses (IPDMAs) agree in their overall results and how frequently interactions are detected in IPDMAs and ADMAs.ADMA articles immediately published before the IPDMA and matching the research topic were identified.", "Agreement in the overall result was achieved if the estimate was in the same direction.", "The number of subgroup analyses, in particular that of significant interactions, was compared between the 2 types of meta-analyses.A total of 829 IPDMA articles were identified; 129 (15.6%) were found to have a matched ADMA article and 204 paired meta-analyses were identified.", "Agreement in the overall effect was observed in 187 (91.7%) of the 204 paired meta-analyses.", "Fifty-three (26.0%) ADMAs and 121 (59.3%) IPDMAs conducted subgroup analyses and presented 150 and 634 subgroup analyses, respectively.", "The IPDMAs conducted 7 times more subgroup analyses on interaction (544 in IPDMAs vs 68 in ADMAs) and identified 14 times more potential interactions (44 in IPDMAs vs 3 in ADMAs).ADMAs will almost always agree with their corresponding IPDMAs in the overall result if greater efforts are made to improve the methodology in conducting ADMAs.", "The IPDMA is required mostly if interactions are suspected."], "title": "Comparing the Overall Result and Interaction in Aggregate Data Meta-Analysis and Individual Patient Data Meta-Analysis."}
{"paper_id": 27070314, "labels": ["0", "0", "1", "0", "0", "0", "0", "1"], "abstract": "Plants in the Meliaceae family are known to possess interesting biological activities, such as antimalaral, antihypertensive and antitumour activities. Previously, our group reported the plant-derived compound cycloart-24-ene-26-ol-3-one isolated from the hexane extracts of Aglaia exima leaves, which shows cytotoxicity towards various cancer cell lines, in particular, colon cancer cell lines. In this report, we further demonstrate that cycloart-24-ene-26-ol-3-one, from here forth known as cycloartane, reduces the viability of the colon cancer cell lines HT-29 and CaCO-2 in a dose- and time-dependent manner. Further elucidation of the compound's mechanism showed that it binds to tumour necrosis factor-receptor 1 (TNF-R1) leading to the initiation of caspase-8 and, through the activation of Bid, in the activation of caspase-9. This activity causes a reduction in mitochondrial membrane potential (MMP) and the release of cytochrome-C. The activation of caspase-8 and -9 both act to commit the cancer cells to apoptosis through downstream caspase-3/7 activation, PARP cleavage and the lack of NFkB translocation into the nucleus. A molecular docking study showed that the cycloartane binds to the receptor through a hydrophobic interaction with cysteine-96 and hydrogen bonds with lysine-75 and -132. The results show that further development of the cycloartane as an anti-cancer drug is worthwhile.", "journal": "PloS one", "sentences": ["Plants in the Meliaceae family are known to possess interesting biological activities, such as antimalaral, antihypertensive and antitumour activities.", "Previously, our group reported the plant-derived compound cycloart-24-ene-26-ol-3-one isolated from the hexane extracts of Aglaia exima leaves, which shows cytotoxicity towards various cancer cell lines, in particular, colon cancer cell lines.", "In this report, we further demonstrate that cycloart-24-ene-26-ol-3-one, from here forth known as cycloartane, reduces the viability of the colon cancer cell lines HT-29 and CaCO-2 in a dose- and time-dependent manner.", "Further elucidation of the compound's mechanism showed that it binds to tumour necrosis factor-receptor 1 (TNF-R1) leading to the initiation of caspase-8 and, through the activation of Bid, in the activation of caspase-9.", "This activity causes a reduction in mitochondrial membrane potential (MMP) and the release of cytochrome-C.", "The activation of caspase-8 and -9 both act to commit the cancer cells to apoptosis through downstream caspase-3/7 activation, PARP cleavage and the lack of NFkB translocation into the nucleus.", "A molecular docking study showed that the cycloartane binds to the receptor through a hydrophobic interaction with cysteine-96 and hydrogen bonds with lysine-75 and -132.", "The results show that further development of the cycloartane as an anti-cancer drug is worthwhile."], "title": "Cycloart-24-ene-26-ol-3-one, a New Cycloartane Isolated from Leaves of Aglaia exima Triggers Tumour Necrosis Factor-Receptor 1-Mediated Caspase-Dependent Apoptosis in Colon Cancer Cell Line."}
{"paper_id": 26710343, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Human odorant-binding proteins (hOBPs) not only can bind and transport odorants in the surrounding environment for sensing smells, but also play important roles in transmitting lots of biomolecules in different organs. Utilizing the properties of hOBPs, an electrochemical biosensor with nanopore array was developed to detect specific biomolecular ligands, such as aldehydes and fatty acids. The highly ordered nanopores of anodic aluminum oxide with diameter of 20-40nm were fabricated with two-step oxidation. Through 2-carboxyethyl phosphonic acid, hOBPs were self-assembled on nanopores as the sensing membrane. With nanopore arrays, the impedance spectra showed quite different electron transfer processes in the frequency spectra, which could be characterized by the electron transfer resistance and electrical resistance of the porous membrane. Under stimulation of biomolecular ligands, series resistance of nanopores and hOBPs increased and showed a concentration-dependence feature, while the electron transfer resistance hardly changed. The nanopore based biosensor could sensitively detect biological ligands of benzaldehyde, docosahexaenoic acid, and lauric acid, which were closely related to or were potential biomarkers for cancers and other serious diseases. Equipped with hOBPs, the sensor exhibited promising potentials both in odorant and biomolecule detection for olfactory biosensing and in disease diagnosis and evaluation for biochemical detection.", "journal": "Biosensors & bioelectronics", "sentences": ["Human odorant-binding proteins (hOBPs) not only can bind and transport odorants in the surrounding environment for sensing smells, but also play important roles in transmitting lots of biomolecules in different organs.", "Utilizing the properties of hOBPs, an electrochemical biosensor with nanopore array was developed to detect specific biomolecular ligands, such as aldehydes and fatty acids.", "The highly ordered nanopores of anodic aluminum oxide with diameter of 20-40nm were fabricated with two-step oxidation.", "Through 2-carboxyethyl phosphonic acid, hOBPs were self-assembled on nanopores as the sensing membrane.", "With nanopore arrays, the impedance spectra showed quite different electron transfer processes in the frequency spectra, which could be characterized by the electron transfer resistance and electrical resistance of the porous membrane.", "Under stimulation of biomolecular ligands, series resistance of nanopores and hOBPs increased and showed a concentration-dependence feature, while the electron transfer resistance hardly changed.", "The nanopore based biosensor could sensitively detect biological ligands of benzaldehyde, docosahexaenoic acid, and lauric acid, which were closely related to or were potential biomarkers for cancers and other serious diseases.", "Equipped with hOBPs, the sensor exhibited promising potentials both in odorant and biomolecule detection for olfactory biosensing and in disease diagnosis and evaluation for biochemical detection."], "title": "Impedance spectroscopy analysis of human odorant binding proteins immobilized on nanopore arrays for biochemical detection."}
{"paper_id": 23400817, "labels": ["0", "0", "0", "0", "0", "0", "1", "0", "1"], "abstract": "Diwali is one of the largest festivals for Hindu religion which falls in the period October-November every year. During the festival days, extensive burning of firecrackers takes place, especially in the evening hours, constituting a significant source of aerosols, black carbon (BC), organics, and trace gases. The widespread use of sparklers was found to be associated with short-term air quality degradation events. The present study focuses on the influence of Diwali fireworks emissions on surface ozone (O3), nitrogen oxides (NO x ), and BC aerosol concentration over the tropical urban region of Hyderabad, India during three consecutive years (2009-2011). The trace gases are analyzed for pre-Diwali, Diwali, and post-Diwali days in order to reveal the festivity's contribution to the ambient air quality over the city. A twofold to threefold increase is observed in O3, NO x , and BC concentrations during the festival period compared to control days for 2009-2011, which is mainly attributed to firecrackers burning. The high correlation coefficient (~0.74) between NO x and SO2 concentrations and higher SO2/NO x (S/N) index suggested air quality degradation due to firecrackers burning. Furthermore, the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation-derived aerosol subtyping map also confirmed the presence of smoke aerosols emitted from firecrackers burning over the region. Nevertheless, the concentration level of pollutants exhibited substantial decline over the region during the years 2010 and 2011 compared to 2009 ascribed to various awareness campaigns and increased cost of firecrackers.", "journal": "Environmental monitoring and assessment", "sentences": ["Diwali is one of the largest festivals for Hindu religion which falls in the period October-November every year.", "During the festival days, extensive burning of firecrackers takes place, especially in the evening hours, constituting a significant source of aerosols, black carbon (BC), organics, and trace gases.", "The widespread use of sparklers was found to be associated with short-term air quality degradation events.", "The present study focuses on the influence of Diwali fireworks emissions on surface ozone (O3), nitrogen oxides (NO x ), and BC aerosol concentration over the tropical urban region of Hyderabad, India during three consecutive years (2009-2011).", "The trace gases are analyzed for pre-Diwali, Diwali, and post-Diwali days in order to reveal the festivity's contribution to the ambient air quality over the city.", "A twofold to threefold increase is observed in O3, NO x , and BC concentrations during the festival period compared to control days for 2009-2011, which is mainly attributed to firecrackers burning.", "The high correlation coefficient (~0.74) between NO x and SO2 concentrations and higher SO2/NO x (S/N) index suggested air quality degradation due to firecrackers burning.", "Furthermore, the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation-derived aerosol subtyping map also confirmed the presence of smoke aerosols emitted from firecrackers burning over the region.", "Nevertheless, the concentration level of pollutants exhibited substantial decline over the region during the years 2010 and 2011 compared to 2009 ascribed to various awareness campaigns and increased cost of firecrackers."], "title": "The impact assessment of Diwali fireworks emissions on the air quality of a tropical urban site, Hyderabad, India, during three consecutive years."}
{"paper_id": 26374212, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Health Canada regulates gene therapy products and many cell therapy products as biological drugs under the Canadian Food and Drugs Act and its attendant regulations. Cellular products that meet certain criteria, including minimal manipulation and homologous use, may be subjected to a standards-based approach under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations. The manufacture and clinical testing of cell and gene therapy products (CGTPs) presents many challenges beyond those for protein biologics. Cells cannot be subjected to pathogen removal or inactivation procedures and must frequently be administered shortly after final formulation. Viral vector design and manufacturing control are critically important to overall product quality and linked to safety and efficacy in patients through concerns such as replication competence, vector integration, and vector shedding. In addition, for many CGTPs, the value of nonclinical studies is largely limited to providing proof of concept, and the first meaningful data relating to appropriate dosing, safety parameters, and validity of surrogate or true determinants of efficacy must come from carefully designed clinical trials in patients. Addressing these numerous challenges requires application of various risk mitigation strategies and meeting regulatory expectations specifically adapted to the product types. Regulatory cooperation and harmonisation at an international level are essential for progress in the development and commercialisation of these products. However, particularly in the area of cell therapy, new regulatory paradigms may be needed to harness the benefits of clinical progress in situations where the resources and motivation to pursue a typical drug product approval pathway may be lacking.", "journal": "Advances in experimental medicine and biology", "sentences": ["Health Canada regulates gene therapy products and many cell therapy products as biological drugs under the Canadian Food and Drugs Act and its attendant regulations.", "Cellular products that meet certain criteria, including minimal manipulation and homologous use, may be subjected to a standards-based approach under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations.", "The manufacture and clinical testing of cell and gene therapy products (CGTPs) presents many challenges beyond those for protein biologics.", "Cells cannot be subjected to pathogen removal or inactivation procedures and must frequently be administered shortly after final formulation.", "Viral vector design and manufacturing control are critically important to overall product quality and linked to safety and efficacy in patients through concerns such as replication competence, vector integration, and vector shedding.", "In addition, for many CGTPs, the value of nonclinical studies is largely limited to providing proof of concept, and the first meaningful data relating to appropriate dosing, safety parameters, and validity of surrogate or true determinants of efficacy must come from carefully designed clinical trials in patients.", "Addressing these numerous challenges requires application of various risk mitigation strategies and meeting regulatory expectations specifically adapted to the product types.", "Regulatory cooperation and harmonisation at an international level are essential for progress in the development and commercialisation of these products.", "However, particularly in the area of cell therapy, new regulatory paradigms may be needed to harness the benefits of clinical progress in situations where the resources and motivation to pursue a typical drug product approval pathway may be lacking."], "title": "Regulatory Oversight of Cell and Gene Therapy Products in Canada."}
{"paper_id": 27028653, "labels": ["0", "0", "0", "0", "0", "1", "0", "1"], "abstract": "\u03b1-Actinin is an essential actin cross-linker involved in cytoskeletal organization and dynamics. The molecular conformation of \u03b1-actinin's actin-binding domain (ABD) regulates its association with actin and thus mutations in this domain can lead to severe pathogenic conditions. A point mutation at lysine 255 in human \u03b1-actinin-4 to glutamate increases the binding affinity resulting in stiffer cytoskeletal structures. The role of different ABD conformations and the effect of K255E mutation on ABD conformations remain elusive. To evaluate the impact of K255E mutation on ABD binding to actin we use all-atom molecular dynamics and free energy calculation methods and study the molecular mechanism of actin association in both wild-type \u03b1-actinin and in the K225E mutant. Our models illustrate that the strength of actin association is indeed sensitive to the ABD conformation, predict the effect of K255E mutation-based on simulations with the K237E mutant chicken \u03b1-actinin-and evaluate the mechanism of \u03b1-actinin binding to actin. Furthermore, our simulations showed that the calmodulin domain binding to the linker region was important for regulating the distance between actin and ABD. Our results provide valuable insights into the molecular details of this critical cellular phenomenon and further contribute to an understanding of cytoskeletal dynamics in health and disease.", "journal": "Biophysical journal", "sentences": ["\u03b1-Actinin is an essential actin cross-linker involved in cytoskeletal organization and dynamics.", "The molecular conformation of \u03b1-actinin's actin-binding domain (ABD) regulates its association with actin and thus mutations in this domain can lead to severe pathogenic conditions.", "A point mutation at lysine 255 in human \u03b1-actinin-4 to glutamate increases the binding affinity resulting in stiffer cytoskeletal structures.", "The role of different ABD conformations and the effect of K255E mutation on ABD conformations remain elusive.", "To evaluate the impact of K255E mutation on ABD binding to actin we use all-atom molecular dynamics and free energy calculation methods and study the molecular mechanism of actin association in both wild-type \u03b1-actinin and in the K225E mutant.", "Our models illustrate that the strength of actin association is indeed sensitive to the ABD conformation, predict the effect of K255E mutation-based on simulations with the K237E mutant chicken \u03b1-actinin-and evaluate the mechanism of \u03b1-actinin binding to actin.", "Furthermore, our simulations showed that the calmodulin domain binding to the linker region was important for regulating the distance between actin and ABD.", "Our results provide valuable insights into the molecular details of this critical cellular phenomenon and further contribute to an understanding of cytoskeletal dynamics in health and disease."], "title": "Dynamic Regulation of \u03b1-Actinin's Calponin Homology Domains on F-Actin."}
{"paper_id": 22569486, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "0"], "abstract": "Insulin secretory granules (ISGs) are pivotal organelles of pancreatic \u00df-cells and represent a key participant to glucose homeostasis. Indeed, insulin is packed and processed within these vesicles before its release by exocytosis. It is therefore crucial to acquire qualitative and quantitative data on the ISG proteome, in order to increase our knowledge on ISG biogenesis, maturation and exocytosis. Despites efforts made in the past years, the coverage of the ISG proteome is still incomplete and comprises many potential protein contaminants most likely coming from suboptimal sample preparations. We developed here a 3-step gradient purification procedure combined to Stable Isotope Labeling with Amino acids in Cell culture (SILAC) to further characterize the ISG protein content. Our results allowed to build three complementary proteomes containing 1/ proteins which are enriched in mature ISGs, 2/ proteins sharing multiple localizations including ISGs, and finally 3/ proteins sorted out from immature ISGs and/or co-purifying contaminants. As a proof of concept, the ProSAAS, a neuronal protein found in ISGs was further characterized and its granular localization proved. ProSAAS might represent a novel potential target allowing to better understand the defaults in insulin processing and secretion observed during type 2 diabetes progression. This article is part of a special issue entitled: Translational Proteomics.", "journal": "Journal of proteomics", "sentences": ["Insulin secretory granules (ISGs) are pivotal organelles of pancreatic \u00df-cells and represent a key participant to glucose homeostasis.", "Indeed, insulin is packed and processed within these vesicles before its release by exocytosis.", "It is therefore crucial to acquire qualitative and quantitative data on the ISG proteome, in order to increase our knowledge on ISG biogenesis, maturation and exocytosis.", "Despites efforts made in the past years, the coverage of the ISG proteome is still incomplete and comprises many potential protein contaminants most likely coming from suboptimal sample preparations.", "We developed here a 3-step gradient purification procedure combined to Stable Isotope Labeling with Amino acids in Cell culture (SILAC) to further characterize the ISG protein content.", "Our results allowed to build three complementary proteomes containing 1/ proteins which are enriched in mature ISGs, 2/ proteins sharing multiple localizations including ISGs, and finally 3/ proteins sorted out from immature ISGs and/or co-purifying contaminants.", "As a proof of concept, the ProSAAS, a neuronal protein found in ISGs was further characterized and its granular localization proved.", "ProSAAS might represent a novel potential target allowing to better understand the defaults in insulin processing and secretion observed during type 2 diabetes progression.", "This article is part of a special issue entitled: Translational Proteomics."], "title": "Improved characterization of the insulin secretory granule proteomes."}
{"paper_id": 26840305, "labels": ["0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "The hydrophilic nature of peptides and proteins renders them impermeable to cell membranes. Thus, in order to successfully deliver peptide and protein-based therapeutics across the plasma membrane or epithelial and endothelial barriers, a permeation enhancing strategy must be employed. Cell-penetrating peptides (CPPs) constitute a promising tool and have shown applications for peptide and protein delivery into cells as well as across various epithelia and the blood-brain barrier (BBB). CPP-mediated delivery of peptides and proteins may be pursued via covalent conjugation of the CPP to the cargo peptide or protein or via physical complexation obtained by simple bulk-mixing of the CPP with its cargo. Both approaches have their pros and cons, and which is the better choice likely relates to the physicochemical properties of the CPP and its cargo as well as the route of administration, the specific barrier and the target cell. Besides the physical barrier, a metabolic barrier must be taken into consideration when applying peptide-based delivery vectors, such as the CPPs, and stability-enhancing strategies are commonly employed to prolong the CPP half-life. The mechanisms by which CPPs translocate cell membranes are believed to involve both endocytosis and direct translocation, but are still widely investigated and discussed. The fact that multiple factors influence the mechanisms responsible for cellular CPP internalization and the lack of sensitive methods for detection of the CPP, and in some cases the cargo, further complicates the design and conduction of conclusive mechanistic studies.", "journal": "International journal of molecular sciences", "sentences": ["The hydrophilic nature of peptides and proteins renders them impermeable to cell membranes.", "Thus, in order to successfully deliver peptide and protein-based therapeutics across the plasma membrane or epithelial and endothelial barriers, a permeation enhancing strategy must be employed.", "Cell-penetrating peptides (CPPs) constitute a promising tool and have shown applications for peptide and protein delivery into cells as well as across various epithelia and the blood-brain barrier (BBB).", "CPP-mediated delivery of peptides and proteins may be pursued via covalent conjugation of the CPP to the cargo peptide or protein or via physical complexation obtained by simple bulk-mixing of the CPP with its cargo.", "Both approaches have their pros and cons, and which is the better choice likely relates to the physicochemical properties of the CPP and its cargo as well as the route of administration, the specific barrier and the target cell.", "Besides the physical barrier, a metabolic barrier must be taken into consideration when applying peptide-based delivery vectors, such as the CPPs, and stability-enhancing strategies are commonly employed to prolong the CPP half-life.", "The mechanisms by which CPPs translocate cell membranes are believed to involve both endocytosis and direct translocation, but are still widely investigated and discussed.", "The fact that multiple factors influence the mechanisms responsible for cellular CPP internalization and the lack of sensitive methods for detection of the CPP, and in some cases the cargo, further complicates the design and conduction of conclusive mechanistic studies."], "title": "Applications and Challenges for Use of Cell-Penetrating Peptides as Delivery Vectors for Peptide and Protein Cargos."}
{"paper_id": 27098035, "labels": ["0", "0", "0", "0", "0", "1", "0"], "abstract": "GIANT API provides biomedical researchers programmatic access to tissue-specific and global networks in humans and model organisms, and associated tools, which includes functional re-prioritization of existing genome-wide association study (GWAS) data. Using tissue-specific interaction networks, researchers are able to predict relationships between genes specific to a tissue or cell lineage, identify the changing roles of genes across tissues and uncover disease-gene associations. Additionally, GIANT API enables computational tools like NetWAS, which leverages tissue-specific networks for re-prioritization of GWAS results. The web services covered by the API include 144 tissue-specific functional gene networks in human, global functional networks for human and six common model organisms and the NetWAS method. GIANT API conforms to the REST architecture, which makes it stateless, cacheable and highly scalable. It can be used by a diverse range of clients including web browsers, command terminals, programming languages and standalone apps for data analysis and visualization. The API is freely available for use at http://giant-api.princeton.edu.", "journal": "Nucleic acids research", "sentences": ["GIANT API provides biomedical researchers programmatic access to tissue-specific and global networks in humans and model organisms, and associated tools, which includes functional re-prioritization of existing genome-wide association study (GWAS) data.", "Using tissue-specific interaction networks, researchers are able to predict relationships between genes specific to a tissue or cell lineage, identify the changing roles of genes across tissues and uncover disease-gene associations.", "Additionally, GIANT API enables computational tools like NetWAS, which leverages tissue-specific networks for re-prioritization of GWAS results.", "The web services covered by the API include 144 tissue-specific functional gene networks in human, global functional networks for human and six common model organisms and the NetWAS method.", "GIANT API conforms to the REST architecture, which makes it stateless, cacheable and highly scalable.", "It can be used by a diverse range of clients including web browsers, command terminals, programming languages and standalone apps for data analysis and visualization.", "The API is freely available for use at http://giant-api.princeton.edu."], "title": "GIANT API: an application programming interface for functional genomics."}
{"paper_id": 23824597, "labels": ["0", "0", "0", "0", "0", "0", "1", "0", "1", "1"], "abstract": "Functionally polarized CD4+ T helper (Th) cells such as Th1, Th2 and Th17 cells are central to the regulation of acquired immunity. However, the molecular mechanisms governing the maintenance of the polarized functions of Th cells remain unclear. GATA3, a master regulator of Th2 cell differentiation, initiates the expressions of Th2 cytokine genes and other Th2-specific genes. GATA3 also plays important roles in maintaining Th2 cell function and in continuous chromatin remodeling of Th2 cytokine gene loci. However, it is unclear whether continuous expression of GATA3 is required to maintain the expression of various other Th2-specific genes. In this report, genome-wide DNA gene expression profiling revealed that GATA3 expression is critical for the expression of a certain set of Th2-specific genes. We demonstrated that GATA3 dependency is reduced for some Th2-specific genes in fully developed Th2 cells compared to that observed in effector Th2 cells, whereas it is unchanged for other genes. Moreover, effects of a loss of GATA3 expression in Th2 cells on the expression of cytokine and cytokine receptor genes were examined in detail. A critical role of GATA3 in the regulation of Th2-specific gene expression is confirmed in in vivo generated antigen-specific memory Th2 cells. Therefore, GATA3 is required for the continuous expression of the majority of Th2-specific genes involved in maintaining the Th2 cell identity.", "journal": "PloS one", "sentences": ["Functionally polarized CD4+ T helper (Th) cells such as Th1, Th2 and Th17 cells are central to the regulation of acquired immunity.", "However, the molecular mechanisms governing the maintenance of the polarized functions of Th cells remain unclear.", "GATA3, a master regulator of Th2 cell differentiation, initiates the expressions of Th2 cytokine genes and other Th2-specific genes.", "GATA3 also plays important roles in maintaining Th2 cell function and in continuous chromatin remodeling of Th2 cytokine gene loci.", "However, it is unclear whether continuous expression of GATA3 is required to maintain the expression of various other Th2-specific genes.", "In this report, genome-wide DNA gene expression profiling revealed that GATA3 expression is critical for the expression of a certain set of Th2-specific genes.", "We demonstrated that GATA3 dependency is reduced for some Th2-specific genes in fully developed Th2 cells compared to that observed in effector Th2 cells, whereas it is unchanged for other genes.", "Moreover, effects of a loss of GATA3 expression in Th2 cells on the expression of cytokine and cytokine receptor genes were examined in detail.", "A critical role of GATA3 in the regulation of Th2-specific gene expression is confirmed in in vivo generated antigen-specific memory Th2 cells.", "Therefore, GATA3 is required for the continuous expression of the majority of Th2-specific genes involved in maintaining the Th2 cell identity."], "title": "Genome-Wide Gene Expression Profiling Revealed a Critical Role for GATA3 in the Maintenance of the Th2 Cell Identity."}
{"paper_id": 26337909, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "In normal cells exposed to stress, the central transcription factor NF-\u03baB is activated only transiently, to modulate the activation of downstream immune responses. However, in most cancers, NF-\u03baB is abnormally activated constitutively, contributing thus to oncogenesis and tumor progression. Therefore, downregulating NF-\u03baB activity is an important goal of cancer treatment. In order to control NF-\u03baB activity therapeutically, it is helpful to understand the molecular mechanisms that normally govern its activation and how dysregulated NF-\u03baB activity may aid the development of disease. Recent evidence from our laboratories and others indicates that, in addition to various posttranslational modifications of NF-\u03baB that have been observed previously, including phosphorylation, ubiquitination, and acetylation, NF-\u03baB can be methylated reversibly on lysine or arginine residues by histone-modifying enzymes, including lysine and arginine methyl transferases and demethylases. Furthermore, these methylations are required to activate many downstream genes. Interestingly, amplifications and mutations of several such enzymes have been linked to cancer. We propose that some of these mutations may alter the methylation not only of histones but also of NF-\u03baB, making them attractive therapeutic targets.", "journal": "Cancer research", "sentences": ["In normal cells exposed to stress, the central transcription factor NF-\u03baB is activated only transiently, to modulate the activation of downstream immune responses.", "However, in most cancers, NF-\u03baB is abnormally activated constitutively, contributing thus to oncogenesis and tumor progression.", "Therefore, downregulating NF-\u03baB activity is an important goal of cancer treatment.", "In order to control NF-\u03baB activity therapeutically, it is helpful to understand the molecular mechanisms that normally govern its activation and how dysregulated NF-\u03baB activity may aid the development of disease.", "Recent evidence from our laboratories and others indicates that, in addition to various posttranslational modifications of NF-\u03baB that have been observed previously, including phosphorylation, ubiquitination, and acetylation, NF-\u03baB can be methylated reversibly on lysine or arginine residues by histone-modifying enzymes, including lysine and arginine methyl transferases and demethylases.", "Furthermore, these methylations are required to activate many downstream genes.", "Interestingly, amplifications and mutations of several such enzymes have been linked to cancer.", "We propose that some of these mutations may alter the methylation not only of histones but also of NF-\u03baB, making them attractive therapeutic targets."], "title": "NF-\u03baB: Regulation by Methylation."}
{"paper_id": 23931703, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The objective of this study was to investigate the relationship between the concentrations of 19 amino acids, glucose, and seven carboxylic acids in the blood and milk of dairy cows and their correlations with established markers of ketosis. To that end, blood plasma and milk specimens were collected throughout lactation in two breeds of dairy cows of different milk yield. Plasma concentrations of glucose, pyruvate, lactate, \u03b1-aminobutyrate, \u03b2-hydroxybutyrate (BHBA), and most amino acids, except for glutamate and aspartate, were on average 9.9-fold higher than their respective milk levels. In contrast, glutamate, aspartate, and the Krebs cycle intermediates succinate, fumarate, malate, and citrate were on average 9.1-fold higher in milk than in plasma. For most metabolites, with the exception of BHBA and threonine, no significant correlations were observed between their levels in plasma and milk. Additionally, milk levels of acetone showed significant direct relationships with the glycine-to-alanine ratio and the BHBA concentration in plasma. The marked decline in plasma concentrations of glucose, pyruvate, lactate, and alanine in cows with plasma BHBA levels above the diagnostic cutoff point for subclinical ketosis suggests that these animals fail to meet their glucose demand and, as a consequence, rely increasingly on ketone bodies as a source of energy. The concomitant increase in plasma glycine may reflect not only the excessive depletion of protein reserves but also a potential deficiency of vitamin B6.", "journal": "Journal of proteome research", "sentences": ["The objective of this study was to investigate the relationship between the concentrations of 19 amino acids, glucose, and seven carboxylic acids in the blood and milk of dairy cows and their correlations with established markers of ketosis.", "To that end, blood plasma and milk specimens were collected throughout lactation in two breeds of dairy cows of different milk yield.", "Plasma concentrations of glucose, pyruvate, lactate, \u03b1-aminobutyrate, \u03b2-hydroxybutyrate (BHBA), and most amino acids, except for glutamate and aspartate, were on average 9.9-fold higher than their respective milk levels.", "In contrast, glutamate, aspartate, and the Krebs cycle intermediates succinate, fumarate, malate, and citrate were on average 9.1-fold higher in milk than in plasma.", "For most metabolites, with the exception of BHBA and threonine, no significant correlations were observed between their levels in plasma and milk.", "Additionally, milk levels of acetone showed significant direct relationships with the glycine-to-alanine ratio and the BHBA concentration in plasma.", "The marked decline in plasma concentrations of glucose, pyruvate, lactate, and alanine in cows with plasma BHBA levels above the diagnostic cutoff point for subclinical ketosis suggests that these animals fail to meet their glucose demand and, as a consequence, rely increasingly on ketone bodies as a source of energy.", "The concomitant increase in plasma glycine may reflect not only the excessive depletion of protein reserves but also a potential deficiency of vitamin B6."], "title": "Correlations between milk and plasma levels of amino and carboxylic acids in dairy cows."}
{"paper_id": 21037092, "labels": ["0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "There are >2 million new cases of leishmaniasis annually, and no effective vaccine has been developed to prevent infection. In murine infection, Leishmania mexicana, which lives intracellularly in host macrophages, has developed pathways to hijack host IgG to induce a suppressive IL-10 response through Fc\u03b3Rs, the cell-surface receptors for IgG. To guide vaccine development away from detrimental Ab responses, which can accompany attempts to induce cell-mediated immunity, it is crucial to know which isotypes of IgG are pathogenic in this infection. We found that IgG1 and IgG2a/c induce IL-10 from macrophages in vitro equally well but through different Fc\u03b3R subtypes: IgG1 through Fc\u03b3RIII and IgG2a/c through Fc\u03b3RI primarily, but also through Fc\u03b3RIII. In sharp contrast, mice lacking IgG1 develop earlier and stronger IgG2a/c, IgG3, and IgM responses to L. mexicana infection and yet are more resistant to the infection. Thus, IgG1, but not IgG2a/c or IgG3, is pathogenic in vivo, in agreement with prior studies indicating that Fc\u03b3RIII is required for chronic disease. This calls into question the assumption that macrophages, which should secrete IL-10 in response to IgG1 and IgG2a/c immune complexes, are the most important source of IL-10 generated by IgG-Fc\u03b3R engagement in L. mexicana infection. Further investigations are required to better determine the cell type responsible for this immunosuppressive Fc\u03b3RIII-induced IL-10 pathway and whether IgG2a/c is protective.", "journal": "Journal of immunology (Baltimore, Md. : 1950)", "sentences": ["There are >2 million new cases of leishmaniasis annually, and no effective vaccine has been developed to prevent infection.", "In murine infection, Leishmania mexicana, which lives intracellularly in host macrophages, has developed pathways to hijack host IgG to induce a suppressive IL-10 response through Fc\u03b3Rs, the cell-surface receptors for IgG.", "To guide vaccine development away from detrimental Ab responses, which can accompany attempts to induce cell-mediated immunity, it is crucial to know which isotypes of IgG are pathogenic in this infection.", "We found that IgG1 and IgG2a/c induce IL-10 from macrophages in vitro equally well but through different Fc\u03b3R subtypes: IgG1 through Fc\u03b3RIII and IgG2a/c through Fc\u03b3RI primarily, but also through Fc\u03b3RIII.", "In sharp contrast, mice lacking IgG1 develop earlier and stronger IgG2a/c, IgG3, and IgM responses to L. mexicana infection and yet are more resistant to the infection.", "Thus, IgG1, but not IgG2a/c or IgG3, is pathogenic in vivo, in agreement with prior studies indicating that Fc\u03b3RIII is required for chronic disease.", "This calls into question the assumption that macrophages, which should secrete IL-10 in response to IgG1 and IgG2a/c immune complexes, are the most important source of IL-10 generated by IgG-Fc\u03b3R engagement in L. mexicana infection.", "Further investigations are required to better determine the cell type responsible for this immunosuppressive Fc\u03b3RIII-induced IL-10 pathway and whether IgG2a/c is protective."], "title": "IgG1 is pathogenic in Leishmania mexicana infection."}
{"paper_id": 25490093, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Osteosarcoma (OS) is the most common primary malignant bone tumor and prevalently occurs in the second decade of life. Etoposide, a chemotherapeutic agent used in combined treatments of recurrent human OS, belongs to the topoisomerase inhibitor family and causes DNA breakage. In this study we evaluated the cascade of events determined by etoposide-induced DNA damage in OS cell lines with different p53 status focusing on methylation status and expression of miR-34a that modulate tumor cell growth and cell cycle progression. Wild-type p53 U2-OS cells and U2-OS cells expressing dominant-negative form of p53 (U2- OS175) were more sensitive to etoposide than p53-deficient MG63 and Saos-2 cells, showing increased levels of unmethylated miR-34a, reduced expression of CDK4 and cell cycle arrest in G1 phase. In contrast, MG63 and Saos-2 cell lines presented aberrant methylation of miR-34a promoter gene with no miR-34a induction after etoposide treatment, underlining the close connection between p53 expression and miR-34a methylation status. Consistently, in p53siRNA transfected U2-OS cells we observed loss of miR-34a induction after etoposide exposure associated with a partial gain of gene methylation and cell cycle progress towards G2/M phase. Our results suggest that the open and unmethylated conformation of the miR-34a gene may be regulated by p53 able to bind the gene promoter. In conclusion, cell response to etoposide-induced DNA damage was not compromised in cells with dominant-negative p53 expression.", "journal": "PloS one", "sentences": ["Osteosarcoma (OS) is the most common primary malignant bone tumor and prevalently occurs in the second decade of life.", "Etoposide, a chemotherapeutic agent used in combined treatments of recurrent human OS, belongs to the topoisomerase inhibitor family and causes DNA breakage.", "In this study we evaluated the cascade of events determined by etoposide-induced DNA damage in OS cell lines with different p53 status focusing on methylation status and expression of miR-34a that modulate tumor cell growth and cell cycle progression.", "Wild-type p53 U2-OS cells and U2-OS cells expressing dominant-negative form of p53 (U2- OS175) were more sensitive to etoposide than p53-deficient MG63 and Saos-2 cells, showing increased levels of unmethylated miR-34a, reduced expression of CDK4 and cell cycle arrest in G1 phase.", "In contrast, MG63 and Saos-2 cell lines presented aberrant methylation of miR-34a promoter gene with no miR-34a induction after etoposide treatment, underlining the close connection between p53 expression and miR-34a methylation status.", "Consistently, in p53siRNA transfected U2-OS cells we observed loss of miR-34a induction after etoposide exposure associated with a partial gain of gene methylation and cell cycle progress towards G2/M phase.", "Our results suggest that the open and unmethylated conformation of the miR-34a gene may be regulated by p53 able to bind the gene promoter.", "In conclusion, cell response to etoposide-induced DNA damage was not compromised in cells with dominant-negative p53 expression."], "title": "p53-dependent activation of microRNA-34a in response to etoposide-induced DNA damage in osteosarcoma cell lines not impaired by dominant negative p53 expression."}
{"paper_id": 26120817, "labels": ["0", "0", "0", "0", "0", "1", "0"], "abstract": "A high sensitive label-free electrochemiluminescence (ECL) immunosensor was fabricated for the detection of prostate specific antigen (PSA) based on potassium niobate-Au nanoparticles@bismuth sulfide (KNbO3-Au NPs@Bi2S3) modified glassy carbon electrode (GCE). The prepared Bi2S3 nanosheets exhibited strong and stable cathodic ECL activity. The synthesized KNbO3-Au NPs was firstly used to fabricate ECL modified electrodes and Bi2S3 nanosheets worked as luminophores for the first time in ECL sensors. Au NPs were used to combine with Bi2S3 and anti-PSA via the Au-S covalent bond and Au-NH2 covalent bond without the usage of crosslinking agents respectively, further enhancing the sensitivity and stability of immunosensor. Under the optimum experimental conditions, the ECL signal of KNbO3-Au NPs@Bi2S3 linearly decreased with the increase of PSA concentration in the range of 0.005-5 ng/mL with a detection limit of 3 pg/mL. The preparated label-free ECL immunosensor exhibited high sensitivity and selectivity, good repeatability and long-term stability. The applicability of the proposed ECL immunosensor was also evaluated by detecting PSA in real samples.", "journal": "Biosensors & bioelectronics", "sentences": ["A high sensitive label-free electrochemiluminescence (ECL) immunosensor was fabricated for the detection of prostate specific antigen (PSA) based on potassium niobate-Au nanoparticles@bismuth sulfide (KNbO3-Au NPs@Bi2S3) modified glassy carbon electrode (GCE).", "The prepared Bi2S3 nanosheets exhibited strong and stable cathodic ECL activity.", "The synthesized KNbO3-Au NPs was firstly used to fabricate ECL modified electrodes and Bi2S3 nanosheets worked as luminophores for the first time in ECL sensors.", "Au NPs were used to combine with Bi2S3 and anti-PSA via the Au-S covalent bond and Au-NH2 covalent bond without the usage of crosslinking agents respectively, further enhancing the sensitivity and stability of immunosensor.", "Under the optimum experimental conditions, the ECL signal of KNbO3-Au NPs@Bi2S3 linearly decreased with the increase of PSA concentration in the range of 0.005-5 ng/mL with a detection limit of 3 pg/mL.", "The preparated label-free ECL immunosensor exhibited high sensitivity and selectivity, good repeatability and long-term stability.", "The applicability of the proposed ECL immunosensor was also evaluated by detecting PSA in real samples."], "title": "A label-free electrochemiluminescence immunosensor based on KNbO3-Au nanoparticles@Bi2S3 for the detection of prostate specific antigen."}
{"paper_id": 23151418, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The World Health Organization's (WHO) recommendation on the need for further research for radio-frequency dosimetry has promoted studies on the whole-body average-specific absorption rate (WBA-SAR) in various kinds of anatomical-based numerical models. For experimental validation of GHz-band WBA-SARs in a real human, however, there have not so far been any published papers, despite the fact that, in 1982, Hill measured WBA-SARs at frequencies less than 40\u00a0MHz in human volunteers using a TEM-cell exposure system. In this study, we provide a measurement technique with a reverberation chamber for validating numerical dosimetry results on GHz-band WBA-SARs in living humans. We measured WBA-SARs at 1, 1.5 and 2\u00a0GHz for a 22\u00a0year old male volunteer, with a height of 173\u00a0cm and a weight of 73\u00a0kg, in the reverberation chamber, and compared the results with the finite-difference time-domain (FDTD) simulation. The reverberation chamber was excited by using a signal generator through an amplifier with an output power of 30-40 mW, which produced inside the chamber with the volunteer an average electric field strength of 5\u00a0V m(-1) equivalent to an average power spectral density of 6.6 \u03bcW cm(-2). The WBA-SARs were obtained from the measured S(11) and S(21) together with the power density. On the other hand, the WBA-SARs have been calculated using the FDTD method for an adult male model with almost the same physique as that of the volunteer exposed to the electromagnetic field in the reverberation chamber. From the comparison between the measured and the calculated WBA-SARs, we could confirm that the measured GHz-band WBA-SARs approximately agree with the FDTD calculated results.", "journal": "Physics in medicine and biology", "sentences": ["The World Health Organization's (WHO) recommendation on the need for further research for radio-frequency dosimetry has promoted studies on the whole-body average-specific absorption rate (WBA-SAR) in various kinds of anatomical-based numerical models.", "For experimental validation of GHz-band WBA-SARs in a real human, however, there have not so far been any published papers, despite the fact that, in 1982, Hill measured WBA-SARs at frequencies less than 40\u00a0MHz in human volunteers using a TEM-cell exposure system.", "In this study, we provide a measurement technique with a reverberation chamber for validating numerical dosimetry results on GHz-band WBA-SARs in living humans.", "We measured WBA-SARs at 1, 1.5 and 2\u00a0GHz for a 22\u00a0year old male volunteer, with a height of 173\u00a0cm and a weight of 73\u00a0kg, in the reverberation chamber, and compared the results with the finite-difference time-domain (FDTD) simulation.", "The reverberation chamber was excited by using a signal generator through an amplifier with an output power of 30-40 mW, which produced inside the chamber with the volunteer an average electric field strength of 5\u00a0V m(-1) equivalent to an average power spectral density of 6.6 \u03bcW cm(-2).", "The WBA-SARs were obtained from the measured S(11) and S(21) together with the power density.", "On the other hand, the WBA-SARs have been calculated using the FDTD method for an adult male model with almost the same physique as that of the volunteer exposed to the electromagnetic field in the reverberation chamber.", "From the comparison between the measured and the calculated WBA-SARs, we could confirm that the measured GHz-band WBA-SARs approximately agree with the FDTD calculated results."], "title": "Measurement and validation of GHz-band whole-body average SAR in a human volunteer using reverberation chamber."}
{"paper_id": 20566891, "labels": ["0", "0", "0", "0", "1"], "abstract": "To limit mean global warming to 2 degrees C, a goal supported by more than 100 countries, it will likely be necessary to reduce emissions not only of greenhouse gases but also of air pollutants with high radiative forcing (RF), particularly black carbon (BC). Although several recent research papers have attempted to quantify the effects of BC on climate, not all these analyses have incorporated all the mechanisms that contribute to its RF (including the effects of BC on cloud albedo, cloud coverage, and snow and ice albedo, and the optical consequences of aerosol mixing) and have reported their results in different units and with different ranges of uncertainty. Here we attempt to reconcile their results and present them in uniform units that include the same forcing factors. We use the best estimate of effective RF obtained from these results to analyze the benefits of mitigating BC emissions for achieving a specific equilibrium temperature target. For a 500 ppm CO(2)e (3.1 W m(-2)) effective RF target in 2100, which would offer about a 50% chance of limiting equilibrium warming to 2.5 degrees C above preindustrial temperatures, we estimate that failing to reduce carbonaceous aerosol emissions from contained combustion would require CO(2) emission cuts about 8 years (range of 1-15 years) earlier than would be necessary with full mitigation of these emissions.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["To limit mean global warming to 2 degrees C, a goal supported by more than 100 countries, it will likely be necessary to reduce emissions not only of greenhouse gases but also of air pollutants with high radiative forcing (RF), particularly black carbon (BC).", "Although several recent research papers have attempted to quantify the effects of BC on climate, not all these analyses have incorporated all the mechanisms that contribute to its RF (including the effects of BC on cloud albedo, cloud coverage, and snow and ice albedo, and the optical consequences of aerosol mixing) and have reported their results in different units and with different ranges of uncertainty.", "Here we attempt to reconcile their results and present them in uniform units that include the same forcing factors.", "We use the best estimate of effective RF obtained from these results to analyze the benefits of mitigating BC emissions for achieving a specific equilibrium temperature target.", "For a 500 ppm CO(2)e (3.1 W m(-2)) effective RF target in 2100, which would offer about a 50% chance of limiting equilibrium warming to 2.5 degrees C above preindustrial temperatures, we estimate that failing to reduce carbonaceous aerosol emissions from contained combustion would require CO(2) emission cuts about 8 years (range of 1-15 years) earlier than would be necessary with full mitigation of these emissions."], "title": "Assessing the climatic benefits of black carbon mitigation."}
{"paper_id": 23285265, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Increased renal clearance of thiamine (vitamin B(1)) occurs in experimental and clinical diabetes producing thiamine insufficiency mediated by impaired tubular re-uptake and linked to the development of diabetic nephropathy. We studied the mechanism of impaired renal re-uptake of thiamine in diabetes. Expression of thiamine transporter proteins THTR-1 and THTR-2 in normal human kidney sections examined by immunohistochemistry showed intense polarised staining of the apical, luminal membranes in proximal tubules for THTR-1 and THTR-2 of the cortex and uniform, diffuse staining throughout cells of the collecting duct for THTR-1 and THTR-2 of the medulla. Human primary proximal tubule epithelial cells were incubated with low and high glucose concentration, 5 and 26 mmol/l, respectively. In high glucose concentration there was decreased expression of THTR-1 and THTR-2 (transporter mRNA: -76% and -53% respectively, p<0.001; transporter protein -77% and -83% respectively, p<0.05), concomitant with decreased expression of transcription factor specificity protein-1. High glucose concentration also produced a 37% decrease in apical to basolateral transport of thiamine transport across cell monolayers. Intensification of glycemic control corrected increased fractional excretion of thiamine in experimental diabetes. We conclude that glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. This is a novel mechanism of thiamine insufficiency linked to diabetic nephropathy.", "journal": "PloS one", "sentences": ["Increased renal clearance of thiamine (vitamin B(1)) occurs in experimental and clinical diabetes producing thiamine insufficiency mediated by impaired tubular re-uptake and linked to the development of diabetic nephropathy.", "We studied the mechanism of impaired renal re-uptake of thiamine in diabetes.", "Expression of thiamine transporter proteins THTR-1 and THTR-2 in normal human kidney sections examined by immunohistochemistry showed intense polarised staining of the apical, luminal membranes in proximal tubules for THTR-1 and THTR-2 of the cortex and uniform, diffuse staining throughout cells of the collecting duct for THTR-1 and THTR-2 of the medulla.", "Human primary proximal tubule epithelial cells were incubated with low and high glucose concentration, 5 and 26 mmol/l, respectively.", "In high glucose concentration there was decreased expression of THTR-1 and THTR-2 (transporter mRNA: -76% and -53% respectively, p<0.001; transporter protein -77% and -83% respectively, p<0.05), concomitant with decreased expression of transcription factor specificity protein-1.", "High glucose concentration also produced a 37% decrease in apical to basolateral transport of thiamine transport across cell monolayers.", "Intensification of glycemic control corrected increased fractional excretion of thiamine in experimental diabetes.", "We conclude that glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes.", "This is a novel mechanism of thiamine insufficiency linked to diabetic nephropathy."], "title": "Glucose-induced down regulation of thiamine transporters in the kidney proximal tubular epithelium produces thiamine insufficiency in diabetes."}
{"paper_id": 23524965, "labels": ["0", "1", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Patients with cholestatic disease exhibit pruritus and analgesia, but the mechanisms underlying these symptoms are unknown. We report that bile acids, which are elevated in the circulation and tissues during cholestasis, cause itch and analgesia by activating the GPCR TGR5. TGR5 was detected in peptidergic neurons of mouse dorsal root ganglia and spinal cord that transmit itch and pain, and in dermal macrophages that contain opioids. Bile acids and a TGR5-selective agonist induced hyperexcitability of dorsal root ganglia neurons and stimulated the release of the itch and analgesia transmitters gastrin-releasing peptide and leucine-enkephalin. Intradermal injection of bile acids and a TGR5-selective agonist stimulated scratching behavior by gastrin-releasing peptide- and opioid-dependent mechanisms in mice. Scratching was attenuated in Tgr5-KO mice but exacerbated in Tgr5-Tg mice (overexpressing mouse TGR5), which exhibited spontaneous pruritus. Intraplantar and intrathecal injection of bile acids caused analgesia to mechanical stimulation of the paw by an opioid-dependent mechanism. Both peripheral and central mechanisms of analgesia were absent from Tgr5-KO mice. Thus, bile acids activate TGR5 on sensory nerves, stimulating the release of neuropeptides in the spinal cord that transmit itch and analgesia. These mechanisms could contribute to pruritus and painless jaundice that occur during cholestatic liver diseases.", "journal": "The Journal of clinical investigation", "sentences": ["Patients with cholestatic disease exhibit pruritus and analgesia, but the mechanisms underlying these symptoms are unknown.", "We report that bile acids, which are elevated in the circulation and tissues during cholestasis, cause itch and analgesia by activating the GPCR TGR5.", "TGR5 was detected in peptidergic neurons of mouse dorsal root ganglia and spinal cord that transmit itch and pain, and in dermal macrophages that contain opioids.", "Bile acids and a TGR5-selective agonist induced hyperexcitability of dorsal root ganglia neurons and stimulated the release of the itch and analgesia transmitters gastrin-releasing peptide and leucine-enkephalin.", "Intradermal injection of bile acids and a TGR5-selective agonist stimulated scratching behavior by gastrin-releasing peptide- and opioid-dependent mechanisms in mice.", "Scratching was attenuated in Tgr5-KO mice but exacerbated in Tgr5-Tg mice (overexpressing mouse TGR5), which exhibited spontaneous pruritus.", "Intraplantar and intrathecal injection of bile acids caused analgesia to mechanical stimulation of the paw by an opioid-dependent mechanism.", "Both peripheral and central mechanisms of analgesia were absent from Tgr5-KO mice.", "Thus, bile acids activate TGR5 on sensory nerves, stimulating the release of neuropeptides in the spinal cord that transmit itch and analgesia.", "These mechanisms could contribute to pruritus and painless jaundice that occur during cholestatic liver diseases."], "title": "The TGR5 receptor mediates bile acid-induced itch and analgesia."}
{"paper_id": 22905562, "labels": ["0", "0", "0", "0", "1"], "abstract": "In this work, simulations of magnetic properties of nanocomposites formed by magnetic nanoparticles embedded in a non magnetic matrix are presented. These simulations were carried by means of the Monte Carlo Method and Heisenberg model. Properties as magnetization and Hysteresis loops were obtained varying different parameters as the nanoparticle size, distance between nanoparticles and temperature. The model employed includes interaction between ions belonging to each nanoparticle and also the interaction between nanoparticles. Results show that the magnetization and the coercive force decrease as a function of the nanoparticles distance.", "journal": "Journal of nanoscience and nanotechnology", "sentences": ["In this work, simulations of magnetic properties of nanocomposites formed by magnetic nanoparticles embedded in a non magnetic matrix are presented.", "These simulations were carried by means of the Monte Carlo Method and Heisenberg model.", "Properties as magnetization and Hysteresis loops were obtained varying different parameters as the nanoparticle size, distance between nanoparticles and temperature.", "The model employed includes interaction between ions belonging to each nanoparticle and also the interaction between nanoparticles.", "Results show that the magnetization and the coercive force decrease as a function of the nanoparticles distance."], "title": "Magnetic properties of nanocomposites formed by magnetic nanoparticles embedded in a non-magnetic matrix: a simulation approach."}
{"paper_id": 25281606, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Although fludarabine, cyclophosphamide, and rituximab (FCR) together are established as a standard first-line treatment of younger patients with chronic lymphocytic leukemia (CLL), there is little information to guide the management of patients with CLL refractory to, or who have relapsed after, receiving frontline FCR treatment. To define optimal salvage strategy and identify patients unsuitable for retreatment with FCR, we examined the survival and treatment outcome of 300 patients enrolled in a phase 2 study of FCR. After a median 142 months of follow-up, 156 patients developed progressive CLL, with a median survival of 51 months after disease progression. The duration of first remission (REM1) was a key determinant of survival after disease progression and first salvage. Patients with a short REM1 (<3 years) had a short survival period, irrespective of salvage therapy received; these patients have high unmet medical needs and are good candidates for investigation of novel therapies. In patients with a long REM1 (\u22653 years), salvage treatment with either repeat FCR or lenalidomide-based therapy results in subsequent median survival exceeding 5 years; for these patients, FCR rechallenge represents a reasonable standard of care.", "journal": "Blood", "sentences": ["Although fludarabine, cyclophosphamide, and rituximab (FCR) together are established as a standard first-line treatment of younger patients with chronic lymphocytic leukemia (CLL), there is little information to guide the management of patients with CLL refractory to, or who have relapsed after, receiving frontline FCR treatment.", "To define optimal salvage strategy and identify patients unsuitable for retreatment with FCR, we examined the survival and treatment outcome of 300 patients enrolled in a phase 2 study of FCR.", "After a median 142 months of follow-up, 156 patients developed progressive CLL, with a median survival of 51 months after disease progression.", "The duration of first remission (REM1) was a key determinant of survival after disease progression and first salvage.", "Patients with a short REM1 (<3 years) had a short survival period, irrespective of salvage therapy received; these patients have high unmet medical needs and are good candidates for investigation of novel therapies.", "In patients with a long REM1 (\u22653 years), salvage treatment with either repeat FCR or lenalidomide-based therapy results in subsequent median survival exceeding 5 years; for these patients, FCR rechallenge represents a reasonable standard of care."], "title": "Long-term results of first salvage treatment in CLL patients treated initially with FCR (fludarabine, cyclophosphamide, rituximab)."}
{"paper_id": 24797331, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Selection of a model organism creates tension between competing constraints. The recent explosion of modern molecular techniques has revolutionized the analysis of neural systems in organisms that are amenable to genetic techniques. Yet, the non-human primate remains the gold-standard for the analysis of the neural basis of behavior, and as a bridge to the operation of the human brain. The challenge is to generalize across species in a way that exposes the operation of circuits as well as the relationship of circuits to behavior. Eye movements provide an opportunity to cross the bridge from mechanism to behavior through research on diverse species. Here, we review experiments and computational studies on a circuit function called \"neural integration\" that occurs in the brainstems of larval zebrafish, primates, and species \"in between\". We show that analysis of circuit structure using modern molecular and imaging approaches in zebrafish has remarkable explanatory power for details of the responses of integrator neurons in the monkey. The combination of research from the two species has led to a much stronger hypothesis for the implementation of the neural integrator than could have been achieved using either species alone.", "journal": "Neuroscience", "sentences": ["Selection of a model organism creates tension between competing constraints.", "The recent explosion of modern molecular techniques has revolutionized the analysis of neural systems in organisms that are amenable to genetic techniques.", "Yet, the non-human primate remains the gold-standard for the analysis of the neural basis of behavior, and as a bridge to the operation of the human brain.", "The challenge is to generalize across species in a way that exposes the operation of circuits as well as the relationship of circuits to behavior.", "Eye movements provide an opportunity to cross the bridge from mechanism to behavior through research on diverse species.", "Here, we review experiments and computational studies on a circuit function called \"neural integration\" that occurs in the brainstems of larval zebrafish, primates, and species \"in between\".", "We show that analysis of circuit structure using modern molecular and imaging approaches in zebrafish has remarkable explanatory power for details of the responses of integrator neurons in the monkey.", "The combination of research from the two species has led to a much stronger hypothesis for the implementation of the neural integrator than could have been achieved using either species alone."], "title": "A tale of two species: Neural integration in zebrafish and monkeys."}
{"paper_id": 25902435, "labels": ["0", "0", "1", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Solid-state NMR has been used to determine the structures of membrane proteins in native-like lipid bilayer environments. Most structure calculations based on solid-state NMR observables are performed using simulated annealing with restrained molecular dynamics and an energy function, where all nonbonded interactions are represented by a single, purely repulsive term with no contributions from van der Waals attractive, electrostatic, or solvation energy. To our knowledge, this is the first application of an ensemble dynamics technique performed in explicit membranes that uses experimental solid-state NMR observables to obtain the refined structure of a membrane protein together with information about its dynamics and its interactions with lipids. Using the membrane-bound form of the fd coat protein as a model membrane protein and its experimental solid-state NMR data, we performed restrained ensemble dynamics simulations with different ensemble sizes in explicit membranes. For comparison, a molecular dynamics simulation of fd coat protein was also performed without any restraints. The average orientation of each protein helix is similar to a structure determined by traditional single-conformer approaches. However, their variations are limited in the resulting ensemble of structures with one or two replicas, as they are under the strong influence of solid-state NMR restraints. Although highly consistent with all solid-state NMR observables, the ensembles of more than two replicas show larger orientational variations similar to those observed in the molecular dynamics simulation without restraints. In particular, in these explicit membrane simulations, Lys(40), residing at the C-terminal side of the\u00a0transmembrane helix, is observed to cause local membrane curvature. Therefore, compared to traditional single-conformer approaches in implicit environments, solid-state NMR restrained ensemble simulations in explicit membranes readily characterize not only protein dynamics but also protein-lipid interactions in detail.", "journal": "Biophysical journal", "sentences": ["Solid-state NMR has been used to determine the structures of membrane proteins in native-like lipid bilayer environments.", "Most structure calculations based on solid-state NMR observables are performed using simulated annealing with restrained molecular dynamics and an energy function, where all nonbonded interactions are represented by a single, purely repulsive term with no contributions from van der Waals attractive, electrostatic, or solvation energy.", "To our knowledge, this is the first application of an ensemble dynamics technique performed in explicit membranes that uses experimental solid-state NMR observables to obtain the refined structure of a membrane protein together with information about its dynamics and its interactions with lipids.", "Using the membrane-bound form of the fd coat protein as a model membrane protein and its experimental solid-state NMR data, we performed restrained ensemble dynamics simulations with different ensemble sizes in explicit membranes.", "For comparison, a molecular dynamics simulation of fd coat protein was also performed without any restraints.", "The average orientation of each protein helix is similar to a structure determined by traditional single-conformer approaches.", "However, their variations are limited in the resulting ensemble of structures with one or two replicas, as they are under the strong influence of solid-state NMR restraints.", "Although highly consistent with all solid-state NMR observables, the ensembles of more than two replicas show larger orientational variations similar to those observed in the molecular dynamics simulation without restraints.", "In particular, in these explicit membrane simulations, Lys(40), residing at the C-terminal side of the\u00a0transmembrane helix, is observed to cause local membrane curvature.", "Therefore, compared to traditional single-conformer approaches in implicit environments, solid-state NMR restrained ensemble simulations in explicit membranes readily characterize not only protein dynamics but also protein-lipid interactions in detail."], "title": "Solid-State NMR-Restrained Ensemble Dynamics of a Membrane Protein in Explicit Membranes."}
{"paper_id": 26478351, "labels": ["0", "0", "0", "0", "0"], "abstract": "The collagen/chitosan/hydroxyapatite (COL/CS/HA) composite microspheres with a good spherical form and a high dispersity were successfully obtained using an in-situ synthesis method. The FT-IR and XRD results revealed that the inorganic phase in the microspheres was crystalline HA containing carbonate ions. The morphology of the composite microspheres was dependent on the HA content, and a more desirable morphology was achieved when 20 wt.% HA was contained. The composite microspheres exhibited a narrow particle distribution, most of which ranged from 5 to 10 \u03bcm. In addition, the needle-like HA nano-particles were uniformly distributed in the composite microspheres, and their crystallinity and crystal size decreased with the HA content.", "journal": "Materials science & engineering. C, Materials for biological applications", "sentences": ["The collagen/chitosan/hydroxyapatite (COL/CS/HA) composite microspheres with a good spherical form and a high dispersity were successfully obtained using an in-situ synthesis method.", "The FT-IR and XRD results revealed that the inorganic phase in the microspheres was crystalline HA containing carbonate ions.", "The morphology of the composite microspheres was dependent on the HA content, and a more desirable morphology was achieved when 20 wt.% HA was contained.", "The composite microspheres exhibited a narrow particle distribution, most of which ranged from 5 to 10 \u03bcm.", "In addition, the needle-like HA nano-particles were uniformly distributed in the composite microspheres, and their crystallinity and crystal size decreased with the HA content."], "title": "Biomimetic composite microspheres of collagen/chitosan/nano-hydroxyapatite: In-situ synthesis and characterization."}
{"paper_id": 27002116, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Neutrophils are polymorphonuclear leukocytes of the phagocytic system that act as first line of host defense against invading pathogens but are also important mediators of inflammation-induced injury. In contrast to other members of the innate immune system, neutrophils are classically considered a homogenous population of terminally differentiated cells with a well-defined and highly conserved function. Indeed, their short lifespan, the absent proliferative capacity, their limited ability to produce large amounts of cytokines, and the failure to recirculate from the tissue to the bloodstream have sustained this idea. However, increasing evidence over the last decade has demonstrated an unexpected phenotypic heterogeneity and functional versatility of the neutrophil population. Far beyond their antimicrobial functions, neutrophils are emerging as decision-shapers during innate and adaptive immune responses. These emerging discoveries open a new door to understand the role of neutrophils during homeostatic but also pathogenic immune processes. Thus, this review details novel insights of neutrophil phenotypic and functional heterogeneity during homeostasis and disease.", "journal": "Blood", "sentences": ["Neutrophils are polymorphonuclear leukocytes of the phagocytic system that act as first line of host defense against invading pathogens but are also important mediators of inflammation-induced injury.", "In contrast to other members of the innate immune system, neutrophils are classically considered a homogenous population of terminally differentiated cells with a well-defined and highly conserved function.", "Indeed, their short lifespan, the absent proliferative capacity, their limited ability to produce large amounts of cytokines, and the failure to recirculate from the tissue to the bloodstream have sustained this idea.", "However, increasing evidence over the last decade has demonstrated an unexpected phenotypic heterogeneity and functional versatility of the neutrophil population.", "Far beyond their antimicrobial functions, neutrophils are emerging as decision-shapers during innate and adaptive immune responses.", "These emerging discoveries open a new door to understand the role of neutrophils during homeostatic but also pathogenic immune processes.", "Thus, this review details novel insights of neutrophil phenotypic and functional heterogeneity during homeostasis and disease."], "title": "Neutrophil heterogeneity: implications for homeostasis and pathogenesis."}
{"paper_id": 21346217, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "To examine the neural correlates of contextually differing control mechanisms in saccade initiation, we studied 18 subjects who performed two saccade paradigms in a pseudo-random order, while their eye movements were recorded in the MRI scanner (1.5 T). In the gap task the fixation point was extinguished 200 ms before target onset, and in the overlap task the fixation point vanished 500 ms after target onset. Subjects were asked to maintain stable fixation in the fixation period and to quickly saccade to peripherally presented targets. Inter-individual activation differences were assessed using regression analyses at the second level, with mean saccadic reaction time (SRT) of subjects as a covariate. To identify brain regions varying with trial-by-trial changes in SRTs, we included SRTs as a parametric modulation regressor in the general linear model. All analyses were regions of interest based and were performed separately for the gap and overlap conditions. For the gap paradigm, we did not obtain activation in regions previously shown to be involved in preparatory processes with much longer gap periods. Interestingly, both inter- and intra-individual variability analyses revealed a positive correlation of activation in frontal and parietal eye-movement regions with SRTs, indicating that slower saccade performance is possibly associated with higher cortical control. For the overlap paradigm, the trial-by-trial variability analysis revealed a positive correlation of activation in the right opercular inferior frontal gyrus with SRTs, possibly linked to fixation-related processes that have to be overcome to perform a speeded saccade in presence of a fixation point.", "journal": "Journal of neurophysiology", "sentences": ["To examine the neural correlates of contextually differing control mechanisms in saccade initiation, we studied 18 subjects who performed two saccade paradigms in a pseudo-random order, while their eye movements were recorded in the MRI scanner (1.5 T).", "In the gap task the fixation point was extinguished 200 ms before target onset, and in the overlap task the fixation point vanished 500 ms after target onset.", "Subjects were asked to maintain stable fixation in the fixation period and to quickly saccade to peripherally presented targets.", "Inter-individual activation differences were assessed using regression analyses at the second level, with mean saccadic reaction time (SRT) of subjects as a covariate.", "To identify brain regions varying with trial-by-trial changes in SRTs, we included SRTs as a parametric modulation regressor in the general linear model.", "All analyses were regions of interest based and were performed separately for the gap and overlap conditions.", "For the gap paradigm, we did not obtain activation in regions previously shown to be involved in preparatory processes with much longer gap periods.", "Interestingly, both inter- and intra-individual variability analyses revealed a positive correlation of activation in frontal and parietal eye-movement regions with SRTs, indicating that slower saccade performance is possibly associated with higher cortical control.", "For the overlap paradigm, the trial-by-trial variability analysis revealed a positive correlation of activation in the right opercular inferior frontal gyrus with SRTs, possibly linked to fixation-related processes that have to be overcome to perform a speeded saccade in presence of a fixation point."], "title": "Neural correlates of inter- and intra-individual saccadic reaction time differences in the gap/overlap paradigm."}
{"paper_id": 26820304, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The ratio of early mitral inflow velocity (E) to the global diastolic strain rate (E'sr) has been correlated with left ventricular filling pressure and predicts adverse cardiac outcomes in atrial fibrillation (AF). The relationship between the E/E'sr ratio and renal outcomes in AF has not been evaluated. This study examined the ability of the E/E'sr ratio in predicting progression to the renal endpoint, which is defined as a \u2265 25% decline in the estimated glomerular filtration rate in patients with AF. Comprehensive echocardiography was performed on 149 patients with persistent AF, and E'sr was assessed from three standard apical views using the index beat method. During a median follow-up period of 2.3 years, 63 patients (42.3%) were reaching the renal endpoint. Multivariate analysis showed that an increased E/E'sr ratio (per 10 cm) (hazard ratio, 1.230; 95% confidence interval, 1.088 to 1.391; p = 0.001) was associated with an increased renal endpoint. In a direct comparison, the E/E'sr ratio outperformed the ratio of E to early diastolic mitral annular velocity (E') in predicting progression to the renal endpoint in both univariate and multivariate models (p \u2264 0.039). Moreover, adding the E/E'sr ratio to a clinical model and echocardiographic parameters provided an additional benefit in the prediction of progression to the renal endpoint (p = 0.006). The E/E'sr ratio is a useful parameter and is stronger than the E/E' ratio in predicting the progression to the renal endpoint, and it may offer an additional prognostic benefit over conventional clinical and echocardiographic parameters in patients with AF.", "journal": "PloS one", "sentences": ["The ratio of early mitral inflow velocity (E) to the global diastolic strain rate (E'sr) has been correlated with left ventricular filling pressure and predicts adverse cardiac outcomes in atrial fibrillation (AF).", "The relationship between the E/E'sr ratio and renal outcomes in AF has not been evaluated.", "This study examined the ability of the E/E'sr ratio in predicting progression to the renal endpoint, which is defined as a \u2265 25% decline in the estimated glomerular filtration rate in patients with AF.", "Comprehensive echocardiography was performed on 149 patients with persistent AF, and E'sr was assessed from three standard apical views using the index beat method.", "During a median follow-up period of 2.3 years, 63 patients (42.3%) were reaching the renal endpoint.", "Multivariate analysis showed that an increased E/E'sr ratio (per 10 cm) (hazard ratio, 1.230; 95% confidence interval, 1.088 to 1.391; p = 0.001) was associated with an increased renal endpoint.", "In a direct comparison, the E/E'sr ratio outperformed the ratio of E to early diastolic mitral annular velocity (E') in predicting progression to the renal endpoint in both univariate and multivariate models (p \u2264 0.039).", "Moreover, adding the E/E'sr ratio to a clinical model and echocardiographic parameters provided an additional benefit in the prediction of progression to the renal endpoint (p = 0.006).", "The E/E'sr ratio is a useful parameter and is stronger than the E/E' ratio in predicting the progression to the renal endpoint, and it may offer an additional prognostic benefit over conventional clinical and echocardiographic parameters in patients with AF."], "title": "Association of the Ratio of Early Mitral Inflow Velocity to the Global Diastolic Strain Rate with a Rapid Renal Function Decline in Atrial Fibrillation."}
{"paper_id": 24594602, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "RNA interference (RNAi) is a powerful approach for elucidating gene functions in a variety of organisms, including phytopathogenic fungi. In such fungi, RNAi has been induced by expressing hairpin RNAs delivered through plasmids, sequences integrated in fungal or plant genomes, or by RNAi generated in planta by a plant virus infection. All these approaches have some drawbacks ranging from instability of hairpin constructs in fungal cells to difficulties in preparing and handling transgenic plants to silence homologous sequences in fungi grown on these plants. Here we show that RNAi can be expressed in the phytopathogenic fungus Colletotrichum acutatum (strain C71) by virus-induced gene silencing (VIGS) without a plant intermediate, but by using the direct infection of a recombinant virus vector based on the plant virus, tobacco mosaic virus (TMV). We provide evidence that a wild-type isolate of TMV is able to enter C71 cells grown in liquid medium, replicate, and persist therein. With a similar approach, a recombinant TMV vector carrying a gene for the ectopic expression of the green fluorescent protein (GFP) induced the stable silencing of the GFP in the C. acutatum transformant line 10 expressing GFP derived from C71. The TMV-based vector also enabled C. acutatum to transiently express exogenous GFP up to six subcultures and for at least 2 mo after infection, without the need to develop transformation technology. With these characteristics, we anticipate this approach will find wider application as a tool in functional genomics of filamentous fungi.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["RNA interference (RNAi) is a powerful approach for elucidating gene functions in a variety of organisms, including phytopathogenic fungi.", "In such fungi, RNAi has been induced by expressing hairpin RNAs delivered through plasmids, sequences integrated in fungal or plant genomes, or by RNAi generated in planta by a plant virus infection.", "All these approaches have some drawbacks ranging from instability of hairpin constructs in fungal cells to difficulties in preparing and handling transgenic plants to silence homologous sequences in fungi grown on these plants.", "Here we show that RNAi can be expressed in the phytopathogenic fungus Colletotrichum acutatum (strain C71) by virus-induced gene silencing (VIGS) without a plant intermediate, but by using the direct infection of a recombinant virus vector based on the plant virus, tobacco mosaic virus (TMV).", "We provide evidence that a wild-type isolate of TMV is able to enter C71 cells grown in liquid medium, replicate, and persist therein.", "With a similar approach, a recombinant TMV vector carrying a gene for the ectopic expression of the green fluorescent protein (GFP) induced the stable silencing of the GFP in the C. acutatum transformant line 10 expressing GFP derived from C71.", "The TMV-based vector also enabled C. acutatum to transiently express exogenous GFP up to six subcultures and for at least 2 mo after infection, without the need to develop transformation technology.", "With these characteristics, we anticipate this approach will find wider application as a tool in functional genomics of filamentous fungi."], "title": "Gene silencing and gene expression in phytopathogenic fungi using a plant virus vector."}
{"paper_id": 26877608, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The link between cytomegalovirus (CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis (UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools (numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flare-ups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease.", "journal": "World journal of gastroenterology", "sentences": ["The link between cytomegalovirus (CMV) infection and inflammatory bowel diseases remains an important subject of debate.", "CMV infection is frequent in ulcerative colitis (UC) and has been shown to be potentially harmful.", "CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques.", "Determination of the density of infection using quantitative tools (numbers of infected cells or copies of the genome) is particularly important.", "Although CMV reactivation can be considered as an innocent bystander in active flare-ups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation.", "The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents.", "Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs.", "According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease."], "title": "Cytomegalovirus and ulcerative colitis: Place of antiviral therapy."}
{"paper_id": 21187465, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "In the search for agents with cancer chemopreventive potential, 14-chloromethyl-12H-5,11a-diazadibenzo[b,h]fluoren-11-one (compound 1), originally synthesized as a potential topoisomerase I inhibitor, and 2,4-dibromo-1-hydroxyphenazine (compound 2), an analog of a substance found in the marine bacteria Streptomyces CNS284, were found to significantly enhance NADP(H):quinone oxidoreductase 1 (QR1), glutathione S-transferase (GST), and glutathione (GSH) levels in cell culture. However, following a short-term absorption study, analyses of livers from the treatment groups did not reveal a significant increase in QR1 or GST activity, or GSH levels. This was consistent with RT-PCR analyses of tissue samples. The compounds were absorbed, as judged by LC/MS analyses of serum and tissue samples, although levels were well below the concentrations required to mediate in vitro responses. Metabolites of compound 2 formed in vitro by human liver microzones were characterized using high resolution tandem mass spectrometry. In sum, the in vivo activity of these compounds appears to be diminished by low bioavailability, but this experimental approach indicates the importance of systematic biomarker investigation.", "journal": "Anticancer research", "sentences": ["In the search for agents with cancer chemopreventive potential, 14-chloromethyl-12H-5,11a-diazadibenzo[b,h]fluoren-11-one (compound 1), originally synthesized as a potential topoisomerase I inhibitor, and 2,4-dibromo-1-hydroxyphenazine (compound 2), an analog of a substance found in the marine bacteria Streptomyces CNS284, were found to significantly enhance NADP(H):quinone oxidoreductase 1 (QR1), glutathione S-transferase (GST), and glutathione (GSH) levels in cell culture.", "However, following a short-term absorption study, analyses of livers from the treatment groups did not reveal a significant increase in QR1 or GST activity, or GSH levels.", "This was consistent with RT-PCR analyses of tissue samples.", "The compounds were absorbed, as judged by LC/MS analyses of serum and tissue samples, although levels were well below the concentrations required to mediate in vitro responses.", "Metabolites of compound 2 formed in vitro by human liver microzones were characterized using high resolution tandem mass spectrometry.", "In sum, the in vivo activity of these compounds appears to be diminished by low bioavailability, but this experimental approach indicates the importance of systematic biomarker investigation."], "title": "Cancer chemopreventive potential of aromathecins and phenazines, novel natural product derivatives."}
{"paper_id": 20453199, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Inositol phosphates (InsPs) are signaling molecules with multiple roles in cells. In particular (InsP(6)) is involved in mRNA export and editing or chromatin remodeling among other events. InsP(6) accumulates as mixed salts (phytate) in storage tissues of plants and plays a key role in their physiology. Human diets that are exclusively grain-based provide an excess of InsP(6) that, through chelation of metal ions, may have a detrimental effect on human health. Ins(1,3,4,5,6)P(5) 2-kinase (InsP(5) 2-kinase or Ipk1) catalyses the synthesis of InsP(6) from InsP(5) and ATP, and is the only enzyme that transfers a phosphate group to the axial 2-OH of the myo-inositide. We present the first structure for an InsP(5) 2-kinase in complex with both substrates and products. This enzyme presents a singular structural region for inositide binding that encompasses almost half of the protein. The key residues in substrate binding are identified, with Asp368 being responsible for recognition of the axial 2-OH. This study sheds light on the unique molecular mechanism for the synthesis of the precursor of inositol pyrophosphates.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Inositol phosphates (InsPs) are signaling molecules with multiple roles in cells.", "In particular (InsP(6)) is involved in mRNA export and editing or chromatin remodeling among other events.", "InsP(6) accumulates as mixed salts (phytate) in storage tissues of plants and plays a key role in their physiology.", "Human diets that are exclusively grain-based provide an excess of InsP(6) that, through chelation of metal ions, may have a detrimental effect on human health.", "Ins(1,3,4,5,6)P(5) 2-kinase (InsP(5) 2-kinase or Ipk1) catalyses the synthesis of InsP(6) from InsP(5) and ATP, and is the only enzyme that transfers a phosphate group to the axial 2-OH of the myo-inositide.", "We present the first structure for an InsP(5) 2-kinase in complex with both substrates and products.", "This enzyme presents a singular structural region for inositide binding that encompasses almost half of the protein.", "The key residues in substrate binding are identified, with Asp368 being responsible for recognition of the axial 2-OH.", "This study sheds light on the unique molecular mechanism for the synthesis of the precursor of inositol pyrophosphates."], "title": "Inositol 1,3,4,5,6-pentakisphosphate 2-kinase is a distant IPK member with a singular inositide binding site for axial 2-OH recognition."}
{"paper_id": 25910699, "labels": ["0", "0", "0", "0", "0", "0", "1", "0", "0"], "abstract": "UNLABELLED\nWe have developed CiVi, a user-friendly web-based tool to create custom circular maps to aid the analysis of microbial genomes and sequence elements. Sequence related data such as gene-name, COG class, PFAM domain, GC%, and subcellular location can be comprehensively viewed. Quantitative gene-related data (e.g. expression ratios or read counts) as well as predicted sequence elements (e.g. regulatory sequences) can be uploaded and visualized. CiVi accommodates the analysis of genomic elements by allowing a visual interpretation in the context of: (i) their genome-wide distribution, (ii) provided experimental data and (iii) the local orientation and location with respect to neighboring genes. CiVi thus enables both experts and non-experts to conveniently integrate public genome data with the results of genome analyses in circular genome maps suitable for publication.\n\n\nCONTACT\nL.Overmars@gmail.com\n\n\nSUPPLEMENTARY INFORMATION\nSupplementary data are available at Bioinformatics online.\n\n\nAVAILABILITY AND IMPLEMENTATION\nCiVi is freely available at http://civi.cmbi.ru.nl.", "journal": "Bioinformatics (Oxford, England)", "sentences": ["UNLABELLED\nWe have developed CiVi, a user-friendly web-based tool to create custom circular maps to aid the analysis of microbial genomes and sequence elements.", "Sequence related data such as gene-name, COG class, PFAM domain, GC%, and subcellular location can be comprehensively viewed.", "Quantitative gene-related data (e.g.", "expression ratios or read counts) as well as predicted sequence elements (e.g.", "regulatory sequences) can be uploaded and visualized.", "CiVi accommodates the analysis of genomic elements by allowing a visual interpretation in the context of: (i) their genome-wide distribution, (ii) provided experimental data and (iii) the local orientation and location with respect to neighboring genes.", "CiVi thus enables both experts and non-experts to conveniently integrate public genome data with the results of genome analyses in circular genome maps suitable for publication.", "CONTACT\nL.Overmars@gmail.com\n\n\nSUPPLEMENTARY INFORMATION\nSupplementary data are available at Bioinformatics online.", "AVAILABILITY AND IMPLEMENTATION\nCiVi is freely available at http://civi.cmbi.ru.nl."], "title": "CiVi: circular genome visualization with unique features to analyze sequence elements."}
{"paper_id": 25429064, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity. Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci. A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns. We carried out a GWA meta-analysis in 93 926 individuals from East Asia. We identified 98 loci, including 17 novel and 81 previously reported loci, associated with height at P < 5 \u00d7 10(-8), together explaining 8.89% of phenotypic variance. Among the newly identified variants, 10 are commonly distributed (minor allele frequency, MAF > 5%) in Europeans, with comparable frequencies with in Asians, and 7 single-nucleotide polymorphisms are with low frequency (MAF < 5%) in Europeans. In addition, our data suggest that novel biological pathway such as the protein tyrosine phosphatase family is involved in regulation of height. The findings from this study considerably expand our knowledge of the genetic architecture of human height in Asians.", "journal": "Human molecular genetics", "sentences": ["Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity.", "Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci.", "A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns.", "We carried out a GWA meta-analysis in 93 926 individuals from East Asia.", "We identified 98 loci, including 17 novel and 81 previously reported loci, associated with height at P < 5 \u00d7 10(-8), together explaining 8.89% of phenotypic variance.", "Among the newly identified variants, 10 are commonly distributed (minor allele frequency, MAF > 5%) in Europeans, with comparable frequencies with in Asians, and 7 single-nucleotide polymorphisms are with low frequency (MAF < 5%) in Europeans.", "In addition, our data suggest that novel biological pathway such as the protein tyrosine phosphatase family is involved in regulation of height.", "The findings from this study considerably expand our knowledge of the genetic architecture of human height in Asians."], "title": "Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci."}
{"paper_id": 26650398, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Pigment-based coloration is a common trait found in a variety of organisms across the tree of life. For example, calcareous avian eggs are natural structures that vary greatly in color, yet just a handful of tetrapyrrole pigment compounds are responsible for generating this myriad of colors. To fully understand the diversity and constraints shaping nature's palette, it is imperative to characterize the similarities and differences in the types of compounds involved in color production across diverse lineages. Pigment composition was investigated in eggshells of eleven paleognath bird taxa, covering several extinct and extant lineages, and shells of four extant species of mollusks. Birds and mollusks are two distantly related, calcareous shell-building groups, thus characterization of pigments in their calcareous structures would provide insights to whether similar compounds are found in different phyla (Chordata and Mollusca). An ethylenediaminetetraacetic acid (EDTA) extraction protocol was used to analyze the presence and concentration of biliverdin and protoporphyrin, two known and ubiquitous tetrapyrrole avian eggshell pigments, in all avian and molluscan samples. Biliverdin was solely detected in birds, including the colorful eggshells of four tinamou species. In contrast, protoporphyrin was detected in both the eggshells of several avian species and in the shells of all mollusks. These findings support previous hypotheses about the ubiquitous deposition of tetrapyrroles in the eggshells of various bird lineages and provide evidence for its presence also across distantly related animal taxa.", "journal": "PloS one", "sentences": ["Pigment-based coloration is a common trait found in a variety of organisms across the tree of life.", "For example, calcareous avian eggs are natural structures that vary greatly in color, yet just a handful of tetrapyrrole pigment compounds are responsible for generating this myriad of colors.", "To fully understand the diversity and constraints shaping nature's palette, it is imperative to characterize the similarities and differences in the types of compounds involved in color production across diverse lineages.", "Pigment composition was investigated in eggshells of eleven paleognath bird taxa, covering several extinct and extant lineages, and shells of four extant species of mollusks.", "Birds and mollusks are two distantly related, calcareous shell-building groups, thus characterization of pigments in their calcareous structures would provide insights to whether similar compounds are found in different phyla (Chordata and Mollusca).", "An ethylenediaminetetraacetic acid (EDTA) extraction protocol was used to analyze the presence and concentration of biliverdin and protoporphyrin, two known and ubiquitous tetrapyrrole avian eggshell pigments, in all avian and molluscan samples.", "Biliverdin was solely detected in birds, including the colorful eggshells of four tinamou species.", "In contrast, protoporphyrin was detected in both the eggshells of several avian species and in the shells of all mollusks.", "These findings support previous hypotheses about the ubiquitous deposition of tetrapyrroles in the eggshells of various bird lineages and provide evidence for its presence also across distantly related animal taxa."], "title": "Nature's Palette: Characterization of Shared Pigments in Colorful Avian and Mollusk Shells."}
{"paper_id": 26862736, "labels": ["0", "0", "1", "0", "0", "1"], "abstract": "ErbB3, a member of the ErbB family receptors, has a key role in the development and progression of several cancers, including non-small cell lung cancer (NSCLC), and in the establishment of resistance to therapies, leading to the development of anti-ErbB3 therapies.In this study we demonstrated, in a set of malignant pleural effusion-derived cultures of NSCLC, the synergistic antitumor effect of a histone deacetylase inhibitor (HDACi), such as vorinostat or valproic acid (VPA), in combination with the anti-ErbB3 monoclonal antibody (MoAb) A3. Synergistic interaction was observed in 2D and in 3D cultures conditions, both in fully epithelial cells expressing all ErbB receptors, and in cells that had undergone epithelial to mesenchymal transition and expressed low levels of ErbB3. We provided evidences suggesting that differential modulation of ErbB receptors by vorinostat or VPA, also at low doses corresponding to plasma levels easily reached in treated patients, is responsible for the observed synergism. In details, we showed in epithelial cells that both vorinostat and VPA induced time- and dose-dependent down-regulation of all three ErbB receptors and of downstream signaling. On the contrary, in A3-resistant mesenchymal cells, we observed time- and dose-dependent increase of mRNA and protein levels as well as surface expression of ErbB3, paralleled by down-regulation of EGFR and ErbB2. Our results suggest that the combination of a HDACi plus an anti-ErbB3 MoAb represents a viable strategy that warrants further evaluation for the treatment of NSCLC patients.", "journal": "Oncotarget", "sentences": ["ErbB3, a member of the ErbB family receptors, has a key role in the development and progression of several cancers, including non-small cell lung cancer (NSCLC), and in the establishment of resistance to therapies, leading to the development of anti-ErbB3 therapies.In this study we demonstrated, in a set of malignant pleural effusion-derived cultures of NSCLC, the synergistic antitumor effect of a histone deacetylase inhibitor (HDACi), such as vorinostat or valproic acid (VPA), in combination with the anti-ErbB3 monoclonal antibody (MoAb) A3.", "Synergistic interaction was observed in 2D and in 3D cultures conditions, both in fully epithelial cells expressing all ErbB receptors, and in cells that had undergone epithelial to mesenchymal transition and expressed low levels of ErbB3.", "We provided evidences suggesting that differential modulation of ErbB receptors by vorinostat or VPA, also at low doses corresponding to plasma levels easily reached in treated patients, is responsible for the observed synergism.", "In details, we showed in epithelial cells that both vorinostat and VPA induced time- and dose-dependent down-regulation of all three ErbB receptors and of downstream signaling.", "On the contrary, in A3-resistant mesenchymal cells, we observed time- and dose-dependent increase of mRNA and protein levels as well as surface expression of ErbB3, paralleled by down-regulation of EGFR and ErbB2.", "Our results suggest that the combination of a HDACi plus an anti-ErbB3 MoAb represents a viable strategy that warrants further evaluation for the treatment of NSCLC patients."], "title": "Synergistic antitumor activity of histone deacetylase inhibitors and anti-ErbB3 antibody in NSCLC primary cultures via modulation of ErbB receptors expression."}
{"paper_id": 22064071, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The cell-surface receptor for advanced glycation end-products (RAGE) has been implicated in the development of diabetic vascular complications and Alzheimer's disease. RAGE has been considered to be involved in amyloid-\u03b21-42 (A\u03b21-42) uptake into brain. In the present study, we demonstrate that endogenous secretory RAGE (esRAGE), a decoy form of RAGE generated by alternative RNA processing, is able to inhibit A\u03b21-42 influx into mouse brain. Surface plasmon resonance and competitive binding assays revealed that human A\u03b21-42 interacted with human esRAGE within the immunoglobulin V type region. We next examined the uptake and distribution of 125I-labeled human A\u03b21-42 in various organs and body fluids of newly created mice overexpressing human esRAGE as well as RAGE-null and wild-type (WT) mice. The transition of the 125I-labeled A\u03b21-42 from circulation to brain parenchyma peaked at 30 min after the injection into WT mice, but this was significantly blunted in esRAGE-overexpressing and RAGE-null mice. Significant reduction in 125I-labeled A\u03b21-42-derived photo-stimulated luminescence were marked in ventricles, cerebral cortex, hippocampus, especially CA1 and CA3 regions, putamen, and thalamus. The results thus suggest the potential of esRAGE in protection against the development of Alzheimer's disease.", "journal": "Journal of Alzheimer's disease : JAD", "sentences": ["The cell-surface receptor for advanced glycation end-products (RAGE) has been implicated in the development of diabetic vascular complications and Alzheimer's disease.", "RAGE has been considered to be involved in amyloid-\u03b21-42 (A\u03b21-42) uptake into brain.", "In the present study, we demonstrate that endogenous secretory RAGE (esRAGE), a decoy form of RAGE generated by alternative RNA processing, is able to inhibit A\u03b21-42 influx into mouse brain.", "Surface plasmon resonance and competitive binding assays revealed that human A\u03b21-42 interacted with human esRAGE within the immunoglobulin V type region.", "We next examined the uptake and distribution of 125I-labeled human A\u03b21-42 in various organs and body fluids of newly created mice overexpressing human esRAGE as well as RAGE-null and wild-type (WT) mice.", "The transition of the 125I-labeled A\u03b21-42 from circulation to brain parenchyma peaked at 30 min after the injection into WT mice, but this was significantly blunted in esRAGE-overexpressing and RAGE-null mice.", "Significant reduction in 125I-labeled A\u03b21-42-derived photo-stimulated luminescence were marked in ventricles, cerebral cortex, hippocampus, especially CA1 and CA3 regions, putamen, and thalamus.", "The results thus suggest the potential of esRAGE in protection against the development of Alzheimer's disease."], "title": "Endogenous secretory receptor for advanced glycation end-products inhibits amyloid-\u03b21-42 uptake into mouse brain."}
{"paper_id": 25451110, "labels": ["0", "0", "0", "0", "0", "1", "1", "0"], "abstract": "Results from clinical studies provide evidence that cognitive changes relatively late in life may be traced to antecedent conditions including diabetes, obesity, a sedentary lifestyle, and an atherogenic diet. As such, several traits of Type 2 diabetes (T2DM) could be considered pathogenic factors of aging, contributing to age-dependent cognitive decline and our susceptibility to Alzheimer's disease. It appears that both the duration of metabolic condition and the age of the individual, together can contribute to the potential impact on peripheral as well as brain health. Because of robust evidence that in animal models of aging, Ca(2+) dysregulation alters neuronal health, synaptic plasticity, and learning and memory processes, we tested the hypothesis that peripheral metabolic dysregulation could exacerbate Ca(2+) dysfunction in hippocampal CA1 neurons. Using intracellular/ extracellular electrophysiological and Ca(2+) imaging techniques, we show that Ca(2+)levels at rest or during synaptic stimulation, the Ca(2+)-dependent afterhyperpolarization, baseline field potentials, and short-term synaptic plasticity were not significantly altered in young-adult male Zucker diabetic fatty rats compare to their lean counterparts. Our observations suggest that early phases of T2DM characterized by high levels of glucose and insulin may be too transient to alter hippocampal CA1 physiology in this animal model of diabetes. These results are supported by clinical data showing that longer T2DM duration can have greater negative impact on cognitive functions. This article is part of a Special Issue entitled SI: Brain and Memory.", "journal": "Brain research", "sentences": ["Results from clinical studies provide evidence that cognitive changes relatively late in life may be traced to antecedent conditions including diabetes, obesity, a sedentary lifestyle, and an atherogenic diet.", "As such, several traits of Type 2 diabetes (T2DM) could be considered pathogenic factors of aging, contributing to age-dependent cognitive decline and our susceptibility to Alzheimer's disease.", "It appears that both the duration of metabolic condition and the age of the individual, together can contribute to the potential impact on peripheral as well as brain health.", "Because of robust evidence that in animal models of aging, Ca(2+) dysregulation alters neuronal health, synaptic plasticity, and learning and memory processes, we tested the hypothesis that peripheral metabolic dysregulation could exacerbate Ca(2+) dysfunction in hippocampal CA1 neurons.", "Using intracellular/ extracellular electrophysiological and Ca(2+) imaging techniques, we show that Ca(2+)levels at rest or during synaptic stimulation, the Ca(2+)-dependent afterhyperpolarization, baseline field potentials, and short-term synaptic plasticity were not significantly altered in young-adult male Zucker diabetic fatty rats compare to their lean counterparts.", "Our observations suggest that early phases of T2DM characterized by high levels of glucose and insulin may be too transient to alter hippocampal CA1 physiology in this animal model of diabetes.", "These results are supported by clinical data showing that longer T2DM duration can have greater negative impact on cognitive functions.", "This article is part of a Special Issue entitled SI: Brain and Memory."], "title": "Short-lived diabetes in the young-adult ZDF rat does not exacerbate neuronal Ca(2+) biomarkers of aging."}
{"paper_id": 20853105, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Microbial products formed in biological wastewater treatment systems are closely related to system performance and status, and many of them have fluorescence spectral characteristics. In this work, the fluorescence spectral characteristics of the supernatants from an anaerobic hydrogen-producing bioreactor were studied using three-dimensional excitation-emission matrix (EEM) fluorescence spectroscopy. Since the components of the microbial products are complex, the parallel factor analysis (PARAFAC) method was used to extract the real spectra from the overlapped spectra. Two principal components were identified from the EEM spectra. The peaks at excitation-emission maxima of 280/350 and 350/440 nm were, respectively, attributed to the fluorescence of proteins and NADH. Their real concentrations were quantified using the PARAFAC coupled with the second-order calibration method. Results show that the formation rate of proteins was correlated to the production rate of hydrogen and volatile fatty acids, as well as the substrate degradation rate. A close correlation between the hydrogen partial pressure and the two fluorophores was found out. This study provides a reliable and convenient approach, which could be potentially used for monitoring the wastewater treatment reactor performance through measuring the fluorescence spectra of the supernatant.", "journal": "Applied microbiology and biotechnology", "sentences": ["Microbial products formed in biological wastewater treatment systems are closely related to system performance and status, and many of them have fluorescence spectral characteristics.", "In this work, the fluorescence spectral characteristics of the supernatants from an anaerobic hydrogen-producing bioreactor were studied using three-dimensional excitation-emission matrix (EEM) fluorescence spectroscopy.", "Since the components of the microbial products are complex, the parallel factor analysis (PARAFAC) method was used to extract the real spectra from the overlapped spectra.", "Two principal components were identified from the EEM spectra.", "The peaks at excitation-emission maxima of 280/350 and 350/440 nm were, respectively, attributed to the fluorescence of proteins and NADH.", "Their real concentrations were quantified using the PARAFAC coupled with the second-order calibration method.", "Results show that the formation rate of proteins was correlated to the production rate of hydrogen and volatile fatty acids, as well as the substrate degradation rate.", "A close correlation between the hydrogen partial pressure and the two fluorophores was found out.", "This study provides a reliable and convenient approach, which could be potentially used for monitoring the wastewater treatment reactor performance through measuring the fluorescence spectra of the supernatant."], "title": "Fluorescence spectral characteristics of the supernatants from an anaerobic hydrogen-producing bioreactor."}
{"paper_id": 26975471, "labels": ["0", "0", "0", "0", "1", "1"], "abstract": "Autophagy is a lysosomal degradation pathway that degrades cytosolic constituents, including whole organelles and intracellular pathogens. Previous studies on various autophagy related genes revealed the importance of the Atg12-Atg5-Atg16 complex in autophagy. Atg16L1 is an effector of Golgi-resident Rab33B and the molecular mechanism of the interaction of Rab33B with either Atg16L1 or in complex with Atg5 is still elusive. In the current study, using the pull down and calorimetric approaches, we have dissected the molecular insights into the interaction of Rab33B with different regions of mouse Atg16L1 as well as with the dimeric complex, Atg5-mAtg16L1. Our in vitro observation suggests that Atg5 is pre-requisite for the augmented nucleotide dependent interaction of Rab33B with the dimeric complex, Atg5-Atg16L1. Moreover, the results reported here suggest that Arg-24 of Atg16L1 is crucial for its interaction with Atg5 which will have further implication in the binding of the dimeric complex to Rab33B.", "journal": "Biochemical and biophysical research communications", "sentences": ["Autophagy is a lysosomal degradation pathway that degrades cytosolic constituents, including whole organelles and intracellular pathogens.", "Previous studies on various autophagy related genes revealed the importance of the Atg12-Atg5-Atg16 complex in autophagy.", "Atg16L1 is an effector of Golgi-resident Rab33B and the molecular mechanism of the interaction of Rab33B with either Atg16L1 or in complex with Atg5 is still elusive.", "In the current study, using the pull down and calorimetric approaches, we have dissected the molecular insights into the interaction of Rab33B with different regions of mouse Atg16L1 as well as with the dimeric complex, Atg5-mAtg16L1.", "Our in vitro observation suggests that Atg5 is pre-requisite for the augmented nucleotide dependent interaction of Rab33B with the dimeric complex, Atg5-Atg16L1.", "Moreover, the results reported here suggest that Arg-24 of Atg16L1 is crucial for its interaction with Atg5 which will have further implication in the binding of the dimeric complex to Rab33B."], "title": "Deciphering the role of Atg5 in nucleotide dependent interaction of Rab33B with the dimeric complex, Atg5-Atg16L1."}
{"paper_id": 23660650, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Nicotine withdrawal is associated with numerous symptoms including impaired hippocampus-dependent learning. Theories of nicotine withdrawal suggest that nicotinic acetylcholine receptors (nAChRs) are hypersensitive during withdrawal, which suggests enhanced sensitivity to nicotine challenge. Research indicates that prior exposure to nicotine enhances sensitivity to nicotine challenge, but it is unclear if this is due to prior nicotine exposure or specific to nicotine withdrawal. Therefore, the present experiments examined if prior nicotine exposure or nicotine withdrawal altered the effects of nicotine challenge on hippocampus-dependent learning. C57BL/6J mice were trained and tested in contextual conditioning following saline or nicotine challenge either during (24h after cessation) or after (14 days after cessation) a period of nicotine withdrawal symptoms. Nicotine challenge produced a greater enhancement of contextual conditioning relative to control withdrawal state in mice withdrawn from chronic nicotine for 24h compared to 14 days and corresponding saline controls. These experiments support the suggestion that during periods of abstinence, smokers may perceive tobacco providing a large boost in cognition.", "journal": "Behavioural brain research", "sentences": ["Nicotine withdrawal is associated with numerous symptoms including impaired hippocampus-dependent learning.", "Theories of nicotine withdrawal suggest that nicotinic acetylcholine receptors (nAChRs) are hypersensitive during withdrawal, which suggests enhanced sensitivity to nicotine challenge.", "Research indicates that prior exposure to nicotine enhances sensitivity to nicotine challenge, but it is unclear if this is due to prior nicotine exposure or specific to nicotine withdrawal.", "Therefore, the present experiments examined if prior nicotine exposure or nicotine withdrawal altered the effects of nicotine challenge on hippocampus-dependent learning.", "C57BL/6J mice were trained and tested in contextual conditioning following saline or nicotine challenge either during (24h after cessation) or after (14 days after cessation) a period of nicotine withdrawal symptoms.", "Nicotine challenge produced a greater enhancement of contextual conditioning relative to control withdrawal state in mice withdrawn from chronic nicotine for 24h compared to 14 days and corresponding saline controls.", "These experiments support the suggestion that during periods of abstinence, smokers may perceive tobacco providing a large boost in cognition."], "title": "Withdrawal from chronic nicotine and subsequent sensitivity to nicotine challenge on contextual learning."}
{"paper_id": 24495810, "labels": ["0", "0", "0", "1", "0", "0", "1", "1"], "abstract": "This study investigated the neurocognitive mechanisms underlying the role of the eye and the mouth regions in the recognition of facial happiness, anger, and surprise. To this end, face stimuli were shown in three formats (whole face, upper half visible, and lower half visible) and behavioral categorization, computational modeling, and ERP (event-related potentials) measures were combined. N170 (150-180 ms post-stimulus; right hemisphere) and EPN (early posterior negativity; 200-300 ms; mainly, right hemisphere) were modulated by expression of whole faces, but not by separate halves. This suggests that expression encoding (N170) and emotional assessment (EPN) require holistic processing, mainly in the right hemisphere. In contrast, the mouth region of happy faces enhanced left temporo-occipital activity (150-180 ms), and also the LPC (late positive complex; centro-parietal) activity (350-450 ms) earlier than the angry eyes (450-600 ms) or other face regions. Relatedly, computational modeling revealed that the mouth region of happy faces was also visually salient by 150 ms following stimulus onset. This suggests that analytical or part-based processing of the salient smile occurs early (150-180 ms) and lateralized (left), and is subsequently used as a shortcut to identify the expression of happiness (350-450 ms). This would account for the happy face advantage in behavioral recognition tasks when the smile is visible.", "journal": "NeuroImage", "sentences": ["This study investigated the neurocognitive mechanisms underlying the role of the eye and the mouth regions in the recognition of facial happiness, anger, and surprise.", "To this end, face stimuli were shown in three formats (whole face, upper half visible, and lower half visible) and behavioral categorization, computational modeling, and ERP (event-related potentials) measures were combined.", "N170 (150-180 ms post-stimulus; right hemisphere) and EPN (early posterior negativity; 200-300 ms; mainly, right hemisphere) were modulated by expression of whole faces, but not by separate halves.", "This suggests that expression encoding (N170) and emotional assessment (EPN) require holistic processing, mainly in the right hemisphere.", "In contrast, the mouth region of happy faces enhanced left temporo-occipital activity (150-180 ms), and also the LPC (late positive complex; centro-parietal) activity (350-450 ms) earlier than the angry eyes (450-600 ms) or other face regions.", "Relatedly, computational modeling revealed that the mouth region of happy faces was also visually salient by 150 ms following stimulus onset.", "This suggests that analytical or part-based processing of the salient smile occurs early (150-180 ms) and lateralized (left), and is subsequently used as a shortcut to identify the expression of happiness (350-450 ms).", "This would account for the happy face advantage in behavioral recognition tasks when the smile is visible."], "title": "Brain lateralization of holistic versus analytic processing of emotional facial expressions."}
{"paper_id": 23393659, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Hepatocellular carcinoma is a frequent and fatal disease. Recent researches on rodent models and human hepatocarcinogenesis contributed to unravel the molecular mechanisms of hepatocellular carcinoma dedifferentiation and progression, and allowed the discovery of several alterations underlying the deregulation of cell cycle and signalling pathways. This review provides an interpretive analysis of the results of these studies. Mounting evidence emphasises the role of up-regulation of RAS/ERK, P13K/AKT, IKK/NF-kB, WNT, TGF-\u00df, NOTCH, Hedgehog, and Hippo signalling pathways as well as of aberrant proteasomal activity in hepatocarcinogenesis. Signalling deregulation often occurs in preneoplastic stages of rodent and human hepatocarcinogenesis and progressively increases in carcinomas, being most pronounced in more aggressive tumours. Numerous changes in signalling cascades are involved in the deregulation of carbohydrate, lipid, and methionine metabolism, which play a role in the maintenance of the transformed phenotype. Recent studies on the role of microRNAs in signalling deregulation, and on the interplay between signalling pathways led to crucial achievements in the knowledge of the network of signalling cascades, essential for the development of adjuvant therapies of liver cancer. Furthermore, the analysis of the mechanisms involved in signalling deregulation allowed the identification of numerous putative prognostic markers and novel therapeutic targets of specific hepatocellular carcinoma subtypes associated with different biologic and clinical features. This is of prime importance for the selection of patient subgroups that are most likely to obtain clinical benefit and, hence, for successful development of targeted therapies for liver cancer.", "journal": "Biochimica et biophysica acta", "sentences": ["Hepatocellular carcinoma is a frequent and fatal disease.", "Recent researches on rodent models and human hepatocarcinogenesis contributed to unravel the molecular mechanisms of hepatocellular carcinoma dedifferentiation and progression, and allowed the discovery of several alterations underlying the deregulation of cell cycle and signalling pathways.", "This review provides an interpretive analysis of the results of these studies.", "Mounting evidence emphasises the role of up-regulation of RAS/ERK, P13K/AKT, IKK/NF-kB, WNT, TGF-\u00df, NOTCH, Hedgehog, and Hippo signalling pathways as well as of aberrant proteasomal activity in hepatocarcinogenesis.", "Signalling deregulation often occurs in preneoplastic stages of rodent and human hepatocarcinogenesis and progressively increases in carcinomas, being most pronounced in more aggressive tumours.", "Numerous changes in signalling cascades are involved in the deregulation of carbohydrate, lipid, and methionine metabolism, which play a role in the maintenance of the transformed phenotype.", "Recent studies on the role of microRNAs in signalling deregulation, and on the interplay between signalling pathways led to crucial achievements in the knowledge of the network of signalling cascades, essential for the development of adjuvant therapies of liver cancer.", "Furthermore, the analysis of the mechanisms involved in signalling deregulation allowed the identification of numerous putative prognostic markers and novel therapeutic targets of specific hepatocellular carcinoma subtypes associated with different biologic and clinical features.", "This is of prime importance for the selection of patient subgroups that are most likely to obtain clinical benefit and, hence, for successful development of targeted therapies for liver cancer."], "title": "Deregulation of signalling pathways in prognostic subtypes of hepatocellular carcinoma: novel insights from interspecies comparison."}
{"paper_id": 26203655, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Stomata, valves on the plant epidermis, are critical for plant growth and survival, and the presence of stomata impacts the global water and carbon cycle. Although transcription factors and cell-cell signaling components regulating stomatal development have been identified, it remains unclear as to how their regulatory interactions are translated into two-dimensional patterns of stomatal initial cells. Using molecular genetics, imaging, and mathematical simulation, we report a regulatory circuit that initiates the stomatal cell-lineage. The circuit includes a positive feedback loop constituting self-activation of SCREAMs that requires SPEECHLESS. This transcription factor module directly binds to the promoters and activates a secreted signal, EPIDERMAL PATTERNING FACTOR2, and the receptor modifier TOO MANY MOUTHS, while the receptor ERECTA lies outside of this module. This in turn inhibits SPCH, and hence SCRMs, thus constituting a negative feedback loop. Our mathematical model accurately predicts all known stomatal phenotypes with the inclusion of two additional components to the circuit: an EPF2-independent negative-feedback loop and a signal that lies outside of the SPCH\u2022SCRM module. Our work reveals the intricate molecular framework governing self-organizing two-dimensional patterning in the plant epidermis.", "journal": "PLoS genetics", "sentences": ["Stomata, valves on the plant epidermis, are critical for plant growth and survival, and the presence of stomata impacts the global water and carbon cycle.", "Although transcription factors and cell-cell signaling components regulating stomatal development have been identified, it remains unclear as to how their regulatory interactions are translated into two-dimensional patterns of stomatal initial cells.", "Using molecular genetics, imaging, and mathematical simulation, we report a regulatory circuit that initiates the stomatal cell-lineage.", "The circuit includes a positive feedback loop constituting self-activation of SCREAMs that requires SPEECHLESS.", "This transcription factor module directly binds to the promoters and activates a secreted signal, EPIDERMAL PATTERNING FACTOR2, and the receptor modifier TOO MANY MOUTHS, while the receptor ERECTA lies outside of this module.", "This in turn inhibits SPCH, and hence SCRMs, thus constituting a negative feedback loop.", "Our mathematical model accurately predicts all known stomatal phenotypes with the inclusion of two additional components to the circuit: an EPF2-independent negative-feedback loop and a signal that lies outside of the SPCH\u2022SCRM module.", "Our work reveals the intricate molecular framework governing self-organizing two-dimensional patterning in the plant epidermis."], "title": "Molecular Framework of a Regulatory Circuit Initiating Two-Dimensional Spatial Patterning of Stomatal Lineage."}
{"paper_id": 24757414, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "This paper describes an experimental investigation into the pore structure of cement mortar using mercury porosimeter. Ordinary Portland cement, manufactured sand, and natural sand were used. The porosity of the manufactured sand mortar is higher than that of natural sand at the same mix proportion; on the contrary, the probable pore size and threshold radius of manufactured sand mortar are finer. Besides, the probable pore size and threshold radius increased with increasing water to cement ratio and sand to cement ratio. In addition, the existing models of pore size distribution of cement-based materials have been reviewed and compared with test results in this paper. Finally, the extended Bhattacharjee model was built to examine the relationship between compressive strength and pore structure.", "journal": "TheScientificWorldJournal", "sentences": ["This paper describes an experimental investigation into the pore structure of cement mortar using mercury porosimeter.", "Ordinary Portland cement, manufactured sand, and natural sand were used.", "The porosity of the manufactured sand mortar is higher than that of natural sand at the same mix proportion; on the contrary, the probable pore size and threshold radius of manufactured sand mortar are finer.", "Besides, the probable pore size and threshold radius increased with increasing water to cement ratio and sand to cement ratio.", "In addition, the existing models of pore size distribution of cement-based materials have been reviewed and compared with test results in this paper.", "Finally, the extended Bhattacharjee model was built to examine the relationship between compressive strength and pore structure."], "title": "Influence of pore structure on compressive strength of cement mortar."}
{"paper_id": 25091197, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The ability to derivatize antibodies is currently limited by the chemical structure of antibodies as polypeptides. Modern methods of bioorthogonal and biocompatible chemical modifications could make antibody functionalization more predictable and easier, without compromising the functions of the antibody. To explore this concept, we modified the well-known anti-epidermal growth factor receptor (EGFR) drug, cetuximab (Erbitux\u00ae), with 5-azido-2-nitro-benzoyl (ANB) modifications by optimization of an acylation protocol. We then show that the resulting ANB-cetuximab can be reliably modified with dyes (TAMRA and carboxyrhodamine) or a novel synthesized cyclooctyne modified biotin. The resulting dye- and biotin-modified cetuximabs were then tested across several assay platforms with several cell lines including U87, LN229, F98EGFR, F98WT and HEK293 cells. The assay platforms included fluorescence microscopy, FACS and biotin-avidin based immunoprecipitation methods. The modified antibody performs consistently in all of these assay platforms, reliably determining relative abundances of EGFR expression on EGFR expressing cells (LN229 and F98EGFR) and failing to cross react with weak to negative EGFR expressing cells (U87, F98WT and HEK293). The ease of achieving diverse and assay relevant functionalizations as well as the consequent rapid construction of highly correlated antigen expression data sets highlights the power of bioorthogonal and biocompatible methods to conjugate macromolecules. These data provide a proof of concept for a multifunctionalization strategy that leverages the biochemical versatility and antigen specificity of antibodies.", "journal": "Biochimica et biophysica acta", "sentences": ["The ability to derivatize antibodies is currently limited by the chemical structure of antibodies as polypeptides.", "Modern methods of bioorthogonal and biocompatible chemical modifications could make antibody functionalization more predictable and easier, without compromising the functions of the antibody.", "To explore this concept, we modified the well-known anti-epidermal growth factor receptor (EGFR) drug, cetuximab (Erbitux\u00ae), with 5-azido-2-nitro-benzoyl (ANB) modifications by optimization of an acylation protocol.", "We then show that the resulting ANB-cetuximab can be reliably modified with dyes (TAMRA and carboxyrhodamine) or a novel synthesized cyclooctyne modified biotin.", "The resulting dye- and biotin-modified cetuximabs were then tested across several assay platforms with several cell lines including U87, LN229, F98EGFR, F98WT and HEK293 cells.", "The assay platforms included fluorescence microscopy, FACS and biotin-avidin based immunoprecipitation methods.", "The modified antibody performs consistently in all of these assay platforms, reliably determining relative abundances of EGFR expression on EGFR expressing cells (LN229 and F98EGFR) and failing to cross react with weak to negative EGFR expressing cells (U87, F98WT and HEK293).", "The ease of achieving diverse and assay relevant functionalizations as well as the consequent rapid construction of highly correlated antigen expression data sets highlights the power of bioorthogonal and biocompatible methods to conjugate macromolecules.", "These data provide a proof of concept for a multifunctionalization strategy that leverages the biochemical versatility and antigen specificity of antibodies."], "title": "Multifunctionalization of cetuximab with bioorthogonal chemistries and parallel EGFR profiling of cell-lines using imaging, FACS and immunoprecipitation approaches."}
{"paper_id": 20532741, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Although the primary photochemical events in the facultative photoheterotrophic purple bacterium Rhodobacter sphaeroides are now well understood, comparatively little is known about how their photosynthetic apparatus is assembled. Here we present a proteomic analysis of the intracytoplasmic membrane (ICM) assembly process during adaptation to lowered light intensity, in which the size of the photosynthetic units is greatly expanded by addition of the light-harvesting 2 (LH2) peripheral antenna complex. When the isolated ICM-derived chromatophore vesicles were subjected to clear native gel electrophoresis (CNE), four pigmented bands appeared; the top and bottom bands contained the reaction center - light-harvesting 1 (RC-LH1) core complex and LH2 peripheral antenna, respectively, while the two bands of intermediate migration contained associations of the LH2 and core complexes. Proteomic analysis revealed a large array of other proteins associated with the CNE gel bands - in particular, several F(1)F(O)-ATP synthase subunits gave unexpectedly high spectral counts, given the inability to detect this coupling factor, as well as the more abundant cytochrome bc (1) complex, by atomic force microscopy. Significant levels of general membrane assembly factors were also found, as well as numerous proteins of unknown function including high counts for RSP6124 that were correlated with LH2 levels. When combined with further AFM and spectroscopic studies, these proteomic approaches are expected to provide a much-improved understanding of the overall assembly process.", "journal": "Advances in experimental medicine and biology", "sentences": ["Although the primary photochemical events in the facultative photoheterotrophic purple bacterium Rhodobacter sphaeroides are now well understood, comparatively little is known about how their photosynthetic apparatus is assembled.", "Here we present a proteomic analysis of the intracytoplasmic membrane (ICM) assembly process during adaptation to lowered light intensity, in which the size of the photosynthetic units is greatly expanded by addition of the light-harvesting 2 (LH2) peripheral antenna complex.", "When the isolated ICM-derived chromatophore vesicles were subjected to clear native gel electrophoresis (CNE), four pigmented bands appeared; the top and bottom bands contained the reaction center - light-harvesting 1 (RC-LH1) core complex and LH2 peripheral antenna, respectively, while the two bands of intermediate migration contained associations of the LH2 and core complexes.", "Proteomic analysis revealed a large array of other proteins associated with the CNE gel bands - in particular, several F(1)F(O)-ATP synthase subunits gave unexpectedly high spectral counts, given the inability to detect this coupling factor, as well as the more abundant cytochrome bc (1) complex, by atomic force microscopy.", "Significant levels of general membrane assembly factors were also found, as well as numerous proteins of unknown function including high counts for RSP6124 that were correlated with LH2 levels.", "When combined with further AFM and spectroscopic studies, these proteomic approaches are expected to provide a much-improved understanding of the overall assembly process."], "title": "Proteomic analysis of the developing intracytoplasmic membrane in Rhodobacter sphaeroides during adaptation to low light intensity."}
{"paper_id": 23370062, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "A voxel-based algorithm to correct for partial volume effect in PET brain volumes is presented. This method (named LoReAn) is based on MRI based segmentation of anatomical regions and accurate measurements of the effective point spread function of the PET imaging process. The objective is to correct for the spill-out of activity from high-uptake anatomical structures (e.g. grey matter) into low-uptake anatomical structures (e.g. white matter) in order to quantify physiological uptake in the white matter. The new algorithm is presented and validated against the state of the art region-based geometric transfer matrix (GTM) method with synthetic and clinical data. Using synthetic data, both bias and coefficient of variation were improved in the white matter region using LoReAn compared to GTM. An increased number of anatomical regions doesn't affect the bias (<5%) and misregistration affects equally LoReAn and GTM algorithms. The LoReAn algorithm appears to be a simple and promising voxel-based algorithm for studying metabolism in white matter regions.", "journal": "NeuroImage", "sentences": ["A voxel-based algorithm to correct for partial volume effect in PET brain volumes is presented.", "This method (named LoReAn) is based on MRI based segmentation of anatomical regions and accurate measurements of the effective point spread function of the PET imaging process.", "The objective is to correct for the spill-out of activity from high-uptake anatomical structures (e.g.", "grey matter) into low-uptake anatomical structures (e.g.", "white matter) in order to quantify physiological uptake in the white matter.", "The new algorithm is presented and validated against the state of the art region-based geometric transfer matrix (GTM) method with synthetic and clinical data.", "Using synthetic data, both bias and coefficient of variation were improved in the white matter region using LoReAn compared to GTM.", "An increased number of anatomical regions doesn't affect the bias (<5%) and misregistration affects equally LoReAn and GTM algorithms.", "The LoReAn algorithm appears to be a simple and promising voxel-based algorithm for studying metabolism in white matter regions."], "title": "Correction of partial volume effect in (18)F-FDG PET brain studies using coregistered MR volumes: voxel based analysis of tracer uptake in the white matter."}
{"paper_id": 21393506, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "Human melanoma is composed of distinct cell types reminiscent of neural crest derivatives and contains multipotent cells that express the neural crest stem cell markers CD271(p75(NTR)) and Sox10. When isolated from solid tumors by using a method that leaves intact cell surface epitopes, CD271-positive, but not CD271-negative, cells formed tumors on transplantation into nude or nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. These tumors fully mirrored the heterogeneity of the parental melanoma and could be passaged more than 5 times. In contrast, in more immunocompromised NOD/SCID/IL2r\u03b3(null) mice, or in natural killer cell-depleted nude or NOD/SCID mice, both CD271-positive and CD271-negative tumor cell fractions established tumors. However, tumors resulting from either fraction did not phenocopy the parental tumors, and tumors derived from the CD271-negative cell fraction could not be passaged multiple times. Together, our findings identify CD271-positive cells as melanoma stem cells. Our observation that a relatively high frequency of CD271/Sox10-positive cells correlates with higher metastatic potential and worse prognosis further supports that CD271-positive cells within human melanoma represent genuine cancer stem cells.", "journal": "Cancer research", "sentences": ["Human melanoma is composed of distinct cell types reminiscent of neural crest derivatives and contains multipotent cells that express the neural crest stem cell markers CD271(p75(NTR)) and Sox10.", "When isolated from solid tumors by using a method that leaves intact cell surface epitopes, CD271-positive, but not CD271-negative, cells formed tumors on transplantation into nude or nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice.", "These tumors fully mirrored the heterogeneity of the parental melanoma and could be passaged more than 5 times.", "In contrast, in more immunocompromised NOD/SCID/IL2r\u03b3(null) mice, or in natural killer cell-depleted nude or NOD/SCID mice, both CD271-positive and CD271-negative tumor cell fractions established tumors.", "However, tumors resulting from either fraction did not phenocopy the parental tumors, and tumors derived from the CD271-negative cell fraction could not be passaged multiple times.", "Together, our findings identify CD271-positive cells as melanoma stem cells.", "Our observation that a relatively high frequency of CD271/Sox10-positive cells correlates with higher metastatic potential and worse prognosis further supports that CD271-positive cells within human melanoma represent genuine cancer stem cells."], "title": "Human CD271-positive melanoma stem cells associated with metastasis establish tumor heterogeneity and long-term growth."}
{"paper_id": 20516286, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The relationship between susceptibilities to fluconazole and itraconazole and microsatellite CAI genotypes were examined from a total of 154 Candida albicans isolates (97 isolates causing vulvovaginitis in Chinese women and 6 vaginal isolates and 51 oral cavity isolates from asymptomatic carriers). The two dominant genotypes, CAI 30-45 (45 isolates) and CAI 32-46 (33 isolates), associated with vulvovaginitis showed significantly different azole susceptibility patterns with strong statistical support. CAI 32-46 isolates were usually less susceptible to both fluconazole and itraconazole than CAI 30-45 isolates and than the oral isolates with other diversified CAI genotypes. Remarkably different mutation patterns in the azole target gene ERG11 were correspondingly observed among C. albicans isolates representing different genotypes and sources. Isolates with the same or similar CAI genotypes usually possessed identical or phylogenetically closely related ERG11 sequences. Loss of heterozygosity in ERG11 was observed in all the CAI 32-46 isolates but not in the CAI 30-45 isolates and most of the oral isolates sequenced. Compared with the ERG11 sequence of strain SC5314 (X13296), two homozygous missense mutations (G487T and T916C) leading to two amino acid changes (A114S and Y257H) in Erg11p were found in CAI 32-46 isolates. The correlation between azole susceptibility and C. albicans genotype may be of potential therapeutic significance.", "journal": "Antimicrobial agents and chemotherapy", "sentences": ["The relationship between susceptibilities to fluconazole and itraconazole and microsatellite CAI genotypes were examined from a total of 154 Candida albicans isolates (97 isolates causing vulvovaginitis in Chinese women and 6 vaginal isolates and 51 oral cavity isolates from asymptomatic carriers).", "The two dominant genotypes, CAI 30-45 (45 isolates) and CAI 32-46 (33 isolates), associated with vulvovaginitis showed significantly different azole susceptibility patterns with strong statistical support.", "CAI 32-46 isolates were usually less susceptible to both fluconazole and itraconazole than CAI 30-45 isolates and than the oral isolates with other diversified CAI genotypes.", "Remarkably different mutation patterns in the azole target gene ERG11 were correspondingly observed among C. albicans isolates representing different genotypes and sources.", "Isolates with the same or similar CAI genotypes usually possessed identical or phylogenetically closely related ERG11 sequences.", "Loss of heterozygosity in ERG11 was observed in all the CAI 32-46 isolates but not in the CAI 30-45 isolates and most of the oral isolates sequenced.", "Compared with the ERG11 sequence of strain SC5314 (X13296), two homozygous missense mutations (G487T and T916C) leading to two amino acid changes (A114S and Y257H) in Erg11p were found in CAI 32-46 isolates.", "The correlation between azole susceptibility and C. albicans genotype may be of potential therapeutic significance."], "title": "Correlation between azole susceptibilities, genotypes, and ERG11 mutations in Candida albicans isolates associated with vulvovaginal candidiasis in China."}
{"paper_id": 26354146, "labels": ["0", "0", "1", "0", "0", "1", "0", "1", "1"], "abstract": "Polyomaviruses are a family of small DNA viruses that are associated with a number of severe human diseases, particularly in immunocompromised individuals. The detailed virus-host interactions during lytic polyomavirus infection are not fully understood. Here, we report the first nuclear proteomic study with BK polyomavirus (BKPyV) in a primary renal proximal tubule epithelial cell culture system using stable isotope labeling by amino acids in cell culture (SILAC) proteomic profiling coupled with liquid chromatography-tandem mass spectrometry. We demonstrated the feasibility of SILAC labeling in these primary cells and subsequently performed reciprocal labeling-infection experiments to identify proteins that are altered by BKPyV infection. Our analyses revealed specific proteins that are significantly up- or down-regulated in the infected nuclear proteome. The genes encoding many of these proteins were not identified in a previous microarray study, suggesting that differential regulation of these proteins may be independent of transcriptional control. Western blotting experiments verified the SILAC proteomic findings. Finally, pathway and network analyses indicated that the host cell DNA damage response signaling and DNA repair pathways are among the cellular processes most affected at the protein level during polyomavirus infection. Our study provides a comprehensive view of the host nuclear proteomic changes during polyomavirus lytic infection and suggests potential novel host factors required for a productive polyomavirus infection.", "journal": "Journal of proteome research", "sentences": ["Polyomaviruses are a family of small DNA viruses that are associated with a number of severe human diseases, particularly in immunocompromised individuals.", "The detailed virus-host interactions during lytic polyomavirus infection are not fully understood.", "Here, we report the first nuclear proteomic study with BK polyomavirus (BKPyV) in a primary renal proximal tubule epithelial cell culture system using stable isotope labeling by amino acids in cell culture (SILAC) proteomic profiling coupled with liquid chromatography-tandem mass spectrometry.", "We demonstrated the feasibility of SILAC labeling in these primary cells and subsequently performed reciprocal labeling-infection experiments to identify proteins that are altered by BKPyV infection.", "Our analyses revealed specific proteins that are significantly up- or down-regulated in the infected nuclear proteome.", "The genes encoding many of these proteins were not identified in a previous microarray study, suggesting that differential regulation of these proteins may be independent of transcriptional control.", "Western blotting experiments verified the SILAC proteomic findings.", "Finally, pathway and network analyses indicated that the host cell DNA damage response signaling and DNA repair pathways are among the cellular processes most affected at the protein level during polyomavirus infection.", "Our study provides a comprehensive view of the host nuclear proteomic changes during polyomavirus lytic infection and suggests potential novel host factors required for a productive polyomavirus infection."], "title": "Quantitative Proteomic Analysis of Enriched Nuclear Fractions from BK Polyomavirus-Infected Primary Renal Proximal Tubule Epithelial Cells."}
{"paper_id": 22689639, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Genome-wide association studies (GWAS) have discovered many loci associated with common disease and quantitative traits. However, most GWAS have not studied the gene-gene interactions (epistasis) that could be important in complex trait genetics. A major challenge in analysing epistasis in GWAS is the enormous computational demands of analysing billions of SNP combinations. Several methods have been developed recently to address this, some using computers equipped with particular graphical processing units, most restricted to binary disease traits and all poorly suited to general usage on the most widely used operating systems. We have developed the BiForce Toolbox to address the demand for high-throughput analysis of pairwise epistasis in GWAS of quantitative and disease traits across all commonly used computer systems. BiForce Toolbox is a stand-alone Java program that integrates bitwise computing with multithreaded parallelization and thus allows rapid full pairwise genome scans via a graphical user interface or the command line. Furthermore, BiForce Toolbox incorporates additional tests of interactions involving SNPs with significant marginal effects, potentially increasing the power of detection of epistasis. BiForce Toolbox is easy to use and has been applied in multiple studies of epistasis in large GWAS data sets, identifying interesting interaction signals and pathways.", "journal": "Nucleic acids research", "sentences": ["Genome-wide association studies (GWAS) have discovered many loci associated with common disease and quantitative traits.", "However, most GWAS have not studied the gene-gene interactions (epistasis) that could be important in complex trait genetics.", "A major challenge in analysing epistasis in GWAS is the enormous computational demands of analysing billions of SNP combinations.", "Several methods have been developed recently to address this, some using computers equipped with particular graphical processing units, most restricted to binary disease traits and all poorly suited to general usage on the most widely used operating systems.", "We have developed the BiForce Toolbox to address the demand for high-throughput analysis of pairwise epistasis in GWAS of quantitative and disease traits across all commonly used computer systems.", "BiForce Toolbox is a stand-alone Java program that integrates bitwise computing with multithreaded parallelization and thus allows rapid full pairwise genome scans via a graphical user interface or the command line.", "Furthermore, BiForce Toolbox incorporates additional tests of interactions involving SNPs with significant marginal effects, potentially increasing the power of detection of epistasis.", "BiForce Toolbox is easy to use and has been applied in multiple studies of epistasis in large GWAS data sets, identifying interesting interaction signals and pathways."], "title": "BiForce Toolbox: powerful high-throughput computational analysis of gene-gene interactions in genome-wide association studies."}
{"paper_id": 26372642, "labels": ["0", "0", "0", "0", "1", "1", "1", "1"], "abstract": "Which factors select for long juvenile periods in some species is not well understood. One potential reason to delay the onset of reproduction is slow food acquisition rates, either due to competition (part of the ecological risk avoidance hypothesis), or due to a decreased foraging efficiency (a version of the needing to learn hypothesis). Capuchins provide a useful genus to test the needing to learn hypothesis because they are known for having long juvenile periods and a difficult-to-acquire diet. Generalized, linear, mixed models with data from 609 fruit forage focal follows on 49, habituated, wild Cebus capucinus were used to test two predictions from the needing-to-learn hypothesis as it applies to fruit foraging skills: 1) capuchin monkeys do not achieve adult foraging return rates for difficult-to-acquire fruits before late in the juvenile period; and 2) variance in return rates for these fruits is at least partially associated with differences in foraging skill. In support of the first prediction, adults, compared with all younger age classes, had significantly higher foraging return rates when foraging for fruits that were ranked as difficult-to-acquire (return rates relative to adults: 0.30-0.41, p-value range 0.008-0.016), indicating that the individuals in the group who have the most foraging experience also achieve the highest return rates. In contrast, and in support of the second prediction, there were no significant differences between age classes for fruits that were ranked as easy to acquire (return rates relative to adults: 0.97-1.42, p-value range 0.086-0.896), indicating that strength and/or skill are likely to affect return rates. In addition, fruits that were difficult to acquire were foraged at nearly identical rates by adult males and significantly smaller (and presumably weaker) adult females (males relative to females: 1.01, p = 0.978), while subadult females had much lower foraging efficiency than the similarly-sized but more experienced adult females (subadults relative to adults: 0.34, p = 0.052), indicating that skill, specifically, is likely to have an effect on return rates. These results are consistent with the needing to learn hypothesis and indicate that long juvenile periods in capuchins may be the result of selection for more time to learn foraging skills for difficult-to-acquire fruits.", "journal": "PloS one", "sentences": ["Which factors select for long juvenile periods in some species is not well understood.", "One potential reason to delay the onset of reproduction is slow food acquisition rates, either due to competition (part of the ecological risk avoidance hypothesis), or due to a decreased foraging efficiency (a version of the needing to learn hypothesis).", "Capuchins provide a useful genus to test the needing to learn hypothesis because they are known for having long juvenile periods and a difficult-to-acquire diet.", "Generalized, linear, mixed models with data from 609 fruit forage focal follows on 49, habituated, wild Cebus capucinus were used to test two predictions from the needing-to-learn hypothesis as it applies to fruit foraging skills: 1) capuchin monkeys do not achieve adult foraging return rates for difficult-to-acquire fruits before late in the juvenile period; and 2) variance in return rates for these fruits is at least partially associated with differences in foraging skill.", "In support of the first prediction, adults, compared with all younger age classes, had significantly higher foraging return rates when foraging for fruits that were ranked as difficult-to-acquire (return rates relative to adults: 0.30-0.41, p-value range 0.008-0.016), indicating that the individuals in the group who have the most foraging experience also achieve the highest return rates.", "In contrast, and in support of the second prediction, there were no significant differences between age classes for fruits that were ranked as easy to acquire (return rates relative to adults: 0.97-1.42, p-value range 0.086-0.896), indicating that strength and/or skill are likely to affect return rates.", "In addition, fruits that were difficult to acquire were foraged at nearly identical rates by adult males and significantly smaller (and presumably weaker) adult females (males relative to females: 1.01, p = 0.978), while subadult females had much lower foraging efficiency than the similarly-sized but more experienced adult females (subadults relative to adults: 0.34, p = 0.052), indicating that skill, specifically, is likely to have an effect on return rates.", "These results are consistent with the needing to learn hypothesis and indicate that long juvenile periods in capuchins may be the result of selection for more time to learn foraging skills for difficult-to-acquire fruits."], "title": "Ontogeny of Foraging Competence in Capuchin Monkeys (Cebus capucinus) for Easy versus Difficult to Acquire Fruits: A Test of the Needing to Learn Hypothesis."}
{"paper_id": 22761833, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "A major cause of amphibian declines worldwide is habitat destruction or alteration. Public green spaces, such as golf courses and parks, could serve as safe havens to curb the effects of habitat loss if managed in ways to bolster local amphibian communities. We reared larval Blanchard's cricket frogs (Acris blanchardi) and green frogs (Rana clamitans) in golf course ponds with and without 1 m terrestrial buffer zones, and released marked cricket frog metamorphs at the golf course ponds they were reared in. Larval survival of both species was affected by the presence of a buffer zone, with increased survival for cricket frogs and decreased survival for green frogs when reared in ponds with buffer zones. No marked cricket frog juveniles were recovered at any golf course pond in the following year, suggesting that most animals died or migrated. In a separate study, we released cricket frogs in a terrestrial pen and allowed them to choose between mown and unmown grass. Cricket frogs had a greater probability of using unmown versus mown grass. Our results suggest that incorporating buffer zones around ponds can offer suitable habitat for some amphibian species and can improve the quality of the aquatic environment for some sensitive local amphibians.", "journal": "PloS one", "sentences": ["A major cause of amphibian declines worldwide is habitat destruction or alteration.", "Public green spaces, such as golf courses and parks, could serve as safe havens to curb the effects of habitat loss if managed in ways to bolster local amphibian communities.", "We reared larval Blanchard's cricket frogs (Acris blanchardi) and green frogs (Rana clamitans) in golf course ponds with and without 1 m terrestrial buffer zones, and released marked cricket frog metamorphs at the golf course ponds they were reared in.", "Larval survival of both species was affected by the presence of a buffer zone, with increased survival for cricket frogs and decreased survival for green frogs when reared in ponds with buffer zones.", "No marked cricket frog juveniles were recovered at any golf course pond in the following year, suggesting that most animals died or migrated.", "In a separate study, we released cricket frogs in a terrestrial pen and allowed them to choose between mown and unmown grass.", "Cricket frogs had a greater probability of using unmown versus mown grass.", "Our results suggest that incorporating buffer zones around ponds can offer suitable habitat for some amphibian species and can improve the quality of the aquatic environment for some sensitive local amphibians."], "title": "Effects of terrestrial buffer zones on amphibians on golf courses."}
{"paper_id": 25471879, "labels": ["0", "0", "0", "1", "0", "1"], "abstract": "Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates; however, the regulatory circuits specifying these states and enabling transitions between them are not well understood. Here we set out to characterize transcriptional heterogeneity in mouse PSCs by single-cell expression profiling under different chemical and genetic perturbations. Signalling factors and developmental regulators show highly variable expression, with expression states for some variable genes heritable through multiple cell divisions. Expression variability and population heterogeneity can be influenced by perturbation of signalling pathways and chromatin regulators. Notably, either removal of mature microRNAs or pharmacological blockage of signalling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency network, enhanced self-renewal and a distinct chromatin state, an effect mediated by opposing microRNA families acting on the Myc/Lin28/let-7 axis. These data provide insight into the nature of transcriptional heterogeneity in PSCs.", "journal": "Nature", "sentences": ["Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates; however, the regulatory circuits specifying these states and enabling transitions between them are not well understood.", "Here we set out to characterize transcriptional heterogeneity in mouse PSCs by single-cell expression profiling under different chemical and genetic perturbations.", "Signalling factors and developmental regulators show highly variable expression, with expression states for some variable genes heritable through multiple cell divisions.", "Expression variability and population heterogeneity can be influenced by perturbation of signalling pathways and chromatin regulators.", "Notably, either removal of mature microRNAs or pharmacological blockage of signalling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency network, enhanced self-renewal and a distinct chromatin state, an effect mediated by opposing microRNA families acting on the Myc/Lin28/let-7 axis.", "These data provide insight into the nature of transcriptional heterogeneity in PSCs."], "title": "Deconstructing transcriptional heterogeneity in pluripotent stem cells."}
{"paper_id": 27078750, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "In this paper, a magnetoelastic (ME) sensing system for the detection of classical swine fever virus (CSFV) is presented. The detection system comprises a test paper and a measurement circuit. The test paper consists mainly of an ME biosensor to detect the CSFV. Based on the impedance analysis technique, the measurement circuit is designed to measure the resonance frequency of the ME biosensor. The anti-CSFV IgG is immobilized onto the ME sensor surface to form the ME biosensor through a physical absorption approach. The experimental results show that the shift in the resonance frequency of the ME biosensor increases with the augmentation of the CSFV concentration. The effectiveness of the combination between the anti-CSFV IgG and CSFV is confirmed by the scanning electron microscopy (SEM) images, the sandwich-based enzyme-linked immunosorbent assay (ELISA) analysis, the interference study and the reference biosensor test method. The resonance frequency shift is linearly proportional to the concentration in the range from 0 to 2.5\u03bcg/ml, and becomes sub-linear at higher concentrations. The ME biosensor for CSFV detection has a sensitivity of about 95Hz/\u03bcg\u00b7ml(-1), with a detection limit of 0.6\u03bcg/ml.", "journal": "Biosensors & bioelectronics", "sentences": ["In this paper, a magnetoelastic (ME) sensing system for the detection of classical swine fever virus (CSFV) is presented.", "The detection system comprises a test paper and a measurement circuit.", "The test paper consists mainly of an ME biosensor to detect the CSFV.", "Based on the impedance analysis technique, the measurement circuit is designed to measure the resonance frequency of the ME biosensor.", "The anti-CSFV IgG is immobilized onto the ME sensor surface to form the ME biosensor through a physical absorption approach.", "The experimental results show that the shift in the resonance frequency of the ME biosensor increases with the augmentation of the CSFV concentration.", "The effectiveness of the combination between the anti-CSFV IgG and CSFV is confirmed by the scanning electron microscopy (SEM) images, the sandwich-based enzyme-linked immunosorbent assay (ELISA) analysis, the interference study and the reference biosensor test method.", "The resonance frequency shift is linearly proportional to the concentration in the range from 0 to 2.5\u03bcg/ml, and becomes sub-linear at higher concentrations.", "The ME biosensor for CSFV detection has a sensitivity of about 95Hz/\u03bcg\u00b7ml(-1), with a detection limit of 0.6\u03bcg/ml."], "title": "Detection system based on magnetoelastic sensor for classical swine fever virus."}
{"paper_id": 25015549, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Though tumor necrosis factor related apoptosis inducing ligand (TRAIL) has been used as a potent anticancer agent, TRAIL resistance is a hot-issue in cancer therapy. We investigated the antitumor mechanism of Tanshinone I to sensitize prostate cancer cells to TRAIL. Comibination of Tanshinone I and TRAIL exerted synergistic cytotoxicity, increased cleaved PARP, sub G1 population, the number of TUNELpositive cells, activated caspase 8, 9 and ROS production in PC-3 and DU145 cells. Of note, combination of Tanshinone I and TRAIL enhanced the protein expression of death receptor 5 (DR5) and attenuated anti-apoptotic proteins. RT-PCR and RT-qPCR analyses confirmed that co-treatment of Tanshinone I and TRAIL up-regulated DR5 and microRNA 135a-3p at mRNA level or activity of DR5 promoter and attenuated phosphorylation of extracellular signal regulated kinases in PC-3. Conversely, the silencing of DR5 blocked the increased cytotoxicity, sub G1 population and PARP cleavages induced by co-treatment of Tanshinone I and TRAIL. Interestingly, miR135a-3p mimic enhanced DR5 at mRNA, increased PARP cleavage, Bax and the number of TUNEL positive cells in Tanshinone I and TRAIL cotreated PC-3. Overall, our findings suggest that Tanshinone I enhances TRAIL mediated apoptosis via upregulation of miR135a-3p mediated DR5 in prostate cancer cells as a potent TRAIL sensitizer.", "journal": "Oncotarget", "sentences": ["Though tumor necrosis factor related apoptosis inducing ligand (TRAIL) has been used as a potent anticancer agent, TRAIL resistance is a hot-issue in cancer therapy.", "We investigated the antitumor mechanism of Tanshinone I to sensitize prostate cancer cells to TRAIL.", "Comibination of Tanshinone I and TRAIL exerted synergistic cytotoxicity, increased cleaved PARP, sub G1 population, the number of TUNELpositive cells, activated caspase 8, 9 and ROS production in PC-3 and DU145 cells.", "Of note, combination of Tanshinone I and TRAIL enhanced the protein expression of death receptor 5 (DR5) and attenuated anti-apoptotic proteins.", "RT-PCR and RT-qPCR analyses confirmed that co-treatment of Tanshinone I and TRAIL up-regulated DR5 and microRNA 135a-3p at mRNA level or activity of DR5 promoter and attenuated phosphorylation of extracellular signal regulated kinases in PC-3.", "Conversely, the silencing of DR5 blocked the increased cytotoxicity, sub G1 population and PARP cleavages induced by co-treatment of Tanshinone I and TRAIL.", "Interestingly, miR135a-3p mimic enhanced DR5 at mRNA, increased PARP cleavage, Bax and the number of TUNEL positive cells in Tanshinone I and TRAIL cotreated PC-3.", "Overall, our findings suggest that Tanshinone I enhances TRAIL mediated apoptosis via upregulation of miR135a-3p mediated DR5 in prostate cancer cells as a potent TRAIL sensitizer."], "title": "Upregulation of microRNA135a-3p and death receptor 5 plays a critical role in Tanshinone I sensitized prostate cancer cells to TRAIL induced apoptosis."}
{"paper_id": 26450986, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "We used an N-ethyl-N-nitrosurea-based forward genetic screen in mice to identify new genes and alleles that regulate erythropoiesis. Here, we describe a mouse line expressing an activated form of the K-Cl cotransporter Slc12a4 (Kcc1), which results in a semi-dominant microcytosis of red cells. A missense mutation from methionine to lysine in the cytoplasmic tail of Kcc1 impairs phosphorylation of adjacent threonines required for inhibiting cotransporter activity. We bred Kcc1(M935K) mutant mice with a humanized mouse model of sickle cell disease to directly explore the relevance of the reported increase in KCC activity in disease pathogenesis. We show that a single mutant allele of Kcc1 induces widespread sickling and tissue damage, leading to premature death. This mouse model reveals important new insights into the regulation of K-Cl cotransporters and provides in vivo evidence that increased KCC activity worsened end-organ damage and diminished survival in sickle cell disease.", "journal": "Blood", "sentences": ["We used an N-ethyl-N-nitrosurea-based forward genetic screen in mice to identify new genes and alleles that regulate erythropoiesis.", "Here, we describe a mouse line expressing an activated form of the K-Cl cotransporter Slc12a4 (Kcc1), which results in a semi-dominant microcytosis of red cells.", "A missense mutation from methionine to lysine in the cytoplasmic tail of Kcc1 impairs phosphorylation of adjacent threonines required for inhibiting cotransporter activity.", "We bred Kcc1(M935K) mutant mice with a humanized mouse model of sickle cell disease to directly explore the relevance of the reported increase in KCC activity in disease pathogenesis.", "We show that a single mutant allele of Kcc1 induces widespread sickling and tissue damage, leading to premature death.", "This mouse model reveals important new insights into the regulation of K-Cl cotransporters and provides in vivo evidence that increased KCC activity worsened end-organ damage and diminished survival in sickle cell disease."], "title": "Activation of the erythroid K-Cl cotransporter Kcc1 enhances sickle cell disease pathology in a humanized mouse model."}
{"paper_id": 24847314, "labels": ["0", "0", "0", "1", "0", "0", "0", "1"], "abstract": "We conducted a series of roller tank incubations with surface seawater from the Green Canyon oil reservoir, northern Gulf of Mexico, amended with either a natural oil slick (GCS-oil) or pristine oil. The goal was to test whether bacterial activities of natural surface water communities facilitate the formation of oil-rich marine snow (oil snow). Although oil snow did not form during any of our experiments, we found specific bacterial metabolic responses to the addition of GCS-oil that profoundly affected carbon cycling within our 4-days incubations. Peptidase and \u03b2-glucosidase activities indicative of bacterial enzymatic hydrolysis of peptides and carbohydrates, respectively, were suppressed upon the addition of GCS-oil relative to the non-oil treatment, suggesting that ascending oil and gas initially inhibits bacterial metabolism in surface water. Biodegradation of physically dispersed GCS-oil components, indicated by the degradation of lower molecular weight n-alkanes as well as the rapid transformation of particulate oil-carbon (C: N >40) into the DOC pool, led to the production of carbohydrate- and peptide-rich degradation byproducts and bacterial metabolites such as transparent exopolymer particles (TEP). TEP formation was highest at day 4 in the presence of GCS-oil; in contrast, TEP levels in the non-oil treatment already peaked at day 2. Cell-specific enzymatic activities closely followed TEP concentrations in the presence and absence of GCS-oil. These results demonstrate that the formation of oil slicks and activities of oil-degrading bacteria result in a temporal offset of microbial cycling of organic matter, affecting food web interactions and carbon cycling in surface waters over cold seeps.", "journal": "Frontiers in microbiology", "sentences": ["We conducted a series of roller tank incubations with surface seawater from the Green Canyon oil reservoir, northern Gulf of Mexico, amended with either a natural oil slick (GCS-oil) or pristine oil.", "The goal was to test whether bacterial activities of natural surface water communities facilitate the formation of oil-rich marine snow (oil snow).", "Although oil snow did not form during any of our experiments, we found specific bacterial metabolic responses to the addition of GCS-oil that profoundly affected carbon cycling within our 4-days incubations.", "Peptidase and \u03b2-glucosidase activities indicative of bacterial enzymatic hydrolysis of peptides and carbohydrates, respectively, were suppressed upon the addition of GCS-oil relative to the non-oil treatment, suggesting that ascending oil and gas initially inhibits bacterial metabolism in surface water.", "Biodegradation of physically dispersed GCS-oil components, indicated by the degradation of lower molecular weight n-alkanes as well as the rapid transformation of particulate oil-carbon (C: N >40) into the DOC pool, led to the production of carbohydrate- and peptide-rich degradation byproducts and bacterial metabolites such as transparent exopolymer particles (TEP).", "TEP formation was highest at day 4 in the presence of GCS-oil; in contrast, TEP levels in the non-oil treatment already peaked at day 2.", "Cell-specific enzymatic activities closely followed TEP concentrations in the presence and absence of GCS-oil.", "These results demonstrate that the formation of oil slicks and activities of oil-degrading bacteria result in a temporal offset of microbial cycling of organic matter, affecting food web interactions and carbon cycling in surface waters over cold seeps."], "title": "Natural oil slicks fuel surface water microbial activities in the northern Gulf of Mexico."}
{"paper_id": 21110944, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Uptake of external sterols in the yeast Saccharomyces cerevisiae is a multistep process limited to anaerobiosis or heme deficiency. It includes crossing the cell wall, insertion of sterol molecules into plasma membrane and their internalization and integration into intracellular membranes. We applied the fluorescent ergosterol analog dehydroergosterol (DHE) to monitor the initial steps of sterol uptake by three independent approaches: fluorescence spectroscopy, fluorescence microscopy and sterol quantification by HPLC. Using specific fluorescence characteristics of DHE we showed that the entry of sterol molecules into plasma membrane is not spontaneous but requires assistance of two ABC (ATP-binding cassette) pumps--Aus1p or Pdr11p. DHE taken up by uptake-competent hem1\u0394AUS1PDR11 cells could be directly visualized by UV-sensitive wide field fluorescence microscopy. HPLC analysis of sterols revealed significant amounts of exogenous ergosterol and DHE (but not cholesterol) associated with uptake-deficient hem1\u0394aus1\u0394pdr11\u0394 cells. Fluorescent sterol associated with these cells did not show the characteristic emission spectrum of membrane-integrated DHE. The amount of cell-associated DHE was significantly reduced after enzymatic removal of the cell wall. Our results demonstrate that the yeast cell wall is actively involved in binding and uptake of ergosterol-like sterols.", "journal": "Biochemical and biophysical research communications", "sentences": ["Uptake of external sterols in the yeast Saccharomyces cerevisiae is a multistep process limited to anaerobiosis or heme deficiency.", "It includes crossing the cell wall, insertion of sterol molecules into plasma membrane and their internalization and integration into intracellular membranes.", "We applied the fluorescent ergosterol analog dehydroergosterol (DHE) to monitor the initial steps of sterol uptake by three independent approaches: fluorescence spectroscopy, fluorescence microscopy and sterol quantification by HPLC.", "Using specific fluorescence characteristics of DHE we showed that the entry of sterol molecules into plasma membrane is not spontaneous but requires assistance of two ABC (ATP-binding cassette) pumps--Aus1p or Pdr11p.", "DHE taken up by uptake-competent hem1\u0394AUS1PDR11 cells could be directly visualized by UV-sensitive wide field fluorescence microscopy.", "HPLC analysis of sterols revealed significant amounts of exogenous ergosterol and DHE (but not cholesterol) associated with uptake-deficient hem1\u0394aus1\u0394pdr11\u0394 cells.", "Fluorescent sterol associated with these cells did not show the characteristic emission spectrum of membrane-integrated DHE.", "The amount of cell-associated DHE was significantly reduced after enzymatic removal of the cell wall.", "Our results demonstrate that the yeast cell wall is actively involved in binding and uptake of ergosterol-like sterols."], "title": "The role of ABC proteins Aus1p and Pdr11p in the uptake of external sterols in yeast: dehydroergosterol fluorescence study."}
{"paper_id": 21814202, "labels": ["0", "0", "0", "0", "1", "0", "0", "0", "0", "1"], "abstract": "Global warming is predicted to induce desiccation in many world regions through increases in evaporative demand. Rising CO(2) may counter that trend by improving plant water-use efficiency. However, it is not clear how important this CO(2)-enhanced water use efficiency might be in offsetting warming-induced desiccation because higher CO(2) also leads to higher plant biomass, and therefore greater transpirational surface. Furthermore, although warming is predicted to favour warm-season, C(4) grasses, rising CO(2) should favour C(3), or cool-season plants. Here we show in a semi-arid grassland that elevated CO(2) can completely reverse the desiccating effects of moderate warming. Although enrichment of air to 600\u2009p.p.m.v. CO(2) increased soil water content (SWC), 1.5/3.0\u2009\u00b0C day/night warming resulted in desiccation, such that combined CO(2) enrichment and warming had no effect on SWC relative to control plots. As predicted, elevated CO(2) favoured C(3) grasses and enhanced stand productivity, whereas warming favoured C(4) grasses. Combined warming and CO(2) enrichment stimulated above-ground growth of C(4) grasses in 2 of 3\u2009years when soil moisture most limited plant productivity. The results indicate that in a warmer, CO(2)-enriched world, both SWC and productivity in semi-arid grasslands may be higher than previously expected.", "journal": "Nature", "sentences": ["Global warming is predicted to induce desiccation in many world regions through increases in evaporative demand.", "Rising CO(2) may counter that trend by improving plant water-use efficiency.", "However, it is not clear how important this CO(2)-enhanced water use efficiency might be in offsetting warming-induced desiccation because higher CO(2) also leads to higher plant biomass, and therefore greater transpirational surface.", "Furthermore, although warming is predicted to favour warm-season, C(4) grasses, rising CO(2) should favour C(3), or cool-season plants.", "Here we show in a semi-arid grassland that elevated CO(2) can completely reverse the desiccating effects of moderate warming.", "Although enrichment of air to 600\u2009p.p.m.v.", "CO(2) increased soil water content (SWC), 1.5/3.0\u2009\u00b0C day/night warming resulted in desiccation, such that combined CO(2) enrichment and warming had no effect on SWC relative to control plots.", "As predicted, elevated CO(2) favoured C(3) grasses and enhanced stand productivity, whereas warming favoured C(4) grasses.", "Combined warming and CO(2) enrichment stimulated above-ground growth of C(4) grasses in 2 of 3\u2009years when soil moisture most limited plant productivity.", "The results indicate that in a warmer, CO(2)-enriched world, both SWC and productivity in semi-arid grasslands may be higher than previously expected."], "title": "C4 grasses prosper as carbon dioxide eliminates desiccation in warmed semi-arid grassland."}
{"paper_id": 23980206, "labels": ["0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "Despite an abundance of peptides inside a cell, only a small fraction is ultimately presented by HLA-I on the cell surface. The presented peptides have HLA-I allomorph-specific motifs and are restricted in length. So far, detailed length studies have been limited to few allomorphs. Peptide-HLA-I (pHLA-I) complexes of different allomorphs are qualitatively and quantitatively influenced by tapasin to different degrees, but again, its effect has only been investigated for a small number of HLA-I allomorphs. Although both peptide length and tapasin dependence are known to be important for HLA-I peptide presentation, the relationship between them has never been studied. In this study, we used random peptide libraries from 7- to 13-mers and studied binding in the presence and absence of a recombinant truncated form of tapasin. The data show that HLA-I allomorphs are differentially affected by tapasin, different lengths of peptides generated different amounts of pHLA-I complexes, and HLA-A allomorphs are generally less restricted than HLA-B allomorphs to peptides of the classical length of 8-10 aa. We also demonstrate that tapasin facilitation varies for different peptide lengths, and that the correlation between high degree of tapasin facilitation and low stability is valid for different random peptide mixes of specific lengths. In conclusion, these data show that tapasin has specificity for the combination of peptide length and HLA-I allomorph, and suggest that tapasin promotes formation of pHLA-I complexes with high on and off rates, an important intermediary step in the HLA-I maturation process.", "journal": "Journal of immunology (Baltimore, Md. : 1950)", "sentences": ["Despite an abundance of peptides inside a cell, only a small fraction is ultimately presented by HLA-I on the cell surface.", "The presented peptides have HLA-I allomorph-specific motifs and are restricted in length.", "So far, detailed length studies have been limited to few allomorphs.", "Peptide-HLA-I (pHLA-I) complexes of different allomorphs are qualitatively and quantitatively influenced by tapasin to different degrees, but again, its effect has only been investigated for a small number of HLA-I allomorphs.", "Although both peptide length and tapasin dependence are known to be important for HLA-I peptide presentation, the relationship between them has never been studied.", "In this study, we used random peptide libraries from 7- to 13-mers and studied binding in the presence and absence of a recombinant truncated form of tapasin.", "The data show that HLA-I allomorphs are differentially affected by tapasin, different lengths of peptides generated different amounts of pHLA-I complexes, and HLA-A allomorphs are generally less restricted than HLA-B allomorphs to peptides of the classical length of 8-10 aa.", "We also demonstrate that tapasin facilitation varies for different peptide lengths, and that the correlation between high degree of tapasin facilitation and low stability is valid for different random peptide mixes of specific lengths.", "In conclusion, these data show that tapasin has specificity for the combination of peptide length and HLA-I allomorph, and suggest that tapasin promotes formation of pHLA-I complexes with high on and off rates, an important intermediary step in the HLA-I maturation process."], "title": "Tapasin facilitation of natural HLA-A and -B allomorphs is strongly influenced by peptide length, depends on stability, and separates closely related allomorphs."}
{"paper_id": 24069167, "labels": ["0", "0", "0", "0", "0", "1", "0", "1", "0", "1"], "abstract": "The rate at which mutations are generated is central to the pace of evolution. Although this rate is remarkably similar amongst all cellular organisms, bacterial strains with mutation rates 100 fold greater than the modal rates of their species are commonly isolated from natural sources and emerge in experimental populations. Theoretical studies postulate and empirical studies teort the hypotheses that these \"mutator\" strains evolved in response to selection for elevated rates of generation of inherited variation that enable bacteria to adapt to novel and/or rapidly changing environments. Less clear are the conditions under which selection will favor reductions in mutation rates. Declines in rates of mutation for established populations of mutator bacteria are not anticipated if such changes are attributed to the costs of augmented rates of generation of deleterious mutations. Here we report experimental evidence of evolution towards reduced mutation rates in a clinical isolate of Escherichia coli with an hyper-mutable phenotype due a deletion in a mismatch repair gene, (\u0394mutS). The emergence in a \u0394mutS background of variants with mutation rates approaching those of the normal rates of strains carrying wild-type MutS was associated with increase in fitness with respect to ancestral strain. We postulate that such an increase in fitness could be attributed to the emergence of mechanisms driving a permanent \"aerobic style of life\", the negative consequence of this behavior being regulated by the evolution of mechanisms protecting the cell against increased endogenous oxidative radicals involved in DNA damage, and thus reducing mutation rate. Gene expression assays and full sequencing of evolved mutator and normo-mutable variants supports the hypothesis. In conclusion, we postulate that the observed reductions in mutation rate are coincidental to, rather than, the selective force responsible for this evolution.", "journal": "PloS one", "sentences": ["The rate at which mutations are generated is central to the pace of evolution.", "Although this rate is remarkably similar amongst all cellular organisms, bacterial strains with mutation rates 100 fold greater than the modal rates of their species are commonly isolated from natural sources and emerge in experimental populations.", "Theoretical studies postulate and empirical studies teort the hypotheses that these \"mutator\" strains evolved in response to selection for elevated rates of generation of inherited variation that enable bacteria to adapt to novel and/or rapidly changing environments.", "Less clear are the conditions under which selection will favor reductions in mutation rates.", "Declines in rates of mutation for established populations of mutator bacteria are not anticipated if such changes are attributed to the costs of augmented rates of generation of deleterious mutations.", "Here we report experimental evidence of evolution towards reduced mutation rates in a clinical isolate of Escherichia coli with an hyper-mutable phenotype due a deletion in a mismatch repair gene, (\u0394mutS).", "The emergence in a \u0394mutS background of variants with mutation rates approaching those of the normal rates of strains carrying wild-type MutS was associated with increase in fitness with respect to ancestral strain.", "We postulate that such an increase in fitness could be attributed to the emergence of mechanisms driving a permanent \"aerobic style of life\", the negative consequence of this behavior being regulated by the evolution of mechanisms protecting the cell against increased endogenous oxidative radicals involved in DNA damage, and thus reducing mutation rate.", "Gene expression assays and full sequencing of evolved mutator and normo-mutable variants supports the hypothesis.", "In conclusion, we postulate that the observed reductions in mutation rate are coincidental to, rather than, the selective force responsible for this evolution."], "title": "Normal mutation rate variants arise in a Mutator (Mut S) Escherichia coli population."}
{"paper_id": 22337128, "labels": ["0", "0", "1", "0", "0", "0", "0"], "abstract": "The extraordinary properties of graphene and carbon nanotubes motivate the development of methods for their use in producing continuous, strong, tough fibres. Previous work has shown that the toughness of the carbon nanotube-reinforced polymer fibres exceeds that of previously known materials. Here we show that further increased toughness results from combining carbon nanotubes and reduced graphene oxide flakes in solution-spun polymer fibres. The gravimetric toughness approaches 1,000 J g(-1), far exceeding spider dragline silk (165 J g(-1)) and Kevlar (78 J g(-1)). This toughness enhancement is consistent with the observed formation of an interconnected network of partially aligned reduced graphene oxide flakes and carbon nanotubes during solution spinning, which act to deflect cracks and allow energy-consuming polymer deformation. Toughness is sensitive to the volume ratio of the reduced graphene oxide flakes to the carbon nanotubes in the spinning solution and the degree of graphene oxidation. The hybrid fibres were sewable and weavable, and could be shaped into high-modulus helical springs.", "journal": "Nature communications", "sentences": ["The extraordinary properties of graphene and carbon nanotubes motivate the development of methods for their use in producing continuous, strong, tough fibres.", "Previous work has shown that the toughness of the carbon nanotube-reinforced polymer fibres exceeds that of previously known materials.", "Here we show that further increased toughness results from combining carbon nanotubes and reduced graphene oxide flakes in solution-spun polymer fibres.", "The gravimetric toughness approaches 1,000 J g(-1), far exceeding spider dragline silk (165 J g(-1)) and Kevlar (78 J g(-1)).", "This toughness enhancement is consistent with the observed formation of an interconnected network of partially aligned reduced graphene oxide flakes and carbon nanotubes during solution spinning, which act to deflect cracks and allow energy-consuming polymer deformation.", "Toughness is sensitive to the volume ratio of the reduced graphene oxide flakes to the carbon nanotubes in the spinning solution and the degree of graphene oxidation.", "The hybrid fibres were sewable and weavable, and could be shaped into high-modulus helical springs."], "title": "Synergistic toughening of composite fibres by self-alignment of reduced graphene oxide and carbon nanotubes."}
{"paper_id": 24386622, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The increasing prevalence of environmental pollution, especially soil contamination with heavy metals has led to their uptake in the human food chains through plant parts. Accumulation and magnification of heavy metals in human tissues through consumption of herbal remedies can cause hazardous impacts on health. Therefore, chemical profiling of nine heavy metals (Mn, Cr, Pb, Fe, Cd, Co, Zn, Ni and Hg) was undertaken in stem and leaf samples of ten medicinal plants (Acacia nilotica, Bacopa monnieri, Commiphora wightii, Ficus religiosa, Glycyrrhiza glabra, Hemidesmus indicus, Salvadora oleoides, Terminalia bellirica, Terminalia chebula and Withania somnifera) collected from environmentally diverse regions of Haryana and Rajasthan states in North-Western India. Concentration of all heavy metals, except Cr, was within permissible limits in the tested stem and leaf samples. Leaf samples had consistently more Cr compared to respective stem samples with highest concentration in leaf samples of Bacopa monnieri (13.19\u2009\u00b1\u20090.0480 ppm) and stem samples of Withania somnifera (4.93\u2009\u00b1\u20090.0185 ppm) both collected from Bahadurgarh (heavy industrial area), Haryana. This amount was beyond the permissible limit of 2.0 ppm defined by WHO for raw herbal material. Other two most perilous metals Pb (2.64\u2009\u00b1\u20090.0260) and Cd (0.04\u2009\u00b1\u20090.0274) were also recorded in Bahadurgarh region, although below permissible limits. Concentration of Hg remained below detectable levels in all the leaf and stem samples tested. These results suggested that cultivation of medicinal plants and other dietary herbs should be curtailed near environmentally polluted especially industrial areas for avoidance of health hazards.", "journal": "SpringerPlus", "sentences": ["The increasing prevalence of environmental pollution, especially soil contamination with heavy metals has led to their uptake in the human food chains through plant parts.", "Accumulation and magnification of heavy metals in human tissues through consumption of herbal remedies can cause hazardous impacts on health.", "Therefore, chemical profiling of nine heavy metals (Mn, Cr, Pb, Fe, Cd, Co, Zn, Ni and Hg) was undertaken in stem and leaf samples of ten medicinal plants (Acacia nilotica, Bacopa monnieri, Commiphora wightii, Ficus religiosa, Glycyrrhiza glabra, Hemidesmus indicus, Salvadora oleoides, Terminalia bellirica, Terminalia chebula and Withania somnifera) collected from environmentally diverse regions of Haryana and Rajasthan states in North-Western India.", "Concentration of all heavy metals, except Cr, was within permissible limits in the tested stem and leaf samples.", "Leaf samples had consistently more Cr compared to respective stem samples with highest concentration in leaf samples of Bacopa monnieri (13.19\u2009\u00b1\u20090.0480 ppm) and stem samples of Withania somnifera (4.93\u2009\u00b1\u20090.0185 ppm) both collected from Bahadurgarh (heavy industrial area), Haryana.", "This amount was beyond the permissible limit of 2.0 ppm defined by WHO for raw herbal material.", "Other two most perilous metals Pb (2.64\u2009\u00b1\u20090.0260) and Cd (0.04\u2009\u00b1\u20090.0274) were also recorded in Bahadurgarh region, although below permissible limits.", "Concentration of Hg remained below detectable levels in all the leaf and stem samples tested.", "These results suggested that cultivation of medicinal plants and other dietary herbs should be curtailed near environmentally polluted especially industrial areas for avoidance of health hazards."], "title": "Investigation of heavy metals in frequently utilized medicinal plants collected from environmentally diverse locations of north western India."}
{"paper_id": 26975048, "labels": ["0", "0", "0", "0", "1", "0", "1", "1"], "abstract": "Numerous studies have identified the effects of prematurity on the neonate's physical health, however few studies have explored the effects of prematurity on both the physical and mental health of the child as they develop. Secondary analysis of data from the Millennium Cohort Study, a longitudinal study of infants (n = 18 818, born 2000-2002 in the United Kingdom) was performed. Effects of gestational age at birth on health outcomes at 5 years were measured using parental rating of their children's general health and severity of behavior problems. The association between parent's general health ratings and behavior problem ratings was low: 86% of those reporting serious behavior problems (5% of the sample, n = 764) rated their child as being in excellent, very good, or good health. Still, a gradient of increasing risk of poorer outcome with decreasing gestational age was observed for a composite health measure (poor/fair health and/or serious behavior problems), suggesting an association with prematurity for this composite assessment of health status. The greatest contribution to the childhood composite health measure at 5 years was for children born at 32-36 weeks gestation: population attributable fractions for having poor outcomes was 3.4% (Bonferroni-adjusted 95% confidence interval 1.1%-6.2%), compared to 1% (0.2-2.3) for birth at less than 32 weeks. Results suggest that preterm children, by school entry, are not only at high risk of physical health problems, but also of behavioral health problems. The recognition of, and response to comprehensive health and well-being outcomes related to prematurity are important in order to correctly plan and deliver adequate paediatric health services and policies.", "journal": "PloS one", "sentences": ["Numerous studies have identified the effects of prematurity on the neonate's physical health, however few studies have explored the effects of prematurity on both the physical and mental health of the child as they develop.", "Secondary analysis of data from the Millennium Cohort Study, a longitudinal study of infants (n = 18 818, born 2000-2002 in the United Kingdom) was performed.", "Effects of gestational age at birth on health outcomes at 5 years were measured using parental rating of their children's general health and severity of behavior problems.", "The association between parent's general health ratings and behavior problem ratings was low: 86% of those reporting serious behavior problems (5% of the sample, n = 764) rated their child as being in excellent, very good, or good health.", "Still, a gradient of increasing risk of poorer outcome with decreasing gestational age was observed for a composite health measure (poor/fair health and/or serious behavior problems), suggesting an association with prematurity for this composite assessment of health status.", "The greatest contribution to the childhood composite health measure at 5 years was for children born at 32-36 weeks gestation: population attributable fractions for having poor outcomes was 3.4% (Bonferroni-adjusted 95% confidence interval 1.1%-6.2%), compared to 1% (0.2-2.3) for birth at less than 32 weeks.", "Results suggest that preterm children, by school entry, are not only at high risk of physical health problems, but also of behavioral health problems.", "The recognition of, and response to comprehensive health and well-being outcomes related to prematurity are important in order to correctly plan and deliver adequate paediatric health services and policies."], "title": "Gestational Age at Birth and 'Body-Mind' Health at 5 Years of Age: A Population Based Cohort Study."}
{"paper_id": 21156139, "labels": ["0", "0", "0", "0", "1"], "abstract": "In this work we use transition network analysis for the first time to investigate ligand migration in truncated hemoglobin (trHbN) and obtain kinetic information about the docking-site dynamics in the protein. A comparison with explicit water molecular dynamics simulations (100 ns in total) shows that the rate constants derived from the network analysis are realistic. The transition network analysis provides 1) The time-resolved connectivity network in the protein; 2) The half-lives of the docking sites; 3) The transition timescales between two given docking sites; and 4) The extent of population transfer among different docking sites of the protein as a function of lag time. We investigate the role of the Tyr33 and Gln58 residues in ligand migration by studying ligand migration in four mutants of trHbN. The mutation study suggests that residues Tyr33 and Gln58 stabilize the NO ligand in the Xe2 docking site of trHbN, thus facilitating the efficiency of the NO detoxification reaction.", "journal": "Biophysical journal", "sentences": ["In this work we use transition network analysis for the first time to investigate ligand migration in truncated hemoglobin (trHbN) and obtain kinetic information about the docking-site dynamics in the protein.", "A comparison with explicit water molecular dynamics simulations (100 ns in total) shows that the rate constants derived from the network analysis are realistic.", "The transition network analysis provides 1) The time-resolved connectivity network in the protein; 2) The half-lives of the docking sites; 3) The transition timescales between two given docking sites; and 4) The extent of population transfer among different docking sites of the protein as a function of lag time.", "We investigate the role of the Tyr33 and Gln58 residues in ligand migration by studying ligand migration in four mutants of trHbN.", "The mutation study suggests that residues Tyr33 and Gln58 stabilize the NO ligand in the Xe2 docking site of trHbN, thus facilitating the efficiency of the NO detoxification reaction."], "title": "Quantitative analysis of ligand migration from transition networks."}
{"paper_id": 22456882, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "There are two highly interconnected clusters of visually responsive areas in the primate cortex. These two clusters have relatively few interconnections with each other, though those interconnections are undoubtedly important. One of the two main clusters (the dorsal stream) links the primary visual cortex (V1) to superior regions of the occipito-parietal cortex, while the other (the ventral stream) links V1 to inferior regions of the occipito-temporal cortex. According to our current understanding of the functional anatomy of these two systems, the dorsal stream's principal role is to provide real-time 'bottom-up' visual guidance of our movements online. In contrast, the ventral stream, in conjunction with top-down information from visual and semantic memory, provides perceptual representations that can serve recognition, visual thought, planning and memory offline. In recent years, this interpretation, initially based chiefly on studies of non-human primates and human neurological patients, has been well supported by functional MRI studies in humans. This perspective presents empirical evidence for the contention that the dorsal stream governs the visual control of movement without the intervention of visual awareness.", "journal": "Proceedings. Biological sciences / The Royal Society", "sentences": ["There are two highly interconnected clusters of visually responsive areas in the primate cortex.", "These two clusters have relatively few interconnections with each other, though those interconnections are undoubtedly important.", "One of the two main clusters (the dorsal stream) links the primary visual cortex (V1) to superior regions of the occipito-parietal cortex, while the other (the ventral stream) links V1 to inferior regions of the occipito-temporal cortex.", "According to our current understanding of the functional anatomy of these two systems, the dorsal stream's principal role is to provide real-time 'bottom-up' visual guidance of our movements online.", "In contrast, the ventral stream, in conjunction with top-down information from visual and semantic memory, provides perceptual representations that can serve recognition, visual thought, planning and memory offline.", "In recent years, this interpretation, initially based chiefly on studies of non-human primates and human neurological patients, has been well supported by functional MRI studies in humans.", "This perspective presents empirical evidence for the contention that the dorsal stream governs the visual control of movement without the intervention of visual awareness."], "title": "Is visual processing in the dorsal stream accessible to consciousness?"}
{"paper_id": 24068814, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Cortical activity was measured with functional magnetic resonance imaging (fMRI) while human subjects viewed 12 stimulus colors and performed either a color-naming or diverted attention task. A forward model was used to extract lower dimensional neural color spaces from the high-dimensional fMRI responses. The neural color spaces in two visual areas, human ventral V4 (V4v) and VO1, exhibited clustering (greater similarity between activity patterns evoked by stimulus colors within a perceptual category, compared to between-category colors) for the color-naming task, but not for the diverted attention task. Response amplitudes and signal-to-noise ratios were higher in most visual cortical areas for color naming compared to diverted attention. But only in V4v and VO1 did the cortical representation of color change to a categorical color space. A model is presented that induces such a categorical representation by changing the response gains of subpopulations of color-selective neurons.", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "sentences": ["Cortical activity was measured with functional magnetic resonance imaging (fMRI) while human subjects viewed 12 stimulus colors and performed either a color-naming or diverted attention task.", "A forward model was used to extract lower dimensional neural color spaces from the high-dimensional fMRI responses.", "The neural color spaces in two visual areas, human ventral V4 (V4v) and VO1, exhibited clustering (greater similarity between activity patterns evoked by stimulus colors within a perceptual category, compared to between-category colors) for the color-naming task, but not for the diverted attention task.", "Response amplitudes and signal-to-noise ratios were higher in most visual cortical areas for color naming compared to diverted attention.", "But only in V4v and VO1 did the cortical representation of color change to a categorical color space.", "A model is presented that induces such a categorical representation by changing the response gains of subpopulations of color-selective neurons."], "title": "Categorical clustering of the neural representation of color."}
{"paper_id": 20664174, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Targeted cancer therapeutics can be effective when patients are preselected to maximize the chance of response. Increasingly, molecular markers such as oncogenic DNA mutations are being exploited to help guide patient preselection. These DNA lesions can predict for either a positive or negative response to a given drug. Finding such predictive biomarkers is an ongoing challenge. New work by Di Nicolantonio and colleagues in this issue of the JCI demonstrates that PI3K catalytic alpha subunit (PIK3CA) mutations can sensitize cancer cells to the mammalian target of rapamycin (mTOR) inhibitor everolimus. In addition, they show that the concurrent presence of PIK3CA mutations and mutations in either KRAS or BRAF predict for resistance to this drug. These data suggest that mTOR inhibitors currently in use will be ineffective against cancers that have a mutation in either KRAS or BRAF despite having PI3K/AKT/mTOR pathway activation.", "journal": "The Journal of clinical investigation", "sentences": ["Targeted cancer therapeutics can be effective when patients are preselected to maximize the chance of response.", "Increasingly, molecular markers such as oncogenic DNA mutations are being exploited to help guide patient preselection.", "These DNA lesions can predict for either a positive or negative response to a given drug.", "Finding such predictive biomarkers is an ongoing challenge.", "New work by Di Nicolantonio and colleagues in this issue of the JCI demonstrates that PI3K catalytic alpha subunit (PIK3CA) mutations can sensitize cancer cells to the mammalian target of rapamycin (mTOR) inhibitor everolimus.", "In addition, they show that the concurrent presence of PIK3CA mutations and mutations in either KRAS or BRAF predict for resistance to this drug.", "These data suggest that mTOR inhibitors currently in use will be ineffective against cancers that have a mutation in either KRAS or BRAF despite having PI3K/AKT/mTOR pathway activation."], "title": "PIK3CA and KRAS mutations predict for response to everolimus therapy: now that's RAD001."}
{"paper_id": 26090398, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Cytarabine is one of the most effective antineoplastic agents among those used for the treatment of acute myeloid leukemia. However, some patients develop resistance and/or severe side effects to the drug, which may interfere with the efficacy of the treatment. The polymorphisms of some Ara-C metabolizing enzymes seem to affect outcome and toxicity in AML patients receiving cytarabine. We conducted this study in a cohort of Mexican pediatric patients with AML to investigate whether the polymorphisms of the deoxycytidine kinase and cytidine deaminase enzymes are implicated in clinical response and toxicity. Bone marrow and/or peripheral blood samples obtained at diagnosis from 27 previously untreated pediatric patients with de novo AML were processed for genotyping and in vitro chemosensitivity assay, and we analyzed the impact of genotypes and in vitro sensitivity on disease outcome and toxicity. In the multivariate Cox regression analysis, we found that age at diagnosis, wild-type genotype of the CDA A79C polymorphism, and wild-type genotype of the dCK C360G polymorphism were the most significant prognostic factors for predicting the risk of death.", "journal": "BioMed research international", "sentences": ["Cytarabine is one of the most effective antineoplastic agents among those used for the treatment of acute myeloid leukemia.", "However, some patients develop resistance and/or severe side effects to the drug, which may interfere with the efficacy of the treatment.", "The polymorphisms of some Ara-C metabolizing enzymes seem to affect outcome and toxicity in AML patients receiving cytarabine.", "We conducted this study in a cohort of Mexican pediatric patients with AML to investigate whether the polymorphisms of the deoxycytidine kinase and cytidine deaminase enzymes are implicated in clinical response and toxicity.", "Bone marrow and/or peripheral blood samples obtained at diagnosis from 27 previously untreated pediatric patients with de novo AML were processed for genotyping and in vitro chemosensitivity assay, and we analyzed the impact of genotypes and in vitro sensitivity on disease outcome and toxicity.", "In the multivariate Cox regression analysis, we found that age at diagnosis, wild-type genotype of the CDA A79C polymorphism, and wild-type genotype of the dCK C360G polymorphism were the most significant prognostic factors for predicting the risk of death."], "title": "Role of Genetic Polymorphisms of Deoxycytidine Kinase and Cytidine Deaminase to Predict Risk of Death in Children with Acute Myeloid Leukemia."}
{"paper_id": 25978416, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The antigenic variability of influenza viruses has always made influenza vaccine development challenging. The punctuated nature of antigenic drift of influenza virus suggests that a relatively small number of genetic changes or combinations of genetic changes may drive changes in antigenic phenotype. The present study aimed to identify antigenicity-associated sites in the hemagglutinin protein of A/H1N1 seasonal influenza virus using computational approaches. Random Forest Regression (RFR) and Support Vector Regression based on Recursive Feature Elimination (SVR-RFE) were applied to H1N1 seasonal influenza viruses and used to analyze the associations between amino acid changes in the HA1 polypeptide and antigenic variation based on hemagglutination-inhibition (HI) assay data. Twenty-three and twenty antigenicity-associated sites were identified by RFR and SVR-RFE, respectively, by considering the joint effects of amino acid residues on antigenic drift. Our proposed approaches were further validated with the H3N2 dataset. The prediction models developed in this study can quantitatively predict antigenic differences with high prediction accuracy based only on HA1 sequences. Application of the study results can increase understanding of H1N1 seasonal influenza virus antigenic evolution and accelerate the selection of vaccine strains.", "journal": "PloS one", "sentences": ["The antigenic variability of influenza viruses has always made influenza vaccine development challenging.", "The punctuated nature of antigenic drift of influenza virus suggests that a relatively small number of genetic changes or combinations of genetic changes may drive changes in antigenic phenotype.", "The present study aimed to identify antigenicity-associated sites in the hemagglutinin protein of A/H1N1 seasonal influenza virus using computational approaches.", "Random Forest Regression (RFR) and Support Vector Regression based on Recursive Feature Elimination (SVR-RFE) were applied to H1N1 seasonal influenza viruses and used to analyze the associations between amino acid changes in the HA1 polypeptide and antigenic variation based on hemagglutination-inhibition (HI) assay data.", "Twenty-three and twenty antigenicity-associated sites were identified by RFR and SVR-RFE, respectively, by considering the joint effects of amino acid residues on antigenic drift.", "Our proposed approaches were further validated with the H3N2 dataset.", "The prediction models developed in this study can quantitatively predict antigenic differences with high prediction accuracy based only on HA1 sequences.", "Application of the study results can increase understanding of H1N1 seasonal influenza virus antigenic evolution and accelerate the selection of vaccine strains."], "title": "Computational Identification of Antigenicity-Associated Sites in the Hemagglutinin Protein of A/H1N1 Seasonal Influenza Virus."}
{"paper_id": 20067847, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "Differential expression of proteins in needles of the extreme freeze tolerant conifer Picea obovata during September, October and November was analyzed using DIGE technology and multivariate analysis. More than 1200 spots were detected, and the abundance of 252 of these spots was significantly altered during the course of acclimation. The 252 spots were clustered into five distinct expression profiles. Among the protein spots showing differential expression, 43 were identified by MALDI-TOF/TOF and twelve of them matched proteins associated with various biotic and abiotic stress responses in other plants. Dehydrins, Hsp70s, AAA(+) ATPases, lipocalin, cyclophilins, glycine-rich protein (GNP) and several reactive oxygen intermediate scavenging proteins showed increased accumulation levels from September to November. The expression profiles and putative role of the identified proteins during acclimation and freezing tolerance are discussed.", "journal": "Journal of proteomics", "sentences": ["Differential expression of proteins in needles of the extreme freeze tolerant conifer Picea obovata during September, October and November was analyzed using DIGE technology and multivariate analysis.", "More than 1200 spots were detected, and the abundance of 252 of these spots was significantly altered during the course of acclimation.", "The 252 spots were clustered into five distinct expression profiles.", "Among the protein spots showing differential expression, 43 were identified by MALDI-TOF/TOF and twelve of them matched proteins associated with various biotic and abiotic stress responses in other plants.", "Dehydrins, Hsp70s, AAA(+) ATPases, lipocalin, cyclophilins, glycine-rich protein (GNP) and several reactive oxygen intermediate scavenging proteins showed increased accumulation levels from September to November.", "The expression profiles and putative role of the identified proteins during acclimation and freezing tolerance are discussed."], "title": "Proteomics of extreme freezing tolerance in Siberian spruce (Picea obovata)."}
{"paper_id": 23756184, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "The hippocampus, derived from medial regions of the telencephalon, constitutes a remarkable brain structure. It is part of the limbic system, and it plays important roles in information encoding, related to short-term and long-term memory, and spatial navigation. It has also attracted the attention of many clinicians and neuroscientists for its involvement in a wide spectrum of pathological conditions, including epilepsy, intellectual disability, Alzheimer disease and others. Here we address the topic of hippocampal development. As well as original landmark findings, modern techniques such as large-scale in situ hybridizations, in utero electroporation and the study of mouse mutants with hippocampal phenotypes, add further detail to our knowledge of the finely regulated processes which form this intricate structure. Molecular signatures are being revealed related to field, intra-field and laminar cell identity, as well as, cell compartments expressing surface proteins instrumental for connectivity. We summarize here old and new findings, and highlight elegant tools used to fine-study hippocampal development.", "journal": "Neuroscience", "sentences": ["The hippocampus, derived from medial regions of the telencephalon, constitutes a remarkable brain structure.", "It is part of the limbic system, and it plays important roles in information encoding, related to short-term and long-term memory, and spatial navigation.", "It has also attracted the attention of many clinicians and neuroscientists for its involvement in a wide spectrum of pathological conditions, including epilepsy, intellectual disability, Alzheimer disease and others.", "Here we address the topic of hippocampal development.", "As well as original landmark findings, modern techniques such as large-scale in situ hybridizations, in utero electroporation and the study of mouse mutants with hippocampal phenotypes, add further detail to our knowledge of the finely regulated processes which form this intricate structure.", "Molecular signatures are being revealed related to field, intra-field and laminar cell identity, as well as, cell compartments expressing surface proteins instrumental for connectivity.", "We summarize here old and new findings, and highlight elegant tools used to fine-study hippocampal development."], "title": "Hippocampal development - old and new findings."}
{"paper_id": 21543496, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Chronic fatigue syndrome (CFS) is a multisystem disorder characterized by prolonged and severe fatigue that is not relieved by rest. Attempts to treat CFS have been largely ineffective primarily because the etiology of the disorder is unknown. Recently, CFS has been associated with xenotropic murine leukemia virus-related virus (XMRV) as well as other murine leukemia virus (MLV)-related viruses, though not all studies have found these associations. We collected blood samples from 100 CFS patients and 200 self-reported healthy volunteers from the same geographical area. We analyzed these in a blind manner using molecular, serological, and viral replication assays. We also analyzed samples from patients in the original study that reported XMRV in CFS patients. We did not find XMRV or related MLVs either as viral sequences or infectious viruses, nor did we find antibodies to these viruses in any of the patient samples, including those from the original study. We show that at least some of the discrepancy with previous studies is due to the presence of trace amounts of mouse DNA in the Taq polymerase enzymes used in these previous studies. Our findings do not support an association between CFS and MLV-related viruses, including XMRV, and the off-label use of antiretrovirals for the treatment of CFS does not seem justified at present.", "journal": "Journal of virology", "sentences": ["Chronic fatigue syndrome (CFS) is a multisystem disorder characterized by prolonged and severe fatigue that is not relieved by rest.", "Attempts to treat CFS have been largely ineffective primarily because the etiology of the disorder is unknown.", "Recently, CFS has been associated with xenotropic murine leukemia virus-related virus (XMRV) as well as other murine leukemia virus (MLV)-related viruses, though not all studies have found these associations.", "We collected blood samples from 100 CFS patients and 200 self-reported healthy volunteers from the same geographical area.", "We analyzed these in a blind manner using molecular, serological, and viral replication assays.", "We also analyzed samples from patients in the original study that reported XMRV in CFS patients.", "We did not find XMRV or related MLVs either as viral sequences or infectious viruses, nor did we find antibodies to these viruses in any of the patient samples, including those from the original study.", "We show that at least some of the discrepancy with previous studies is due to the presence of trace amounts of mouse DNA in the Taq polymerase enzymes used in these previous studies.", "Our findings do not support an association between CFS and MLV-related viruses, including XMRV, and the off-label use of antiretrovirals for the treatment of CFS does not seem justified at present."], "title": "Absence of XMRV retrovirus and other murine leukemia virus-related viruses in patients with chronic fatigue syndrome."}
{"paper_id": 26162091, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Retinoic acid (RA) is a vitamin A metabolite that is essential for early embryonic development and promotes stem cell neural lineage specification; however, little is known regarding the impact of RA on mRNA transcription and microRNA levels on embryonic stem cell differentiation. Here, we present mRNA microarray and microRNA high-output sequencing to clarify how RA regulates gene expression. Using mRNA microarray analysis, we showed that RA repressed pluripotency-associated genes while activating ectoderm markers in mouse embryonic stem cells (mESCs). Moreover, RA modulated the DNA methylation of mESCs by altering the expression of epigenetic-associated genes such as Dnmt3b and Dnmt3l. Furthermore, H3K4me2, a pluripotent histone modification, was repressed by RA stimulation. From microRNA sequence data, we identified two downregulated microRNAs, namely, miR-200b and miR-200c, which regulated the pluripotency of stem cells. We found that miR-200b or miR-200c deficiency suppressed the expression of pluripotent genes, including Oct4 and Nanog, and activated the expression of the ectodermal marker gene Nestin. These results demonstrate that retinoid induces mESCs to differentiate by regulating miR-200b/200c. Our findings provide the landscapes of mRNA and microRNA gene networks and indicate the crucial role of miR-200b/200c in the RA-induced differentiation of mESCs.", "journal": "PloS one", "sentences": ["Retinoic acid (RA) is a vitamin A metabolite that is essential for early embryonic development and promotes stem cell neural lineage specification; however, little is known regarding the impact of RA on mRNA transcription and microRNA levels on embryonic stem cell differentiation.", "Here, we present mRNA microarray and microRNA high-output sequencing to clarify how RA regulates gene expression.", "Using mRNA microarray analysis, we showed that RA repressed pluripotency-associated genes while activating ectoderm markers in mouse embryonic stem cells (mESCs).", "Moreover, RA modulated the DNA methylation of mESCs by altering the expression of epigenetic-associated genes such as Dnmt3b and Dnmt3l.", "Furthermore, H3K4me2, a pluripotent histone modification, was repressed by RA stimulation.", "From microRNA sequence data, we identified two downregulated microRNAs, namely, miR-200b and miR-200c, which regulated the pluripotency of stem cells.", "We found that miR-200b or miR-200c deficiency suppressed the expression of pluripotent genes, including Oct4 and Nanog, and activated the expression of the ectodermal marker gene Nestin.", "These results demonstrate that retinoid induces mESCs to differentiate by regulating miR-200b/200c.", "Our findings provide the landscapes of mRNA and microRNA gene networks and indicate the crucial role of miR-200b/200c in the RA-induced differentiation of mESCs."], "title": "Retinoic Acid Induces Embryonic Stem Cell Differentiation by Altering Both Encoding RNA and microRNA Expression."}
{"paper_id": 24695991, "labels": ["0", "0", "0", "0", "1", "0", "1"], "abstract": "The ability to make rapid and accurate decisions based on limited sensory information is a critical component of visual cognition. Available evidence suggests that simple perceptual discriminations are based on the accumulation and integration of sensory evidence over time. However, the memory system(s) mediating this accumulation are unclear. One candidate system is working memory (WM), which enables the temporary maintenance of information in a readily accessible state. Here, we show that individual variability in WM capacity is strongly correlated with the speed of evidence accumulation in speeded two-alternative forced choice tasks. This relationship generalized across different decision-making tasks, and could not be easily explained by variability in general arousal or vigilance. Moreover, we show that performing a difficult discrimination task while maintaining a concurrent memory load has a deleterious effect on the latter, suggesting that WM storage and decision making are directly linked.", "journal": "Journal of vision", "sentences": ["The ability to make rapid and accurate decisions based on limited sensory information is a critical component of visual cognition.", "Available evidence suggests that simple perceptual discriminations are based on the accumulation and integration of sensory evidence over time.", "However, the memory system(s) mediating this accumulation are unclear.", "One candidate system is working memory (WM), which enables the temporary maintenance of information in a readily accessible state.", "Here, we show that individual variability in WM capacity is strongly correlated with the speed of evidence accumulation in speeded two-alternative forced choice tasks.", "This relationship generalized across different decision-making tasks, and could not be easily explained by variability in general arousal or vigilance.", "Moreover, we show that performing a difficult discrimination task while maintaining a concurrent memory load has a deleterious effect on the latter, suggesting that WM storage and decision making are directly linked."], "title": "Variability in visual working memory ability limits the efficiency of perceptual decision making."}
{"paper_id": 27494319, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "We propose a method for non-rigid face alignment which only needs a single template, such as using a person's smile face to match his surprise face. First, in order to be robust to outliers caused by complex geometric deformations, a new local feature matching method called K Patch Pairs (K-PP) is proposed. Specifically, inspired by the state-of-art similarity measure used in template matching, K-PP is to find the mutual K nearest neighbors between two images. A weight matrix is then presented to balance the similarity and the number of local matching. Second, we proposed a modified Lucas-Kanade algorithm combined with local matching constraint to solve the non-rigid face alignment, so that a holistic face representation and local features can be jointly modeled in the object function. Both the flexible ability of local matching and the robust ability of holistic fitting are included in our method. Furthermore, we show that the optimization problem can be efficiently solved by the inverse compositional algorithm. Comparison results with conventional methods demonstrate our superiority in terms of both accuracy and robustness.", "journal": "PloS one", "sentences": ["We propose a method for non-rigid face alignment which only needs a single template, such as using a person's smile face to match his surprise face.", "First, in order to be robust to outliers caused by complex geometric deformations, a new local feature matching method called K Patch Pairs (K-PP) is proposed.", "Specifically, inspired by the state-of-art similarity measure used in template matching, K-PP is to find the mutual K nearest neighbors between two images.", "A weight matrix is then presented to balance the similarity and the number of local matching.", "Second, we proposed a modified Lucas-Kanade algorithm combined with local matching constraint to solve the non-rigid face alignment, so that a holistic face representation and local features can be jointly modeled in the object function.", "Both the flexible ability of local matching and the robust ability of holistic fitting are included in our method.", "Furthermore, we show that the optimization problem can be efficiently solved by the inverse compositional algorithm.", "Comparison results with conventional methods demonstrate our superiority in terms of both accuracy and robustness."], "title": "A Method for Non-Rigid Face Alignment via Combining Local and Holistic Matching."}
{"paper_id": 21050902, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Eradication of chronic Hepatitis B virus (HBV) infection, marked by HBs seroconversion, is very rarely achieved by treatment with nucleoside and nucleotide analogs. Therapeutic cell based approaches, like interferon therapy, have a higher chance of seroconversion. Dendritic cells (DC) are key players in the cellular immune response and have been shown to play an important role in controlling HBV infection. In this study, the potential of ex vivo activated DC to induce specific immune responses against HBV was examined. DC derived from bone-marrow of BALB/c or C56BL/6 mice were pulsed with HBV subviral particles (HBVsvp), derived from the HepG2.2.15 cell line. HepG2.2.15 produces subviral particles consisting of the HBc and HBs proteins. Thus, the entire \"viral surface\" is presented to DC to induce an immune reaction. In vitro pulsation with HBVsvp successfully activated bone-marrow derived DC, demonstrated by FACS analysis showing increased MHCII, CD 86 and CCR-7. Immunization of mice, via subcutaneous injection of the activated DC, induced HBV specific immune reactions which were measured by ELISA, ELISPOT and T-cell proliferation analysis. Vaccination with ex vivo activated DC may be a promising tool for therapeutic or prophylactic approaches against the Hepatitis B virus.", "journal": "Vaccine", "sentences": ["Eradication of chronic Hepatitis B virus (HBV) infection, marked by HBs seroconversion, is very rarely achieved by treatment with nucleoside and nucleotide analogs.", "Therapeutic cell based approaches, like interferon therapy, have a higher chance of seroconversion.", "Dendritic cells (DC) are key players in the cellular immune response and have been shown to play an important role in controlling HBV infection.", "In this study, the potential of ex vivo activated DC to induce specific immune responses against HBV was examined.", "DC derived from bone-marrow of BALB/c or C56BL/6 mice were pulsed with HBV subviral particles (HBVsvp), derived from the HepG2.2.15 cell line.", "HepG2.2.15 produces subviral particles consisting of the HBc and HBs proteins.", "Thus, the entire \"viral surface\" is presented to DC to induce an immune reaction.", "In vitro pulsation with HBVsvp successfully activated bone-marrow derived DC, demonstrated by FACS analysis showing increased MHCII, CD 86 and CCR-7.", "Immunization of mice, via subcutaneous injection of the activated DC, induced HBV specific immune reactions which were measured by ELISA, ELISPOT and T-cell proliferation analysis.", "Vaccination with ex vivo activated DC may be a promising tool for therapeutic or prophylactic approaches against the Hepatitis B virus."], "title": "Dendritic cells can effectively be pulsed by HBVsvp and induce specific immune reactions in mice."}
{"paper_id": 25017802, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "While an increasing number of structural biology studies successfully demonstrate the power of high-resolution structures and dynamics of membrane proteins in fully understanding their function, there is considerable interest in developing NMR approaches to obtain such information in a cellular setting. As long as the proteins inside the living cell tumble rapidly in the NMR timescale, recently developed in-cell solution NMR approaches can provide 3D structural information. However, there are numerous challenges to study membrane proteins inside a cell. Research in our laboratory is focused on developing a combination of solid-state NMR and biological approaches to overcome these challenges in order to obtain high-resolution structural insights into electron transfer processes mediated by membrane-bound proteins like mammalian cytochrome-b5, cytochrome-P450 and cytochrome-P450-reductase. In this study, we demonstrate the feasibility of using dynamic nuclear polarization (DNP) magic angle spinning (MAS) NMR spectroscopy for in-cell studies on a membrane-anchored protein. Our experimental results obtained from \u00b9\u00b3C-labeled membrane-anchored cytochrome-b5 in native Escherichia coli cells show a ~16-fold DNP signal enhancement. Further, results obtained from a 2D \u00b9\u00b3C/\u00b9\u00b3C chemical shift correlation MAS experiment demonstrate the feasibility of suppressing the background signals from other cellular contents for high-resolution structural studies on membrane proteins. We believe that this study would pave new avenues for high-resolution structural studies on a variety of membrane-associated proteins and their complexes in the cellular context to fully understand their functional roles in physiological processes.", "journal": "Biochimica et biophysica acta", "sentences": ["While an increasing number of structural biology studies successfully demonstrate the power of high-resolution structures and dynamics of membrane proteins in fully understanding their function, there is considerable interest in developing NMR approaches to obtain such information in a cellular setting.", "As long as the proteins inside the living cell tumble rapidly in the NMR timescale, recently developed in-cell solution NMR approaches can provide 3D structural information.", "However, there are numerous challenges to study membrane proteins inside a cell.", "Research in our laboratory is focused on developing a combination of solid-state NMR and biological approaches to overcome these challenges in order to obtain high-resolution structural insights into electron transfer processes mediated by membrane-bound proteins like mammalian cytochrome-b5, cytochrome-P450 and cytochrome-P450-reductase.", "In this study, we demonstrate the feasibility of using dynamic nuclear polarization (DNP) magic angle spinning (MAS) NMR spectroscopy for in-cell studies on a membrane-anchored protein.", "Our experimental results obtained from \u00b9\u00b3C-labeled membrane-anchored cytochrome-b5 in native Escherichia coli cells show a ~16-fold DNP signal enhancement.", "Further, results obtained from a 2D \u00b9\u00b3C/\u00b9\u00b3C chemical shift correlation MAS experiment demonstrate the feasibility of suppressing the background signals from other cellular contents for high-resolution structural studies on membrane proteins.", "We believe that this study would pave new avenues for high-resolution structural studies on a variety of membrane-associated proteins and their complexes in the cellular context to fully understand their functional roles in physiological processes."], "title": "Cellular solid-state NMR investigation of a membrane protein using dynamic nuclear polarization."}
{"paper_id": 26551464, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Ribonuclease P (RNase P) catalyzes the processing of 5' leader sequences of tRNA precursors in all three phylogenetic domains. RNase P also plays an essential role in non-tRNA biogenesis in bacterial and eukaryotic cells. For archaeal RNase Ps, additional functions, however, remain poorly understood. To gain insight into the biological function of archaeal RNase Ps in\u00a0vivo, we prepared archaeal mutants KUW\u0394P3, KUW\u0394P8, and KUW\u0394P16, in which the gene segments encoding stem-loops containing helices, respectively, P3, P8 and P16 in RNase P RNA (TkopRNA) of the hyperthermophilic archaeon Thermococcus kodakarensis were deleted. Phenotypic analysis showed that KUW\u0394P3 and KUW\u0394P16 grew slowly compared with wild-type T.\u00a0kodakarensis KUW1, while KUW\u0394P8 displayed no difference from T.\u00a0kodakarensis KUW1. RNase P isolated using an affinity-tag from KUW\u0394P3 had reduced pre-tRNA cleavage activity compared with that from T.\u00a0kodakarensis KUW1. Moreover, quantitative RT-PCR (qRT-PCR) and Northern blots analyses of KUW\u0394P3 showed greater accumulation of unprocessed transcripts for pre-tRNAs than that of T.\u00a0kodakarensis KUW1. The current study represents the first attempt to prepare mutant T.\u00a0kodakarensis with impaired RNase P for functional investigation. Comparative whole-transcriptome analysis of T.\u00a0kodakarensis KUW1 and KUW\u0394P3 should allow for the comprehensive identification of RNA substrates for archaeal RNase Ps.", "journal": "Biochemical and biophysical research communications", "sentences": ["Ribonuclease P (RNase P) catalyzes the processing of 5' leader sequences of tRNA precursors in all three phylogenetic domains.", "RNase P also plays an essential role in non-tRNA biogenesis in bacterial and eukaryotic cells.", "For archaeal RNase Ps, additional functions, however, remain poorly understood.", "To gain insight into the biological function of archaeal RNase Ps in\u00a0vivo, we prepared archaeal mutants KUW\u0394P3, KUW\u0394P8, and KUW\u0394P16, in which the gene segments encoding stem-loops containing helices, respectively, P3, P8 and P16 in RNase P RNA (TkopRNA) of the hyperthermophilic archaeon Thermococcus kodakarensis were deleted.", "Phenotypic analysis showed that KUW\u0394P3 and KUW\u0394P16 grew slowly compared with wild-type T.\u00a0kodakarensis KUW1, while KUW\u0394P8 displayed no difference from T.\u00a0kodakarensis KUW1.", "RNase P isolated using an affinity-tag from KUW\u0394P3 had reduced pre-tRNA cleavage activity compared with that from T.\u00a0kodakarensis KUW1.", "Moreover, quantitative RT-PCR (qRT-PCR) and Northern blots analyses of KUW\u0394P3 showed greater accumulation of unprocessed transcripts for pre-tRNAs than that of T.\u00a0kodakarensis KUW1.", "The current study represents the first attempt to prepare mutant T.\u00a0kodakarensis with impaired RNase P for functional investigation.", "Comparative whole-transcriptome analysis of T.\u00a0kodakarensis KUW1 and KUW\u0394P3 should allow for the comprehensive identification of RNA substrates for archaeal RNase Ps."], "title": "Mutation of the gene encoding the ribonuclease P RNA in the hyperthermophilic archaeon Thermococcus kodakarensis causes decreased growth rate and impaired processing of tRNA precursors."}
{"paper_id": 23738010, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Microglia plays a crucial role in the pathogenesis of HIV-1-associated neurocognitive disorders. Increasing evidence indicates the voltage-gated potassium (Kv) channels are involved in the regulation of microglia function, prompting us to hypothesize Kv channels may also be involved in microglia-mediated neurotoxic activity in HIV-1-infected brain. To test this hypothesis, we investigated the involvement of Kv channels in the response of microglia to HIV-1 Tat protein. Treatment of rat microglia with HIV-1 Tat protein (200 ng/ml) resulted in pro-inflammatory microglial activation, as indicated by increases in TNF-\u03b1, IL-1\u03b2, reactive oxygen species, and nitric oxide, which were accompanied by enhanced outward K(+) current and Kv1.3 channel expression. Suppression of microglial Kv1.3 channel activity, either with Kv1.3 channel blockers Margatoxin, 5-(4-Phenoxybutoxy)psoralen, or broad-spectrum K(+) channel blocker 4-Aminopyridine, or by knockdown of Kv1.3 expression via transfection of microglia with Kv1.3 siRNA, was found to abrogate the neurotoxic activity of microglia resulting from HIV-1 Tat exposure. Furthermore, HIV-1 Tat-induced neuronal apoptosis was attenuated with the application of supernatant collected from K(+) channel blocker-treated microglia. Lastly, the intracellular signaling pathways associated with Kv1.3 were investigated and enhancement of microglial Kv1.3 was found to correspond with an increase in Erk1/2 mitogen-activated protein kinase activation. These data suggest targeting microglial Kv1.3 channels may be a potential new avenue of therapy for inflammation-mediated neurological disorders.", "journal": "PloS one", "sentences": ["Microglia plays a crucial role in the pathogenesis of HIV-1-associated neurocognitive disorders.", "Increasing evidence indicates the voltage-gated potassium (Kv) channels are involved in the regulation of microglia function, prompting us to hypothesize Kv channels may also be involved in microglia-mediated neurotoxic activity in HIV-1-infected brain.", "To test this hypothesis, we investigated the involvement of Kv channels in the response of microglia to HIV-1 Tat protein.", "Treatment of rat microglia with HIV-1 Tat protein (200 ng/ml) resulted in pro-inflammatory microglial activation, as indicated by increases in TNF-\u03b1, IL-1\u03b2, reactive oxygen species, and nitric oxide, which were accompanied by enhanced outward K(+) current and Kv1.3 channel expression.", "Suppression of microglial Kv1.3 channel activity, either with Kv1.3 channel blockers Margatoxin, 5-(4-Phenoxybutoxy)psoralen, or broad-spectrum K(+) channel blocker 4-Aminopyridine, or by knockdown of Kv1.3 expression via transfection of microglia with Kv1.3 siRNA, was found to abrogate the neurotoxic activity of microglia resulting from HIV-1 Tat exposure.", "Furthermore, HIV-1 Tat-induced neuronal apoptosis was attenuated with the application of supernatant collected from K(+) channel blocker-treated microglia.", "Lastly, the intracellular signaling pathways associated with Kv1.3 were investigated and enhancement of microglial Kv1.3 was found to correspond with an increase in Erk1/2 mitogen-activated protein kinase activation.", "These data suggest targeting microglial Kv1.3 channels may be a potential new avenue of therapy for inflammation-mediated neurological disorders."], "title": "HIV-1 Tat protein increases microglial outward K(+) current and resultant neurotoxic activity."}
{"paper_id": 26400039, "labels": ["0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "UNLABELLED\nPathwaysWeb is a resource-based, well-documented web system that provides publicly available information on genes, biological pathways, Gene Ontology (GO) terms, gene-gene interaction networks (importantly, with the directionality of interactions) and links to key-related PubMed documents. The PathwaysWeb API simplifies the construction of applications that need to retrieve and interrelate information across multiple, pathway-related data types from a variety of original data sources. PathwaysBrowser is a companion website that enables users to explore the same integrated pathway data. The PathwaysWeb system facilitates reproducible analyses by providing access to all versions of the integrated datasets. Although its GO subsystem includes data for mouse, PathwaysWeb currently focuses on human data. However, pathways for mouse and many other species can be inferred with a high success rate from human pathways.\n\n\nAVAILABILITY AND IMPLEMENTATION\nPathwaysWeb can be accessed via the Internet at http://bioinformatics.mdanderson.org/main/PathwaysWeb:Overview.\n\n\nCONTACT\njmmelott@mdanderson.org\n\n\nSUPPLEMENTARY INFORMATION\nSupplementary data are available at Bioinformatics online.", "journal": "Bioinformatics (Oxford, England)", "sentences": ["UNLABELLED\nPathwaysWeb is a resource-based, well-documented web system that provides publicly available information on genes, biological pathways, Gene Ontology (GO) terms, gene-gene interaction networks (importantly, with the directionality of interactions) and links to key-related PubMed documents.", "The PathwaysWeb API simplifies the construction of applications that need to retrieve and interrelate information across multiple, pathway-related data types from a variety of original data sources.", "PathwaysBrowser is a companion website that enables users to explore the same integrated pathway data.", "The PathwaysWeb system facilitates reproducible analyses by providing access to all versions of the integrated datasets.", "Although its GO subsystem includes data for mouse, PathwaysWeb currently focuses on human data.", "However, pathways for mouse and many other species can be inferred with a high success rate from human pathways.", "AVAILABILITY AND IMPLEMENTATION\nPathwaysWeb can be accessed via the Internet at http://bioinformatics.mdanderson.org/main/PathwaysWeb:Overview.", "CONTACT\njmmelott@mdanderson.org\n\n\nSUPPLEMENTARY INFORMATION\nSupplementary data are available at Bioinformatics online."], "title": "PathwaysWeb: a gene pathways API with directional interactions, expanded gene ontology, and versioning."}
{"paper_id": 21829610, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Fusions of the first two enzymes in the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconolactonase (6PGL), have been previously described in two distant clades, chordates and species of the malarial parasite Plasmodium. We have analyzed genome and expressed sequence data from a variety of organisms to identify the origins of these gene fusion events. Based on the orientation of the domains and range of species in which homologs can be found, the fusions appear to have occurred independently, near the base of the metazoan and apicomplexan lineages. Only one of the two metazoan paralogs of G6PD is fused, showing that the fusion occurred after a duplication event, which we have traced back to an ancestor of choanoflagellates and metazoans. The Plasmodium genes are known to contain a functionally important insertion that is not seen in the other apicomplexan fusions, highlighting this as a unique characteristic of this group. Surprisingly, our search revealed two additional fusion events, one that combined 6PGL and G6PD in an ancestor of the protozoan parasites Trichomonas and Giardia, and another fusing G6PD with phosphogluconate dehydrogenase (6PGD) in a species of diatoms. This study extends the range of species known to contain fusions in the pentose phosphate pathway to many new medically and economically important organisms.", "journal": "PloS one", "sentences": ["Fusions of the first two enzymes in the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconolactonase (6PGL), have been previously described in two distant clades, chordates and species of the malarial parasite Plasmodium.", "We have analyzed genome and expressed sequence data from a variety of organisms to identify the origins of these gene fusion events.", "Based on the orientation of the domains and range of species in which homologs can be found, the fusions appear to have occurred independently, near the base of the metazoan and apicomplexan lineages.", "Only one of the two metazoan paralogs of G6PD is fused, showing that the fusion occurred after a duplication event, which we have traced back to an ancestor of choanoflagellates and metazoans.", "The Plasmodium genes are known to contain a functionally important insertion that is not seen in the other apicomplexan fusions, highlighting this as a unique characteristic of this group.", "Surprisingly, our search revealed two additional fusion events, one that combined 6PGL and G6PD in an ancestor of the protozoan parasites Trichomonas and Giardia, and another fusing G6PD with phosphogluconate dehydrogenase (6PGD) in a species of diatoms.", "This study extends the range of species known to contain fusions in the pentose phosphate pathway to many new medically and economically important organisms."], "title": "Multiple independent fusions of glucose-6-phosphate dehydrogenase with enzymes in the pentose phosphate pathway."}
{"paper_id": 26618174, "labels": ["0", "0", "0", "0", "0", "1", "0", "0", "1"], "abstract": "The epigenetic marks located throughout the genome exhibit great variation between normal and transformed cancer cells. While normal cells contain hypomethylated CpG islands near gene promoters and hypermethylated repetitive DNA, the opposite pattern is observed in cancer cells. Recently, it has been reported that alteration in the microenvironment of melanocyte cells, such as substrate adhesion blockade, results in the selection of anoikis-resistant cells, which have tumorigenic characteristics. Melanoma cells obtained through this model show an altered epigenetic pattern, which represents one of the first events during the melanocytes malignant transformation. Because microRNAs are involved in controlling components of the epigenetic machinery, the aim of this work was to evaluate the potential association between the expression of miR-203, miR-26, and miR-29 family members and the genes Dnmt3a, Dnmt3b, Mecp2, and Ezh2 during cells transformation. Our results show that microRNAs and their validated or predicted targets are inversely expressed, indicating that these molecules are involved in epigenetic reprogramming. We also show that miR-203 downregulates Dnmt3b in mouse melanocyte cells. In addition, treatment with 5-aza-CdR promotes the expression of miR-26 and miR-29 in a nonmetastatic melanoma cell line. Considering the occurrence of CpG islands near the miR-26 and miR-29 promoters, these data suggest that they might be epigenetically regulated in cancer.", "journal": "BioMed research international", "sentences": ["The epigenetic marks located throughout the genome exhibit great variation between normal and transformed cancer cells.", "While normal cells contain hypomethylated CpG islands near gene promoters and hypermethylated repetitive DNA, the opposite pattern is observed in cancer cells.", "Recently, it has been reported that alteration in the microenvironment of melanocyte cells, such as substrate adhesion blockade, results in the selection of anoikis-resistant cells, which have tumorigenic characteristics.", "Melanoma cells obtained through this model show an altered epigenetic pattern, which represents one of the first events during the melanocytes malignant transformation.", "Because microRNAs are involved in controlling components of the epigenetic machinery, the aim of this work was to evaluate the potential association between the expression of miR-203, miR-26, and miR-29 family members and the genes Dnmt3a, Dnmt3b, Mecp2, and Ezh2 during cells transformation.", "Our results show that microRNAs and their validated or predicted targets are inversely expressed, indicating that these molecules are involved in epigenetic reprogramming.", "We also show that miR-203 downregulates Dnmt3b in mouse melanocyte cells.", "In addition, treatment with 5-aza-CdR promotes the expression of miR-26 and miR-29 in a nonmetastatic melanoma cell line.", "Considering the occurrence of CpG islands near the miR-26 and miR-29 promoters, these data suggest that they might be epigenetically regulated in cancer."], "title": "The Roles of miR-26, miR-29, and miR-203 in the Silencing of the Epigenetic Machinery during Melanocyte Transformation."}
{"paper_id": 22847432, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "The transition from the Middle Stone Age (MSA) to the Later Stone Age (LSA) in South Africa was not associated with the appearance of anatomically modern humans and the extinction of Neandertals, as in the Middle to Upper Paleolithic transition in Western Europe. It has therefore attracted less attention, yet it provides insights into patterns of technological evolution not associated with a new hominin. Data from Border Cave (KwaZulu-Natal) show a strong pattern of technological change at approximately 44-42 ka cal BP, marked by adoption of techniques and materials that were present but scarcely used in the previous MSA, and some novelties. The agent of change was neither a revolution nor the advent of a new species of human. Although most evident in personal ornaments and symbolic markings, the change from one way of living to another was not restricted to aesthetics. Our analysis shows that: (i) at Border Cave two assemblages, dated to 45-49 and >49 ka, show a gradual abandonment of the technology and tool types of the post-Howiesons Poort period and can be considered transitional industries; (ii) the 44-42 ka cal BP assemblages are based on an expedient technology dominated by bipolar knapping, with microliths hafted with pitch from Podocarpus bark, worked suid tusks, ostrich eggshell beads, bone arrowheads, engraved bones, bored stones, and digging sticks; (iii) these assemblages mark the beginning of the LSA in South Africa; (iv) the LSA emerged by internal evolution; and (v) the process of change began sometime after 56 ka.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["The transition from the Middle Stone Age (MSA) to the Later Stone Age (LSA) in South Africa was not associated with the appearance of anatomically modern humans and the extinction of Neandertals, as in the Middle to Upper Paleolithic transition in Western Europe.", "It has therefore attracted less attention, yet it provides insights into patterns of technological evolution not associated with a new hominin.", "Data from Border Cave (KwaZulu-Natal) show a strong pattern of technological change at approximately 44-42 ka cal BP, marked by adoption of techniques and materials that were present but scarcely used in the previous MSA, and some novelties.", "The agent of change was neither a revolution nor the advent of a new species of human.", "Although most evident in personal ornaments and symbolic markings, the change from one way of living to another was not restricted to aesthetics.", "Our analysis shows that: (i) at Border Cave two assemblages, dated to 45-49 and >49 ka, show a gradual abandonment of the technology and tool types of the post-Howiesons Poort period and can be considered transitional industries; (ii) the 44-42 ka cal BP assemblages are based on an expedient technology dominated by bipolar knapping, with microliths hafted with pitch from Podocarpus bark, worked suid tusks, ostrich eggshell beads, bone arrowheads, engraved bones, bored stones, and digging sticks; (iii) these assemblages mark the beginning of the LSA in South Africa; (iv) the LSA emerged by internal evolution; and (v) the process of change began sometime after 56 ka."], "title": "Border Cave and the beginning of the Later Stone Age in South Africa."}
{"paper_id": 21388798, "labels": ["0", "0", "0", "0", "1", "1"], "abstract": "Ultrasensitive sandwich type electrochemical immunosensors for the detection of cancer biomarker prostate specific antigen (PSA) is described which uses graphene sheet (GS) sensor platform and ferrocene functionalized iron oxide (Fe(3)O(4)) as label. To fabricate the labels, dopamine (DA) was first anchored onto Fe(3)O(4) surface followed by conjugating ferrocene monocarboxylic acid (FC) and secondary-antibody (Ab(2)) onto Fe(3)O(4) through the amino groups of DA (DA-Fe(3)O(4)-FC-Ab(2)). The great amount of DA molecules anchored onto Fe(3)O(4) surface increased the immobilization of FC and Ab(2) onto the Fe(3)O(4) nanoparticle, which in turn increased the sensitivity of the immunosensor. GS used as biosensor platform increased the surface area to capture a great amount of primary antibodies (Ab(1)) and the good conductivity of GS enhanced the detection sensitivity to FC. Using the redox current of FC as signal, the immunosensor displays high sensitivity, wide linear range (0.01-40 ng/mL), low detection limit (2 pg/mL), good reproducibility and stability. In addition, this method could be extended to the immobilization of other interesting materials (fluorescence dyes) onto Fe(3)O(4) for preparing various kinds of labels to meet the different requirements in immunoassays.", "journal": "Biosensors & bioelectronics", "sentences": ["Ultrasensitive sandwich type electrochemical immunosensors for the detection of cancer biomarker prostate specific antigen (PSA) is described which uses graphene sheet (GS) sensor platform and ferrocene functionalized iron oxide (Fe(3)O(4)) as label.", "To fabricate the labels, dopamine (DA) was first anchored onto Fe(3)O(4) surface followed by conjugating ferrocene monocarboxylic acid (FC) and secondary-antibody (Ab(2)) onto Fe(3)O(4) through the amino groups of DA (DA-Fe(3)O(4)-FC-Ab(2)).", "The great amount of DA molecules anchored onto Fe(3)O(4) surface increased the immobilization of FC and Ab(2) onto the Fe(3)O(4) nanoparticle, which in turn increased the sensitivity of the immunosensor.", "GS used as biosensor platform increased the surface area to capture a great amount of primary antibodies (Ab(1)) and the good conductivity of GS enhanced the detection sensitivity to FC.", "Using the redox current of FC as signal, the immunosensor displays high sensitivity, wide linear range (0.01-40 ng/mL), low detection limit (2 pg/mL), good reproducibility and stability.", "In addition, this method could be extended to the immobilization of other interesting materials (fluorescence dyes) onto Fe(3)O(4) for preparing various kinds of labels to meet the different requirements in immunoassays."], "title": "Electrochemical immunosensors for cancer biomarker with signal amplification based on ferrocene functionalized iron oxide nanoparticles."}
{"paper_id": 23816846, "labels": ["0", "0", "0", "0", "1", "0", "0", "0", "1"], "abstract": "House dust mites are the major source of indoor allergens that are responsible for asthma. The major dust mite allergen is the group II allergen, Der p2. Myeloid differentiation-2 (MD-2) acts as an essential component in the CD14-TLR4 (toll-like receptor)/MD-2 receptor complex for Der p2 recognition. Mutations of the MD-2 associated gene on chromosome 8 degrade a human's innate responses. In this study, we report the effective detection of mutations to the MD-2 gene promoter, using a sensitive nanostructured biosensor with a sensing electrode of gold nanoparticles (GNPs) uniformly deposited in a nanohemisphere array. The 70 mer MD-2 expressed gene fragment was used to probe gene mutation. The complementary target, containing 156 mer nucleotide, was prepared using the fresh blood from patients with allergic disease. A total of 37 target samples, including 19 gene mutated samples and 18 normal samples, were prepared by a 20 cycles PCR process, and used for discrimination experiments. Experimental results illustrated that the nanostructured biosensor clearly discriminates between mutated and non-mutated MD-2 allergy genes.", "journal": "Biosensors & bioelectronics", "sentences": ["House dust mites are the major source of indoor allergens that are responsible for asthma.", "The major dust mite allergen is the group II allergen, Der p2.", "Myeloid differentiation-2 (MD-2) acts as an essential component in the CD14-TLR4 (toll-like receptor)/MD-2 receptor complex for Der p2 recognition.", "Mutations of the MD-2 associated gene on chromosome 8 degrade a human's innate responses.", "In this study, we report the effective detection of mutations to the MD-2 gene promoter, using a sensitive nanostructured biosensor with a sensing electrode of gold nanoparticles (GNPs) uniformly deposited in a nanohemisphere array.", "The 70 mer MD-2 expressed gene fragment was used to probe gene mutation.", "The complementary target, containing 156 mer nucleotide, was prepared using the fresh blood from patients with allergic disease.", "A total of 37 target samples, including 19 gene mutated samples and 18 normal samples, were prepared by a 20 cycles PCR process, and used for discrimination experiments.", "Experimental results illustrated that the nanostructured biosensor clearly discriminates between mutated and non-mutated MD-2 allergy genes."], "title": "Label-free detection of single-nucleotide polymorphisms associated with myeloid differentiation-2 using a nanostructured biosensor."}
{"paper_id": 27575932, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Governments across Europe are required to make decisions about how best to allocate scarce health care resources. There are legitimate arguments for eliciting societal vales in relation to health care resource allocation given the roles of the general public as payers and potential patients. However, relatively little is known about the views of the general public on general principles which could guide these decisions. In this paper we present five societal viewpoints on principles for health care resources allocation and develop a new approach, Q2S, designed to investigate the extent to which these views are held across a range of European countries. An online survey was developed, based on a previously completed study Q methodology, and delivered between November 2009 and February 2010 across nine countries to 33,515 respondents. The largest proportion of our respondents (44%), were found to most associate themselves with an egalitarian perspective. Differences in views were more strongly associated with countries than with socio-demographic characteristics. These results provide information which could be useful for decision makers in understanding the pluralistic context in which they are making health care resource allocation decisions and how different groups in society may respond to such decisions.", "journal": "Social science & medicine (1982)", "sentences": ["Governments across Europe are required to make decisions about how best to allocate scarce health care resources.", "There are legitimate arguments for eliciting societal vales in relation to health care resource allocation given the roles of the general public as payers and potential patients.", "However, relatively little is known about the views of the general public on general principles which could guide these decisions.", "In this paper we present five societal viewpoints on principles for health care resources allocation and develop a new approach, Q2S, designed to investigate the extent to which these views are held across a range of European countries.", "An online survey was developed, based on a previously completed study Q methodology, and delivered between November 2009 and February 2010 across nine countries to 33,515 respondents.", "The largest proportion of our respondents (44%), were found to most associate themselves with an egalitarian perspective.", "Differences in views were more strongly associated with countries than with socio-demographic characteristics.", "These results provide information which could be useful for decision makers in understanding the pluralistic context in which they are making health care resource allocation decisions and how different groups in society may respond to such decisions."], "title": "From representing views to representativeness of views: Illustrating a new (Q2S) approach in the context of health care priority setting in nine European countries."}
{"paper_id": 20171306, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Ixodes ricinus is one the most abundant tick species in Europe and these ticks transmit pathogens causing human and animal diseases. The cattle ticks, Rhipicephalus (Boophilus) spp., affect cattle production in tropical and subtropical regions of the world. Development of vaccines directed against tick proteins may reduce tick infestations and the transmission of tick-borne pathogens. However, a limiting step in tick vaccine development has been the identification of tick protective antigens. Herein, the tick iron metabolism pathway was targeted in an effort to identify new tick protective antigens. Recombinant I. ricinus (IrFER2) and Rhipicephalus microplus (RmFER2) ferritin 2 proteins were expressed in Escherichia coli and used to immunize rabbits and cattle, respectively. Vaccination with IrFER2 reduced I. ricinus tick numbers, weight and fertility in rabbits with an overall vaccine efficacy (E) of 98%. Control of cattle tick, R. microplus and Rhipicephalus annulatus infestations was obtained in vaccinated cattle with overall E of 64% and 72%, respectively. Notably, the efficacy of the RmFER2 vaccine was similar to that obtained with Bm86 against R. microplus. These collective results demonstrated the feasibility of using ferritin 2 to develop vaccines for the control of tick infestations.", "journal": "Vaccine", "sentences": ["Ixodes ricinus is one the most abundant tick species in Europe and these ticks transmit pathogens causing human and animal diseases.", "The cattle ticks, Rhipicephalus (Boophilus) spp., affect cattle production in tropical and subtropical regions of the world.", "Development of vaccines directed against tick proteins may reduce tick infestations and the transmission of tick-borne pathogens.", "However, a limiting step in tick vaccine development has been the identification of tick protective antigens.", "Herein, the tick iron metabolism pathway was targeted in an effort to identify new tick protective antigens.", "Recombinant I. ricinus (IrFER2) and Rhipicephalus microplus (RmFER2) ferritin 2 proteins were expressed in Escherichia coli and used to immunize rabbits and cattle, respectively.", "Vaccination with IrFER2 reduced I. ricinus tick numbers, weight and fertility in rabbits with an overall vaccine efficacy (E) of 98%.", "Control of cattle tick, R. microplus and Rhipicephalus annulatus infestations was obtained in vaccinated cattle with overall E of 64% and 72%, respectively.", "Notably, the efficacy of the RmFER2 vaccine was similar to that obtained with Bm86 against R. microplus.", "These collective results demonstrated the feasibility of using ferritin 2 to develop vaccines for the control of tick infestations."], "title": "Characterization of ferritin 2 for the control of tick infestations."}
{"paper_id": 26669856, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "Airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) are characterized by excessive inflammation and are exacerbated by nontypeable Haemophilus influenzae (NTHi). Airway epithelial cells mount the initial innate immune responses to invading pathogens and thus modulate inflammation. While inflammation is necessary to eliminate a pathogen, excessive inflammation can cause damage to the host tissue. Therefore, the inflammatory response must be tightly regulated and deciphering the signaling pathways involved in this response will enhance our understanding of the regulation of the host inflammatory response. NTHi binds to TLR2 and signal propagation requires the adaptor molecule myeloid differentiation factor 88 (MyD88). An alternative spliced form of MyD88 is called MyD88 short (MyD88s) and has been identified in macrophages and embryonic cell lines as a negative regulator of inflammation. However, the role of MyD88s in NTHi-induced inflammation in airway epithelial cells remains unknown. Here we show that NTHi induces MyD88s expression and MyD88s is a negative regulator of inflammation in airway epithelial cells. We further demonstrate that MyD88s is positively regulated by IKK\u03b2 and CREB and negatively regulated by ERK1/2 signaling pathways. Taken together these data indicate that airway inflammation is controlled in a negative feedback manner involving MyD88s and suggest that airway epithelial cells are essential to maintain immune homeostasis.", "journal": "PloS one", "sentences": ["Airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) are characterized by excessive inflammation and are exacerbated by nontypeable Haemophilus influenzae (NTHi).", "Airway epithelial cells mount the initial innate immune responses to invading pathogens and thus modulate inflammation.", "While inflammation is necessary to eliminate a pathogen, excessive inflammation can cause damage to the host tissue.", "Therefore, the inflammatory response must be tightly regulated and deciphering the signaling pathways involved in this response will enhance our understanding of the regulation of the host inflammatory response.", "NTHi binds to TLR2 and signal propagation requires the adaptor molecule myeloid differentiation factor 88 (MyD88).", "An alternative spliced form of MyD88 is called MyD88 short (MyD88s) and has been identified in macrophages and embryonic cell lines as a negative regulator of inflammation.", "However, the role of MyD88s in NTHi-induced inflammation in airway epithelial cells remains unknown.", "Here we show that NTHi induces MyD88s expression and MyD88s is a negative regulator of inflammation in airway epithelial cells.", "We further demonstrate that MyD88s is positively regulated by IKK\u03b2 and CREB and negatively regulated by ERK1/2 signaling pathways.", "Taken together these data indicate that airway inflammation is controlled in a negative feedback manner involving MyD88s and suggest that airway epithelial cells are essential to maintain immune homeostasis."], "title": "Nontypeable Haemophilus influenzae-Induced MyD88 Short Expression Is Regulated by Positive IKK\u03b2 and CREB Pathways and Negative ERK1/2 Pathway."}
{"paper_id": 27197229, "labels": ["0", "0", "0", "0", "1", "0", "0"], "abstract": "Strong lines of evidence have established a critical role for the homeodomain protein HOXB7 in cancer. Specifically, molecular and cellular studies have demonstrated that HOXB7 is a master regulatory gene, capable of orchestrating a variety of target molecules, resulting in the activation of several oncogenic pathways. HOXB7 overexpression correlates with clinical progression and poor outcome of cancer patients. Specific inhibition of HOXB7 is particularly relevant in cancers still lacking effective therapies, such as tamoxifen-resistant breast cancer and melanoma. Mechanistic studies are providing additional targets of therapy, and biomarker studies are further establishing its importance in early diagnosis and prognosis. Cancer Res; 76(10); 2857-62. \u00a92016 AACR.", "journal": "Cancer research", "sentences": ["Strong lines of evidence have established a critical role for the homeodomain protein HOXB7 in cancer.", "Specifically, molecular and cellular studies have demonstrated that HOXB7 is a master regulatory gene, capable of orchestrating a variety of target molecules, resulting in the activation of several oncogenic pathways.", "HOXB7 overexpression correlates with clinical progression and poor outcome of cancer patients.", "Specific inhibition of HOXB7 is particularly relevant in cancers still lacking effective therapies, such as tamoxifen-resistant breast cancer and melanoma.", "Mechanistic studies are providing additional targets of therapy, and biomarker studies are further establishing its importance in early diagnosis and prognosis.", "Cancer Res; 76(10); 2857-62.", "\u00a92016 AACR."], "title": "The Widening Sphere of Influence of HOXB7 in Solid Tumors."}
{"paper_id": 21625574, "labels": ["0", "0", "1", "0", "0", "0", "0", "0", "1"], "abstract": "Streptococcus pyogenes is a Gram-positive human pathogen that is recognized by yet unknown pattern recognition receptors (PRRs). Engagement of these receptor molecules during infection with S. pyogenes, a largely extracellular bacterium with limited capacity for intracellular survival, causes innate immune cells to produce inflammatory mediators such as TNF, but also type I interferon (IFN). Here we show that signaling elicited by type I IFNs is required for successful defense of mice against lethal subcutaneous cellulitis caused by S. pyogenes. Type I IFN signaling was accompanied with reduced neutrophil recruitment to the site of infection. Mechanistic analysis revealed that macrophages and conventional dendritic cells (cDCs) employ different signaling pathways leading to IFN-beta production. Macrophages required IRF3, STING, TBK1 and partially MyD88, whereas in cDCs the IFN-beta production was fully dependent on IRF5 and MyD88. Furthermore, IFN-beta production by macrophages was dependent on the endosomal delivery of streptococcal DNA, while in cDCs streptococcal RNA was identified as the IFN-beta inducer. Despite a role of MyD88 in both cell types, the known IFN-inducing TLRs were individually not required for generation of the IFN-beta response. These results demonstrate that the innate immune system employs several strategies to efficiently recognize S. pyogenes, a pathogenic bacterium that succeeded in avoiding recognition by the standard arsenal of TLRs.", "journal": "PLoS pathogens", "sentences": ["Streptococcus pyogenes is a Gram-positive human pathogen that is recognized by yet unknown pattern recognition receptors (PRRs).", "Engagement of these receptor molecules during infection with S. pyogenes, a largely extracellular bacterium with limited capacity for intracellular survival, causes innate immune cells to produce inflammatory mediators such as TNF, but also type I interferon (IFN).", "Here we show that signaling elicited by type I IFNs is required for successful defense of mice against lethal subcutaneous cellulitis caused by S. pyogenes.", "Type I IFN signaling was accompanied with reduced neutrophil recruitment to the site of infection.", "Mechanistic analysis revealed that macrophages and conventional dendritic cells (cDCs) employ different signaling pathways leading to IFN-beta production.", "Macrophages required IRF3, STING, TBK1 and partially MyD88, whereas in cDCs the IFN-beta production was fully dependent on IRF5 and MyD88.", "Furthermore, IFN-beta production by macrophages was dependent on the endosomal delivery of streptococcal DNA, while in cDCs streptococcal RNA was identified as the IFN-beta inducer.", "Despite a role of MyD88 in both cell types, the known IFN-inducing TLRs were individually not required for generation of the IFN-beta response.", "These results demonstrate that the innate immune system employs several strategies to efficiently recognize S. pyogenes, a pathogenic bacterium that succeeded in avoiding recognition by the standard arsenal of TLRs."], "title": "Type I interferon production induced by Streptococcus pyogenes-derived nucleic acids is required for host protection."}
{"paper_id": 26400178, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "CouR, a MarR-type transcriptional repressor, regulates the cou genes, encoding p-hydroxycinnamate catabolism in the soil bacterium Rhodococcus jostii RHA1. The CouR dimer bound two molecules of the catabolite p-coumaroyl-CoA (Kd = 11 \u00b1 1 \u03bcM). The presence of p-coumaroyl-CoA, but neither p-coumarate nor CoASH, abrogated CouR's binding to its operator DNA in vitro. The crystal structures of ligand-free CouR and its p-coumaroyl-CoA-bound form showed no significant conformational differences, in contrast to other MarR regulators. The CouR-p-coumaroyl-CoA structure revealed two ligand molecules bound to the CouR dimer with their phenolic moieties occupying equivalent hydrophobic pockets in each protomer and their CoA moieties adopting non-equivalent positions to mask the regulator's predicted DNA-binding surface. More specifically, the CoA phosphates formed salt bridges with predicted DNA-binding residues Arg36 and Arg38, changing the overall charge of the DNA-binding surface. The substitution of either arginine with alanine completely abrogated the ability of CouR to bind DNA. By contrast, the R36A/R38A double variant retained a relatively high affinity for p-coumaroyl-CoA (Kd = 89 \u00b1 6 \u03bcM). Together, our data point to a novel mechanism of action in which the ligand abrogates the repressor's ability to bind DNA by steric occlusion of key DNA-binding residues and charge repulsion of the DNA backbone.", "journal": "Nucleic acids research", "sentences": ["CouR, a MarR-type transcriptional repressor, regulates the cou genes, encoding p-hydroxycinnamate catabolism in the soil bacterium Rhodococcus jostii RHA1.", "The CouR dimer bound two molecules of the catabolite p-coumaroyl-CoA (Kd = 11 \u00b1 1 \u03bcM).", "The presence of p-coumaroyl-CoA, but neither p-coumarate nor CoASH, abrogated CouR's binding to its operator DNA in vitro.", "The crystal structures of ligand-free CouR and its p-coumaroyl-CoA-bound form showed no significant conformational differences, in contrast to other MarR regulators.", "The CouR-p-coumaroyl-CoA structure revealed two ligand molecules bound to the CouR dimer with their phenolic moieties occupying equivalent hydrophobic pockets in each protomer and their CoA moieties adopting non-equivalent positions to mask the regulator's predicted DNA-binding surface.", "More specifically, the CoA phosphates formed salt bridges with predicted DNA-binding residues Arg36 and Arg38, changing the overall charge of the DNA-binding surface.", "The substitution of either arginine with alanine completely abrogated the ability of CouR to bind DNA.", "By contrast, the R36A/R38A double variant retained a relatively high affinity for p-coumaroyl-CoA (Kd = 89 \u00b1 6 \u03bcM).", "Together, our data point to a novel mechanism of action in which the ligand abrogates the repressor's ability to bind DNA by steric occlusion of key DNA-binding residues and charge repulsion of the DNA backbone."], "title": "The activity of CouR, a MarR family transcriptional regulator, is modulated through a novel molecular mechanism."}
{"paper_id": 20159157, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Progressive force loss in Duchenne muscular dystrophy is characterized by degeneration/regeneration cycles and fibrosis. Disease progression may involve structural remodeling of muscle tissue. An effect on molecular motorprotein function may also be possible. We used second harmonic generation imaging to reveal vastly altered subcellular sarcomere microarchitecture in intact single dystrophic mdx muscle cells (approximately 1 year old). Myofibril tilting, twisting, and local axis deviations explain at least up to 20% of force drop during unsynchronized contractile activation as judged from cosine angle sums of myofibril orientations within mdx fibers. In contrast, in vitro motility assays showed unaltered sliding velocities of single mdx fiber myosin extracts. Closer quantification of the microarchitecture revealed that dystrophic fibers had significantly more Y-shaped sarcomere irregularities (\"verniers\") than wild-type fibers (approximately 130/1000 microm(3) vs. approximately 36/1000 microm(3)). In transgenic mini-dystrophin-expressing fibers, ultrastructure was restored (approximately 38/1000 microm(3) counts). We suggest that in aged dystrophic toe muscle, progressive force loss is reflected by a vastly deranged micromorphology that prevents a coordinated and aligned contraction. Second harmonic generation imaging may soon be available in routine clinical diagnostics, and in this work we provide valuable imaging tools to track and quantify ultrastructural worsening in Duchenne muscular dystrophy, and to judge the beneficial effects of possible drug or gene therapies.", "journal": "Biophysical journal", "sentences": ["Progressive force loss in Duchenne muscular dystrophy is characterized by degeneration/regeneration cycles and fibrosis.", "Disease progression may involve structural remodeling of muscle tissue.", "An effect on molecular motorprotein function may also be possible.", "We used second harmonic generation imaging to reveal vastly altered subcellular sarcomere microarchitecture in intact single dystrophic mdx muscle cells (approximately 1 year old).", "Myofibril tilting, twisting, and local axis deviations explain at least up to 20% of force drop during unsynchronized contractile activation as judged from cosine angle sums of myofibril orientations within mdx fibers.", "In contrast, in vitro motility assays showed unaltered sliding velocities of single mdx fiber myosin extracts.", "Closer quantification of the microarchitecture revealed that dystrophic fibers had significantly more Y-shaped sarcomere irregularities (\"verniers\") than wild-type fibers (approximately 130/1000 microm(3) vs. approximately 36/1000 microm(3)).", "In transgenic mini-dystrophin-expressing fibers, ultrastructure was restored (approximately 38/1000 microm(3) counts).", "We suggest that in aged dystrophic toe muscle, progressive force loss is reflected by a vastly deranged micromorphology that prevents a coordinated and aligned contraction.", "Second harmonic generation imaging may soon be available in routine clinical diagnostics, and in this work we provide valuable imaging tools to track and quantify ultrastructural worsening in Duchenne muscular dystrophy, and to judge the beneficial effects of possible drug or gene therapies."], "title": "Microarchitecture is severely compromised but motor protein function is preserved in dystrophic mdx skeletal muscle."}
{"paper_id": 22411804, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Respiratory syncytial virus (RSV) is the major viral cause of severe pulmonary disease in young infants worldwide. However, the mechanisms by which RSV causes disease in humans remain poorly understood. To help bridge this gap, we developed an ex vivo/in vitro model of RSV infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs), the primary targets of RSV infection in vivo. Our RSV/WD-PBEC model demonstrated remarkable similarities to hallmarks of RSV infection in infant lungs. These hallmarks included restriction of infection to noncontiguous or small clumps of apical ciliated and occasional nonciliated epithelial cells, apoptosis and sloughing of apical epithelial cells, occasional syncytium formation, goblet cell hyperplasia/metaplasia, and mucus hypersecretion. RSV was shed exclusively from the apical surface at titers consistent with those in airway aspirates from hospitalized infants. Furthermore, secretion of proinflammatory chemokines such as CXCL10, CCL5, IL-6, and CXCL8 reflected those chemokines present in airway aspirates. Interestingly, a recent RSV clinical isolate induced more cytopathogenesis than the prototypic A2 strain. Our findings indicate that this RSV/WD-PBEC model provides an authentic surrogate for RSV infection of airway epithelium in vivo. As such, this model may provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines or therapeutics.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Respiratory syncytial virus (RSV) is the major viral cause of severe pulmonary disease in young infants worldwide.", "However, the mechanisms by which RSV causes disease in humans remain poorly understood.", "To help bridge this gap, we developed an ex vivo/in vitro model of RSV infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs), the primary targets of RSV infection in vivo.", "Our RSV/WD-PBEC model demonstrated remarkable similarities to hallmarks of RSV infection in infant lungs.", "These hallmarks included restriction of infection to noncontiguous or small clumps of apical ciliated and occasional nonciliated epithelial cells, apoptosis and sloughing of apical epithelial cells, occasional syncytium formation, goblet cell hyperplasia/metaplasia, and mucus hypersecretion.", "RSV was shed exclusively from the apical surface at titers consistent with those in airway aspirates from hospitalized infants.", "Furthermore, secretion of proinflammatory chemokines such as CXCL10, CCL5, IL-6, and CXCL8 reflected those chemokines present in airway aspirates.", "Interestingly, a recent RSV clinical isolate induced more cytopathogenesis than the prototypic A2 strain.", "Our findings indicate that this RSV/WD-PBEC model provides an authentic surrogate for RSV infection of airway epithelium in vivo.", "As such, this model may provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines or therapeutics."], "title": "In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo."}
{"paper_id": 26869969, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Studies comparing musicians and non-musicians have shown that musical training can improve rhythmic perception and production. These findings tell us that training can result in rhythm processing advantages, but they do not tell us whether practicing a particular instrument could lead to specific effects on rhythm perception or production. The current study used a battery of four rhythm perception and production tasks that were designed to test both higher- and lower-level aspects of rhythm processing. Four groups of musicians (drummers, singers, pianists, string players) and a control group of non-musicians were tested. Within-task differences in performance showed that factors such as meter, metrical complexity, tempo, and beat phase significantly affected the ability to perceive and synchronize taps to a rhythm or beat. Musicians showed better performance on all rhythm tasks compared to non-musicians. Interestingly, our results revealed no significant differences between musician groups for the vast majority of task measures. This was despite the fact that all musicians were selected to have the majority of their training on the target instrument, had on average more than 10 years of experience on their instrument, and were currently practicing. These results suggest that general musical experience is more important than specialized musical experience with regards to perception and production of rhythms.", "journal": "Frontiers in psychology", "sentences": ["Studies comparing musicians and non-musicians have shown that musical training can improve rhythmic perception and production.", "These findings tell us that training can result in rhythm processing advantages, but they do not tell us whether practicing a particular instrument could lead to specific effects on rhythm perception or production.", "The current study used a battery of four rhythm perception and production tasks that were designed to test both higher- and lower-level aspects of rhythm processing.", "Four groups of musicians (drummers, singers, pianists, string players) and a control group of non-musicians were tested.", "Within-task differences in performance showed that factors such as meter, metrical complexity, tempo, and beat phase significantly affected the ability to perceive and synchronize taps to a rhythm or beat.", "Musicians showed better performance on all rhythm tasks compared to non-musicians.", "Interestingly, our results revealed no significant differences between musician groups for the vast majority of task measures.", "This was despite the fact that all musicians were selected to have the majority of their training on the target instrument, had on average more than 10 years of experience on their instrument, and were currently practicing.", "These results suggest that general musical experience is more important than specialized musical experience with regards to perception and production of rhythms."], "title": "The Impact of Instrument-Specific Musical Training on Rhythm Perception and Production."}
{"paper_id": 26016997, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Leukemic stem cells (LSCs) reside within bone marrow niches that maintain their relatively quiescent state and convey resistance to conventional treatment. Many of the microenvironmental signals converge on RAC GTPases. Although it has become clear that RAC proteins fulfill important roles in the hematopoietic compartment, little has been revealed about the downstream effectors and molecular mechanisms. We observed that in BCR-ABL-transduced human hematopoietic stem/progenitor cells (HSPCs) depletion of RAC2 but not RAC1 induced a marked and immediate decrease in proliferation, progenitor frequency, cobblestone formation and replating capacity, indicative for reduced self-renewal. Cell cycle analyses showed reduced cell cycle activity in RAC2-depleted BCR-ABL leukemic cobblestones coinciding with an increased apoptosis. Moreover, a decrease in mitochondrial membrane potential was observed upon RAC2 downregulation, paralleled by severe mitochondrial ultrastructural malformations as determined by automated electron microscopy. Proteome analysis revealed that RAC2 specifically interacted with a set of mitochondrial proteins including mitochondrial transport proteins SAM50 and Metaxin 1, and interactions were confirmed in independent co-immunoprecipitation studies. Downregulation of SAM50 also impaired the proliferation and replating capacity of BCR-ABL-expressing cells, again associated with a decreased mitochondrial membrane potential. Taken together, these data suggest an important role for RAC2 in maintaining mitochondrial integrity.", "journal": "PloS one", "sentences": ["Leukemic stem cells (LSCs) reside within bone marrow niches that maintain their relatively quiescent state and convey resistance to conventional treatment.", "Many of the microenvironmental signals converge on RAC GTPases.", "Although it has become clear that RAC proteins fulfill important roles in the hematopoietic compartment, little has been revealed about the downstream effectors and molecular mechanisms.", "We observed that in BCR-ABL-transduced human hematopoietic stem/progenitor cells (HSPCs) depletion of RAC2 but not RAC1 induced a marked and immediate decrease in proliferation, progenitor frequency, cobblestone formation and replating capacity, indicative for reduced self-renewal.", "Cell cycle analyses showed reduced cell cycle activity in RAC2-depleted BCR-ABL leukemic cobblestones coinciding with an increased apoptosis.", "Moreover, a decrease in mitochondrial membrane potential was observed upon RAC2 downregulation, paralleled by severe mitochondrial ultrastructural malformations as determined by automated electron microscopy.", "Proteome analysis revealed that RAC2 specifically interacted with a set of mitochondrial proteins including mitochondrial transport proteins SAM50 and Metaxin 1, and interactions were confirmed in independent co-immunoprecipitation studies.", "Downregulation of SAM50 also impaired the proliferation and replating capacity of BCR-ABL-expressing cells, again associated with a decreased mitochondrial membrane potential.", "Taken together, these data suggest an important role for RAC2 in maintaining mitochondrial integrity."], "title": "Mitochondrial Dysfunction in Human Leukemic Stem/Progenitor Cells upon Loss of RAC2."}
{"paper_id": 26642936, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The microscopic magnetization variation in magnetic domain walls in thin films is a crucial property when considering the torques driving their dynamic behaviour. For films possessing out-of-plane anisotropy normally the presence of N\u00e9el walls is not favoured due to magnetostatic considerations. However, they have the right structure to respond to the torques exerted by the spin Hall effect. Their existence is an indicator of the interfacial Dzyaloshinskii-Moriya interaction (DMI). Here we present direct imaging of N\u00e9el domain walls with a fixed chirality in device-ready Pt/Co/AlOx films using Lorentz transmission electron and Kerr microscopies. It is shown that any independently nucleated pair of walls in our films form winding pairs when they meet that are difficult to annihilate with field, confirming that they all possess the same topological winding number. The latter is enforced by the DMI. The field required to annihilate these winding wall pairs is used to give a measure of the DMI strength. Such domain walls, which are robust against collisions with each other, are good candidates for dense data storage.", "journal": "Nature communications", "sentences": ["The microscopic magnetization variation in magnetic domain walls in thin films is a crucial property when considering the torques driving their dynamic behaviour.", "For films possessing out-of-plane anisotropy normally the presence of N\u00e9el walls is not favoured due to magnetostatic considerations.", "However, they have the right structure to respond to the torques exerted by the spin Hall effect.", "Their existence is an indicator of the interfacial Dzyaloshinskii-Moriya interaction (DMI).", "Here we present direct imaging of N\u00e9el domain walls with a fixed chirality in device-ready Pt/Co/AlOx films using Lorentz transmission electron and Kerr microscopies.", "It is shown that any independently nucleated pair of walls in our films form winding pairs when they meet that are difficult to annihilate with field, confirming that they all possess the same topological winding number.", "The latter is enforced by the DMI.", "The field required to annihilate these winding wall pairs is used to give a measure of the DMI strength.", "Such domain walls, which are robust against collisions with each other, are good candidates for dense data storage."], "title": "Magnetic microscopy and topological stability of homochiral N\u00e9el domain walls in a Pt/Co/AlOx trilayer."}
{"paper_id": 26452133, "labels": ["0", "0", "1", "0", "0", "0", "1"], "abstract": "PRIMA-1met (APR-246) is a methylated derivative and structural analog of PRIMA-1 (p53 re-activation and induction of massive apoptosis). PRIMA-1met has been reported to restore both the wild type (wt) structure and function of mutant p53. Here, we show that PRIMA-1met is highly effective at limiting the growth of CRC cells regardless of p53 status. However, PRIMA-1met induces robust apoptosis only in CRC cells with mutant p53. Upregulation of Noxa, a proapoptotic molecule, is crucial for PRIMA-1met mediated activity. In human xenograft model of disease, PRIMA-1met effectively suppresses CRC tumor growth. Our results uncover distinct mechanisms of PRIMA-1met in CRC with different p53 status, thus providing a mechanistic rationale to evaluate the clinical efficacy of PRIMA-1met in CRC patients with different p53 status.", "journal": "Oncotarget", "sentences": ["PRIMA-1met (APR-246) is a methylated derivative and structural analog of PRIMA-1 (p53 re-activation and induction of massive apoptosis).", "PRIMA-1met has been reported to restore both the wild type (wt) structure and function of mutant p53.", "Here, we show that PRIMA-1met is highly effective at limiting the growth of CRC cells regardless of p53 status.", "However, PRIMA-1met induces robust apoptosis only in CRC cells with mutant p53.", "Upregulation of Noxa, a proapoptotic molecule, is crucial for PRIMA-1met mediated activity.", "In human xenograft model of disease, PRIMA-1met effectively suppresses CRC tumor growth.", "Our results uncover distinct mechanisms of PRIMA-1met in CRC with different p53 status, thus providing a mechanistic rationale to evaluate the clinical efficacy of PRIMA-1met in CRC patients with different p53 status."], "title": "PRIMA-1met (APR-246) inhibits growth of colorectal cancer cells with different p53 status through distinct mechanisms."}
{"paper_id": 25966243, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The aim of this study was to select putative Terra Maranh\u00e3o plantain cultivar mutants obtained by gamma radiation, with good agronomic traits and short height. A total of 315 buds were irradiated in vitro with gamma rays in doses of 20 Gy and were subcultivated and evaluated in the field over 2 production cycles. The clones were evaluated to select the best 10% of the plants. Cultivation was undertaken at a spacing of 3 x 4 m, and fertilization was carried out according to the technical recommendations for the crop. A total of 111 irradiated plants and 41 controls were evaluated in the field. Among the irradiated plants selected, genotypes that exhibited reduced height were observed. The genotypes Irra 04, Irra 13, Irra 19, and Irra 21 exhibited a height of 3.6 m, which was below the mean value of the controls selected. Other irradiated genotypes selected such as Irra 14 and Irra 16, with a height of 3.65 m, are promising because, in addition to reduced height, they exhibited good bunch weight and shorter period to flowering in relation to the mean value of the controls, which is a significant factor for the next stages in breeding. These results confirm the possibility of inducing mutations in Terra type banana plants to obtain desirable agronomic traits and short height.", "journal": "Genetics and molecular research : GMR", "sentences": ["The aim of this study was to select putative Terra Maranh\u00e3o plantain cultivar mutants obtained by gamma radiation, with good agronomic traits and short height.", "A total of 315 buds were irradiated in vitro with gamma rays in doses of 20 Gy and were subcultivated and evaluated in the field over 2 production cycles.", "The clones were evaluated to select the best 10% of the plants.", "Cultivation was undertaken at a spacing of 3 x 4 m, and fertilization was carried out according to the technical recommendations for the crop.", "A total of 111 irradiated plants and 41 controls were evaluated in the field.", "Among the irradiated plants selected, genotypes that exhibited reduced height were observed.", "The genotypes Irra 04, Irra 13, Irra 19, and Irra 21 exhibited a height of 3.6 m, which was below the mean value of the controls selected.", "Other irradiated genotypes selected such as Irra 14 and Irra 16, with a height of 3.65 m, are promising because, in addition to reduced height, they exhibited good bunch weight and shorter period to flowering in relation to the mean value of the controls, which is a significant factor for the next stages in breeding.", "These results confirm the possibility of inducing mutations in Terra type banana plants to obtain desirable agronomic traits and short height."], "title": "Selection of putative Terra Maranh\u00e3o plantain cultivar mutants obtained by gamma radiation."}
{"paper_id": 20348323, "labels": ["0", "0", "0", "0", "0", "1", "1", "0"], "abstract": "A Gram-stain-negative, yellow-pigmented, rod-shaped, strictly aerobic, non-flagellated, non-gliding and oxidase- and catalase-positive bacterium, designated A6(T), was isolated from a marine sponge, Halichondria oshoro, collected on the coast of Jeju Island, South Korea. Phylogenetic analysis based on the nearly complete 16S rRNA gene sequence revealed that strain A6(T) was a member of the family Flavobacteriaceae. The closest relatives were Aquimarina intermedia LMG 23204(T), A. latercula ATCC 23177(T), A. brevivitae SMK-19(T) and A. muelleri KMM 6020(T), with which strain A6(T) shared 95.7, 95.1, 94.7 and 94.6\u200a% 16S rRNA gene sequence similarity, respectively. The dominant fatty acids of strain A6(T) were iso-C(15\u200a:\u200a0) (32.2\u200a%), iso-C(17\u200a:\u200a0) 3-OH (20.0\u200a%), iso-C(15\u200a:\u200a0) 3-OH (12.3\u200a%), iso-C(15\u200a:\u200a1) G (7.2\u200a%) and summed feature 3 (comprising iso-C(15\u200a:\u200a0) 2-OH and/or C(16\u200a:\u200a1)\u03c97c; 6.8\u200a%). The DNA G+C content of strain A6(T) was 36.0 mol% and the major respiratory quinone was MK-6. On the basis of combined phenotypic and phylogenetic analyses, strain A6(T) represents a novel species of the genus Aquimarina, for which the name Aquimarina spongiae sp. nov. is proposed. The type strain is A6(T) (=KCTC 22663(T) =DSM 22623(T)).", "journal": "International journal of systematic and evolutionary microbiology", "sentences": ["A Gram-stain-negative, yellow-pigmented, rod-shaped, strictly aerobic, non-flagellated, non-gliding and oxidase- and catalase-positive bacterium, designated A6(T), was isolated from a marine sponge, Halichondria oshoro, collected on the coast of Jeju Island, South Korea.", "Phylogenetic analysis based on the nearly complete 16S rRNA gene sequence revealed that strain A6(T) was a member of the family Flavobacteriaceae.", "The closest relatives were Aquimarina intermedia LMG 23204(T), A. latercula ATCC 23177(T), A. brevivitae SMK-19(T) and A. muelleri KMM 6020(T), with which strain A6(T) shared 95.7, 95.1, 94.7 and 94.6\u200a% 16S rRNA gene sequence similarity, respectively.", "The dominant fatty acids of strain A6(T) were iso-C(15\u200a:\u200a0) (32.2\u200a%), iso-C(17\u200a:\u200a0) 3-OH (20.0\u200a%), iso-C(15\u200a:\u200a0) 3-OH (12.3\u200a%), iso-C(15\u200a:\u200a1) G (7.2\u200a%) and summed feature 3 (comprising iso-C(15\u200a:\u200a0) 2-OH and/or C(16\u200a:\u200a1)\u03c97c; 6.8\u200a%).", "The DNA G+C content of strain A6(T) was 36.0 mol% and the major respiratory quinone was MK-6.", "On the basis of combined phenotypic and phylogenetic analyses, strain A6(T) represents a novel species of the genus Aquimarina, for which the name Aquimarina spongiae sp.", "nov. is proposed.", "The type strain is A6(T) (=KCTC 22663(T) =DSM 22623(T))."], "title": "Aquimarina spongiae sp. nov., isolated from marine sponge Halichondria oshoro."}
{"paper_id": 25856372, "labels": ["0", "0", "0", "1", "0"], "abstract": "People use dialectical thinking to be holistic, reconcile contradictions, and emphasize changes when processing information and managing problems. Using a questionnaire survey, this study examined the relationship between dialectical thinking and creative personality in the Chinese culture, which encourages a holistic and collective thinking style. Undergraduates majoring in different subjects and adults in different professions were surveyed. The results showed that 1) compared with undergraduates majoring in art and adults from the design industry, undergraduates majoring in other disciplines significantly showed the least creative personality; 2) the highest score for dialectical thinking was found in the group of undergraduates who majored in other disciplines, followed by the adult group, and the undergraduates majoring in art had the lowest score; and 3) A negative relationship between dialectical thinking and creative personality was found mostly in the UMA group. The limitations of this study and suggestions for future research are discussed.", "journal": "PloS one", "sentences": ["People use dialectical thinking to be holistic, reconcile contradictions, and emphasize changes when processing information and managing problems.", "Using a questionnaire survey, this study examined the relationship between dialectical thinking and creative personality in the Chinese culture, which encourages a holistic and collective thinking style.", "Undergraduates majoring in different subjects and adults in different professions were surveyed.", "The results showed that 1) compared with undergraduates majoring in art and adults from the design industry, undergraduates majoring in other disciplines significantly showed the least creative personality; 2) the highest score for dialectical thinking was found in the group of undergraduates who majored in other disciplines, followed by the adult group, and the undergraduates majoring in art had the lowest score; and 3) A negative relationship between dialectical thinking and creative personality was found mostly in the UMA group.", "The limitations of this study and suggestions for future research are discussed."], "title": "More dialectical thinking, less creativity? The relationship between dialectical thinking style and creative personality: the case of China."}
{"paper_id": 26635391, "labels": ["0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "We previously presented DriverDB, a database that incorporates \u223c6000 cases of exome-seq data, in addition to annotation databases and published bioinformatics algorithms dedicated to driver gene/mutation identification. The database provides two points of view, 'Cancer' and 'Gene', to help researchers visualize the relationships between cancers and driver genes/mutations. In the updated DriverDBv2 database (http://ngs.ym.edu.tw/driverdb) presented herein, we incorporated >9500 cancer-related RNA-seq datasets and >7000 more exome-seq datasets from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and published papers. Seven additional computational algorithms (meaning that the updated database contains 15 in total), which were developed for driver gene identification, are incorporated into our analysis pipeline, and the results are provided in the 'Cancer' section. Furthermore, there are two main new features, 'Expression' and 'Hotspot', in the 'Gene' section. 'Expression' displays two expression profiles of a gene in terms of sample types and mutation types, respectively. 'Hotspot' indicates the hotspot mutation regions of a gene according to the results provided by four bioinformatics tools. A new function, 'Gene Set', allows users to investigate the relationships among mutations, expression levels and clinical data for a set of genes, a specific dataset and clinical features.", "journal": "Nucleic acids research", "sentences": ["We previously presented DriverDB, a database that incorporates \u223c6000 cases of exome-seq data, in addition to annotation databases and published bioinformatics algorithms dedicated to driver gene/mutation identification.", "The database provides two points of view, 'Cancer' and 'Gene', to help researchers visualize the relationships between cancers and driver genes/mutations.", "In the updated DriverDBv2 database (http://ngs.ym.edu.tw/driverdb) presented herein, we incorporated >9500 cancer-related RNA-seq datasets and >7000 more exome-seq datasets from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and published papers.", "Seven additional computational algorithms (meaning that the updated database contains 15 in total), which were developed for driver gene identification, are incorporated into our analysis pipeline, and the results are provided in the 'Cancer' section.", "Furthermore, there are two main new features, 'Expression' and 'Hotspot', in the 'Gene' section.", "'Expression' displays two expression profiles of a gene in terms of sample types and mutation types, respectively.", "'Hotspot' indicates the hotspot mutation regions of a gene according to the results provided by four bioinformatics tools.", "A new function, 'Gene Set', allows users to investigate the relationships among mutations, expression levels and clinical data for a set of genes, a specific dataset and clinical features."], "title": "DriverDBv2: a database for human cancer driver gene research."}
{"paper_id": 27399681, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Short-term persistence of transplanted cells during early post-implant period limits clinical efficacy of cell therapy. Poor cell survival is mainly due to the harsh hypoxic microenvironment transplanted cells face at the site of implantation and to anoikis, driven by cell adhesion loss. We evaluated the hypothesis that viral-mediated expression of a gene conferring hypoxia resistance to cells before transplant could enhance survival of grafted cells in early stages after implant. We used adipose tissue as cell source because it consistently provides high yields of adipose-tissue-derived stromal and vascular cells (ASCs), suitable for regenerative purposes. Luciferase positive cells were transduced with lentiviral vectors expressing either green fluorescent protein as control or human manganese superoxide dismutase (SOD2). Cells were then exposed in vitro to hypoxic conditions, mimicking cell transplantation into an ischemic site. Cells overexpressing SOD2 displayed survival rates significantly greater compared to mock transduced cells. Similar results were also obtained in vivo after implantation into syngeneic mice and assessment of cell engraftment by in vivo bioluminescent imaging. Taken together, these findings suggest that ex vivo gene transfer of SOD2 into ASCs before implantation confers a cytoprotective effect leading to improved survival and engraftment rates, therefore enhancing cell therapy regenerative potential.", "journal": "International journal of molecular sciences", "sentences": ["Short-term persistence of transplanted cells during early post-implant period limits clinical efficacy of cell therapy.", "Poor cell survival is mainly due to the harsh hypoxic microenvironment transplanted cells face at the site of implantation and to anoikis, driven by cell adhesion loss.", "We evaluated the hypothesis that viral-mediated expression of a gene conferring hypoxia resistance to cells before transplant could enhance survival of grafted cells in early stages after implant.", "We used adipose tissue as cell source because it consistently provides high yields of adipose-tissue-derived stromal and vascular cells (ASCs), suitable for regenerative purposes.", "Luciferase positive cells were transduced with lentiviral vectors expressing either green fluorescent protein as control or human manganese superoxide dismutase (SOD2).", "Cells were then exposed in vitro to hypoxic conditions, mimicking cell transplantation into an ischemic site.", "Cells overexpressing SOD2 displayed survival rates significantly greater compared to mock transduced cells.", "Similar results were also obtained in vivo after implantation into syngeneic mice and assessment of cell engraftment by in vivo bioluminescent imaging.", "Taken together, these findings suggest that ex vivo gene transfer of SOD2 into ASCs before implantation confers a cytoprotective effect leading to improved survival and engraftment rates, therefore enhancing cell therapy regenerative potential."], "title": "Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase."}
{"paper_id": 24504373, "labels": ["0", "0", "0", "0", "1", "1", "1"], "abstract": "Diguanylate cyclase and phosphodiesterase enzymatic activities control c-di-GMP levels modulating planktonic versus sessile lifestyle behavior in bacteria. The PilZ domain is described as a sensor of c-di-GMP intracellular levels and the proteins containing a PilZ domain represent the best studied class of c-di-GMP receptors forming part of the c-di-GMP signaling cascade. In P. fluorescens F113 we have found two diguanylate cyclases (WspR, SadC) and one phosphodiesterase (BifA) implicated in regulation of swimming motility and biofilm formation. Here we identify a flgZ gene located in a flagellar operon encoding a protein that contains a PilZ domain. Moreover, we show that FlgZ subcellular localization depends on the c-di-GMP intracellular levels. The overexpression analysis of flgZ in P. fluorescens F113 and P. putida KT2440 backgrounds reveal a participation of FlgZ in Pseudomonas swimming motility regulation. Besides, the epistasis of flgZ over wspR and bifA clearly shows that c-di-GMP intracellular levels produced by the enzymatic activity of the diguanylate cyclase WspR and the phosphodiesterase BifA regulates biofilm formation through FlgZ.", "journal": "PloS one", "sentences": ["Diguanylate cyclase and phosphodiesterase enzymatic activities control c-di-GMP levels modulating planktonic versus sessile lifestyle behavior in bacteria.", "The PilZ domain is described as a sensor of c-di-GMP intracellular levels and the proteins containing a PilZ domain represent the best studied class of c-di-GMP receptors forming part of the c-di-GMP signaling cascade.", "In P. fluorescens F113 we have found two diguanylate cyclases (WspR, SadC) and one phosphodiesterase (BifA) implicated in regulation of swimming motility and biofilm formation.", "Here we identify a flgZ gene located in a flagellar operon encoding a protein that contains a PilZ domain.", "Moreover, we show that FlgZ subcellular localization depends on the c-di-GMP intracellular levels.", "The overexpression analysis of flgZ in P. fluorescens F113 and P. putida KT2440 backgrounds reveal a participation of FlgZ in Pseudomonas swimming motility regulation.", "Besides, the epistasis of flgZ over wspR and bifA clearly shows that c-di-GMP intracellular levels produced by the enzymatic activity of the diguanylate cyclase WspR and the phosphodiesterase BifA regulates biofilm formation through FlgZ."], "title": "Identification of flgZ as a flagellar gene encoding a PilZ domain protein that regulates swimming motility and biofilm formation in Pseudomonas."}
{"paper_id": 26883069, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Non-invasive transcranial brain stimulation (NTBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS) are important tools in human systems and cognitive neuroscience because they are able to reveal the relevance of certain brain structures or neuronal activity patterns for a given brain function. It is nowadays feasible to combine NTBS, either consecutively or concurrently, with a variety of neuroimaging and electrophysiological techniques. Here we discuss what kind of information can be gained from combined approaches, which often are technically demanding. We argue that the benefit from this combination is twofold. Firstly, neuroimaging and electrophysiology can inform subsequent NTBS, providing the required information to optimize where, when, and how to stimulate the brain. Information can be achieved both before and during the NTBS experiment, requiring consecutive and concurrent applications, respectively. Secondly, neuroimaging and electrophysiology can provide the readout for neural changes induced by NTBS. Again, using either concurrent or consecutive applications, both \"online\" NTBS effects immediately following the stimulation and \"offline\" NTBS effects outlasting plasticity-inducing NTBS protocols can be assessed. Finally, both strategies can be combined to close the loop between measuring and modulating brain activity by means of closed-loop brain state-dependent NTBS. In this paper, we will provide a conceptual framework, emphasizing principal strategies and highlighting promising future directions to exploit the benefits of combining NTBS with neuroimaging or electrophysiology.", "journal": "NeuroImage", "sentences": ["Non-invasive transcranial brain stimulation (NTBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS) are important tools in human systems and cognitive neuroscience because they are able to reveal the relevance of certain brain structures or neuronal activity patterns for a given brain function.", "It is nowadays feasible to combine NTBS, either consecutively or concurrently, with a variety of neuroimaging and electrophysiological techniques.", "Here we discuss what kind of information can be gained from combined approaches, which often are technically demanding.", "We argue that the benefit from this combination is twofold.", "Firstly, neuroimaging and electrophysiology can inform subsequent NTBS, providing the required information to optimize where, when, and how to stimulate the brain.", "Information can be achieved both before and during the NTBS experiment, requiring consecutive and concurrent applications, respectively.", "Secondly, neuroimaging and electrophysiology can provide the readout for neural changes induced by NTBS.", "Again, using either concurrent or consecutive applications, both \"online\" NTBS effects immediately following the stimulation and \"offline\" NTBS effects outlasting plasticity-inducing NTBS protocols can be assessed.", "Finally, both strategies can be combined to close the loop between measuring and modulating brain activity by means of closed-loop brain state-dependent NTBS.", "In this paper, we will provide a conceptual framework, emphasizing principal strategies and highlighting promising future directions to exploit the benefits of combining NTBS with neuroimaging or electrophysiology."], "title": "Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives."}
{"paper_id": 23196364, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The sonication technique has been shown to be a promising tool for microbiological diagnosis of device-related infections. We evaluated the usefulness of the sonication method for pathogen detection in 80 explanted cardiac components collected from 40 patients, and the results were compared with those of conventional cultures. Forty subjects undergoing cardiac device removal were studied: 20 had cardiac device infection, and 20 subjects underwent elective generator replacement or revision in the absence of infection. Sonication of explanted devices was more sensitive than traditional culture for microbial detection (67% and 50%, respectively; P = 0.0005). The bacterial count detected in sonication fluid culture was significantly higher than that detected in traditional culture in both infected (P = 0.019) and uninfected (P = 0.029) devices. In the infected patients, sonication fluid culture yielded a significantly higher rate of pathogen detection in explanted electrodes than traditional culture (65% versus 45%; P = 0.02), while no differences were found in the generators. Ten strains were detected only through sonication fluid culture: 6 Staphylococcus epidermidis strains, 1 Staphylococcus hominis strain, 2 Corynebacterium striatum strains, and 1 Brevundimonas sp. Neither the type nor the duration of antimicrobial therapy before device removal had an effect on the diagnostic performance of sonication fluid culture (P = 0.75 and P = 0.56, respectively). In the patients without infection, sonication fluid culture was positive in 8 cases (40%), whereas conventional culture was positive in only 4 (20%). In summary, the sonication technique improves the microbiological diagnosis of explanted cardiac devices.", "journal": "Journal of clinical microbiology", "sentences": ["The sonication technique has been shown to be a promising tool for microbiological diagnosis of device-related infections.", "We evaluated the usefulness of the sonication method for pathogen detection in 80 explanted cardiac components collected from 40 patients, and the results were compared with those of conventional cultures.", "Forty subjects undergoing cardiac device removal were studied: 20 had cardiac device infection, and 20 subjects underwent elective generator replacement or revision in the absence of infection.", "Sonication of explanted devices was more sensitive than traditional culture for microbial detection (67% and 50%, respectively; P = 0.0005).", "The bacterial count detected in sonication fluid culture was significantly higher than that detected in traditional culture in both infected (P = 0.019) and uninfected (P = 0.029) devices.", "In the infected patients, sonication fluid culture yielded a significantly higher rate of pathogen detection in explanted electrodes than traditional culture (65% versus 45%; P = 0.02), while no differences were found in the generators.", "Ten strains were detected only through sonication fluid culture: 6 Staphylococcus epidermidis strains, 1 Staphylococcus hominis strain, 2 Corynebacterium striatum strains, and 1 Brevundimonas sp.", "Neither the type nor the duration of antimicrobial therapy before device removal had an effect on the diagnostic performance of sonication fluid culture (P = 0.75 and P = 0.56, respectively).", "In the patients without infection, sonication fluid culture was positive in 8 cases (40%), whereas conventional culture was positive in only 4 (20%).", "In summary, the sonication technique improves the microbiological diagnosis of explanted cardiac devices."], "title": "Sonication of explanted cardiac implants improves microbial detection in cardiac device infections."}
{"paper_id": 23724036, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The southern and tropical southeastern regions of the Yunnan Province in southwestern China have similar monsoonal climates and lowland tropical rain forest vegetations. The floras of both regions are dominated by tropical floristic elements (78.3% in southern Yunnan and 68.83% in southeastern Yunnan), and both belong to the Indo-Malaysian flora at the northern margin of tropical Asia. However, some temperate East Asian characteristic families are well represented in the flora of tropical southeastern Yunnan, while families characteristic of tropical Asia are well represented in the flora of southern Yunnan. Additionally, there are 14 mainly east Asian families in tropical southeastern Yunnan that are not found in southern Yunnan. Although the two regions share 80% of their genera, 237 genera are restricted to southern Yunnan, and 349 genera to tropical southeastern Yunnan. Furthermore, 57 genera with an East Asian distribution, 53 genera with a North temperate distribution, 22 genera endemic to China, and 17 genera with an East Asia and North America disjunct distribution are found only in tropical southeastern Yunnan. The flora of tropical southeastern Yunnan is more closely related to Eastern Asian flora, while the flora of southern Yunnan is more closely related to Indo-Malaysian flora. The divergence of the flora is well supported by the geological history of the region; the flora of tropical southeastern Yunnan was mainly derived from the South China Geoblock, while the southern Yunnan flora derived from the Shan-Thai Geoblock.", "journal": "PloS one", "sentences": ["The southern and tropical southeastern regions of the Yunnan Province in southwestern China have similar monsoonal climates and lowland tropical rain forest vegetations.", "The floras of both regions are dominated by tropical floristic elements (78.3% in southern Yunnan and 68.83% in southeastern Yunnan), and both belong to the Indo-Malaysian flora at the northern margin of tropical Asia.", "However, some temperate East Asian characteristic families are well represented in the flora of tropical southeastern Yunnan, while families characteristic of tropical Asia are well represented in the flora of southern Yunnan.", "Additionally, there are 14 mainly east Asian families in tropical southeastern Yunnan that are not found in southern Yunnan.", "Although the two regions share 80% of their genera, 237 genera are restricted to southern Yunnan, and 349 genera to tropical southeastern Yunnan.", "Furthermore, 57 genera with an East Asian distribution, 53 genera with a North temperate distribution, 22 genera endemic to China, and 17 genera with an East Asia and North America disjunct distribution are found only in tropical southeastern Yunnan.", "The flora of tropical southeastern Yunnan is more closely related to Eastern Asian flora, while the flora of southern Yunnan is more closely related to Indo-Malaysian flora.", "The divergence of the flora is well supported by the geological history of the region; the flora of tropical southeastern Yunnan was mainly derived from the South China Geoblock, while the southern Yunnan flora derived from the Shan-Thai Geoblock."], "title": "The floras of southern and tropical southeastern Yunnan have been shaped by divergent geological histories."}
{"paper_id": 22964329, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Epithelial-mesenchymal transition (EMT) is a process by which fully differentiated epithelial cells undergo a phenotypic conversion and assume a mesenchymal cell phenotype, including elongated morphology, enhanced migratory and invasiveness capacity, and greatly increased production of extracellular matrix (ECM) components. The EMTs associated with wound healing, tissue regeneration, and organ fibrosis are termed as type 2 EMT. Over the past two decades, emerging evidence suggested that injured epithelial cells, via type 2 EMT, may serve as important sources of fibroblasts and contribute to organ fibrosis, such as kidney, liver, lung and eyes. There is perhaps no doubt that adult epithelial cells can undergo EMT in vitro in response to transforming growth factor (TGF)-\u03b21 and other inflammatory or pro-fibrotic stimuli. However, whether type 2 EMT really occurs in vivo, whethers it is actually a source of functional and activated interstitial fibroblasts and whether it contributes to tissue fibrosis have already been the subjects of heated debate. In this review, we will describe the main features of EMT, the major findings of type 2 EMT in vitro, the evidences for and against type 2 EMT in vivo and discuss the heterogeneity and pitfalls of the techniques used to detect EMT during fibrotic diseases. We suggest that in order to ascertain the existence of type 2 EMT in vivo, different proper phenotype markers of epithelial and mesenchymal cells should be jointly used and cell lineage tracking techniques should be standardized and avoid false positives. Finally, we believe that if EMT really occurs and contributes to tissue fibrosis, efforts should be made to block or reverse EMT to attenuate fibrotic process.", "journal": "Chinese medical journal", "sentences": ["Epithelial-mesenchymal transition (EMT) is a process by which fully differentiated epithelial cells undergo a phenotypic conversion and assume a mesenchymal cell phenotype, including elongated morphology, enhanced migratory and invasiveness capacity, and greatly increased production of extracellular matrix (ECM) components.", "The EMTs associated with wound healing, tissue regeneration, and organ fibrosis are termed as type 2 EMT.", "Over the past two decades, emerging evidence suggested that injured epithelial cells, via type 2 EMT, may serve as important sources of fibroblasts and contribute to organ fibrosis, such as kidney, liver, lung and eyes.", "There is perhaps no doubt that adult epithelial cells can undergo EMT in vitro in response to transforming growth factor (TGF)-\u03b21 and other inflammatory or pro-fibrotic stimuli.", "However, whether type 2 EMT really occurs in vivo, whethers it is actually a source of functional and activated interstitial fibroblasts and whether it contributes to tissue fibrosis have already been the subjects of heated debate.", "In this review, we will describe the main features of EMT, the major findings of type 2 EMT in vitro, the evidences for and against type 2 EMT in vivo and discuss the heterogeneity and pitfalls of the techniques used to detect EMT during fibrotic diseases.", "We suggest that in order to ascertain the existence of type 2 EMT in vivo, different proper phenotype markers of epithelial and mesenchymal cells should be jointly used and cell lineage tracking techniques should be standardized and avoid false positives.", "Finally, we believe that if EMT really occurs and contributes to tissue fibrosis, efforts should be made to block or reverse EMT to attenuate fibrotic process."], "title": "Type 2 epithelial mesenchymal transition in vivo: truth or pitfalls?"}
{"paper_id": 27069924, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "We used functional fMRI to study the brain activation during active finger movements at different time points during the recovery phase following basal ganglia infarction. Four hemiplegic patients with basal ganglia infarction were serially evaluated at different time points spanning the acute and chronic phase using fMRI. To evaluate motor recovery, the patients were asked to perform functional tasks arranged in a block design manner with their hand. On follow-up (chronic phase), three patients achieved significant recovery of motor function of affected limbs. Activation of bilateral sensorimotor cortex (SMC) was observed in two of these patients, while activation of cerebellum was observed in all patients. No remarkable recovery of motor function was noted in one patient with left basal ganglia infarction. In this patient, the activation domain was located in SMC of both sides in acute phase and in ipsilateral SMC in chronic phase. Contralateral SMC appears to be involved in the functional rehabilitation following basal ganglia infarction. The cerebellum may act as an intermediary during functional recovery following basal ganglia infarction. The activation domain associated with active finger movement may be bilateral in acute phase; one patient was ipsilateral in the chronic stage.", "journal": "BioMed research international", "sentences": ["We used functional fMRI to study the brain activation during active finger movements at different time points during the recovery phase following basal ganglia infarction.", "Four hemiplegic patients with basal ganglia infarction were serially evaluated at different time points spanning the acute and chronic phase using fMRI.", "To evaluate motor recovery, the patients were asked to perform functional tasks arranged in a block design manner with their hand.", "On follow-up (chronic phase), three patients achieved significant recovery of motor function of affected limbs.", "Activation of bilateral sensorimotor cortex (SMC) was observed in two of these patients, while activation of cerebellum was observed in all patients.", "No remarkable recovery of motor function was noted in one patient with left basal ganglia infarction.", "In this patient, the activation domain was located in SMC of both sides in acute phase and in ipsilateral SMC in chronic phase.", "Contralateral SMC appears to be involved in the functional rehabilitation following basal ganglia infarction.", "The cerebellum may act as an intermediary during functional recovery following basal ganglia infarction.", "The activation domain associated with active finger movement may be bilateral in acute phase; one patient was ipsilateral in the chronic stage."], "title": "Longitudinal Assessment of Motor Recovery of Contralateral Hand after Basal Ganglia Infarction Using Functional Magnetic Resonance Imaging."}
{"paper_id": 20554193, "labels": ["0", "0", "0", "0", "1", "1"], "abstract": "This paper describes the preparation and application of a novel bioanode for use in ethanol/O(2) biofuel cells based upon immobilization of alcohol dehydrogenase (ADH) and polyamidoamine (PAMAM) dendrimers onto carbon cloth platforms. The power density measurements indicated a direct relationship between the amount of anchored ADH and the anode power values, which increased upon enzyme loading. The power density values ranged from 0.04 to 0.28 mW cm(-2), and the highest power density was achieved with the bioanode prepared with 28 U of ADH, which provided a power density of 0.28 mW cm(-2) at 0.3 V. The latter power output values were the maximum observed, even for higher enzyme concentrations. Stability of the bioanodes was quite satisfactory, since there was no appreciable reduction of enzymatic activity during the measurements. The method of bioanode preparation described here has proven to be very effective. The PAMAM dendrimer represents a friendly environment for the immobilization of enzymes, and it is stable and capable of generating high power density compared to other immobilization methods.", "journal": "Biosensors & bioelectronics", "sentences": ["This paper describes the preparation and application of a novel bioanode for use in ethanol/O(2) biofuel cells based upon immobilization of alcohol dehydrogenase (ADH) and polyamidoamine (PAMAM) dendrimers onto carbon cloth platforms.", "The power density measurements indicated a direct relationship between the amount of anchored ADH and the anode power values, which increased upon enzyme loading.", "The power density values ranged from 0.04 to 0.28 mW cm(-2), and the highest power density was achieved with the bioanode prepared with 28 U of ADH, which provided a power density of 0.28 mW cm(-2) at 0.3 V. The latter power output values were the maximum observed, even for higher enzyme concentrations.", "Stability of the bioanodes was quite satisfactory, since there was no appreciable reduction of enzymatic activity during the measurements.", "The method of bioanode preparation described here has proven to be very effective.", "The PAMAM dendrimer represents a friendly environment for the immobilization of enzymes, and it is stable and capable of generating high power density compared to other immobilization methods."], "title": "Development of novel bioanodes for ethanol biofuel cell using PAMAM dendrimers as matrix for enzyme immobilization."}
{"paper_id": 22941991, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Production operation of large distributed computing infrastructures (DCI) still requires a lot of human intervention to reach acceptable quality of service. This may be achievable for scientific communities with solid IT support, but it remains a show-stopper for others. Some application execution environments are used to hide runtime technical issues from end users. But they mostly aim at fault-tolerance rather than incident resolution, and their operation still requires substantial manpower. A longer-term support activity is thus needed to ensure sustained quality of service for Virtual Organisations (VO). This paper describes how the biomed VO has addressed this challenge by setting up a technical support team. Its organisation, tooling, daily tasks, and procedures are described. Results are shown in terms of resource usage by end users, amount of reported incidents, and developed software tools. Based on our experience, we suggest ways to measure the impact of the technical support, perspectives to decrease its human cost and make it more community-specific.", "journal": "Studies in health technology and informatics", "sentences": ["Production operation of large distributed computing infrastructures (DCI) still requires a lot of human intervention to reach acceptable quality of service.", "This may be achievable for scientific communities with solid IT support, but it remains a show-stopper for others.", "Some application execution environments are used to hide runtime technical issues from end users.", "But they mostly aim at fault-tolerance rather than incident resolution, and their operation still requires substantial manpower.", "A longer-term support activity is thus needed to ensure sustained quality of service for Virtual Organisations (VO).", "This paper describes how the biomed VO has addressed this challenge by setting up a technical support team.", "Its organisation, tooling, daily tasks, and procedures are described.", "Results are shown in terms of resource usage by end users, amount of reported incidents, and developed software tools.", "Based on our experience, we suggest ways to measure the impact of the technical support, perspectives to decrease its human cost and make it more community-specific."], "title": "Technical support for Life Sciences communities on a production grid infrastructure."}
{"paper_id": 24798283, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "The aim of this study was to evaluate the biopharmaceutical characteristics of three fluoroquinolones (FQs), ciprofloxacin (CIP), moxifloxacin (MXF), and grepafloxacin (GRX), after delivery via a nebulized aerosol to rats. Bronchoalveolar lavages (BAL) were conducted 0.5, 2, 4, and 6 h after FQ intravenous administration and nebulized aerosol delivery to estimate epithelial lining fluid (ELF) drug concentrations. Plasma drug concentrations were also measured, and profiles of drug concentrations versus time after intravenous administration and nebulized aerosol delivery were virtually superimposable, attesting for rapid and complete systemic absorption of FQs. ELF drug concentrations were systematically higher than corresponding plasma drug concentrations, whatever the route of administration, and average ELF-to-unbound plasma drug concentration ratios post-distribution equilibrium did not change significantly between the ways of administration and were equal: 4.0 \u00b1 5.3 for CIP, 12.6 \u00b1 7.3 for MXF, and 19.1 \u00b1 10.5 for GRX (means \u00b1 standard deviations). The impact of macrophage lysis on estimated ELF drug concentrations was significant for GRX but reduced for MXF and CIP; therefore, simultaneous pharmacokinetic modeling of plasma and ELF drug concentrations was only performed for the latter two drugs. The model was characterized by a fixed volume of ELF (VELF), passive diffusion clearance (QELF), and active efflux clearance (CLout) between plasma and ELF, indicating active efflux transport systems. In conclusion, this study demonstrates that ELF drug concentrations of these three FQs are several times higher than plasma drug concentrations, probably due to the presence of efflux transporters at the pulmonary barrier level, but no biopharmaceutical advantage of FQ nebulization was observed compared with intravenous administration.", "journal": "Antimicrobial agents and chemotherapy", "sentences": ["The aim of this study was to evaluate the biopharmaceutical characteristics of three fluoroquinolones (FQs), ciprofloxacin (CIP), moxifloxacin (MXF), and grepafloxacin (GRX), after delivery via a nebulized aerosol to rats.", "Bronchoalveolar lavages (BAL) were conducted 0.5, 2, 4, and 6 h after FQ intravenous administration and nebulized aerosol delivery to estimate epithelial lining fluid (ELF) drug concentrations.", "Plasma drug concentrations were also measured, and profiles of drug concentrations versus time after intravenous administration and nebulized aerosol delivery were virtually superimposable, attesting for rapid and complete systemic absorption of FQs.", "ELF drug concentrations were systematically higher than corresponding plasma drug concentrations, whatever the route of administration, and average ELF-to-unbound plasma drug concentration ratios post-distribution equilibrium did not change significantly between the ways of administration and were equal: 4.0 \u00b1 5.3 for CIP, 12.6 \u00b1 7.3 for MXF, and 19.1 \u00b1 10.5 for GRX (means \u00b1 standard deviations).", "The impact of macrophage lysis on estimated ELF drug concentrations was significant for GRX but reduced for MXF and CIP; therefore, simultaneous pharmacokinetic modeling of plasma and ELF drug concentrations was only performed for the latter two drugs.", "The model was characterized by a fixed volume of ELF (VELF), passive diffusion clearance (QELF), and active efflux clearance (CLout) between plasma and ELF, indicating active efflux transport systems.", "In conclusion, this study demonstrates that ELF drug concentrations of these three FQs are several times higher than plasma drug concentrations, probably due to the presence of efflux transporters at the pulmonary barrier level, but no biopharmaceutical advantage of FQ nebulization was observed compared with intravenous administration."], "title": "Biopharmaceutical characterization of nebulized antimicrobial agents in rats: 1. Ciprofloxacin, moxifloxacin, and grepafloxacin."}
{"paper_id": 22539854, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The intronic GABRG2 mutation, IVS6+2T\u2192G, was identified in an Australian family with childhood absence epilepsy and febrile seizures (Kananura et al., 2002). The GABRG2 intron 6 splice donor site was found to be mutated from GT to GG. We generated wild-type and mutant \u03b32 subunit bacterial artificial chromosomes (BACs) driven by a CMV promoter and expressed them in HEK293T cells and expressed wild-type and mutant \u03b32 subunit BACs containing the endogenous hGABRG2 promoter in transgenic mice. Wild-type and mutant GABRG2 mRNA splicing patterns were determined in both BAC-transfected HEK293T cells and transgenic mouse brain, and in both, the mutation abolished intron 6 splicing at the donor site, activated a cryptic splice site, generated partial intron 6 retention, and produced a frameshift in exon 7 that created a premature translation termination codon (PTC). The resultant mutant mRNA was either degraded partially by nonsense-mediated mRNA decay or translated to a stable, truncated subunit (the \u03b32-PTC subunit) containing the first six GABRG2 exons and a novel frameshifted 29 aa C-terminal tail. The \u03b32-PTC subunit was homologous to the mollusk AChBP (acetylcholine binding protein) but was not secreted from cells. It was retained in the ER and not expressed on the surface membrane, but it did oligomerize with \u03b11 and \u03b22 subunits. These results suggested that the GABRG2 mutation, IVS6+2T\u2192G, reduced surface \u03b1\u03b2\u03b32 receptor levels, thus reducing GABAergic inhibition, by reducing GABRG2 transcript level and producing a stable, nonfunctional truncated subunit that had a dominant-negative effect on \u03b1\u03b2\u03b32 receptor assembly.", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "sentences": ["The intronic GABRG2 mutation, IVS6+2T\u2192G, was identified in an Australian family with childhood absence epilepsy and febrile seizures (Kananura et al., 2002).", "The GABRG2 intron 6 splice donor site was found to be mutated from GT to GG.", "We generated wild-type and mutant \u03b32 subunit bacterial artificial chromosomes (BACs) driven by a CMV promoter and expressed them in HEK293T cells and expressed wild-type and mutant \u03b32 subunit BACs containing the endogenous hGABRG2 promoter in transgenic mice.", "Wild-type and mutant GABRG2 mRNA splicing patterns were determined in both BAC-transfected HEK293T cells and transgenic mouse brain, and in both, the mutation abolished intron 6 splicing at the donor site, activated a cryptic splice site, generated partial intron 6 retention, and produced a frameshift in exon 7 that created a premature translation termination codon (PTC).", "The resultant mutant mRNA was either degraded partially by nonsense-mediated mRNA decay or translated to a stable, truncated subunit (the \u03b32-PTC subunit) containing the first six GABRG2 exons and a novel frameshifted 29 aa C-terminal tail.", "The \u03b32-PTC subunit was homologous to the mollusk AChBP (acetylcholine binding protein) but was not secreted from cells.", "It was retained in the ER and not expressed on the surface membrane, but it did oligomerize with \u03b11 and \u03b22 subunits.", "These results suggested that the GABRG2 mutation, IVS6+2T\u2192G, reduced surface \u03b1\u03b2\u03b32 receptor levels, thus reducing GABAergic inhibition, by reducing GABRG2 transcript level and producing a stable, nonfunctional truncated subunit that had a dominant-negative effect on \u03b1\u03b2\u03b32 receptor assembly."], "title": "The intronic GABRG2 mutation, IVS6+2T->G, associated with childhood absence epilepsy altered subunit mRNA intron splicing, activated nonsense-mediated decay, and produced a stable truncated \u03b32 subunit."}
{"paper_id": 23566819, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "Emotional faces are salient stimuli that play a critical role in social interactions. Following up on previous research suggesting that the event-related potentials (ERPs) show differential amplitudes in response to various facial expressions, the current study used trial-to-trial variability assembled from six discriminating ERP components to predict the facial expression categories in individual trials. In an experiment involved 17 participants, fearful trials were differentiated from non-fearful trials as early as the intervals of N1 and P1, with a mean predictive accuracy of 87%. Single-trial features in the occurrence of N170 and vertex positive potential could distinguish between emotional and neutral expressions (accuracy=90%). Finally, the trials associated with fearful, happy, and neutral faces were completely separated during the window of N3 and P3 (accuracy=83%). These categorization findings elucidated the temporal evolution of facial expression extraction, and demonstrated that the spatio-temporal characteristics of single-trial ERPs can distinguish facial expressions according to a three-stage scheme, with \"fear popup,\" \"emotional/unemotional discrimination,\" and \"complete separation\" as processing stages. This work constitutes the first examination of neural processing dynamics beyond multitrial ERP averaging, and directly relates the prediction performance of single-trial classifiers to the progressive brain functions of emotional face discrimination.", "journal": "Brain research", "sentences": ["Emotional faces are salient stimuli that play a critical role in social interactions.", "Following up on previous research suggesting that the event-related potentials (ERPs) show differential amplitudes in response to various facial expressions, the current study used trial-to-trial variability assembled from six discriminating ERP components to predict the facial expression categories in individual trials.", "In an experiment involved 17 participants, fearful trials were differentiated from non-fearful trials as early as the intervals of N1 and P1, with a mean predictive accuracy of 87%.", "Single-trial features in the occurrence of N170 and vertex positive potential could distinguish between emotional and neutral expressions (accuracy=90%).", "Finally, the trials associated with fearful, happy, and neutral faces were completely separated during the window of N3 and P3 (accuracy=83%).", "These categorization findings elucidated the temporal evolution of facial expression extraction, and demonstrated that the spatio-temporal characteristics of single-trial ERPs can distinguish facial expressions according to a three-stage scheme, with \"fear popup,\" \"emotional/unemotional discrimination,\" and \"complete separation\" as processing stages.", "This work constitutes the first examination of neural processing dynamics beyond multitrial ERP averaging, and directly relates the prediction performance of single-trial classifiers to the progressive brain functions of emotional face discrimination."], "title": "Single-trial ERP analysis reveals facial expression category in a three-stage scheme."}
{"paper_id": 21289186, "labels": ["0", "0", "0", "0", "0", "1", "0", "1"], "abstract": "The distinctive red-green dimension of human and nonhuman primate color perception arose relatively recently in the primate lineage with the appearance of separate long (L) and middle (M) wavelength-sensitive cone photoreceptor types. \"Midget\" ganglion cells of the retina use center-surround receptive field structure to combine L and M cone signals antagonistically and thereby establish a \"red-green, color-opponent\" visual pathway. However, the synaptic origin of red-green opponency is unknown, and conflicting evidence for either random or L versus M cone-selective inhibitory circuits has divergent implications for the developmental and evolutionary origins of trichromatic color vision. Here we directly measure the synaptic conductances evoked by selective L or M cone stimulation in the midget ganglion cell dendritic tree and show that L versus M cone opponency arises presynaptic to the midget cell and is transmitted entirely by modulation of an excitatory conductance. L and M cone synaptic inhibition is feedforward and thus occurs in phase with excitation for both cone types. Block of GABAergic and glycinergic receptors does not attenuate or modify L versus M cone antagonism, discounting both presynaptic and postsynaptic inhibition as sources of cone opponency. In sharp contrast, enrichment of retinal pH-buffering capacity, to attenuate negative feedback from horizontal cells that sum L and M cone inputs linearly and without selectivity, completely abolished both the midget cell surround and all chromatic opponency. Thus, red-green opponency appears to arise via outer retinal horizontal cell feedback that is not cone type selective without recourse to any inner retinal L versus M cone inhibitory pathways.", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "sentences": ["The distinctive red-green dimension of human and nonhuman primate color perception arose relatively recently in the primate lineage with the appearance of separate long (L) and middle (M) wavelength-sensitive cone photoreceptor types.", "\"Midget\" ganglion cells of the retina use center-surround receptive field structure to combine L and M cone signals antagonistically and thereby establish a \"red-green, color-opponent\" visual pathway.", "However, the synaptic origin of red-green opponency is unknown, and conflicting evidence for either random or L versus M cone-selective inhibitory circuits has divergent implications for the developmental and evolutionary origins of trichromatic color vision.", "Here we directly measure the synaptic conductances evoked by selective L or M cone stimulation in the midget ganglion cell dendritic tree and show that L versus M cone opponency arises presynaptic to the midget cell and is transmitted entirely by modulation of an excitatory conductance.", "L and M cone synaptic inhibition is feedforward and thus occurs in phase with excitation for both cone types.", "Block of GABAergic and glycinergic receptors does not attenuate or modify L versus M cone antagonism, discounting both presynaptic and postsynaptic inhibition as sources of cone opponency.", "In sharp contrast, enrichment of retinal pH-buffering capacity, to attenuate negative feedback from horizontal cells that sum L and M cone inputs linearly and without selectivity, completely abolished both the midget cell surround and all chromatic opponency.", "Thus, red-green opponency appears to arise via outer retinal horizontal cell feedback that is not cone type selective without recourse to any inner retinal L versus M cone inhibitory pathways."], "title": "Horizontal cell feedback without cone type-selective inhibition mediates \"red-green\" color opponency in midget ganglion cells of the primate retina."}
{"paper_id": 25862259, "labels": ["0", "0", "0", "0", "1"], "abstract": "Ambiguities in the source reconstruction of magnetoencephalographic (MEG) measurements can cause spurious correlations between estimated source time-courses. In this paper, we propose a symmetric orthogonalisation method to correct for these artificial correlations between a set of multiple regions of interest (ROIs). This process enables the straightforward application of network modelling methods, including partial correlation or multivariate autoregressive modelling, to infer connectomes, or functional networks, from the corrected ROIs. Here, we apply the correction to simulated MEG recordings of simple networks and to a resting-state dataset collected from eight subjects, before computing the partial correlations between power envelopes of the corrected ROItime-courses. We show accurate reconstruction of our simulated networks, and in the analysis of real MEGresting-state connectivity, we find dense bilateral connections within the motor and visual networks, together with longer-range direct fronto-parietal connections.", "journal": "NeuroImage", "sentences": ["Ambiguities in the source reconstruction of magnetoencephalographic (MEG) measurements can cause spurious correlations between estimated source time-courses.", "In this paper, we propose a symmetric orthogonalisation method to correct for these artificial correlations between a set of multiple regions of interest (ROIs).", "This process enables the straightforward application of network modelling methods, including partial correlation or multivariate autoregressive modelling, to infer connectomes, or functional networks, from the corrected ROIs.", "Here, we apply the correction to simulated MEG recordings of simple networks and to a resting-state dataset collected from eight subjects, before computing the partial correlations between power envelopes of the corrected ROItime-courses.", "We show accurate reconstruction of our simulated networks, and in the analysis of real MEGresting-state connectivity, we find dense bilateral connections within the motor and visual networks, together with longer-range direct fronto-parietal connections."], "title": "A symmetric multivariate leakage correction for MEG connectomes."}
{"paper_id": 25057198, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Humans can simultaneously track multiple moving objects with attention. The number of objects that can be tracked is known to be larger when visual stimuli are presented bilaterally rather than presented unilaterally. To elucidate the underlying neuronal mechanism, we trained monkeys to covertly track a single or multiple object(s). We found that neurons in the lateral prefrontal cortex exhibited greater activity for the target passing through the receptive field (RF) than for distractors. During multiple-object tracking, response enhancement for one target presented in the RF was stronger when the other target was located in the opposite than the same visual hemifield. Because the neuronal modulation did not differ depending on relative target locations with respect to upper and lower visual hemifields, the distance between the targets does not explain the results. We propose that inherent, anatomical separation of visual processing for contralateral and ipsilateral visual fields might constrain cognitive capacity.", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "sentences": ["Humans can simultaneously track multiple moving objects with attention.", "The number of objects that can be tracked is known to be larger when visual stimuli are presented bilaterally rather than presented unilaterally.", "To elucidate the underlying neuronal mechanism, we trained monkeys to covertly track a single or multiple object(s).", "We found that neurons in the lateral prefrontal cortex exhibited greater activity for the target passing through the receptive field (RF) than for distractors.", "During multiple-object tracking, response enhancement for one target presented in the RF was stronger when the other target was located in the opposite than the same visual hemifield.", "Because the neuronal modulation did not differ depending on relative target locations with respect to upper and lower visual hemifields, the distance between the targets does not explain the results.", "We propose that inherent, anatomical separation of visual processing for contralateral and ipsilateral visual fields might constrain cognitive capacity."], "title": "Differential neuronal representation of spatial attention dependent on relative target locations during multiple object tracking."}
{"paper_id": 21907763, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Principal cells of the lateral superior olive (LSO) compute interaural intensity differences by comparing converging excitatory and inhibitory inputs. The excitatory input carries information from the ipsilateral ear, and the inhibitory input carries information from the contralateral ear. Throughout life, the excitatory input pathway releases glutamate. In adulthood, the inhibitory input pathway releases glycine. During a period of major developmental refinement in the LSO, however, synaptic terminals of the immature inhibitory input pathway release not only glycine, but also GABA and glutamate. To determine whether glutamate released by terminals in either pathway could spill over to activate postsynaptic N-methyl-d-aspartate (NMDA) receptors under the other pathway, we made whole-cell recordings from LSO principal cells in acute slices of neonatal rat brainstem bathed in the use-dependent NMDA receptor antagonist MK-801 and stimulated in the two opposing pathways. We found that during the first postnatal week glutamate spillover occurs bidirectionally from both immature excitatory terminals and immature inhibitory terminals. We further found that a population of postsynaptic NMDA receptors is shared: glutamate released from either pathway can diffuse to and activate these receptors. We suggest that these shared receptors contain the GluN2B subunit and are located extrasynaptically.", "journal": "Neuroscience", "sentences": ["Principal cells of the lateral superior olive (LSO) compute interaural intensity differences by comparing converging excitatory and inhibitory inputs.", "The excitatory input carries information from the ipsilateral ear, and the inhibitory input carries information from the contralateral ear.", "Throughout life, the excitatory input pathway releases glutamate.", "In adulthood, the inhibitory input pathway releases glycine.", "During a period of major developmental refinement in the LSO, however, synaptic terminals of the immature inhibitory input pathway release not only glycine, but also GABA and glutamate.", "To determine whether glutamate released by terminals in either pathway could spill over to activate postsynaptic N-methyl-d-aspartate (NMDA) receptors under the other pathway, we made whole-cell recordings from LSO principal cells in acute slices of neonatal rat brainstem bathed in the use-dependent NMDA receptor antagonist MK-801 and stimulated in the two opposing pathways.", "We found that during the first postnatal week glutamate spillover occurs bidirectionally from both immature excitatory terminals and immature inhibitory terminals.", "We further found that a population of postsynaptic NMDA receptors is shared: glutamate released from either pathway can diffuse to and activate these receptors.", "We suggest that these shared receptors contain the GluN2B subunit and are located extrasynaptically."], "title": "Glutamatergic inputs and glutamate-releasing immature inhibitory inputs activate a shared postsynaptic receptor population in lateral superior olive."}
{"paper_id": 25248036, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 \u00d7 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.", "journal": "Nature communications", "sentences": ["GWAS have identified a breast cancer susceptibility locus on 2q35.", "Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies.", "We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data.", "All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1.", "The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 \u00d7 10(-43)) per t-allele.", "This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping.", "Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology."], "title": "Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation."}
{"paper_id": 21300881, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Formation of the complex vertebrate nervous system begins when pluripotent cells of the early embryo are directed to acquire a neural fate. Although cell intrinsic controls play an important role in this process, the molecular nature of this regulation is not well defined. Here we assessed the role for Geminin, a nuclear protein expressed in embryonic cells, during neural fate acquisition from mouse embryonic stem (ES) cells. Whereas Geminin knockdown does not affect the ability of ES cells to maintain or exit pluripotency, we found that it significantly impairs their ability to acquire a neural fate. Conversely, Geminin overexpression promotes neural gene expression, even in the presence of growth factor signaling that antagonizes neural transcriptional responses. These data demonstrate that Geminin's activity contributes to mammalian neural cell fate acquisition. We investigated the mechanistic basis of this phenomenon and found that Geminin maintains a hyperacetylated and open chromatin conformation at neural genes. Interestingly, recombinant Geminin protein also rapidly alters chromatin acetylation and accessibility even when Geminin is combined with nuclear extract and chromatin in vitro. Together, these data support a role for Geminin as a cell intrinsic regulator of neural fate acquisition that promotes expression of neural genes by regulating chromatin accessibility and histone acetylation.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Formation of the complex vertebrate nervous system begins when pluripotent cells of the early embryo are directed to acquire a neural fate.", "Although cell intrinsic controls play an important role in this process, the molecular nature of this regulation is not well defined.", "Here we assessed the role for Geminin, a nuclear protein expressed in embryonic cells, during neural fate acquisition from mouse embryonic stem (ES) cells.", "Whereas Geminin knockdown does not affect the ability of ES cells to maintain or exit pluripotency, we found that it significantly impairs their ability to acquire a neural fate.", "Conversely, Geminin overexpression promotes neural gene expression, even in the presence of growth factor signaling that antagonizes neural transcriptional responses.", "These data demonstrate that Geminin's activity contributes to mammalian neural cell fate acquisition.", "We investigated the mechanistic basis of this phenomenon and found that Geminin maintains a hyperacetylated and open chromatin conformation at neural genes.", "Interestingly, recombinant Geminin protein also rapidly alters chromatin acetylation and accessibility even when Geminin is combined with nuclear extract and chromatin in vitro.", "Together, these data support a role for Geminin as a cell intrinsic regulator of neural fate acquisition that promotes expression of neural genes by regulating chromatin accessibility and histone acetylation."], "title": "Geminin promotes neural fate acquisition of embryonic stem cells by maintaining chromatin in an accessible and hyperacetylated state."}
{"paper_id": 26258776, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMN\u03947 SMA mouse model. SMN\u03947 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMN\u03947 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMN\u03947 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMN\u03947 NSCs, and may be potentially involved in the molecular mechanisms of SMA.", "journal": "International journal of molecular sciences", "sentences": ["Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants.", "Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained.", "As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA.", "Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMN\u03947 SMA mouse model.", "SMN\u03947 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers.", "However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells.", "Moreover, SMN\u03947 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMN\u03947 NSCs compared to WT cells.", "We suggest that such miRNAs may be related to the proliferation differences characterizing SMN\u03947 NSCs, and may be potentially involved in the molecular mechanisms of SMA."], "title": "A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA)."}
{"paper_id": 26538210, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Recent studies have shown a remarkable degree of plasticity in the N-glycome of the model nematode Caenorhabditis elegans; ablation of glycosylation-relevant genes can result in radically altered N-glycan profiles despite only minor biological phenotypic effects. Up to four fucose residues and five different linkages of fucose are known on the N-glycans of C. elegans. Due to the complexity in the wild type, we established three mutant strains defective in two core fucosyltransferases each (fut-1;fut-6, fut-1;fut-8, and fut-6;fut-8). Enzymatically released N-glycans were subject to HPLC and MALDI-TOF MS/MS, in combination with various treatments, to verify structural details. The N-glycome of the fut-1;fut-6 mutant was the most complex of the three double-mutant strains due to the extension of the core \u03b11,6-fucose as well as the presence of fucose on the bisecting galactose. In contrast, maximally two fucoses were found on N-glycans of the fut-1;fut-8 and fut-6;fut-8 strains. The different locations and capping of fucose meant that up to 13 isomeric structures, many highly galactosylated, were determined for some single masses. These data not only show the high variability of the N-glycomic capacity of a \"simple\" nematode but also exemplify the need for multiple approaches to reveal individual glycan structures within complex invertebrate glycomes.", "journal": "Journal of proteome research", "sentences": ["Recent studies have shown a remarkable degree of plasticity in the N-glycome of the model nematode Caenorhabditis elegans; ablation of glycosylation-relevant genes can result in radically altered N-glycan profiles despite only minor biological phenotypic effects.", "Up to four fucose residues and five different linkages of fucose are known on the N-glycans of C. elegans.", "Due to the complexity in the wild type, we established three mutant strains defective in two core fucosyltransferases each (fut-1;fut-6, fut-1;fut-8, and fut-6;fut-8).", "Enzymatically released N-glycans were subject to HPLC and MALDI-TOF MS/MS, in combination with various treatments, to verify structural details.", "The N-glycome of the fut-1;fut-6 mutant was the most complex of the three double-mutant strains due to the extension of the core \u03b11,6-fucose as well as the presence of fucose on the bisecting galactose.", "In contrast, maximally two fucoses were found on N-glycans of the fut-1;fut-8 and fut-6;fut-8 strains.", "The different locations and capping of fucose meant that up to 13 isomeric structures, many highly galactosylated, were determined for some single masses.", "These data not only show the high variability of the N-glycomic capacity of a \"simple\" nematode but also exemplify the need for multiple approaches to reveal individual glycan structures within complex invertebrate glycomes."], "title": "Comparisons of Caenorhabditis Fucosyltransferase Mutants Reveal a Multiplicity of Isomeric N-Glycan Structures."}
{"paper_id": 27592004, "labels": ["0", "0", "0", "1", "0", "0", "1"], "abstract": "Although excessive alcohol use and alcohol misuse contribute to a broad range of health problems, recent research indicates that moderate alcohol consumption may in fact be beneficial. The present study builds on previous research to investigate the associations between alcohol use and self-rated health status among young adults. Using data collected in 2008 from the National Longitudinal Survey of Adolescent to Adult Health (Add Health), we use ordered probit models to determine whether the protective effects of moderate alcohol use are present after controlling for demographic, lifestyle, family background, and health-related characteristics. Our findings generally support earlier research with older samples, but some key gender differences are present. For women (n\u00a0=\u00a08275), moderate drinkers have better self-rated health status relative to former drinkers, infrequent drinkers, and light drinkers. Among men (n\u00a0=\u00a07207), the effects are mixed and less often significant. Differences in results between men and women point to the need for further gender-specific research and studies with other measures of health.", "journal": "Social science & medicine (1982)", "sentences": ["Although excessive alcohol use and alcohol misuse contribute to a broad range of health problems, recent research indicates that moderate alcohol consumption may in fact be beneficial.", "The present study builds on previous research to investigate the associations between alcohol use and self-rated health status among young adults.", "Using data collected in 2008 from the National Longitudinal Survey of Adolescent to Adult Health (Add Health), we use ordered probit models to determine whether the protective effects of moderate alcohol use are present after controlling for demographic, lifestyle, family background, and health-related characteristics.", "Our findings generally support earlier research with older samples, but some key gender differences are present.", "For women (n\u00a0=\u00a08275), moderate drinkers have better self-rated health status relative to former drinkers, infrequent drinkers, and light drinkers.", "Among men (n\u00a0=\u00a07207), the effects are mixed and less often significant.", "Differences in results between men and women point to the need for further gender-specific research and studies with other measures of health."], "title": "To your health!: Re-examining the health benefits of moderate alcohol use."}
{"paper_id": 24615579, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The clinical efficacy of anti-angiogenic monotherapies in metastatic breast cancer is less than originally anticipated, and it is not clear what the response of bone metastasis to anti-angiogenic therapies is. Here, we examined the impact of neutralizing tumor-derived vascular endothelial growth factor (VEGF) in animal models of subcutaneous tumor growth and bone metastasis formation. Silencing of VEGF expression (Sh-VEGF) in osteotropic human MDA-MB-231/B02 breast cancer cells led to a substantial growth inhibition of subcutaneous Sh-VEGF B02 tumor xenografts, as a result of reduced angiogenesis, when compared to that observed with animals bearing mock-transfected (Sc-VEGF) B02 tumors. However, there was scant evidence that either the silencing of tumor-derived VEGF or the use of a VEGF-neutralizing antibody (bevacizumab) affected B02 breast cancer bone metastasis progression in animals. We also examined the effect of vatalanib (a VEGF receptor tyrosine kinase inhibitor) in this mouse model of bone metastasis. However, vatalanib failed to inhibit bone metastasis caused by B02 breast cancer cells. In sharp contrast, vatalanib in combination with bevacizumab reduced not only bone destruction but also skeletal tumor growth in animals bearing breast cancer bone metastases, when compared with either agent alone. Thus, our study highlights the importance of targeting both the tumor compartment and the host tissue (i.e., skeleton) to efficiently block the development of bone metastasis. We believe this is a crucially important observation as the clinical benefit of anti-angiogenic monotherapies in metastatic breast cancer is relatively modest.", "journal": "International journal of cancer", "sentences": ["The clinical efficacy of anti-angiogenic monotherapies in metastatic breast cancer is less than originally anticipated, and it is not clear what the response of bone metastasis to anti-angiogenic therapies is.", "Here, we examined the impact of neutralizing tumor-derived vascular endothelial growth factor (VEGF) in animal models of subcutaneous tumor growth and bone metastasis formation.", "Silencing of VEGF expression (Sh-VEGF) in osteotropic human MDA-MB-231/B02 breast cancer cells led to a substantial growth inhibition of subcutaneous Sh-VEGF B02 tumor xenografts, as a result of reduced angiogenesis, when compared to that observed with animals bearing mock-transfected (Sc-VEGF) B02 tumors.", "However, there was scant evidence that either the silencing of tumor-derived VEGF or the use of a VEGF-neutralizing antibody (bevacizumab) affected B02 breast cancer bone metastasis progression in animals.", "We also examined the effect of vatalanib (a VEGF receptor tyrosine kinase inhibitor) in this mouse model of bone metastasis.", "However, vatalanib failed to inhibit bone metastasis caused by B02 breast cancer cells.", "In sharp contrast, vatalanib in combination with bevacizumab reduced not only bone destruction but also skeletal tumor growth in animals bearing breast cancer bone metastases, when compared with either agent alone.", "Thus, our study highlights the importance of targeting both the tumor compartment and the host tissue (i.e., skeleton) to efficiently block the development of bone metastasis.", "We believe this is a crucially important observation as the clinical benefit of anti-angiogenic monotherapies in metastatic breast cancer is relatively modest."], "title": "Combination of anti-angiogenic therapies reduces osteolysis and tumor burden in experimental breast cancer bone metastasis."}
{"paper_id": 24518117, "labels": ["0", "0", "0", "1", "1", "1"], "abstract": "During DNA damage response, the RING E3 ligase RNF168 ubiquitinates nucleosomal H2A at K13-15. Here we show that the ubiquitination reaction is regulated by its substrate. We define a region on the RING domain important for target recognition and identify the H2A/H2B dimer as the minimal substrate to confer lysine specificity to the RNF168 reaction. Importantly, we find an active role for the substrate in the reaction. H2A/H2B dimers and nucleosomes enhance the E3-mediated discharge of ubiquitin from the E2 and redirect the reaction towards the relevant target, in a process that depends on an intact acidic patch. This active contribution of a region distal from the target lysine provides regulation of the specific K13-15 ubiquitination reaction during the complex signalling process at DNA damage sites.", "journal": "Nature communications", "sentences": ["During DNA damage response, the RING E3 ligase RNF168 ubiquitinates nucleosomal H2A at K13-15.", "Here we show that the ubiquitination reaction is regulated by its substrate.", "We define a region on the RING domain important for target recognition and identify the H2A/H2B dimer as the minimal substrate to confer lysine specificity to the RNF168 reaction.", "Importantly, we find an active role for the substrate in the reaction.", "H2A/H2B dimers and nucleosomes enhance the E3-mediated discharge of ubiquitin from the E2 and redirect the reaction towards the relevant target, in a process that depends on an intact acidic patch.", "This active contribution of a region distal from the target lysine provides regulation of the specific K13-15 ubiquitination reaction during the complex signalling process at DNA damage sites."], "title": "The nucleosome acidic patch plays a critical role in RNF168-dependent ubiquitination of histone H2A."}
{"paper_id": 25337707, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Transforming growth factor (TGF)-\u03b2 triggers the epithelial-to-mesenchymal transition (EMT) of cancer cells via well-orchestrated crosstalk between Smad and non-Smad signaling pathways, including Wnt/\u03b2-catenin. Since EMT-induced motility and invasion play a critical role in cancer metastasis, EMT-related molecules are emerging as novel targets of anti-cancer therapies. Traf2- and Nck-interacting kinase (TNIK) has recently been considered as a first-in-class anti-cancer target molecule to regulate Wnt signaling pathway, but pharmacologic inhibition of its EMT activity has not yet been studied. Here, using 5-(4-methylbenzamido)-2-(phenylamino)thiazole-4-carboxamide (KY-05009) with TNIK-inhibitory activity, its efficacy to inhibit EMT in cancer cells was validated. The molecular docking/binding study revealed the binding of KY-05009 in the hinge region of TNIK, and the inhibitory activity of KY-05009 against TNIK was confirmed by an ATP competition assay (Ki, 100 nM). In A549 cells, KY-05009 significantly and strongly inhibited the TGF-\u03b2-activated EMT through the attenuation of Smad and non-Smad signaling pathways, including the Wnt, NF-\u03baB, FAK-Src-paxillin-related focal adhesion, and MAP kinases (ERK and JNK) signaling pathways. Continuing efforts to identify and validate potential therapeutic targets associated with EMT, such as TNIK, provide new and improved therapies for treating and/or preventing EMT-based disorders, such as cancer metastasis and fibrosis.", "journal": "PloS one", "sentences": ["Transforming growth factor (TGF)-\u03b2 triggers the epithelial-to-mesenchymal transition (EMT) of cancer cells via well-orchestrated crosstalk between Smad and non-Smad signaling pathways, including Wnt/\u03b2-catenin.", "Since EMT-induced motility and invasion play a critical role in cancer metastasis, EMT-related molecules are emerging as novel targets of anti-cancer therapies.", "Traf2- and Nck-interacting kinase (TNIK) has recently been considered as a first-in-class anti-cancer target molecule to regulate Wnt signaling pathway, but pharmacologic inhibition of its EMT activity has not yet been studied.", "Here, using 5-(4-methylbenzamido)-2-(phenylamino)thiazole-4-carboxamide (KY-05009) with TNIK-inhibitory activity, its efficacy to inhibit EMT in cancer cells was validated.", "The molecular docking/binding study revealed the binding of KY-05009 in the hinge region of TNIK, and the inhibitory activity of KY-05009 against TNIK was confirmed by an ATP competition assay (Ki, 100 nM).", "In A549 cells, KY-05009 significantly and strongly inhibited the TGF-\u03b2-activated EMT through the attenuation of Smad and non-Smad signaling pathways, including the Wnt, NF-\u03baB, FAK-Src-paxillin-related focal adhesion, and MAP kinases (ERK and JNK) signaling pathways.", "Continuing efforts to identify and validate potential therapeutic targets associated with EMT, such as TNIK, provide new and improved therapies for treating and/or preventing EMT-based disorders, such as cancer metastasis and fibrosis."], "title": "A novel aminothiazole KY-05009 with potential to inhibit Traf2- and Nck-interacting kinase (TNIK) attenuates TGF-\u03b21-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma A549 cells."}
{"paper_id": 23852514, "labels": ["0", "0", "0", "0", "1"], "abstract": "Raised intracranial pressure (ICP) is a key concern following acute brain injury as it may be associated with cerebral hypoperfusion and poor outcome. In this research we describe a mathematical physiological model designed to interpret cerebral physiology from neuromonitoring: ICP, near-infrared spectroscopy and transcranial Doppler flow velocity. This aims to characterise the complex dynamics of cerebral compliance, cerebral blood volume, cerebral blood flow and their regulation in individual patients. Analysis of data from six brain-injured patients produces cohesive predictions of cerebral biomechanics suggesting reduced cerebral compliance, reduced volume compensation and impaired blood flow autoregulation. Patient-specific physiological modelling has the potential to predict the key biomechanical and haemodynamic changes following brain injury in individual patients, and might be used to inform individualised treatment strategies.", "journal": "Advances in experimental medicine and biology", "sentences": ["Raised intracranial pressure (ICP) is a key concern following acute brain injury as it may be associated with cerebral hypoperfusion and poor outcome.", "In this research we describe a mathematical physiological model designed to interpret cerebral physiology from neuromonitoring: ICP, near-infrared spectroscopy and transcranial Doppler flow velocity.", "This aims to characterise the complex dynamics of cerebral compliance, cerebral blood volume, cerebral blood flow and their regulation in individual patients.", "Analysis of data from six brain-injured patients produces cohesive predictions of cerebral biomechanics suggesting reduced cerebral compliance, reduced volume compensation and impaired blood flow autoregulation.", "Patient-specific physiological modelling has the potential to predict the key biomechanical and haemodynamic changes following brain injury in individual patients, and might be used to inform individualised treatment strategies."], "title": "Mathematical modelling of near-infrared spectroscopy signals and intracranial pressure in brain-injured patients."}
{"paper_id": 26678998, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The role of PD-1 expression on CD4 T cells during HIV infection is not well understood. Here, we describe the differential expression of PD-1 in CD127high CD4 T cells within the early/intermediate differentiated (EI) (CD27highCD45RAlow) T cell population among uninfected and HIV-infected subjects, with higher expression associated with decreased viral replication (HIV-1 viral load). A significant loss of circulating PD-1highCTLA-4low CD4 T cells was found specifically in the CD127highCD27highCD45RAlow compartment, while initiation of antiretroviral treatment, particularly in subjects with advanced disease, reversed these dynamics. Increased HIV-1 Gag DNA was also found in PD-1high compared to PD-1low ED CD4 T cells. In line with an increased susceptibility to HIV infection, PD-1 expression in this CD4 T cell subset was associated with increased activation and expression of the HIV co-receptor, CCR5. Rather than exhaustion, this population produced more IFN-g, MIP1-a, IL-4, IL-10, and IL-17a compared to PD-1low EI CD4 T cells. In line with our previous findings, PD-1high EI CD4 T cells were also characterized by a high expression of CCR7, CXCR5 and CCR6, a phenotype associated with increased in vitro B cell help. Our data show that expression of PD-1 on early-differentiated CD4 T cells may represent a population that is highly functional, more susceptible to HIV infection and selectively lost in chronic HIV infection.", "journal": "PloS one", "sentences": ["The role of PD-1 expression on CD4 T cells during HIV infection is not well understood.", "Here, we describe the differential expression of PD-1 in CD127high CD4 T cells within the early/intermediate differentiated (EI) (CD27highCD45RAlow) T cell population among uninfected and HIV-infected subjects, with higher expression associated with decreased viral replication (HIV-1 viral load).", "A significant loss of circulating PD-1highCTLA-4low CD4 T cells was found specifically in the CD127highCD27highCD45RAlow compartment, while initiation of antiretroviral treatment, particularly in subjects with advanced disease, reversed these dynamics.", "Increased HIV-1 Gag DNA was also found in PD-1high compared to PD-1low ED CD4 T cells.", "In line with an increased susceptibility to HIV infection, PD-1 expression in this CD4 T cell subset was associated with increased activation and expression of the HIV co-receptor, CCR5.", "Rather than exhaustion, this population produced more IFN-g, MIP1-a, IL-4, IL-10, and IL-17a compared to PD-1low EI CD4 T cells.", "In line with our previous findings, PD-1high EI CD4 T cells were also characterized by a high expression of CCR7, CXCR5 and CCR6, a phenotype associated with increased in vitro B cell help.", "Our data show that expression of PD-1 on early-differentiated CD4 T cells may represent a population that is highly functional, more susceptible to HIV infection and selectively lost in chronic HIV infection."], "title": "Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression."}
{"paper_id": 24931797, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Rats belonging to three different strains (15 Wistar, 8 Spontaneously Hypertensive - SHR- and 8 Wistar Kyoto - WKY-) were used to evaluate the possible relationship between different levels of impulsivity and development of schedule-induced polydipsia (SIP). We first measured the rats' levels of impulsivity by means of delay-discounting and indifference-point procedures. Secondly, development of SIP was studied under a series of fixed time 15, 30, 60 and 120s food schedules, which were counterbalanced by means of a Latin-square design. Finally, we re-assessed the rats' levels of impulsivity by replicating the delay-discounting test. The findings showed that, starting from equivalent levels of impulsivity, development of SIP differed among the groups of rats. In comparison with the rest of the animals, the SHRs were observed to attain elevated drinking rates under SIP. On the other hand, the Wistar rats which had initial high impulsivity levels similar to those of the SHRs, displayed the lowest rates of induced drinking. Moreover, low levels of impulsivity in Wistar rats prior to SIP acquisition were reflected into high drinking rates. Relation of SIP and impulsivity is questioned by present results, which gives ground to the understanding of the behavioural mechanisms involved in adjunctive behaviour and its usefulness as an animal model of excessive behaviour.", "journal": "Behavioural brain research", "sentences": ["Rats belonging to three different strains (15 Wistar, 8 Spontaneously Hypertensive - SHR- and 8 Wistar Kyoto - WKY-) were used to evaluate the possible relationship between different levels of impulsivity and development of schedule-induced polydipsia (SIP).", "We first measured the rats' levels of impulsivity by means of delay-discounting and indifference-point procedures.", "Secondly, development of SIP was studied under a series of fixed time 15, 30, 60 and 120s food schedules, which were counterbalanced by means of a Latin-square design.", "Finally, we re-assessed the rats' levels of impulsivity by replicating the delay-discounting test.", "The findings showed that, starting from equivalent levels of impulsivity, development of SIP differed among the groups of rats.", "In comparison with the rest of the animals, the SHRs were observed to attain elevated drinking rates under SIP.", "On the other hand, the Wistar rats which had initial high impulsivity levels similar to those of the SHRs, displayed the lowest rates of induced drinking.", "Moreover, low levels of impulsivity in Wistar rats prior to SIP acquisition were reflected into high drinking rates.", "Relation of SIP and impulsivity is questioned by present results, which gives ground to the understanding of the behavioural mechanisms involved in adjunctive behaviour and its usefulness as an animal model of excessive behaviour."], "title": "Different relations between schedule-induced polydipsia and impulsive behaviour in the Spontaneously Hypertensive Rat and in high impulsive Wistar rats: questioning the role of impulsivity in adjunctive behaviour."}
{"paper_id": 26417076, "labels": ["0", "0", "0", "1", "1", "0", "1"], "abstract": "Many biological and physiological processes depend upon directed migration of cells, which is typically mediated by chemical or physical gradients or by signal relay. Here we show that cells can be guided in a single preferred direction based solely on local asymmetries in nano/microtopography on subcellular scales. These asymmetries can be repeated, and thereby provide directional guidance, over arbitrarily large areas. The direction and strength of the guidance is sensitive to the details of the nano/microtopography, suggesting that this phenomenon plays a context-dependent role in vivo. We demonstrate that appropriate asymmetric nano/microtopography can unidirectionally bias internal actin polymerization waves and that cells move with the same preferred direction as these waves. This phenomenon is observed both for the pseudopod-dominated migration of the amoeboid Dictyostelium discoideum and for the lamellipod-driven migration of human neutrophils. The conservation of this mechanism across cell types and the asymmetric shape of many natural scaffolds suggest that actin-wave-based guidance is important in biology and physiology.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Many biological and physiological processes depend upon directed migration of cells, which is typically mediated by chemical or physical gradients or by signal relay.", "Here we show that cells can be guided in a single preferred direction based solely on local asymmetries in nano/microtopography on subcellular scales.", "These asymmetries can be repeated, and thereby provide directional guidance, over arbitrarily large areas.", "The direction and strength of the guidance is sensitive to the details of the nano/microtopography, suggesting that this phenomenon plays a context-dependent role in vivo.", "We demonstrate that appropriate asymmetric nano/microtopography can unidirectionally bias internal actin polymerization waves and that cells move with the same preferred direction as these waves.", "This phenomenon is observed both for the pseudopod-dominated migration of the amoeboid Dictyostelium discoideum and for the lamellipod-driven migration of human neutrophils.", "The conservation of this mechanism across cell types and the asymmetric shape of many natural scaffolds suggest that actin-wave-based guidance is important in biology and physiology."], "title": "Asymmetric nanotopography biases cytoskeletal dynamics and promotes unidirectional cell guidance."}
{"paper_id": 21055942, "labels": ["0", "0", "0", "0", "1", "0", "0", "1"], "abstract": "When nutrient availability becomes limited, animals must actively adjust their metabolism to allocate limited resources and maintain tissue homeostasis. However, it is poorly understood how tissues maintained by adult stem cells respond to chronic changes in metabolism. To begin to address this question, we fed flies a diet lacking protein (protein starvation) and assayed both germline and intestinal stem cells. Our results revealed a decrease in stem cell proliferation and a reduction in stem cell number; however, a small pool of active stem cells remained. Upon refeeding, stem cell number increased dramatically, indicating that the remaining stem cells are competent to respond quickly to changes in nutritional status. Stem cell maintenance is critically dependent upon intrinsic and extrinsic factors that act to regulate stem cell behavior. Activation of the insulin/IGF signaling pathway in stem cells and adjacent support cells in the germline was sufficient to suppress stem cell loss during starvation. Therefore, our data indicate that stem cells can directly sense changes in the systemic environment to coordinate their behavior with the nutritional status of the animal, providing a paradigm for maintaining tissue homeostasis under metabolic stress.", "journal": "Current biology : CB", "sentences": ["When nutrient availability becomes limited, animals must actively adjust their metabolism to allocate limited resources and maintain tissue homeostasis.", "However, it is poorly understood how tissues maintained by adult stem cells respond to chronic changes in metabolism.", "To begin to address this question, we fed flies a diet lacking protein (protein starvation) and assayed both germline and intestinal stem cells.", "Our results revealed a decrease in stem cell proliferation and a reduction in stem cell number; however, a small pool of active stem cells remained.", "Upon refeeding, stem cell number increased dramatically, indicating that the remaining stem cells are competent to respond quickly to changes in nutritional status.", "Stem cell maintenance is critically dependent upon intrinsic and extrinsic factors that act to regulate stem cell behavior.", "Activation of the insulin/IGF signaling pathway in stem cells and adjacent support cells in the germline was sufficient to suppress stem cell loss during starvation.", "Therefore, our data indicate that stem cells can directly sense changes in the systemic environment to coordinate their behavior with the nutritional status of the animal, providing a paradigm for maintaining tissue homeostasis under metabolic stress."], "title": "Stem cell dynamics in response to nutrient availability."}
{"paper_id": 26717362, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "This study was aimed to assess the predictability of intraocular lens (IOL) power calculation after simultaneous pterygium excision and phacoemulsification with IOL implantation. We retrospectively reviewed the clinical charts of 60 eyes of 60 consecutive patients (mean age\u200a\u00b1\u200astandard deviation, 73.5\u200a\u00b1\u200a7.0 years) who developed pterygium and cataract. We determined visual acuity (logMAR), manifest spherical equivalent, manifest astigmatism, corneal astigmatism, and mean keratometry, preoperatively and 3 months postoperatively. Corrected visual acuity was significantly improved from 0.19\u200a\u00b1\u200a0.20 preoperatively to -0.06\u200a\u00b1\u200a0.07 postoperatively (P\u200a<\u200a0.001, Wilcoxon signed-rank test). Uncorrected visual acuity was also significantly improved from 0.62\u200a\u00b1\u200a0.33 preoperatively to 0.31\u200a\u00b1\u200a0.32 postoperatively (P\u200a<\u200a0.001). At 3 months, 48% and 82% of the eyes were within\u200a\u00b1\u200a0.5 and\u200a\u00b1\u200a1.0 D, respectively, of the targeted correction. We found significant correlations of the prediction errors with the changes in the mean keratometry (Spearman signed-rank test, r\u200a=\u200a-0.535, P\u200a<\u200a0.001) and with the pterygium size (r\u200a=\u200a-0.378, P\u200a=\u200a0.033). Simultaneous pterygium and cataract surgery was safe and effective, and the accuracy was moderately predictable. However, it should be noted that a significant myopic shift occurred postoperatively, possibly resulting from the steepening of the cornea after pterygium removal, especially when the size of pterygium was large.", "journal": "Medicine", "sentences": ["This study was aimed to assess the predictability of intraocular lens (IOL) power calculation after simultaneous pterygium excision and phacoemulsification with IOL implantation.", "We retrospectively reviewed the clinical charts of 60 eyes of 60 consecutive patients (mean age\u200a\u00b1\u200astandard deviation, 73.5\u200a\u00b1\u200a7.0 years) who developed pterygium and cataract.", "We determined visual acuity (logMAR), manifest spherical equivalent, manifest astigmatism, corneal astigmatism, and mean keratometry, preoperatively and 3 months postoperatively.", "Corrected visual acuity was significantly improved from 0.19\u200a\u00b1\u200a0.20 preoperatively to -0.06\u200a\u00b1\u200a0.07 postoperatively (P\u200a<\u200a0.001, Wilcoxon signed-rank test).", "Uncorrected visual acuity was also significantly improved from 0.62\u200a\u00b1\u200a0.33 preoperatively to 0.31\u200a\u00b1\u200a0.32 postoperatively (P\u200a<\u200a0.001).", "At 3 months, 48% and 82% of the eyes were within\u200a\u00b1\u200a0.5 and\u200a\u00b1\u200a1.0 D, respectively, of the targeted correction.", "We found significant correlations of the prediction errors with the changes in the mean keratometry (Spearman signed-rank test, r\u200a=\u200a-0.535, P\u200a<\u200a0.001) and with the pterygium size (r\u200a=\u200a-0.378, P\u200a=\u200a0.033).", "Simultaneous pterygium and cataract surgery was safe and effective, and the accuracy was moderately predictable.", "However, it should be noted that a significant myopic shift occurred postoperatively, possibly resulting from the steepening of the cornea after pterygium removal, especially when the size of pterygium was large."], "title": "Predictability of Intraocular Lens Power Calculation After Simultaneous Pterygium Excision and Cataract Surgery."}
{"paper_id": 27009352, "labels": ["0", "1", "0", "0", "1"], "abstract": "Previous work in fishes considers undulation as a means of propulsion without addressing how it may affect other functions such as sensing and respiration. Here we show that undulation can optimize propulsion, flow sensing and respiration concurrently without any apparent tradeoffs when head movements are coupled correctly with the movements of the body. This finding challenges a long-held assumption that head movements are simply an unintended consequence of undulation, existing only because of the recoil of an oscillating tail. We use a combination of theoretical, biological and physical experiments to reveal the hydrodynamic mechanisms underlying this concerted optimization. Based on our results we develop a parsimonious control architecture that can be used by both undulatory animals and machines in dynamic environments.", "journal": "Nature communications", "sentences": ["Previous work in fishes considers undulation as a means of propulsion without addressing how it may affect other functions such as sensing and respiration.", "Here we show that undulation can optimize propulsion, flow sensing and respiration concurrently without any apparent tradeoffs when head movements are coupled correctly with the movements of the body.", "This finding challenges a long-held assumption that head movements are simply an unintended consequence of undulation, existing only because of the recoil of an oscillating tail.", "We use a combination of theoretical, biological and physical experiments to reveal the hydrodynamic mechanisms underlying this concerted optimization.", "Based on our results we develop a parsimonious control architecture that can be used by both undulatory animals and machines in dynamic environments."], "title": "Fish optimize sensing and respiration during undulatory swimming."}
{"paper_id": 22718934, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Rhinoviruses are the most frequent cause of human respiratory infections, and quantitative rhinovirus diagnostic tools are needed for clinical investigations. Although results obtained by real-time reverse-transcription PCR (RT-PCR) assays are frequently converted to viral RNA loads, this presents several limitations regarding accurate virus RNA quantification, particularly given the need to reliably quantify all known rhinovirus genotypes with a single assay. Using an internal extraction control and serial dilutions of an in vitro-transcribed rhinovirus RNA reference standard, we validated a quantitative one-step real-time PCR assay. We then used chimeric rhinovirus genomes with 5'-untranslated regions (5'UTRs) originating from the three rhinovirus species and from one enterovirus to estimate the impact of the 5'UTR diversity. Respiratory specimens from infected patients were then also analyzed. The assay quantification ability ranged from 4.10 to 9.10 log RNA copies/ml, with an estimated error margin of \u00b110%. This variation was mainly linked to target variability and interassay variability. Taken together, our results indicate that our assay can reliably estimate rhinovirus RNA load, provided that the appropriate error margin is used. In contrast, due to the lack of a universal rhinovirus RNA standard and the variability related to sample collection procedures, accurate absolute rhinovirus RNA quantification in respiratory specimens is currently hardly feasible.", "journal": "Journal of clinical microbiology", "sentences": ["Rhinoviruses are the most frequent cause of human respiratory infections, and quantitative rhinovirus diagnostic tools are needed for clinical investigations.", "Although results obtained by real-time reverse-transcription PCR (RT-PCR) assays are frequently converted to viral RNA loads, this presents several limitations regarding accurate virus RNA quantification, particularly given the need to reliably quantify all known rhinovirus genotypes with a single assay.", "Using an internal extraction control and serial dilutions of an in vitro-transcribed rhinovirus RNA reference standard, we validated a quantitative one-step real-time PCR assay.", "We then used chimeric rhinovirus genomes with 5'-untranslated regions (5'UTRs) originating from the three rhinovirus species and from one enterovirus to estimate the impact of the 5'UTR diversity.", "Respiratory specimens from infected patients were then also analyzed.", "The assay quantification ability ranged from 4.10 to 9.10 log RNA copies/ml, with an estimated error margin of \u00b110%.", "This variation was mainly linked to target variability and interassay variability.", "Taken together, our results indicate that our assay can reliably estimate rhinovirus RNA load, provided that the appropriate error margin is used.", "In contrast, due to the lack of a universal rhinovirus RNA standard and the variability related to sample collection procedures, accurate absolute rhinovirus RNA quantification in respiratory specimens is currently hardly feasible."], "title": "Critical analysis of rhinovirus RNA load quantification by real-time reverse transcription-PCR."}
{"paper_id": 27439858, "labels": ["0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "Cell membranes have a vast repertoire of phospholipid species whose structures can be dynamically modified by enzymatic remodeling of acyl chains and polar head groups. Lipid remodeling plays important roles in membrane biology and dysregulation can lead to disease. Although there have been tremendous advances in creating artificial membranes to model the properties of native membranes, a major obstacle has been developing straightforward methods to mimic lipid membrane remodeling. Stable liposomes are typically kinetically trapped and are not prone to exchanging diacylphospholipids. Here, we show that reversible chemoselective reactions can be harnessed to achieve nonenzymatic spontaneous remodeling of phospholipids in synthetic membranes. Our approach relies on transthioesterification/acyl shift reactions that occur spontaneously and reversibly between tertiary amides and thioesters. We demonstrate exchange and remodeling of both lipid acyl chains and head groups. Using our synthetic model system we demonstrate the ability of spontaneous phospholipid remodeling to trigger changes in vesicle spatial organization, composition, and morphology as well as recruit proteins that can affect vesicle curvature. Membranes capable of chemically exchanging lipid fragments could be used to help further understand the specific roles of lipid structure remodeling in biological membranes.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Cell membranes have a vast repertoire of phospholipid species whose structures can be dynamically modified by enzymatic remodeling of acyl chains and polar head groups.", "Lipid remodeling plays important roles in membrane biology and dysregulation can lead to disease.", "Although there have been tremendous advances in creating artificial membranes to model the properties of native membranes, a major obstacle has been developing straightforward methods to mimic lipid membrane remodeling.", "Stable liposomes are typically kinetically trapped and are not prone to exchanging diacylphospholipids.", "Here, we show that reversible chemoselective reactions can be harnessed to achieve nonenzymatic spontaneous remodeling of phospholipids in synthetic membranes.", "Our approach relies on transthioesterification/acyl shift reactions that occur spontaneously and reversibly between tertiary amides and thioesters.", "We demonstrate exchange and remodeling of both lipid acyl chains and head groups.", "Using our synthetic model system we demonstrate the ability of spontaneous phospholipid remodeling to trigger changes in vesicle spatial organization, composition, and morphology as well as recruit proteins that can affect vesicle curvature.", "Membranes capable of chemically exchanging lipid fragments could be used to help further understand the specific roles of lipid structure remodeling in biological membranes."], "title": "Nonenzymatic biomimetic remodeling of phospholipids in synthetic liposomes."}
{"paper_id": 22333568, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "In recent years it has become clear that mesenchymal stem or stromal cells (MSCs) are capable of modulating inflammatory and immune responses through interaction with a wide variety of cells. Whereas several studies indicated that PGE2 is one of the chief soluble mediators involved in these processes, here we investigated prostaglandin E2 (PGE2) production of murine bone marrow- (BM-) and adipose tissue- (Ad-) derived MSCs stimulated with pro-inflammatory cytokines TNF-\u03b1 and IFN-\u03b3, or co-cultured with ConA-induced T-cell blasts. We found that both MSC populations are able to produce high amounts of PGE2 in MSC/activated T-cell co-cultures. This effect was markedly attenuated when direct cell-cell contact was prevented in transwell system, indicating that the elicitation of the PGE2 secretion of MSCs is contact-dependent in this experimental setting. In contrast, when soluble recombinant pro-inflammatory cytokines were added to the MSC cultures, TNF-\u03b1 and IFN-\u03b3 act synergistically to induce PGE2 production, whereas only high amount of TNF-\u03b1 but not IFN-\u03b3 was able to do so alone. Although the PGE2 secretion by MSCs was completely abrogated by addition of indomethacin under all culture conditions tested, L-NMA, a NOS inhibitor could only partially inhibit it when the cells were elicited in the concomitant presence of TNF-\u03b1 and IFN-\u03b3. These results, combined with others, suggest that NO acts downstream of IFN-\u03b3 but upstream of COX2. Taken together, our findings demonstrate that the induction of PGE2 secretion by BM- and Ad-MSCs is not mediated by a single or unique, nonredundant molecular mechanism under different experimental conditions.", "journal": "Biochemical and biophysical research communications", "sentences": ["In recent years it has become clear that mesenchymal stem or stromal cells (MSCs) are capable of modulating inflammatory and immune responses through interaction with a wide variety of cells.", "Whereas several studies indicated that PGE2 is one of the chief soluble mediators involved in these processes, here we investigated prostaglandin E2 (PGE2) production of murine bone marrow- (BM-) and adipose tissue- (Ad-) derived MSCs stimulated with pro-inflammatory cytokines TNF-\u03b1 and IFN-\u03b3, or co-cultured with ConA-induced T-cell blasts.", "We found that both MSC populations are able to produce high amounts of PGE2 in MSC/activated T-cell co-cultures.", "This effect was markedly attenuated when direct cell-cell contact was prevented in transwell system, indicating that the elicitation of the PGE2 secretion of MSCs is contact-dependent in this experimental setting.", "In contrast, when soluble recombinant pro-inflammatory cytokines were added to the MSC cultures, TNF-\u03b1 and IFN-\u03b3 act synergistically to induce PGE2 production, whereas only high amount of TNF-\u03b1 but not IFN-\u03b3 was able to do so alone.", "Although the PGE2 secretion by MSCs was completely abrogated by addition of indomethacin under all culture conditions tested, L-NMA, a NOS inhibitor could only partially inhibit it when the cells were elicited in the concomitant presence of TNF-\u03b1 and IFN-\u03b3.", "These results, combined with others, suggest that NO acts downstream of IFN-\u03b3 but upstream of COX2.", "Taken together, our findings demonstrate that the induction of PGE2 secretion by BM- and Ad-MSCs is not mediated by a single or unique, nonredundant molecular mechanism under different experimental conditions."], "title": "Activated T-cells and pro-inflammatory cytokines differentially regulate prostaglandin E2 secretion by mesenchymal stem cells."}
{"paper_id": 22787202, "labels": ["0", "0", "0", "0", "1", "1", "1"], "abstract": "Hepadnaviral covalently closed circular DNA (cccDNA) exists as an episomal minichromosome in the nucleus of virus-infected hepatocytes, and serves as the transcriptional template for the synthesis of viral mRNAs. To obtain insight on the structure of hepadnaviral cccDNA minichromosomes, we utilized ducks infected with the duck hepatitis B virus (DHBV) as a model and determined the in vivo nucleosome distribution pattern on viral cccDNA by the micrococcal nuclease (MNase) mapping and genome-wide PCR amplification of isolated mononucleosomal DHBV DNA. Several nucleosome-protected sites in a region of the DHBV genome [nucleotides (nt) 2000 to 2700], known to harbor various cis transcription regulatory elements, were consistently identified in all DHBV-positive liver samples. In addition, we observed other nucleosome protection sites in DHBV minichromosomes that may vary among individual ducks, but the pattern of MNase mapping in those regions is transmittable from the adult ducks to the newly infected ducklings. These results imply that the nucleosomes along viral cccDNA in the minichromosomes are not random but sequence-specifically positioned. Furthermore, we showed in ducklings that a significant portion of cccDNA possesses a few negative superhelical turns, suggesting the presence of intermediates of viral minichromosomes assembled in the liver, where dynamic hepatocyte growth and cccDNA formation occur. This study supplies the initial framework for the understanding of the overall complete structure of hepadnaviral cccDNA minichromosomes.", "journal": "Journal of virology", "sentences": ["Hepadnaviral covalently closed circular DNA (cccDNA) exists as an episomal minichromosome in the nucleus of virus-infected hepatocytes, and serves as the transcriptional template for the synthesis of viral mRNAs.", "To obtain insight on the structure of hepadnaviral cccDNA minichromosomes, we utilized ducks infected with the duck hepatitis B virus (DHBV) as a model and determined the in vivo nucleosome distribution pattern on viral cccDNA by the micrococcal nuclease (MNase) mapping and genome-wide PCR amplification of isolated mononucleosomal DHBV DNA.", "Several nucleosome-protected sites in a region of the DHBV genome [nucleotides (nt) 2000 to 2700], known to harbor various cis transcription regulatory elements, were consistently identified in all DHBV-positive liver samples.", "In addition, we observed other nucleosome protection sites in DHBV minichromosomes that may vary among individual ducks, but the pattern of MNase mapping in those regions is transmittable from the adult ducks to the newly infected ducklings.", "These results imply that the nucleosomes along viral cccDNA in the minichromosomes are not random but sequence-specifically positioned.", "Furthermore, we showed in ducklings that a significant portion of cccDNA possesses a few negative superhelical turns, suggesting the presence of intermediates of viral minichromosomes assembled in the liver, where dynamic hepatocyte growth and cccDNA formation occur.", "This study supplies the initial framework for the understanding of the overall complete structure of hepadnaviral cccDNA minichromosomes."], "title": "Characterization of nucleosome positioning in hepadnaviral covalently closed circular DNA minichromosomes."}
{"paper_id": 24339976, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Metastasis is still a major issue in cancer, and the discovery of biomarkers predicting metastatic capacity is essential for the development of better therapeutic strategies for treating lung adenocarcinoma. By using a proteomic approach, we aimed to identify novel predictors for lymph node metastasis in lung adenocarcinoma. Two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis showed 6 spots differentially expressed between lymph node metastasis-positive and lymph node metastasis-negative groups in a discovery set. Subsequent mass spectrometry showed that 2 of these spots were derived from galectin-4, and western blot analysis confirmed the overexpression of galectin-4 in metastatic samples. The predictive value of galectin-4 was confirmed by immunohistochemical analysis for a validation set consisting of 707 surgically resected specimens of lung adenocarcinomas (stages I to IV). We observed that 148 lung adenocarcinomas (20.9%) expressed galectin-4, which was significantly associated with variables of disease progression such as tumor size (p<0.0001), pleural invasion (p = 0.0071), venous invasion (p = 0.0178), nodal status (p = 0.0007), and TNM stage (p<0.0001). By the multivariate analysis, Galectin-4 expression was revealed as one of the independent predictor for lymph node metastasis, together with solid predominant and micropapillary histologic pattern. Furthermore, galectin-4 expression was revealed to be an independent predictor for lymph node metastasis and an adverse survival factor in patients with lung adenocarcinoma of acinar predominant type. Galectin-4 plays an important role in metastatic process of lung adenocarcinoma. Immunohistochemical testing for galectin-4 expression may be useful together with the detection of specific histology to predict the metastatic potential of lung adenocarcinoma.", "journal": "PloS one", "sentences": ["Metastasis is still a major issue in cancer, and the discovery of biomarkers predicting metastatic capacity is essential for the development of better therapeutic strategies for treating lung adenocarcinoma.", "By using a proteomic approach, we aimed to identify novel predictors for lymph node metastasis in lung adenocarcinoma.", "Two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis showed 6 spots differentially expressed between lymph node metastasis-positive and lymph node metastasis-negative groups in a discovery set.", "Subsequent mass spectrometry showed that 2 of these spots were derived from galectin-4, and western blot analysis confirmed the overexpression of galectin-4 in metastatic samples.", "The predictive value of galectin-4 was confirmed by immunohistochemical analysis for a validation set consisting of 707 surgically resected specimens of lung adenocarcinomas (stages I to IV).", "We observed that 148 lung adenocarcinomas (20.9%) expressed galectin-4, which was significantly associated with variables of disease progression such as tumor size (p<0.0001), pleural invasion (p = 0.0071), venous invasion (p = 0.0178), nodal status (p = 0.0007), and TNM stage (p<0.0001).", "By the multivariate analysis, Galectin-4 expression was revealed as one of the independent predictor for lymph node metastasis, together with solid predominant and micropapillary histologic pattern.", "Furthermore, galectin-4 expression was revealed to be an independent predictor for lymph node metastasis and an adverse survival factor in patients with lung adenocarcinoma of acinar predominant type.", "Galectin-4 plays an important role in metastatic process of lung adenocarcinoma.", "Immunohistochemical testing for galectin-4 expression may be useful together with the detection of specific histology to predict the metastatic potential of lung adenocarcinoma."], "title": "Galectin-4, a novel predictor for lymph node metastasis in lung adenocarcinoma."}
{"paper_id": 27376284, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is one of the most common urologic diseases, and no curative treatments have been identified. Low-intensity pulsed ultrasound (LIPUS) has been successfully used in promoting tissue healing, inhibiting inflammation and pain, differentiating stem cells, and stimulating nerve regeneration/muscle regeneration, as well as enhancing angiogenesis. Very recently, LIPUS has been proven an effective approach for CP/CPPS. This review summarizes the possible mechanisms responsible for the therapeutic effect of LIPUS for CP/CPPS. To search publications relevant to the topics of this review, the search engine for life sciences of Entrez was used. We reviewed the available evidence from 1954 through 2015 concerning LIPUS for CP/CPPS. According to the literature, both transrectal and transperineal approaches of LIPUS are effective for CP/CPPS.", "journal": "International journal of molecular sciences", "sentences": ["Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is one of the most common urologic diseases, and no curative treatments have been identified.", "Low-intensity pulsed ultrasound (LIPUS) has been successfully used in promoting tissue healing, inhibiting inflammation and pain, differentiating stem cells, and stimulating nerve regeneration/muscle regeneration, as well as enhancing angiogenesis.", "Very recently, LIPUS has been proven an effective approach for CP/CPPS.", "This review summarizes the possible mechanisms responsible for the therapeutic effect of LIPUS for CP/CPPS.", "To search publications relevant to the topics of this review, the search engine for life sciences of Entrez was used.", "We reviewed the available evidence from 1954 through 2015 concerning LIPUS for CP/CPPS.", "According to the literature, both transrectal and transperineal approaches of LIPUS are effective for CP/CPPS."], "title": "Effects and Mechanisms of Low-Intensity Pulsed Ultrasound for Chronic Prostatitis and Chronic Pelvic Pain Syndrome."}
{"paper_id": 25860911, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Inhibition of carcinogenesis may be a consequence of attenuation of oxidative stress via activation of antioxidant defence system, restoration and stabilization of tumour suppressor proteins along with modulation of inflammatory mediators. Previously we have delineated significant role of curcumin during its long term effect in regulation of glycolytic pathway and angiogenesis, which in turn results in prevention of cancer via modulation of stress activated genes. Present study was designed to investigate long term effect of curcumin in regulation of Nrf2 mediated phase-II antioxidant enzymes, tumour suppressor p53 and inflammation under oxidative tumour microenvironment in liver of T-cell lymphoma bearing mice. Inhibition of Nrf2 signalling observed during lymphoma progression, resulted in down regulation of phase II antioxidant enzymes, p53 as well as activation of inflammatory signals. Curcumin potentiated significant increase in Nrf2 activation. It restored activity of phase-II antioxidant enzymes like GST, GR, NQO1, and tumour suppressor p53 level. In addition, curcumin modulated inflammation via upregulation of TGF-\u03b2 and reciprocal regulation of iNOS and COX2. The study suggests that during long term effect, curcumin leads to prevention of cancer by inducing phase-II antioxidant enzymes via activation of Nrf2 signalling, restoration of tumour suppressor p53 and modulation of inflammatory mediators like iNOS and COX2 in liver of lymphoma bearing mice.", "journal": "PloS one", "sentences": ["Inhibition of carcinogenesis may be a consequence of attenuation of oxidative stress via activation of antioxidant defence system, restoration and stabilization of tumour suppressor proteins along with modulation of inflammatory mediators.", "Previously we have delineated significant role of curcumin during its long term effect in regulation of glycolytic pathway and angiogenesis, which in turn results in prevention of cancer via modulation of stress activated genes.", "Present study was designed to investigate long term effect of curcumin in regulation of Nrf2 mediated phase-II antioxidant enzymes, tumour suppressor p53 and inflammation under oxidative tumour microenvironment in liver of T-cell lymphoma bearing mice.", "Inhibition of Nrf2 signalling observed during lymphoma progression, resulted in down regulation of phase II antioxidant enzymes, p53 as well as activation of inflammatory signals.", "Curcumin potentiated significant increase in Nrf2 activation.", "It restored activity of phase-II antioxidant enzymes like GST, GR, NQO1, and tumour suppressor p53 level.", "In addition, curcumin modulated inflammation via upregulation of TGF-\u03b2 and reciprocal regulation of iNOS and COX2.", "The study suggests that during long term effect, curcumin leads to prevention of cancer by inducing phase-II antioxidant enzymes via activation of Nrf2 signalling, restoration of tumour suppressor p53 and modulation of inflammatory mediators like iNOS and COX2 in liver of lymphoma bearing mice."], "title": "Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of Nrf2 signalling and modulation of inflammation in prevention of cancer."}
{"paper_id": 20543265, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "In this experimental study, we present the results of user motor responses with and without the use of Tracking Feedback to complete correct movements in Virtual Rehabilitation Therapy. To carry out this study, we used a VRT system for standing balance rehabilitation. We applied it under two different conditions to twenty patients (with and without tracking feedback). We then analyzed their motor responses. By means of this analysis, we have confirmed the importance of Tracking Feedback in the achievement of rehabilitation goals. We also tested the possibility of eliminating the tracking components from the system to lower cost to make the integration of Virtual Rehabilitation systems available to more patients. Our results indicate that is currently not feasible.", "journal": "Studies in health technology and informatics", "sentences": ["In this experimental study, we present the results of user motor responses with and without the use of Tracking Feedback to complete correct movements in Virtual Rehabilitation Therapy.", "To carry out this study, we used a VRT system for standing balance rehabilitation.", "We applied it under two different conditions to twenty patients (with and without tracking feedback).", "We then analyzed their motor responses.", "By means of this analysis, we have confirmed the importance of Tracking Feedback in the achievement of rehabilitation goals.", "We also tested the possibility of eliminating the tracking components from the system to lower cost to make the integration of Virtual Rehabilitation systems available to more patients.", "Our results indicate that is currently not feasible."], "title": "Influence of tracking feedback in user motor response in rehabilitation therapy."}
{"paper_id": 25984710, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The purpose of this study is to develop a new global mammographic image feature analysis based computer-aided detection (CAD) scheme and evaluate its performance in detecting positive screening mammography examinations. A dataset that includes images acquired from 1896 full-field digital mammography (FFDM) screening examinations was used in this study. Among them, 812 cases were positive for cancer and 1084 were negative or benign. After segmenting the breast area, a computerized scheme was applied to compute 92 global mammographic tissue density based features on each of four mammograms of the craniocaudal (CC) and mediolateral oblique (MLO) views. After adding three existing popular risk factors (woman's age, subjectively rated mammographic density, and family breast cancer history) into the initial feature pool, we applied a sequential forward floating selection feature selection algorithm to select relevant features from the bilateral CC and MLO view images separately. The selected CC and MLO view image features were used to train two artificial neural networks (ANNs). The results were then fused by a third ANN to build a two-stage classifier to predict the likelihood of the FFDM screening examination being positive. CAD performance was tested using a ten-fold cross-validation method. The computed area under the receiver operating characteristic curve was AUC = 0.779\u2009\u2009\u2009\u00b1\u2009\u2009\u20090.025 and the odds ratio monotonically increased from 1 to 31.55 as CAD-generated detection scores increased. The study demonstrated that this new global image feature based CAD scheme had a relatively higher discriminatory power to cue the FFDM examinations with high risk of being positive, which may provide a new CAD-cueing method to assist radiologists in reading and interpreting screening mammograms.", "journal": "Physics in medicine and biology", "sentences": ["The purpose of this study is to develop a new global mammographic image feature analysis based computer-aided detection (CAD) scheme and evaluate its performance in detecting positive screening mammography examinations.", "A dataset that includes images acquired from 1896 full-field digital mammography (FFDM) screening examinations was used in this study.", "Among them, 812 cases were positive for cancer and 1084 were negative or benign.", "After segmenting the breast area, a computerized scheme was applied to compute 92 global mammographic tissue density based features on each of four mammograms of the craniocaudal (CC) and mediolateral oblique (MLO) views.", "After adding three existing popular risk factors (woman's age, subjectively rated mammographic density, and family breast cancer history) into the initial feature pool, we applied a sequential forward floating selection feature selection algorithm to select relevant features from the bilateral CC and MLO view images separately.", "The selected CC and MLO view image features were used to train two artificial neural networks (ANNs).", "The results were then fused by a third ANN to build a two-stage classifier to predict the likelihood of the FFDM screening examination being positive.", "CAD performance was tested using a ten-fold cross-validation method.", "The computed area under the receiver operating characteristic curve was AUC = 0.779\u2009\u2009\u2009\u00b1\u2009\u2009\u20090.025 and the odds ratio monotonically increased from 1 to 31.55 as CAD-generated detection scores increased.", "The study demonstrated that this new global image feature based CAD scheme had a relatively higher discriminatory power to cue the FFDM examinations with high risk of being positive, which may provide a new CAD-cueing method to assist radiologists in reading and interpreting screening mammograms."], "title": "A new approach to develop computer-aided detection schemes of digital mammograms."}
{"paper_id": 21270030, "labels": ["0", "0", "0", "1", "1"], "abstract": "Emergent infectious diseases represent a major threat for biodiversity in fragmented habitat networks, but their dynamics in host metapopulations remain largely unexplored. We studied a large community of pathogens (including 26 haematozoans, bacteria and viruses as determined through polymerase chain reaction assays) in a highly fragmented mainland bird metapopulation. Contrary to recent studies, which have established that the prevalence of pathogens increase with habitat fragmentation owing to crowding and habitat-edge effects, the analysed pathogen parameters were neither dependent on host densities nor related to the spatial structure of the metapopulation. We provide, to our knowledge, the first empirical evidence for a positive effect of host population size on pathogen prevalence, richness and diversity. These new insights into the interplay between habitat fragmentation and pathogens reveal properties of a host-pathogen system resembling island environments, suggesting that severe habitat loss and fragmentation could lower pathogen pressure in small populations.", "journal": "Proceedings. Biological sciences / The Royal Society", "sentences": ["Emergent infectious diseases represent a major threat for biodiversity in fragmented habitat networks, but their dynamics in host metapopulations remain largely unexplored.", "We studied a large community of pathogens (including 26 haematozoans, bacteria and viruses as determined through polymerase chain reaction assays) in a highly fragmented mainland bird metapopulation.", "Contrary to recent studies, which have established that the prevalence of pathogens increase with habitat fragmentation owing to crowding and habitat-edge effects, the analysed pathogen parameters were neither dependent on host densities nor related to the spatial structure of the metapopulation.", "We provide, to our knowledge, the first empirical evidence for a positive effect of host population size on pathogen prevalence, richness and diversity.", "These new insights into the interplay between habitat fragmentation and pathogens reveal properties of a host-pathogen system resembling island environments, suggesting that severe habitat loss and fragmentation could lower pathogen pressure in small populations."], "title": "An island paradigm on the mainland: host population fragmentation impairs the community of avian pathogens."}
{"paper_id": 21873197, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Tetrahydrofolate (THF), a biologically active form of the vitamin folate (B(9)), is an essential cofactor in one-carbon transfer reactions. In bacteria, expression of folate-related genes is controlled by feedback modulation in response to specific binding of THF and related compounds to a riboswitch. Here, we present the X-ray structures of the THF-sensing domain from the Eubacterium siraeum riboswitch in the ligand-bound and unbound states. The structure reveals an \"inverted\" three-way junctional architecture, most unusual for riboswitches, with the junction located far from the regulatory helix P1 and not directly participating in helix P1 formation. Instead, the three-way junction, stabilized by binding to the ligand, aligns the riboswitch stems for long-range tertiary pseudoknot interactions that contribute to the organization of helix P1 and therefore stipulate the regulatory response of the riboswitch. The pterin moiety of the ligand docks in a semiopen pocket adjacent to the junction, where it forms specific hydrogen bonds with two moderately conserved pyrimidines. The aminobenzoate moiety stacks on a guanine base, whereas the glutamate moiety does not appear to make strong interactions with the RNA. In contrast to other riboswitches, these findings demonstrate that the THF riboswitch uses a limited number of available determinants for ligand recognition. Given that modern antibiotics target folate metabolism, the THF riboswitch structure provides insights on mechanistic aspects of riboswitch function and may help in manipulating THF levels in pathogenic bacteria.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Tetrahydrofolate (THF), a biologically active form of the vitamin folate (B(9)), is an essential cofactor in one-carbon transfer reactions.", "In bacteria, expression of folate-related genes is controlled by feedback modulation in response to specific binding of THF and related compounds to a riboswitch.", "Here, we present the X-ray structures of the THF-sensing domain from the Eubacterium siraeum riboswitch in the ligand-bound and unbound states.", "The structure reveals an \"inverted\" three-way junctional architecture, most unusual for riboswitches, with the junction located far from the regulatory helix P1 and not directly participating in helix P1 formation.", "Instead, the three-way junction, stabilized by binding to the ligand, aligns the riboswitch stems for long-range tertiary pseudoknot interactions that contribute to the organization of helix P1 and therefore stipulate the regulatory response of the riboswitch.", "The pterin moiety of the ligand docks in a semiopen pocket adjacent to the junction, where it forms specific hydrogen bonds with two moderately conserved pyrimidines.", "The aminobenzoate moiety stacks on a guanine base, whereas the glutamate moiety does not appear to make strong interactions with the RNA.", "In contrast to other riboswitches, these findings demonstrate that the THF riboswitch uses a limited number of available determinants for ligand recognition.", "Given that modern antibiotics target folate metabolism, the THF riboswitch structure provides insights on mechanistic aspects of riboswitch function and may help in manipulating THF levels in pathogenic bacteria."], "title": "Long-range pseudoknot interactions dictate the regulatory response in the tetrahydrofolate riboswitch."}
{"paper_id": 27421483, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "0", "1"], "abstract": "TLR9 is an innate immune receptor important for recognizing DNA of host and foreign origin. A mechanism proposed to prevent excessive response to host DNA is the requirement for proteolytic cleavage of TLR9 in endosomes to generate a mature form of the receptor (TLR9(471-1032)). We previously described another cleavage event in the juxtamembrane region of the ectodomain that generated a dominant-negative form of TLR9. Thus, there are at least two independent cleavage events that regulate TLR9. In this study, we investigated whether an N-terminal fragment of TLR9 could be responsible for regulation of the mature or negative-regulatory form. We show that TLR9(471-1032), corresponding to the proteolytically cleaved form, does not function on its own. Furthermore, activity is not rescued by coexpression of the N-terminal fragment (TLR9(1-440)), inclusion of the hinge region (TLR9(441-1032)), or overexpression of UNC93B1, the last of which is critical for trafficking and cleavage of TLR9. TLR9(1-440) coimmunoprecipitates with full-length TLR9 and TLR9(471-1032) but does not rescue the native glycosylation pattern; thus, inappropriate trafficking likely explains why TLR9(471-1032) is nonfunctional. Lastly, we show that TLR9(471-1032) is also a dominant-negative regulator of TLR9 signaling. Together, these data provide a new perspective on the complexity of TLR9 regulation by proteolytic cleavage and offer potential ways to inhibit activity through this receptor, which may dampen autoimmune inflammation.", "journal": "Journal of immunology (Baltimore, Md. : 1950)", "sentences": ["TLR9 is an innate immune receptor important for recognizing DNA of host and foreign origin.", "A mechanism proposed to prevent excessive response to host DNA is the requirement for proteolytic cleavage of TLR9 in endosomes to generate a mature form of the receptor (TLR9(471-1032)).", "We previously described another cleavage event in the juxtamembrane region of the ectodomain that generated a dominant-negative form of TLR9.", "Thus, there are at least two independent cleavage events that regulate TLR9.", "In this study, we investigated whether an N-terminal fragment of TLR9 could be responsible for regulation of the mature or negative-regulatory form.", "We show that TLR9(471-1032), corresponding to the proteolytically cleaved form, does not function on its own.", "Furthermore, activity is not rescued by coexpression of the N-terminal fragment (TLR9(1-440)), inclusion of the hinge region (TLR9(441-1032)), or overexpression of UNC93B1, the last of which is critical for trafficking and cleavage of TLR9.", "TLR9(1-440) coimmunoprecipitates with full-length TLR9 and TLR9(471-1032) but does not rescue the native glycosylation pattern; thus, inappropriate trafficking likely explains why TLR9(471-1032) is nonfunctional.", "Lastly, we show that TLR9(471-1032) is also a dominant-negative regulator of TLR9 signaling.", "Together, these data provide a new perspective on the complexity of TLR9 regulation by proteolytic cleavage and offer potential ways to inhibit activity through this receptor, which may dampen autoimmune inflammation."], "title": "Complex Negative Regulation of TLR9 by Multiple Proteolytic Cleavage Events."}
{"paper_id": 25809603, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Membranous CD44v6 levels in tumors and surrounding samples obtained from 94 patients with squamous cell lung carcinomas were studied and compared to clinical stage, cellular proliferation, membranous CD44v5 levels, epidermal growth factor receptor EGFR and cytoplasmatic concentrations of CYFRA 21.1. CD44v6 positive values were observed in 33/38 non-tumor samples and in 76/94 tumor samples, but there were not statistically significant differences between both subgroups. In CD44v6 positive tumor samples, CD44v6 was not associated with clinical stage, histological grade, ploidy and lymph node involvement, but significant association was found with high cellular proliferation. Likewise, CD44v6 positive tumors had significantly higher levels of EGFR and CD44v5. In patients with squamous cell lung carcinomas and clinical stage I, positive CD44v6 cases were associated with the same parameters. Furthermore, positive CD44v5 squamous tumors were associated significantly with histological grade III and lower levels of CYFRA21.1. Our findings support the value of CD44v6 as a possible indicator of poor outcome in patients with squamous lung carcinomas.", "journal": "International journal of molecular sciences", "sentences": ["Membranous CD44v6 levels in tumors and surrounding samples obtained from 94 patients with squamous cell lung carcinomas were studied and compared to clinical stage, cellular proliferation, membranous CD44v5 levels, epidermal growth factor receptor EGFR and cytoplasmatic concentrations of CYFRA 21.1.", "CD44v6 positive values were observed in 33/38 non-tumor samples and in 76/94 tumor samples, but there were not statistically significant differences between both subgroups.", "In CD44v6 positive tumor samples, CD44v6 was not associated with clinical stage, histological grade, ploidy and lymph node involvement, but significant association was found with high cellular proliferation.", "Likewise, CD44v6 positive tumors had significantly higher levels of EGFR and CD44v5.", "In patients with squamous cell lung carcinomas and clinical stage I, positive CD44v6 cases were associated with the same parameters.", "Furthermore, positive CD44v5 squamous tumors were associated significantly with histological grade III and lower levels of CYFRA21.1.", "Our findings support the value of CD44v6 as a possible indicator of poor outcome in patients with squamous lung carcinomas."], "title": "Cell membrane CD44v6 levels in squamous cell carcinoma of the lung: association with high cellular proliferation and high concentrations of EGFR and CD44v5."}
{"paper_id": 26095253, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Colorectal cancer is a leading cause of cancer-related deaths. Mutations in the innate immune sensor AIM2 are frequently identified in patients with colorectal cancer, but how AIM2 modulates colonic tumorigenesis is unknown. Here, we found that Aim2-deficient mice were hypersusceptible to colonic tumor development. Production of inflammasome-associated cytokines and other inflammatory mediators was largely intact in Aim2-deficient mice; however, intestinal stem cells were prone to uncontrolled proliferation. Aberrant Wnt signaling expanded a population of tumor-initiating stem cells in the absence of AIM2. Susceptibility of Aim2-deficient mice to colorectal tumorigenesis was enhanced by a dysbiotic gut microbiota, which was reduced by reciprocal exchange of gut microbiota with healthy wild-type mice. These findings uncover a synergy between a specific host genetic factor and gut microbiota in determining the susceptibility to colorectal cancer. Therapeutic modulation of AIM2 expression and microbiota has the potential to prevent colorectal cancer.", "journal": "Cell", "sentences": ["Colorectal cancer is a leading cause of cancer-related deaths.", "Mutations in the innate immune sensor AIM2 are frequently identified in patients with colorectal cancer, but how AIM2 modulates colonic tumorigenesis is unknown.", "Here, we found that Aim2-deficient mice were hypersusceptible to colonic tumor development.", "Production of inflammasome-associated cytokines and other inflammatory mediators was largely intact in Aim2-deficient mice; however, intestinal stem cells were prone to uncontrolled proliferation.", "Aberrant Wnt signaling expanded a population of tumor-initiating stem cells in the absence of AIM2.", "Susceptibility of Aim2-deficient mice to colorectal tumorigenesis was enhanced by a dysbiotic gut microbiota, which was reduced by reciprocal exchange of gut microbiota with healthy wild-type mice.", "These findings uncover a synergy between a specific host genetic factor and gut microbiota in determining the susceptibility to colorectal cancer.", "Therapeutic modulation of AIM2 expression and microbiota has the potential to prevent colorectal cancer."], "title": "Critical Role for the DNA Sensor AIM2 in Stem Cell Proliferation and Cancer."}
{"paper_id": 27114530, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Recent studies have indicated that mammalian cells contain a cytosolic protein disaggregation machinery comprised of Hsc70, DnaJ homologs, and Hsp110 proteins, the last of which acts to accelerate a rate-limiting step of nucleotide exchange of Hsc70. We tested the ability of transgenic overexpression of a Thy1 promoter-driven human Hsp110 protein, HspA4L (Apg1), in neuronal cells of a transgenic G85R SOD1YFP ALS mouse strain to improve survival. Notably, G85R is a mutant version of Cu/Zn superoxide dismutase 1 (SOD1) that is unable to reach native form and that is prone to aggregation, with prominent YFP-fluorescent aggregates observed in the motor neurons of the transgenic mice as early as 1 mo of age. The several-fold overexpression of Hsp110 in motor neurons of these mice was associated with an increased median survival from \u223c5.5 to 7.5 mo and increased maximum survival from 6.5 to 12 mo. Improvement of survival was also observed for a G93A mutant SOD1 ALS strain. We conclude that neurodegeneration associated with cytosolic misfolding and aggregation can be ameliorated by overexpression of Hsp110, likely enhancing the function of a cytosolic disaggregation machinery.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Recent studies have indicated that mammalian cells contain a cytosolic protein disaggregation machinery comprised of Hsc70, DnaJ homologs, and Hsp110 proteins, the last of which acts to accelerate a rate-limiting step of nucleotide exchange of Hsc70.", "We tested the ability of transgenic overexpression of a Thy1 promoter-driven human Hsp110 protein, HspA4L (Apg1), in neuronal cells of a transgenic G85R SOD1YFP ALS mouse strain to improve survival.", "Notably, G85R is a mutant version of Cu/Zn superoxide dismutase 1 (SOD1) that is unable to reach native form and that is prone to aggregation, with prominent YFP-fluorescent aggregates observed in the motor neurons of the transgenic mice as early as 1 mo of age.", "The several-fold overexpression of Hsp110 in motor neurons of these mice was associated with an increased median survival from \u223c5.5 to 7.5 mo and increased maximum survival from 6.5 to 12 mo.", "Improvement of survival was also observed for a G93A mutant SOD1 ALS strain.", "We conclude that neurodegeneration associated with cytosolic misfolding and aggregation can be ameliorated by overexpression of Hsp110, likely enhancing the function of a cytosolic disaggregation machinery."], "title": "Extended survival of misfolded G85R SOD1-linked ALS mice by transgenic expression of chaperone Hsp110."}
{"paper_id": 24847306, "labels": ["0", "0", "0", "1", "0", "1", "1"], "abstract": "It is assumed that children's performance in mathematical abilities is influenced by several factors such as working memory (WM), verbal ability, intelligence, and socioeconomic status. The present study explored the contribution of those factors to mathematical performance taking a componential view of both WM and mathematics. We explored the existing relationship between different WM components (verbal and spatial) with tasks that make differential recruitment of the central executive, and simple and complex mathematical skills in a sample of 102 children in grades 4-6. The main findings point to a relationship between the verbal WM component and complex word arithmetic problems, whereas language and non-verbal intelligence were associated with knowledge of quantitative concepts and arithmetic ability. The spatial WM component was associated with the subtest Series, whereas the verbal component was with the subtest Concepts. The results also suggest a positive relationship between parental educational level and children's performance on Quantitative Concepts. These findings suggest that specific cognitive skills might be trained in order to improve different aspects of mathematical ability.", "journal": "Frontiers in psychology", "sentences": ["It is assumed that children's performance in mathematical abilities is influenced by several factors such as working memory (WM), verbal ability, intelligence, and socioeconomic status.", "The present study explored the contribution of those factors to mathematical performance taking a componential view of both WM and mathematics.", "We explored the existing relationship between different WM components (verbal and spatial) with tasks that make differential recruitment of the central executive, and simple and complex mathematical skills in a sample of 102 children in grades 4-6.", "The main findings point to a relationship between the verbal WM component and complex word arithmetic problems, whereas language and non-verbal intelligence were associated with knowledge of quantitative concepts and arithmetic ability.", "The spatial WM component was associated with the subtest Series, whereas the verbal component was with the subtest Concepts.", "The results also suggest a positive relationship between parental educational level and children's performance on Quantitative Concepts.", "These findings suggest that specific cognitive skills might be trained in order to improve different aspects of mathematical ability."], "title": "Disentangling the effects of working memory, language, parental education, and non-verbal intelligence on children's mathematical abilities."}
{"paper_id": 20515923, "labels": ["0", "0", "0", "0", "1", "0"], "abstract": "The immune system comprises an innate and an adaptive immune response to combat pathogenic agents. The human enteropathogen Salmonella enterica serovar Typhimurium invades the intestinal mucosa and triggers an early innate proinflammatory host gene response, which results in diarrheal disease. Several host factors, including transcription factors and transcription coregulators, are involved in the acute early response to Salmonella infection. We found in a mouse model of enterocolitis induced by S. Typhimurium that the absence of the nuclear protein poly(ADP-ribose) polymerase 1 (PARP1), a previously described cofactor for NF-kappaB-mediated proinflammatory gene expression, is associated with a delayed proinflammatory immune response after Salmonella infection. Our data reveal that PARP1 is expressed in the proliferative zone of cecum crypts, where it is required for the efficient expression of proinflammatory genes, many of which are related to interferon signaling. Consequently, animals lacking PARP1 show impaired infiltration of immune cells into the gut, with severely delayed inflammation.", "journal": "Infection and immunity", "sentences": ["The immune system comprises an innate and an adaptive immune response to combat pathogenic agents.", "The human enteropathogen Salmonella enterica serovar Typhimurium invades the intestinal mucosa and triggers an early innate proinflammatory host gene response, which results in diarrheal disease.", "Several host factors, including transcription factors and transcription coregulators, are involved in the acute early response to Salmonella infection.", "We found in a mouse model of enterocolitis induced by S. Typhimurium that the absence of the nuclear protein poly(ADP-ribose) polymerase 1 (PARP1), a previously described cofactor for NF-kappaB-mediated proinflammatory gene expression, is associated with a delayed proinflammatory immune response after Salmonella infection.", "Our data reveal that PARP1 is expressed in the proliferative zone of cecum crypts, where it is required for the efficient expression of proinflammatory genes, many of which are related to interferon signaling.", "Consequently, animals lacking PARP1 show impaired infiltration of immune cells into the gut, with severely delayed inflammation."], "title": "Absence of poly(ADP-ribose) polymerase 1 delays the onset of Salmonella enterica serovar Typhimurium-induced gut inflammation."}
{"paper_id": 26918359, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Analysis of the mouse transcriptional response to Listeria monocytogenes infection reveals that a large set of genes are perturbed in both blood and tissue and that these transcriptional responses are enriched for pathways of the immune response. Further we identified enrichment for both type I and type II interferon (IFN) signaling molecules in the blood and tissues upon infection. Since type I IFN signaling has been reported widely to impair bacterial clearance we examined gene expression from blood and tissues of wild type (WT) and type I IFN\u03b1\u03b2 receptor-deficient (Ifnar1-/-) mice at the basal level and upon infection with L. monocytogenes. Measurement of the fold change response upon infection in the absence of type I IFN signaling demonstrated an upregulation of specific genes at day 1 post infection. A less marked reduction of the global gene expression signature in blood or tissues from infected Ifnar1-/- as compared to WT mice was observed at days 2 and 3 after infection, with marked reduction in key genes such as Oasg1 and Stat2. Moreover, on in depth analysis, changes in gene expression in uninfected mice of key IFN regulatory genes including Irf9, Irf7, Stat1 and others were identified, and although induced by an equivalent degree upon infection this resulted in significantly lower final gene expression levels upon infection of Ifnar1-/- mice. These data highlight how dysregulation of this network in the steady state and temporally upon infection may determine the outcome of this bacterial infection and how basal levels of type I IFN-inducible genes may perturb an optimal host immune response to control intracellular bacterial infections such as L. monocytogenes.", "journal": "PloS one", "sentences": ["Analysis of the mouse transcriptional response to Listeria monocytogenes infection reveals that a large set of genes are perturbed in both blood and tissue and that these transcriptional responses are enriched for pathways of the immune response.", "Further we identified enrichment for both type I and type II interferon (IFN) signaling molecules in the blood and tissues upon infection.", "Since type I IFN signaling has been reported widely to impair bacterial clearance we examined gene expression from blood and tissues of wild type (WT) and type I IFN\u03b1\u03b2 receptor-deficient (Ifnar1-/-) mice at the basal level and upon infection with L. monocytogenes.", "Measurement of the fold change response upon infection in the absence of type I IFN signaling demonstrated an upregulation of specific genes at day 1 post infection.", "A less marked reduction of the global gene expression signature in blood or tissues from infected Ifnar1-/- as compared to WT mice was observed at days 2 and 3 after infection, with marked reduction in key genes such as Oasg1 and Stat2.", "Moreover, on in depth analysis, changes in gene expression in uninfected mice of key IFN regulatory genes including Irf9, Irf7, Stat1 and others were identified, and although induced by an equivalent degree upon infection this resulted in significantly lower final gene expression levels upon infection of Ifnar1-/- mice.", "These data highlight how dysregulation of this network in the steady state and temporally upon infection may determine the outcome of this bacterial infection and how basal levels of type I IFN-inducible genes may perturb an optimal host immune response to control intracellular bacterial infections such as L. monocytogenes."], "title": "Analysis of Transcriptional Signatures in Response to Listeria monocytogenes Infection Reveals Temporal Changes That Result from Type I Interferon Signaling."}
{"paper_id": 19766739, "labels": ["0", "0", "0", "0", "1", "1"], "abstract": "Photoreversible changes in the conformation and enzymatic activity of bovine carbonic anhydrase have been investigated as a function of photoresponsive surfactant concentration and light conditions. The light-responsive surfactant undergoes a photoisomerization from the relatively hydrophobic trans isomer under visible light to the relatively hydrophilic cis isomer upon UV illumination, providing a means to photoreversibly control enzyme-surfactant interactions. Small-angle neutron scattering and dynamic light scattering measurements, along with fluorescence spectroscopy, indicate that carbonic anhydrase unfolds upon addition of the surfactant under visible light, while only a small degree of unfolding is observed under UV light. Therefore, the enzyme is completely inactivated in the presence of the trans surfactant, while 40% of the native activity is preserved under UV light, providing a photoreversible \"on/off switch\" of enzyme activity. Small-angle neutron scattering data provide details of the in vitro conformational changes of the enzyme in response to the photosurfactant and light, with the enzyme found to aggregate as a result of photosurfactant-induced unfolding. Fourier transform infrared (FT-IR) spectroscopy further provides information on the secondary structure changes of the protein in the presence of photosurfactant.", "journal": "Biochimica et biophysica acta", "sentences": ["Photoreversible changes in the conformation and enzymatic activity of bovine carbonic anhydrase have been investigated as a function of photoresponsive surfactant concentration and light conditions.", "The light-responsive surfactant undergoes a photoisomerization from the relatively hydrophobic trans isomer under visible light to the relatively hydrophilic cis isomer upon UV illumination, providing a means to photoreversibly control enzyme-surfactant interactions.", "Small-angle neutron scattering and dynamic light scattering measurements, along with fluorescence spectroscopy, indicate that carbonic anhydrase unfolds upon addition of the surfactant under visible light, while only a small degree of unfolding is observed under UV light.", "Therefore, the enzyme is completely inactivated in the presence of the trans surfactant, while 40% of the native activity is preserved under UV light, providing a photoreversible \"on/off switch\" of enzyme activity.", "Small-angle neutron scattering data provide details of the in vitro conformational changes of the enzyme in response to the photosurfactant and light, with the enzyme found to aggregate as a result of photosurfactant-induced unfolding.", "Fourier transform infrared (FT-IR) spectroscopy further provides information on the secondary structure changes of the protein in the presence of photosurfactant."], "title": "Photo-induced unfolding and inactivation of bovine carbonic anhydrase in the presence of a photoresponsive surfactant."}
{"paper_id": 21799741, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "The history and rate of discovery of the 247 valid Recent stylasterid species are discussed and graphed, with emphasis on five historical pulses of species descriptions. A table listing all genera, their species numbers, and their bathymetric ranges are presented. The number of species in 19 oceanographic regions is mapped, the southwestern temperate Pacific (region including New Zealand) having the most species; species are cosmopolitan from the Arctic Circle to the Antarctic at depths from 0 to 2789 m. The current phylogenetic classification of the genera is briefly discussed. An illustrated glossary of 53 morphological characters is presented. Biological and ecological information pertaining to reproduction, development, commensals, and distribution is discussed. Aspects of stylasterid mineralogy and taxa of commercial value are discussed, concluding with suggestions for future work.", "journal": "PloS one", "sentences": ["The history and rate of discovery of the 247 valid Recent stylasterid species are discussed and graphed, with emphasis on five historical pulses of species descriptions.", "A table listing all genera, their species numbers, and their bathymetric ranges are presented.", "The number of species in 19 oceanographic regions is mapped, the southwestern temperate Pacific (region including New Zealand) having the most species; species are cosmopolitan from the Arctic Circle to the Antarctic at depths from 0 to 2789 m. The current phylogenetic classification of the genera is briefly discussed.", "An illustrated glossary of 53 morphological characters is presented.", "Biological and ecological information pertaining to reproduction, development, commensals, and distribution is discussed.", "Aspects of stylasterid mineralogy and taxa of commercial value are discussed, concluding with suggestions for future work."], "title": "Global diversity of the Stylasteridae (Cnidaria: Hydrozoa: Athecatae)."}
{"paper_id": 27441646, "labels": ["0", "0", "1", "0", "0", "0", "0", "0"], "abstract": "Diabetic Retinopathy (DR) harm retinal blood vessels in the eye causing visual deficiency. The appearance and structure of blood vessels in retinal images play an essential part in the diagnoses of an eye sicknesses. We proposed a less computational unsupervised automated technique with promising results for detection of retinal vasculature by using morphological hessian based approach and region based Otsu thresholding. Contrast Limited Adaptive Histogram Equalization (CLAHE) and morphological filters have been used for enhancement and to remove low frequency noise or geometrical objects, respectively. The hessian matrix and eigenvalues approach used has been in a modified form at two different scales to extract wide and thin vessel enhanced images separately. Otsu thresholding has been further applied in a novel way to classify vessel and non-vessel pixels from both enhanced images. Finally, postprocessing steps has been used to eliminate the unwanted region/segment, non-vessel pixels, disease abnormalities and noise, to obtain a final segmented image. The proposed technique has been analyzed on the openly accessible DRIVE (Digital Retinal Images for Vessel Extraction) and STARE (STructured Analysis of the REtina) databases along with the ground truth data that has been precisely marked by the experts.", "journal": "PloS one", "sentences": ["Diabetic Retinopathy (DR) harm retinal blood vessels in the eye causing visual deficiency.", "The appearance and structure of blood vessels in retinal images play an essential part in the diagnoses of an eye sicknesses.", "We proposed a less computational unsupervised automated technique with promising results for detection of retinal vasculature by using morphological hessian based approach and region based Otsu thresholding.", "Contrast Limited Adaptive Histogram Equalization (CLAHE) and morphological filters have been used for enhancement and to remove low frequency noise or geometrical objects, respectively.", "The hessian matrix and eigenvalues approach used has been in a modified form at two different scales to extract wide and thin vessel enhanced images separately.", "Otsu thresholding has been further applied in a novel way to classify vessel and non-vessel pixels from both enhanced images.", "Finally, postprocessing steps has been used to eliminate the unwanted region/segment, non-vessel pixels, disease abnormalities and noise, to obtain a final segmented image.", "The proposed technique has been analyzed on the openly accessible DRIVE (Digital Retinal Images for Vessel Extraction) and STARE (STructured Analysis of the REtina) databases along with the ground truth data that has been precisely marked by the experts."], "title": "A Morphological Hessian Based Approach for Retinal Blood Vessels Segmentation and Denoising Using Region Based Otsu Thresholding."}
{"paper_id": 24592199, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The study is focused on the water diffusion phenomenon through the Raffia vinifera fibre from the stem. The knowledge on the behavior of those fibres in presence of liquid during the realization of biocomposite, is necessary. The parameters like percentage of water gain at the point of saturation, modelling of the kinetic of water absorption, and the effective diffusion coefficient were the main objectives. Along a stem of raffia, twelve zones of sampling were defined. From Fick's 2nd law of diffusion, a new model was proposed and evaluated compared to four other models at a constant temperature of 23\u00b0C. From the proposed model, the effective diffusion coefficient was deduced. The percentage of water gain was in the range of 303-662%. The proposed model fitted better to the experimental data. The estimated diffusion coefficient was evaluated during the initial phase and at the final phase. In any cross section located along the stem of Raffia vinifera, it was found that the effective diffusion coefficient increases from the periphery to the centre during the initial and final phases.", "journal": "TheScientificWorldJournal", "sentences": ["The study is focused on the water diffusion phenomenon through the Raffia vinifera fibre from the stem.", "The knowledge on the behavior of those fibres in presence of liquid during the realization of biocomposite, is necessary.", "The parameters like percentage of water gain at the point of saturation, modelling of the kinetic of water absorption, and the effective diffusion coefficient were the main objectives.", "Along a stem of raffia, twelve zones of sampling were defined.", "From Fick's 2nd law of diffusion, a new model was proposed and evaluated compared to four other models at a constant temperature of 23\u00b0C.", "From the proposed model, the effective diffusion coefficient was deduced.", "The percentage of water gain was in the range of 303-662%.", "The proposed model fitted better to the experimental data.", "The estimated diffusion coefficient was evaluated during the initial phase and at the final phase.", "In any cross section located along the stem of Raffia vinifera, it was found that the effective diffusion coefficient increases from the periphery to the centre during the initial and final phases."], "title": "Study of water absorption in Raffia vinifera fibres from Bandjoun, Cameroon."}
{"paper_id": 26126115, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Flatfoot (pes planus) is one of the most important physical examination items for military new recruits in Taiwan. Currently, the diagnosis of flatfoot is mainly based on radiographic examination of the calcaneal-fifth metatarsal (CA-MT5) angle, also known as the arch angle. However, manual measurement of the arch angle is time-consuming and often inconsistent between different examiners. In this study, seventy male military new recruits were studied. Lateral radiographic images of their right and left feet were obtained, and mutual information (MI) registration was used to automatically calculate the arch angle. Images of two critical bones, the calcaneus and the fifth metatarsal bone, were isolated from the lateral radiographs to form reference images, and were then compared with template images to calculate the arch angle. The result of this computer-calculated arch angle was compared with manual measurement results from two radiologists, which showed that our automatic arch angle measurement method had a high consistency. In addition, this method had a high accuracy of 97% and 96% as compared with the measurements of radiologists A and B, respectively. The findings indicated that our MI registration measurement method cannot only accurately measure the CA-MT5 angle, but also saves time and reduces human error. This method can increase the consistency of arch angle measurement and has potential clinical application for the diagnosis of flatfoot.", "journal": "PloS one", "sentences": ["Flatfoot (pes planus) is one of the most important physical examination items for military new recruits in Taiwan.", "Currently, the diagnosis of flatfoot is mainly based on radiographic examination of the calcaneal-fifth metatarsal (CA-MT5) angle, also known as the arch angle.", "However, manual measurement of the arch angle is time-consuming and often inconsistent between different examiners.", "In this study, seventy male military new recruits were studied.", "Lateral radiographic images of their right and left feet were obtained, and mutual information (MI) registration was used to automatically calculate the arch angle.", "Images of two critical bones, the calcaneus and the fifth metatarsal bone, were isolated from the lateral radiographs to form reference images, and were then compared with template images to calculate the arch angle.", "The result of this computer-calculated arch angle was compared with manual measurement results from two radiologists, which showed that our automatic arch angle measurement method had a high consistency.", "In addition, this method had a high accuracy of 97% and 96% as compared with the measurements of radiologists A and B, respectively.", "The findings indicated that our MI registration measurement method cannot only accurately measure the CA-MT5 angle, but also saves time and reduces human error.", "This method can increase the consistency of arch angle measurement and has potential clinical application for the diagnosis of flatfoot."], "title": "Automatic Detection of Calcaneal-Fifth Metatarsal Angle Using Radiograph: A Computer-Aided Diagnosis of Flat Foot for Military New Recruits in Taiwan."}
{"paper_id": 22144488, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The adenylate cyclase toxin (ACT) of Bordetella pertussis does not require a receptor to generate intracellular cyclic AMP (cAMP) in a broad range of cell types. To intoxicate cells, ACT binds to the cell surface, translocates its catalytic domain across the cell membrane, and converts intracellular ATP to cAMP. In cells that express the integrin CD11b/CD18 (CR3), ACT is more potent than in CR3-negative cells. We find, however, that the maximum levels of cAMP accumulation inside CR3-positive and -negative cells are comparable. To better understand how CR3 affects the generation of cAMP, we used Chinese hamster ovary and K562 cells transfected to express CR3 and examined the steps in intoxication in the presence and absence of the integrin. The binding of ACT to cells is greater in CR3-expressing cells at all concentrations of ACT, and translocation of the catalytic domain is enhanced by CR3 expression, with \u223c80% of ACT molecules translocating their catalytic domain in CR3-positive cells but only 25% in CR3-negative cells. Once in the cytosol, the unregulated catalytic domain converts ATP to cAMP, and at ACT concentrations >1,000 ng/ml, the intracellular ATP concentration is <5% of that in untreated cells, regardless of CR3 expression. This depletion of ATP prevents further production of cAMP, despite the CR3-mediated enhancement of binding and translocation. In addition to characterizing the effects of CR3 on the actions of ACT, these data show that ATP consumption is yet another concentration-dependent activity of ACT that must be considered when studying how ACT affects target cells.", "journal": "Infection and immunity", "sentences": ["The adenylate cyclase toxin (ACT) of Bordetella pertussis does not require a receptor to generate intracellular cyclic AMP (cAMP) in a broad range of cell types.", "To intoxicate cells, ACT binds to the cell surface, translocates its catalytic domain across the cell membrane, and converts intracellular ATP to cAMP.", "In cells that express the integrin CD11b/CD18 (CR3), ACT is more potent than in CR3-negative cells.", "We find, however, that the maximum levels of cAMP accumulation inside CR3-positive and -negative cells are comparable.", "To better understand how CR3 affects the generation of cAMP, we used Chinese hamster ovary and K562 cells transfected to express CR3 and examined the steps in intoxication in the presence and absence of the integrin.", "The binding of ACT to cells is greater in CR3-expressing cells at all concentrations of ACT, and translocation of the catalytic domain is enhanced by CR3 expression, with \u223c80% of ACT molecules translocating their catalytic domain in CR3-positive cells but only 25% in CR3-negative cells.", "Once in the cytosol, the unregulated catalytic domain converts ATP to cAMP, and at ACT concentrations >1,000 ng/ml, the intracellular ATP concentration is <5% of that in untreated cells, regardless of CR3 expression.", "This depletion of ATP prevents further production of cAMP, despite the CR3-mediated enhancement of binding and translocation.", "In addition to characterizing the effects of CR3 on the actions of ACT, these data show that ATP consumption is yet another concentration-dependent activity of ACT that must be considered when studying how ACT affects target cells."], "title": "Role of CD11b/CD18 in the process of intoxication by the adenylate cyclase toxin of Bordetella pertussis."}
{"paper_id": 23297235, "labels": ["0", "0", "0", "0", "1", "1"], "abstract": "Polarized growth in eukaryotes requires polar multiprotein complexes. Here, we establish that selection and maintenance of cell polarity for growth also requires a dedicated multiprotein assembly in the filamentous bacterium, Streptomyces coelicolor. We present evidence for a tip organizing center and confirm two of its main components: Scy (Streptomyces cytoskeletal element), a unique bacterial coiled-coil protein with an unusual repeat periodicity, and the known polarity determinant DivIVA. We also establish a link between the tip organizing center and the filament-forming protein FilP. Interestingly, both deletion and overproduction of Scy generated multiple polarity centers, suggesting a mechanism wherein Scy can both promote and limit the number of emerging polarity centers via the organization of the Scy-DivIVA assemblies. We propose that Scy is a molecular \"assembler,\" which, by sequestering DivIVA, promotes the establishment of new polarity centers for de novo tip formation during branching, as well as supporting polarized growth at existing hyphal tips.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Polarized growth in eukaryotes requires polar multiprotein complexes.", "Here, we establish that selection and maintenance of cell polarity for growth also requires a dedicated multiprotein assembly in the filamentous bacterium, Streptomyces coelicolor.", "We present evidence for a tip organizing center and confirm two of its main components: Scy (Streptomyces cytoskeletal element), a unique bacterial coiled-coil protein with an unusual repeat periodicity, and the known polarity determinant DivIVA.", "We also establish a link between the tip organizing center and the filament-forming protein FilP.", "Interestingly, both deletion and overproduction of Scy generated multiple polarity centers, suggesting a mechanism wherein Scy can both promote and limit the number of emerging polarity centers via the organization of the Scy-DivIVA assemblies.", "We propose that Scy is a molecular \"assembler,\" which, by sequestering DivIVA, promotes the establishment of new polarity centers for de novo tip formation during branching, as well as supporting polarized growth at existing hyphal tips."], "title": "Coiled-coil protein Scy is a key component of a multiprotein assembly controlling polarized growth in Streptomyces."}
{"paper_id": 26544944, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.", "journal": "Cell", "sentences": ["There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course.", "As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas.", "Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1).", "Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype.", "Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts.", "25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%.", "Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects."], "title": "The Molecular Taxonomy of Primary Prostate Cancer."}
{"paper_id": 24194865, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Secretory phospholipase A2 (sPLA2) is a critical component of insect and snake venoms and is secreted by mammalian leukocytes during inflammation. Elevated secretory PLA2 concentrations are associated with autoimmune diseases and septic shock. Many sPLA2's do not bind to plasma membranes of quiescent cells but bind and digest phospholipids on the membranes of stimulated or apoptotic cells. The capacity of these phospholipases to digest membranes of stimulated or apoptotic cells correlates to the exposure of phosphatidylserine. In the present study, the ability of the phosphatidyl-L-serine-binding protein, lactadherin to inhibit phospholipase enzyme activity has been assessed. Inhibition of human secretory phospholipase A2-V on phospholipid vesicles exceeded 90%, whereas inhibition of Naja mossambica sPLA2 plateaued at 50-60%. Lactadherin inhibited 45% of activity of Naja mossambica sPLA2 and >70% of human secretory phospholipase A2-V on the membranes of human NB4 leukemia cells treated with calcium ionophore A23187. The data indicate that lactadherin may decrease inflammation by inhibiting sPLA2.", "journal": "PloS one", "sentences": ["Secretory phospholipase A2 (sPLA2) is a critical component of insect and snake venoms and is secreted by mammalian leukocytes during inflammation.", "Elevated secretory PLA2 concentrations are associated with autoimmune diseases and septic shock.", "Many sPLA2's do not bind to plasma membranes of quiescent cells but bind and digest phospholipids on the membranes of stimulated or apoptotic cells.", "The capacity of these phospholipases to digest membranes of stimulated or apoptotic cells correlates to the exposure of phosphatidylserine.", "In the present study, the ability of the phosphatidyl-L-serine-binding protein, lactadherin to inhibit phospholipase enzyme activity has been assessed.", "Inhibition of human secretory phospholipase A2-V on phospholipid vesicles exceeded 90%, whereas inhibition of Naja mossambica sPLA2 plateaued at 50-60%.", "Lactadherin inhibited 45% of activity of Naja mossambica sPLA2 and >70% of human secretory phospholipase A2-V on the membranes of human NB4 leukemia cells treated with calcium ionophore A23187.", "The data indicate that lactadherin may decrease inflammation by inhibiting sPLA2."], "title": "Lactadherin inhibits secretory phospholipase A2 activity on pre-apoptotic leukemia cells."}
{"paper_id": 26909577, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "The RAS/MAPK (mitogen-activated protein kinase) signalling pathway is frequently deregulated in non-small-cell lung cancer, often through KRAS activating mutations. A single endogenous mutant Kras allele is sufficient to promote lung tumour formation in mice but malignant progression requires additional genetic alterations. We recently showed that advanced lung tumours from Kras(G12D/+);p53-null mice frequently exhibit Kras(G12D) allelic enrichment (Kras(G12D)/Kras(wild-type)\u2009>\u20091) (ref. 7), implying that mutant Kras copy gains are positively selected during progression. Here we show, through a comprehensive analysis of mutant Kras homozygous and heterozygous mouse embryonic fibroblasts and lung cancer cells, that these genotypes are phenotypically distinct. In particular, Kras(G12D/G12D) cells exhibit a glycolytic switch coupled to increased channelling of glucose-derived metabolites into the tricarboxylic acid cycle and glutathione biosynthesis, resulting in enhanced glutathione-mediated detoxification. This metabolic rewiring is recapitulated in mutant KRAS homozygous non-small-cell lung cancer cells and in vivo, in spontaneous advanced murine lung tumours (which display a high frequency of Kras(G12D) copy gain), but not in the corresponding early tumours (Kras(G12D) heterozygous). Finally, we demonstrate that mutant Kras copy gain creates unique metabolic dependences that can be exploited to selectively target these aggressive mutant Kras tumours. Our data demonstrate that mutant Kras lung tumours are not a single disease but rather a heterogeneous group comprising two classes of tumours with distinct metabolic profiles, prognosis and therapeutic susceptibility, which can be discriminated on the basis of their relative mutant allelic content. We also provide the first, to our knowledge, in vivo evidence of metabolic rewiring during lung cancer malignant progression.", "journal": "Nature", "sentences": ["The RAS/MAPK (mitogen-activated protein kinase) signalling pathway is frequently deregulated in non-small-cell lung cancer, often through KRAS activating mutations.", "A single endogenous mutant Kras allele is sufficient to promote lung tumour formation in mice but malignant progression requires additional genetic alterations.", "We recently showed that advanced lung tumours from Kras(G12D/+);p53-null mice frequently exhibit Kras(G12D) allelic enrichment (Kras(G12D)/Kras(wild-type)\u2009>\u20091) (ref.", "7), implying that mutant Kras copy gains are positively selected during progression.", "Here we show, through a comprehensive analysis of mutant Kras homozygous and heterozygous mouse embryonic fibroblasts and lung cancer cells, that these genotypes are phenotypically distinct.", "In particular, Kras(G12D/G12D) cells exhibit a glycolytic switch coupled to increased channelling of glucose-derived metabolites into the tricarboxylic acid cycle and glutathione biosynthesis, resulting in enhanced glutathione-mediated detoxification.", "This metabolic rewiring is recapitulated in mutant KRAS homozygous non-small-cell lung cancer cells and in vivo, in spontaneous advanced murine lung tumours (which display a high frequency of Kras(G12D) copy gain), but not in the corresponding early tumours (Kras(G12D) heterozygous).", "Finally, we demonstrate that mutant Kras copy gain creates unique metabolic dependences that can be exploited to selectively target these aggressive mutant Kras tumours.", "Our data demonstrate that mutant Kras lung tumours are not a single disease but rather a heterogeneous group comprising two classes of tumours with distinct metabolic profiles, prognosis and therapeutic susceptibility, which can be discriminated on the basis of their relative mutant allelic content.", "We also provide the first, to our knowledge, in vivo evidence of metabolic rewiring during lung cancer malignant progression."], "title": "Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities."}
{"paper_id": 26214523, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Fluid shear forces have established roles in blood vascular development and function, but whether such forces similarly influence the low-flow lymphatic system is unknown. It has been difficult to test the contribution of fluid forces in vivo because mechanical or genetic perturbations that alter flow often have direct effects on vessel growth. Here, we investigated the functional role of flow in lymphatic vessel development using mice deficient for the platelet-specific receptor C-type lectin-like receptor 2 (CLEC2) as blood backfills the lymphatic network and blocks lymph flow in these animals. CLEC2-deficient animals exhibited normal growth of the primary mesenteric lymphatic plexus but failed to form valves in these vessels or remodel them into a structured, hierarchical network. Smooth muscle cell coverage (SMC coverage) of CLEC2-deficient lymphatic vessels was both premature and excessive, a phenotype identical to that observed with loss of the lymphatic endothelial transcription factor FOXC2. In vitro evaluation of lymphatic endothelial cells (LECs) revealed that low, reversing shear stress is sufficient to induce expression of genes required for lymphatic valve development and identified GATA2 as an upstream transcriptional regulator of FOXC2 and the lymphatic valve genetic program. These studies reveal that lymph flow initiates and regulates many of the key steps in collecting lymphatic vessel maturation and development.", "journal": "The Journal of clinical investigation", "sentences": ["Fluid shear forces have established roles in blood vascular development and function, but whether such forces similarly influence the low-flow lymphatic system is unknown.", "It has been difficult to test the contribution of fluid forces in vivo because mechanical or genetic perturbations that alter flow often have direct effects on vessel growth.", "Here, we investigated the functional role of flow in lymphatic vessel development using mice deficient for the platelet-specific receptor C-type lectin-like receptor 2 (CLEC2) as blood backfills the lymphatic network and blocks lymph flow in these animals.", "CLEC2-deficient animals exhibited normal growth of the primary mesenteric lymphatic plexus but failed to form valves in these vessels or remodel them into a structured, hierarchical network.", "Smooth muscle cell coverage (SMC coverage) of CLEC2-deficient lymphatic vessels was both premature and excessive, a phenotype identical to that observed with loss of the lymphatic endothelial transcription factor FOXC2.", "In vitro evaluation of lymphatic endothelial cells (LECs) revealed that low, reversing shear stress is sufficient to induce expression of genes required for lymphatic valve development and identified GATA2 as an upstream transcriptional regulator of FOXC2 and the lymphatic valve genetic program.", "These studies reveal that lymph flow initiates and regulates many of the key steps in collecting lymphatic vessel maturation and development."], "title": "Lymph flow regulates collecting lymphatic vessel maturation in vivo."}
{"paper_id": 26722066, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Enzalutamide is a novel, non-steroidal anti-androgen that was approved for the treatment of patients with castration-resistant prostate cancer (CRPC) in 2014 in Japan. To assess the potency of enzalutamide treatment in Japan, we performed a pilot retrospective study. Among 91 patients who received treatment in our Institution between May 2014 and July 2015, 51 patients with docetaxel-na\u00efve CRPC (56.0%) underwent enzalutamide therapy. The median progression-free survival (PFS) and overall survival (OS) were 10.2 months and 27.9 months, respectively. The remaining 40 patients with CRPC (44.0%) underwent enzalutamide therapy after docetaxel. The median PFS and OS were 4.4 months and not reached, respectively. Among patients with docetaxel-na\u00efve CRPC, 12 (24%) experienced adverse events, whereas 16 (40%) experienced adverse events after docetaxel. Fatigue (15%) and appetite loss (13%) were the most common. We partially clarified the characteristics of enzalutamide therapy in Japan. The PFS associated with enzalutamide might be shorter in Japanese patients.", "journal": "Anticancer research", "sentences": ["Enzalutamide is a novel, non-steroidal anti-androgen that was approved for the treatment of patients with castration-resistant prostate cancer (CRPC) in 2014 in Japan.", "To assess the potency of enzalutamide treatment in Japan, we performed a pilot retrospective study.", "Among 91 patients who received treatment in our Institution between May 2014 and July 2015, 51 patients with docetaxel-na\u00efve CRPC (56.0%) underwent enzalutamide therapy.", "The median progression-free survival (PFS) and overall survival (OS) were 10.2 months and 27.9 months, respectively.", "The remaining 40 patients with CRPC (44.0%) underwent enzalutamide therapy after docetaxel.", "The median PFS and OS were 4.4 months and not reached, respectively.", "Among patients with docetaxel-na\u00efve CRPC, 12 (24%) experienced adverse events, whereas 16 (40%) experienced adverse events after docetaxel.", "Fatigue (15%) and appetite loss (13%) were the most common.", "We partially clarified the characteristics of enzalutamide therapy in Japan.", "The PFS associated with enzalutamide might be shorter in Japanese patients."], "title": "Efficacy and Safety Profile of Enzalutamide for Japanese Patients with Castration-resistant Prostate Cancer."}
{"paper_id": 20082473, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "Collagenous sprue has traditionally been defined as a small intestinal mucosal disorder characterized by persistent diarrhea, severe malabsorption with multiple nutrient deficiencies and progressive weight loss. Pathologically, a severe to variably severe \"flattened\" mucosal biopsy lesion with distinctive sub-epithelial deposits in the lamina propria region is detected. Histochemical stains and ultrastructural studies have confirmed that these deposits contain collagens. Often, an initial diagnosis of celiac disease is considered but no continued response to treatment with a gluten-free diet occurs. Recent reports indicate an intimate relationship between collagenous sprue and celiac disease, sometimes with concomitant T-cell enteropathy. In addition, permanent disappearance of these deposits after resection of a localized colon cancer suggested that this disorder could actually represent a paraneoplastic morphologic marker of an occult malignancy. Studies showing either gastric or colonic involvement (or both) with this unusual collagenous inflammatory mucosal process may also reflect a far more extensive and heterogeneous process than previously appreciated.", "journal": "World journal of gastroenterology", "sentences": ["Collagenous sprue has traditionally been defined as a small intestinal mucosal disorder characterized by persistent diarrhea, severe malabsorption with multiple nutrient deficiencies and progressive weight loss.", "Pathologically, a severe to variably severe \"flattened\" mucosal biopsy lesion with distinctive sub-epithelial deposits in the lamina propria region is detected.", "Histochemical stains and ultrastructural studies have confirmed that these deposits contain collagens.", "Often, an initial diagnosis of celiac disease is considered but no continued response to treatment with a gluten-free diet occurs.", "Recent reports indicate an intimate relationship between collagenous sprue and celiac disease, sometimes with concomitant T-cell enteropathy.", "In addition, permanent disappearance of these deposits after resection of a localized colon cancer suggested that this disorder could actually represent a paraneoplastic morphologic marker of an occult malignancy.", "Studies showing either gastric or colonic involvement (or both) with this unusual collagenous inflammatory mucosal process may also reflect a far more extensive and heterogeneous process than previously appreciated."], "title": "Update on collagenous sprue."}
{"paper_id": 24204239, "labels": ["0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "What are you working on? You have certainly been asked that question many times, whether it be at a Saturday night party, during a discussion with your neighbors, or at a family gathering. Communicating with a lay audience about scientific subjects and making them attractive is a difficult task. But difficult or not, you will have to do it for many years, not only with your family and friends, but also with your colleagues and collaborators. So, better learn now! Although not usually taught, the ability to explain your work to others is an essential skill in science, where communication plays a key role. Using some examples of the French Regional Student Group activities, we discuss here (i) why it is important to have such communication skills, (ii) how you can get involved in these activities by using existing resources or working with people who have previous experience, and (iii) what you get out of this amazing experience. We aim to motivate you and provide you with tips and ideas to get involved in promoting scientific activities while getting all the benefits.", "journal": "PLoS computational biology", "sentences": ["What are you working on?", "You have certainly been asked that question many times, whether it be at a Saturday night party, during a discussion with your neighbors, or at a family gathering.", "Communicating with a lay audience about scientific subjects and making them attractive is a difficult task.", "But difficult or not, you will have to do it for many years, not only with your family and friends, but also with your colleagues and collaborators.", "So, better learn now!", "Although not usually taught, the ability to explain your work to others is an essential skill in science, where communication plays a key role.", "Using some examples of the French Regional Student Group activities, we discuss here (i) why it is important to have such communication skills, (ii) how you can get involved in these activities by using existing resources or working with people who have previous experience, and (iii) what you get out of this amazing experience.", "We aim to motivate you and provide you with tips and ideas to get involved in promoting scientific activities while getting all the benefits."], "title": "Explain bioinformatics to your grandmother!"}
{"paper_id": 26945853, "labels": ["0", "1", "0", "0", "0", "0", "0", "1"], "abstract": "Although triglyceride (TG) accumulation in the pancreas leads to \u03b2-cell dysfunction and raises the chance to develop metabolic disorders such as type 2 diabetes (T2DM), the molecular mechanisms whereby intracellular TG levels are regulated in pancreatic \u03b2 cells have not been fully elucidated. Here, we present evidence that the RNA-binding protein HuD regulates TG production in pancreatic \u03b2 cells. Mouse insulinoma \u03b2TC6 cells stably expressing a small hairpin RNA targeting HuD (shHuD) (\u03b2TC6-shHuD) contained higher TG levels compared to control cells. Moreover, downregulation of HuD resulted in a decrease in insulin-induced gene 1 (INSIG1) levels but not in the levels of sterol regulatory element-binding protein 1c (SREBP1c), a key transcription factor for lipid production. We identified Insig1 mRNA as a direct target of HuD by using ribonucleoprotein immunoprecipitation (RIP) and biotin pulldown analyses. By associating with the 3'-untranslated region (3'UTR) of Insig1 mRNA, HuD promoted INSIG1 translation; accordingly, HuD downregulation reduced while ectopic HuD expression increased INSIG1 levels. We further observed that HuD downregulation facilitated the nuclear localization of SREBP1c, thereby increasing the transcriptional activity of SREBP1c and the expression of target genes involved in lipogenesis; likewise, we observed lower INSIG1 levels in the pancreatic islets of HuD-null mice. Taken together, our results indicate that HuD functions as a novel repressor of lipid synthesis in pancreatic \u03b2 cells.", "journal": "Biochimica et biophysica acta", "sentences": ["Although triglyceride (TG) accumulation in the pancreas leads to \u03b2-cell dysfunction and raises the chance to develop metabolic disorders such as type 2 diabetes (T2DM), the molecular mechanisms whereby intracellular TG levels are regulated in pancreatic \u03b2 cells have not been fully elucidated.", "Here, we present evidence that the RNA-binding protein HuD regulates TG production in pancreatic \u03b2 cells.", "Mouse insulinoma \u03b2TC6 cells stably expressing a small hairpin RNA targeting HuD (shHuD) (\u03b2TC6-shHuD) contained higher TG levels compared to control cells.", "Moreover, downregulation of HuD resulted in a decrease in insulin-induced gene 1 (INSIG1) levels but not in the levels of sterol regulatory element-binding protein 1c (SREBP1c), a key transcription factor for lipid production.", "We identified Insig1 mRNA as a direct target of HuD by using ribonucleoprotein immunoprecipitation (RIP) and biotin pulldown analyses.", "By associating with the 3'-untranslated region (3'UTR) of Insig1 mRNA, HuD promoted INSIG1 translation; accordingly, HuD downregulation reduced while ectopic HuD expression increased INSIG1 levels.", "We further observed that HuD downregulation facilitated the nuclear localization of SREBP1c, thereby increasing the transcriptional activity of SREBP1c and the expression of target genes involved in lipogenesis; likewise, we observed lower INSIG1 levels in the pancreatic islets of HuD-null mice.", "Taken together, our results indicate that HuD functions as a novel repressor of lipid synthesis in pancreatic \u03b2 cells."], "title": "RNA-binding protein HuD reduces triglyceride production in pancreatic \u03b2 cells by enhancing the expression of insulin-induced gene 1."}
{"paper_id": 26351351, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Squamous cell carcinoma of an unknown primary (SCCUP) of the head and neck is a rare disease. As a diagnosis of exclusion, the manner in which it is assigned merits consideration. Despite the development and refinement of several techniques designed to locate an occult tumor, including cross-sectional anatomic imaging, functional imaging, and transoral surgical techniques, delineating SCCUP remains an active clinical problem. Its relative rarity has prevented prospective study of the entity. Hence, investigators must rely on retrospective analyses to understand the disease and its appropriate treatment. The current understanding of SCCUP differs substantially from when it was initially described decades ago. The most common site of a small primary tumor initially thought to represent SCCUP is the tonsil or base of the tongue, and an increasing percentage are associated with human papilloma virus. Modern treatment of SCCUP by neck dissection alone, neck dissection followed by radiation with or without concurrent chemotherapy, or primary chemoradiation according to initial nodal disease burden produces extraordinarily low recurrence rates. Whether the potential mucosal primary site and/or the contralateral neck should be electively treated is controversial. Efficacy data seem to be similar; therefore, an evaluation of the toxicity of both treatment paradigms is warranted.", "journal": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology", "sentences": ["Squamous cell carcinoma of an unknown primary (SCCUP) of the head and neck is a rare disease.", "As a diagnosis of exclusion, the manner in which it is assigned merits consideration.", "Despite the development and refinement of several techniques designed to locate an occult tumor, including cross-sectional anatomic imaging, functional imaging, and transoral surgical techniques, delineating SCCUP remains an active clinical problem.", "Its relative rarity has prevented prospective study of the entity.", "Hence, investigators must rely on retrospective analyses to understand the disease and its appropriate treatment.", "The current understanding of SCCUP differs substantially from when it was initially described decades ago.", "The most common site of a small primary tumor initially thought to represent SCCUP is the tonsil or base of the tongue, and an increasing percentage are associated with human papilloma virus.", "Modern treatment of SCCUP by neck dissection alone, neck dissection followed by radiation with or without concurrent chemotherapy, or primary chemoradiation according to initial nodal disease burden produces extraordinarily low recurrence rates.", "Whether the potential mucosal primary site and/or the contralateral neck should be electively treated is controversial.", "Efficacy data seem to be similar; therefore, an evaluation of the toxicity of both treatment paradigms is warranted."], "title": "Management of Squamous Cancer Metastatic to Cervical Nodes With an Unknown Primary Site."}
{"paper_id": 24442506, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "Toxic compounds including acids, furans, and phenols (AFP) were generated from the pretreatment of lignocellulose. We cultivated Saccharomyces cerevisiae cells in a batch mode, besides the cell culture of original yeast strain in AFP-free medium which was referred as C0, three independent subcultures were cultivated under multiple inhibitors AFP and were referred as C1, C2, and C3 in time sequence. Comparing to C0, the cell density was lowered while the ethanol yield was maintained stably in the three yeast cultures under AFP stress, and the lag phase of C1 was extended while the lag phases of C2 and C3 were not extended. In proteomic analysis, 194 and 215 unique proteins were identified as differently expressed proteins at lag phase and exponential phase, respectively. Specifically, the yeast cells co-regulated protein folding and protein synthesis process to prevent the generation of misfolded proteins and to save cellular energy, they increased the activity of glycolysis, redirected metabolic flux towards phosphate pentose pathway and the biosynthesis of ethanol instead of the biosynthesis of glycerol and acetic acid, and they upregulated several oxidoreductases especially at lag phase and induced programmed cell death at exponential phase. When the yeast cells were cultivated under AFP stress, the new metabolism homeostasis in favor of cellular energy and redox homeostasis was generated in C1, then it was inherited and optimized in C2 and C3, enabling the yeast cells in C2 and C3 to enter the exponential phase in a short period after inoculation, which thus significantly shortened the fermentation time.", "journal": "Applied microbiology and biotechnology", "sentences": ["Toxic compounds including acids, furans, and phenols (AFP) were generated from the pretreatment of lignocellulose.", "We cultivated Saccharomyces cerevisiae cells in a batch mode, besides the cell culture of original yeast strain in AFP-free medium which was referred as C0, three independent subcultures were cultivated under multiple inhibitors AFP and were referred as C1, C2, and C3 in time sequence.", "Comparing to C0, the cell density was lowered while the ethanol yield was maintained stably in the three yeast cultures under AFP stress, and the lag phase of C1 was extended while the lag phases of C2 and C3 were not extended.", "In proteomic analysis, 194 and 215 unique proteins were identified as differently expressed proteins at lag phase and exponential phase, respectively.", "Specifically, the yeast cells co-regulated protein folding and protein synthesis process to prevent the generation of misfolded proteins and to save cellular energy, they increased the activity of glycolysis, redirected metabolic flux towards phosphate pentose pathway and the biosynthesis of ethanol instead of the biosynthesis of glycerol and acetic acid, and they upregulated several oxidoreductases especially at lag phase and induced programmed cell death at exponential phase.", "When the yeast cells were cultivated under AFP stress, the new metabolism homeostasis in favor of cellular energy and redox homeostasis was generated in C1, then it was inherited and optimized in C2 and C3, enabling the yeast cells in C2 and C3 to enter the exponential phase in a short period after inoculation, which thus significantly shortened the fermentation time."], "title": "Proteomic analysis reveals complex metabolic regulation in Saccharomyces cerevisiae cells against multiple inhibitors stress."}
{"paper_id": 22479630, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The brainstem premotor neurons of the facial nucleus (VII) and hypoglossal (XII) nucleus can integrate orofacial nociceptive input from the caudal spinal trigeminal nucleus (Vc) and coordinate orofacial nociceptive reflex (ONR) responses. However, the synaptoarchitectures of the ONR pathways are still unknown. In the current study, we examined the distribution of GABAergic premotor neurons in the brainstem local ONR pathways, their connections with the Vc projections joining the brainstem ONR pathways and the neurochemical properties of these connections. Retrograde tracer fluoro-gold (FG) was injected into the VII or XII, and anterograde tracer biotinylated dextran amine (BDA) was injected into the Vc. Immunofluorescence histochemical labeling for inhibitory/excitatory neurotransmitters combined with BDA/FG tracing showed that GABAergic premotor neurons were mainly distributed bilaterally in the ponto-medullary reticular formation with an ipsilateral dominance. Some GABAergic premotor neurons made close appositions to the BDA-labeled fibers coming from the Vc, and these appostions were mainly distributed in the parvicellular reticular formation (PCRt), dorsal medullary reticular formation (MdD), and supratrigeminal nucleus (Vsup). We further examined the synaptic relationships between the Vc projecting fibers and premotor neurons in the VII or XII under the confocal laser-scanning microscope and electron microscope, and found that the BDA-labeled axonal terminals that made asymmetric synapses on premotor neurons showed vesicular glutamate transporter 2 (VGluT2) like immunoreactivity. These results indicate that the GABAergic premotor neurons receive excitatory neurotransmission from the Vc and may contribute to modulating the generation of the tonic ONR.", "journal": "PloS one", "sentences": ["The brainstem premotor neurons of the facial nucleus (VII) and hypoglossal (XII) nucleus can integrate orofacial nociceptive input from the caudal spinal trigeminal nucleus (Vc) and coordinate orofacial nociceptive reflex (ONR) responses.", "However, the synaptoarchitectures of the ONR pathways are still unknown.", "In the current study, we examined the distribution of GABAergic premotor neurons in the brainstem local ONR pathways, their connections with the Vc projections joining the brainstem ONR pathways and the neurochemical properties of these connections.", "Retrograde tracer fluoro-gold (FG) was injected into the VII or XII, and anterograde tracer biotinylated dextran amine (BDA) was injected into the Vc.", "Immunofluorescence histochemical labeling for inhibitory/excitatory neurotransmitters combined with BDA/FG tracing showed that GABAergic premotor neurons were mainly distributed bilaterally in the ponto-medullary reticular formation with an ipsilateral dominance.", "Some GABAergic premotor neurons made close appositions to the BDA-labeled fibers coming from the Vc, and these appostions were mainly distributed in the parvicellular reticular formation (PCRt), dorsal medullary reticular formation (MdD), and supratrigeminal nucleus (Vsup).", "We further examined the synaptic relationships between the Vc projecting fibers and premotor neurons in the VII or XII under the confocal laser-scanning microscope and electron microscope, and found that the BDA-labeled axonal terminals that made asymmetric synapses on premotor neurons showed vesicular glutamate transporter 2 (VGluT2) like immunoreactivity.", "These results indicate that the GABAergic premotor neurons receive excitatory neurotransmission from the Vc and may contribute to modulating the generation of the tonic ONR."], "title": "Neurochemical properties of the synapses in the pathways of orofacial nociceptive reflexes."}
{"paper_id": 26515729, "labels": ["0", "0", "0", "1", "0", "0", "0", "1"], "abstract": "CD133 is widely used as a surface marker to isolate cancer stem cells (CSCs). Here we show that in CSCs CD133 contributes to \u03b2-catenin-mediated transcriptional activation and to the self-renewal capacity of sphere-forming and side-population (SP) cells in cell lines from brain, colon and lung cancers, but not gastric or breast cancers. In chromatin immunoprecipitation assays, \u03b2-catenin binding to the proximal promoter regions of ITGA2-4 and ITGA10-11 in brain, colon and lung cancer cell lines could be triggered by CD133, and \u03b2-catenin also bound to the proximal promoter regions of ITGB6 and ITGB8 in cell lines from gastric and breast cancers. CD133 thus induces \u03b2-catenin binding and transcriptional activation of diverse targets that are cancer type-specific. Cell migration triggered by wounding CD133+ cells cultured on ECM-coated dishes can induce polarity and lipid raft coalescence, enhancing CD133/integrin signaling and asymmetric cell division. In response to directional cues, integrins, Src and the Par complex were enriched in lipid rafts, and the assembly and activation of an integrated CD133-integrin-Par signaling complex was followed by Src/Akt/GSK3\u03b2 signaling. The subsequent increase and nuclear translocation of \u03b2-catenin may be a regulatory switch to increase drug resistance and stemness properties. Collectively, these findings 1) indicate that a polarized cell migration-induced CD133/integrin/Src/Akt/GSK3\u03b2/\u03b2-catenin axis is required for maintenance of CSC properties, 2) establish a function for CD133 and 3) support the rationale for targeting CD133 in cancer treatment.", "journal": "Oncotarget", "sentences": ["CD133 is widely used as a surface marker to isolate cancer stem cells (CSCs).", "Here we show that in CSCs CD133 contributes to \u03b2-catenin-mediated transcriptional activation and to the self-renewal capacity of sphere-forming and side-population (SP) cells in cell lines from brain, colon and lung cancers, but not gastric or breast cancers.", "In chromatin immunoprecipitation assays, \u03b2-catenin binding to the proximal promoter regions of ITGA2-4 and ITGA10-11 in brain, colon and lung cancer cell lines could be triggered by CD133, and \u03b2-catenin also bound to the proximal promoter regions of ITGB6 and ITGB8 in cell lines from gastric and breast cancers.", "CD133 thus induces \u03b2-catenin binding and transcriptional activation of diverse targets that are cancer type-specific.", "Cell migration triggered by wounding CD133+ cells cultured on ECM-coated dishes can induce polarity and lipid raft coalescence, enhancing CD133/integrin signaling and asymmetric cell division.", "In response to directional cues, integrins, Src and the Par complex were enriched in lipid rafts, and the assembly and activation of an integrated CD133-integrin-Par signaling complex was followed by Src/Akt/GSK3\u03b2 signaling.", "The subsequent increase and nuclear translocation of \u03b2-catenin may be a regulatory switch to increase drug resistance and stemness properties.", "Collectively, these findings 1) indicate that a polarized cell migration-induced CD133/integrin/Src/Akt/GSK3\u03b2/\u03b2-catenin axis is required for maintenance of CSC properties, 2) establish a function for CD133 and 3) support the rationale for targeting CD133 in cancer treatment."], "title": "Polarized cell migration induces cancer type-specific CD133/integrin/Src/Akt/GSK3\u03b2/\u03b2-catenin signaling required for maintenance of cancer stem cell properties."}
{"paper_id": 27413744, "labels": ["0", "0", "0", "0", "0", "0", "1", "1", "0"], "abstract": "Basic and clinical studies on mechanobiology of cells and tissues point to the importance of mechanical forces in the process of skin regeneration and wound healing. These studies result in the development of new therapies that use mechanical force which supports effective healing. A better understanding of mechanobiology will make it possible to develop biomaterials with appropriate physical and chemical properties used to treat poorly healing wounds. In addition, it will make it possible to design devices precisely controlling wound mechanics and to individualize a therapy depending on the type, size, and anatomical location of the wound in specific patients, which will increase the clinical efficiency of the therapy. Linking mechanobiology with the science of biomaterials and nanotechnology will enable in the near future precise interference in abnormal cell signaling responsible for the proliferation, differentiation, cell death, and restoration of the biological balance. The objective of this study is to point to the importance of mechanobiology in regeneration of skin damage and wound healing. The study describes the influence of rigidity of extracellular matrix and special restrictions on cell physiology. The study also defines how and what mechanical changes influence tissue regeneration and wound healing. The influence of mechanical signals in the process of proliferation, differentiation, and skin regeneration is tagged in the study.", "journal": "BioMed research international", "sentences": ["Basic and clinical studies on mechanobiology of cells and tissues point to the importance of mechanical forces in the process of skin regeneration and wound healing.", "These studies result in the development of new therapies that use mechanical force which supports effective healing.", "A better understanding of mechanobiology will make it possible to develop biomaterials with appropriate physical and chemical properties used to treat poorly healing wounds.", "In addition, it will make it possible to design devices precisely controlling wound mechanics and to individualize a therapy depending on the type, size, and anatomical location of the wound in specific patients, which will increase the clinical efficiency of the therapy.", "Linking mechanobiology with the science of biomaterials and nanotechnology will enable in the near future precise interference in abnormal cell signaling responsible for the proliferation, differentiation, cell death, and restoration of the biological balance.", "The objective of this study is to point to the importance of mechanobiology in regeneration of skin damage and wound healing.", "The study describes the influence of rigidity of extracellular matrix and special restrictions on cell physiology.", "The study also defines how and what mechanical changes influence tissue regeneration and wound healing.", "The influence of mechanical signals in the process of proliferation, differentiation, and skin regeneration is tagged in the study."], "title": "Mechanoregulation of Wound Healing and Skin Homeostasis."}
{"paper_id": 21677136, "labels": ["0", "0", "0", "1", "1"], "abstract": "A common denominator among the multiple damage-inducing agents that ultimately lead to activation of NLRP3 has not yet been identified. Recently, production of reactive oxygen species (ROS) has been suggested to act as a common event upstream of the NLRP3 inflammasome machinery. Because de novo translation of NLRP3 is an essential step in the activation of NLRP3, we investigated the role of substances that inhibit either ROS production or its oxidative activity. Although we observe that NLRP3 inflammasome activation is unique among other known inflammasomes in its sensitivity to ROS inhibition, we have found that this phenomenon is attributable to the fact that NLRP3 strictly requires priming by a proinflammatory signal, a step that is blocked by ROS inhibitors. Although these data do not exclude a general role for ROS production in the process of NLRP3-triggered inflammation, they would put ROS upstream of NLRP3 induction, but not activation.", "journal": "Journal of immunology (Baltimore, Md. : 1950)", "sentences": ["A common denominator among the multiple damage-inducing agents that ultimately lead to activation of NLRP3 has not yet been identified.", "Recently, production of reactive oxygen species (ROS) has been suggested to act as a common event upstream of the NLRP3 inflammasome machinery.", "Because de novo translation of NLRP3 is an essential step in the activation of NLRP3, we investigated the role of substances that inhibit either ROS production or its oxidative activity.", "Although we observe that NLRP3 inflammasome activation is unique among other known inflammasomes in its sensitivity to ROS inhibition, we have found that this phenomenon is attributable to the fact that NLRP3 strictly requires priming by a proinflammatory signal, a step that is blocked by ROS inhibitors.", "Although these data do not exclude a general role for ROS production in the process of NLRP3-triggered inflammation, they would put ROS upstream of NLRP3 induction, but not activation."], "title": "Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome."}
{"paper_id": 21791417, "labels": ["0", "0", "1", "0", "1"], "abstract": "In a previous study, we demonstrated unique secretory dynamics of tissue plasminogen activator (tPA) in which tPA was retained on the cell surface in a heavy chain-dependent manner after exocytosis from secretory granules in vascular endothelial cells. Here, we examined how retained tPA expresses its enzymatic activity. Retained tPA effectively increased the lysine binding site-dependent binding of plasminogen on the cell surface and pericellular area; this was abolished by inhibition of enzymatic activity of either tPA or plasmin, which suggests that de novo generation of carboxyl-terminal lysine as a consequence of degradation of surface/pericellular proteins by plasmin is essential. Retained tPA initiated zonal clot lysis of a fibrin network that had been formed on vascular endothelial cells, which was preceded by the binding of plasminogen to the lysis front. Our results provide evidence that secreted and retained tPA is essential for maintaining both high fibrinolytic activity and effective clot lysis on the vascular endothelial cell surface.", "journal": "Blood", "sentences": ["In a previous study, we demonstrated unique secretory dynamics of tissue plasminogen activator (tPA) in which tPA was retained on the cell surface in a heavy chain-dependent manner after exocytosis from secretory granules in vascular endothelial cells.", "Here, we examined how retained tPA expresses its enzymatic activity.", "Retained tPA effectively increased the lysine binding site-dependent binding of plasminogen on the cell surface and pericellular area; this was abolished by inhibition of enzymatic activity of either tPA or plasmin, which suggests that de novo generation of carboxyl-terminal lysine as a consequence of degradation of surface/pericellular proteins by plasmin is essential.", "Retained tPA initiated zonal clot lysis of a fibrin network that had been formed on vascular endothelial cells, which was preceded by the binding of plasminogen to the lysis front.", "Our results provide evidence that secreted and retained tPA is essential for maintaining both high fibrinolytic activity and effective clot lysis on the vascular endothelial cell surface."], "title": "Surface-retained tPA is essential for effective fibrinolysis on vascular endothelial cells."}
{"paper_id": 21423696, "labels": ["0", "0", "0", "0", "0", "1", "0", "1"], "abstract": "Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B(12) are poorly understood. We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA) levels may result in diversion of methyl groups towards DNA in the one carbon metabolic pathway ultimately resulting in DNA methylation. This study was designed to examine the effect of normal and excess folic acid in the absence and presence of vitamin B(12) deficiency on global methylation patterns in the placenta. Further, the effect of maternal omega 3 fatty acid supplementation on the above vitamin B(12) deficient diets was also examined. Our results suggest maternal folic acid supplementation in the absence of vitamin B(12) lowers plasma and placental DHA levels (p<0.05) and reduces global DNA methylation levels (p<0.05). When this group was supplemented with omega 3 fatty acids there was an increase in placental DHA levels and subsequently DNA methylation levels revert back to the levels of the control group. Our results suggest for the first time that DHA plays an important role in one carbon metabolism thereby influencing global DNA methylation in the placenta.", "journal": "PloS one", "sentences": ["Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B(12) are poorly understood.", "We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring.", "We have also reported that reduced docosahexaenoic acid (DHA) levels may result in diversion of methyl groups towards DNA in the one carbon metabolic pathway ultimately resulting in DNA methylation.", "This study was designed to examine the effect of normal and excess folic acid in the absence and presence of vitamin B(12) deficiency on global methylation patterns in the placenta.", "Further, the effect of maternal omega 3 fatty acid supplementation on the above vitamin B(12) deficient diets was also examined.", "Our results suggest maternal folic acid supplementation in the absence of vitamin B(12) lowers plasma and placental DHA levels (p<0.05) and reduces global DNA methylation levels (p<0.05).", "When this group was supplemented with omega 3 fatty acids there was an increase in placental DHA levels and subsequently DNA methylation levels revert back to the levels of the control group.", "Our results suggest for the first time that DHA plays an important role in one carbon metabolism thereby influencing global DNA methylation in the placenta."], "title": "Effects of altered maternal folic acid, vitamin B12 and docosahexaenoic acid on placental global DNA methylation patterns in Wistar rats."}
{"paper_id": 26091039, "labels": ["0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "The existence of extracellular phosphoproteins has been acknowledged for over a century. However, research in this area has been undeveloped largely because the kinases that phosphorylate secreted proteins have escaped identification. Fam20C is a kinase that phosphorylates S-x-E/pS motifs on proteins in milk and in the extracellular matrix of bones and teeth. Here, we show that Fam20C generates the majority of the extracellular phosphoproteome. Using CRISPR/Cas9 genome editing, mass spectrometry, and biochemistry, we identify more than 100 secreted phosphoproteins as genuine Fam20C substrates. Further, we show that Fam20C exhibits broader substrate specificity than previously appreciated. Functional annotations of Fam20C substrates suggest roles for the kinase beyond biomineralization, including lipid homeostasis, wound healing, and cell migration and adhesion. Our results establish Fam20C as the major secretory pathway protein kinase and serve as a foundation for new areas of investigation into the role of secreted protein phosphorylation in human biology and disease.", "journal": "Cell", "sentences": ["The existence of extracellular phosphoproteins has been acknowledged for over a century.", "However, research in this area has been undeveloped largely because the kinases that phosphorylate secreted proteins have escaped identification.", "Fam20C is a kinase that phosphorylates S-x-E/pS motifs on proteins in milk and in the extracellular matrix of bones and teeth.", "Here, we show that Fam20C generates the majority of the extracellular phosphoproteome.", "Using CRISPR/Cas9 genome editing, mass spectrometry, and biochemistry, we identify more than 100 secreted phosphoproteins as genuine Fam20C substrates.", "Further, we show that Fam20C exhibits broader substrate specificity than previously appreciated.", "Functional annotations of Fam20C substrates suggest roles for the kinase beyond biomineralization, including lipid homeostasis, wound healing, and cell migration and adhesion.", "Our results establish Fam20C as the major secretory pathway protein kinase and serve as a foundation for new areas of investigation into the role of secreted protein phosphorylation in human biology and disease."], "title": "A Single Kinase Generates the Majority of the Secreted Phosphoproteome."}
{"paper_id": 25992874, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "We hypothesized that the study of gene expression at 1, 2, 4, 6 and 16 weeks in the substantia nigra (SN) after intrastriatal 6-OHDA in the Sprague-Dawley rat (rattus norvegicus) would identify cellular responses during the degenerative process that could be axoprotective. Specifically, we hypothesized that genes expressed within the SN that followed a profile of being highly upregulated early after the lesion (during active axonal degeneration) and then progressively declined to baseline over 16 weeks as DA neurons died are indicative of potential protective responses to the striatal 6-OHDA insult. Utilizing a \u03ba-means cluster analysis strategy, we demonstrated that one such cluster followed this hypothesized expression pattern over time, and that this cluster contained several interrelated transcripts that are classified as regeneration-associated genes (RAGs) including Atf3, Sprr1a, Ecel1, Gadd45a, Gpnmb, Sox11, Mmp19, Srgap1, Rab15,Lifr, Trib3, Tgfb1, and Sema3c. All exemplar transcripts tested from this cluster (Sprr1a, Ecel1, Gadd45a, Atf3 and Sox11) were validated by qPCR and a smaller subset (Sprr1a, Gadd45a and Sox11) were shown to be exclusively localized to SN DA neurons using a dual label approach with RNAScope in situ hybridization and immunohistochemistry. Upregulation of RAGs is typically associated with the response to axonal injury in the peripheral nerves and was not previously reported as part of the axodegenerative process for DA neurons of the SN. Interestingly, as part of this cluster, other transcripts were identified based on their expression pattern but without a RAG provenance in the literature. These \"RAG-like\" transcripts need further characterization to determine if they possess similar functions to or interact with known RAG transcripts. Ultimately, it is hoped that some of the newly identified axodegeneration-reactive transcripts could be exploited as axoprotective therapies in PD and other neurodegenerative diseases.", "journal": "PloS one", "sentences": ["We hypothesized that the study of gene expression at 1, 2, 4, 6 and 16 weeks in the substantia nigra (SN) after intrastriatal 6-OHDA in the Sprague-Dawley rat (rattus norvegicus) would identify cellular responses during the degenerative process that could be axoprotective.", "Specifically, we hypothesized that genes expressed within the SN that followed a profile of being highly upregulated early after the lesion (during active axonal degeneration) and then progressively declined to baseline over 16 weeks as DA neurons died are indicative of potential protective responses to the striatal 6-OHDA insult.", "Utilizing a \u03ba-means cluster analysis strategy, we demonstrated that one such cluster followed this hypothesized expression pattern over time, and that this cluster contained several interrelated transcripts that are classified as regeneration-associated genes (RAGs) including Atf3, Sprr1a, Ecel1, Gadd45a, Gpnmb, Sox11, Mmp19, Srgap1, Rab15,Lifr, Trib3, Tgfb1, and Sema3c.", "All exemplar transcripts tested from this cluster (Sprr1a, Ecel1, Gadd45a, Atf3 and Sox11) were validated by qPCR and a smaller subset (Sprr1a, Gadd45a and Sox11) were shown to be exclusively localized to SN DA neurons using a dual label approach with RNAScope in situ hybridization and immunohistochemistry.", "Upregulation of RAGs is typically associated with the response to axonal injury in the peripheral nerves and was not previously reported as part of the axodegenerative process for DA neurons of the SN.", "Interestingly, as part of this cluster, other transcripts were identified based on their expression pattern but without a RAG provenance in the literature.", "These \"RAG-like\" transcripts need further characterization to determine if they possess similar functions to or interact with known RAG transcripts.", "Ultimately, it is hoped that some of the newly identified axodegeneration-reactive transcripts could be exploited as axoprotective therapies in PD and other neurodegenerative diseases."], "title": "The longitudinal transcriptomic response of the substantia nigra to intrastriatal 6-hydroxydopamine reveals significant upregulation of regeneration-associated genes."}
{"paper_id": 22120012, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "Diffusion MRI (or dMRI) came into existence in the mid-1980s. During the last 25 years, diffusion MRI has been extraordinarily successful (with more than 300,000 entries on Google Scholar for diffusion MRI). Its main clinical domain of application has been neurological disorders, especially for the management of patients with acute stroke. It is also rapidly becoming a standard for white matter disorders, as diffusion tensor imaging (DTI) can reveal abnormalities in white matter fiber structure and provide outstanding maps of brain connectivity. The ability to visualize anatomical connections between different parts of the brain, non-invasively and on an individual basis, has emerged as a major breakthrough for neurosciences. The driving force of dMRI is to monitor microscopic, natural displacements of water molecules that occur in brain tissues as part of the physical diffusion process. Water molecules are thus used as a probe that can reveal microscopic details about tissue architecture, either normal or in a diseased state.", "journal": "NeuroImage", "sentences": ["Diffusion MRI (or dMRI) came into existence in the mid-1980s.", "During the last 25 years, diffusion MRI has been extraordinarily successful (with more than 300,000 entries on Google Scholar for diffusion MRI).", "Its main clinical domain of application has been neurological disorders, especially for the management of patients with acute stroke.", "It is also rapidly becoming a standard for white matter disorders, as diffusion tensor imaging (DTI) can reveal abnormalities in white matter fiber structure and provide outstanding maps of brain connectivity.", "The ability to visualize anatomical connections between different parts of the brain, non-invasively and on an individual basis, has emerged as a major breakthrough for neurosciences.", "The driving force of dMRI is to monitor microscopic, natural displacements of water molecules that occur in brain tissues as part of the physical diffusion process.", "Water molecules are thus used as a probe that can reveal microscopic details about tissue architecture, either normal or in a diseased state."], "title": "Diffusion MRI at 25: exploring brain tissue structure and function."}
{"paper_id": 22363009, "labels": ["0", "0", "0", "1", "1", "0", "1"], "abstract": "Understanding species' interactions and the robustness of interaction networks to species loss is essential to understand the effects of species' declines and extinctions. In most studies, different types of networks (such as food webs, parasitoid webs, seed dispersal networks, and pollination networks) have been studied separately. We sampled such multiple networks simultaneously in an agroecosystem. We show that the networks varied in their robustness; networks including pollinators appeared to be particularly fragile. We show that, overall, networks did not strongly covary in their robustness, which suggests that ecological restoration (for example, through agri-environment schemes) benefitting one functional group will not inevitably benefit others. Some individual plant species were disproportionately well linked to many other species. This type of information can be used in restoration management, because it identifies the plant taxa that can potentially lead to disproportionate gains in biodiversity.", "journal": "Science (New York, N.Y.)", "sentences": ["Understanding species' interactions and the robustness of interaction networks to species loss is essential to understand the effects of species' declines and extinctions.", "In most studies, different types of networks (such as food webs, parasitoid webs, seed dispersal networks, and pollination networks) have been studied separately.", "We sampled such multiple networks simultaneously in an agroecosystem.", "We show that the networks varied in their robustness; networks including pollinators appeared to be particularly fragile.", "We show that, overall, networks did not strongly covary in their robustness, which suggests that ecological restoration (for example, through agri-environment schemes) benefitting one functional group will not inevitably benefit others.", "Some individual plant species were disproportionately well linked to many other species.", "This type of information can be used in restoration management, because it identifies the plant taxa that can potentially lead to disproportionate gains in biodiversity."], "title": "The robustness and restoration of a network of ecological networks."}
{"paper_id": 22539795, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "Type 1 diabetes is an autoimmune disease characterized by T cell responses to \u03b2 cell Ags, including insulin. Investigations employing the NOD mouse model of the disease have revealed an essential role for \u03b2 cell-specific CD8(+) T cells in the pathogenic process. As CD8(+) T cells specific for \u03b2 cell Ags are also present in patients, these reactivities have the potential to serve as therapeutic targets or markers for autoimmune activity. NOD mice transgenic for human class I MHC molecules have previously been employed to identify T cell epitopes having important relevance to the human disease. However, most studies have focused exclusively on HLA-A*0201. To broaden the reach of epitope-based monitoring and therapeutic strategies, we have looked beyond this allele and developed NOD mice expressing human \u03b2(2)-microglobulin and HLA-A*1101 or HLA-B*0702, which are representative members of the A3 and B7 HLA supertypes, respectively. We have used islet-infiltrating T cells spontaneously arising in these strains to identify \u03b2 cell peptides recognized in the context of the transgenic HLA molecules. This work has identified the insulin C-peptide as an abundant source of CD8(+) T cell epitopes. Responses to these epitopes should be of considerable utility for immune monitoring, as they cannot reflect an immune reaction to exogenously administered insulin, which lacks the C-peptide. Because the peptides bound by one supertype member were found to bind certain other members also, the epitopes identified in this study have the potential to result in therapeutic and monitoring tools applicable to large numbers of patients and at-risk individuals.", "journal": "Journal of immunology (Baltimore, Md. : 1950)", "sentences": ["Type 1 diabetes is an autoimmune disease characterized by T cell responses to \u03b2 cell Ags, including insulin.", "Investigations employing the NOD mouse model of the disease have revealed an essential role for \u03b2 cell-specific CD8(+) T cells in the pathogenic process.", "As CD8(+) T cells specific for \u03b2 cell Ags are also present in patients, these reactivities have the potential to serve as therapeutic targets or markers for autoimmune activity.", "NOD mice transgenic for human class I MHC molecules have previously been employed to identify T cell epitopes having important relevance to the human disease.", "However, most studies have focused exclusively on HLA-A*0201.", "To broaden the reach of epitope-based monitoring and therapeutic strategies, we have looked beyond this allele and developed NOD mice expressing human \u03b2(2)-microglobulin and HLA-A*1101 or HLA-B*0702, which are representative members of the A3 and B7 HLA supertypes, respectively.", "We have used islet-infiltrating T cells spontaneously arising in these strains to identify \u03b2 cell peptides recognized in the context of the transgenic HLA molecules.", "This work has identified the insulin C-peptide as an abundant source of CD8(+) T cell epitopes.", "Responses to these epitopes should be of considerable utility for immune monitoring, as they cannot reflect an immune reaction to exogenously administered insulin, which lacks the C-peptide.", "Because the peptides bound by one supertype member were found to bind certain other members also, the epitopes identified in this study have the potential to result in therapeutic and monitoring tools applicable to large numbers of patients and at-risk individuals."], "title": "Beyond HLA-A*0201: new HLA-transgenic nonobese diabetic mouse models of type 1 diabetes identify the insulin C-peptide as a rich source of CD8+ T cell epitopes."}
{"paper_id": 25795258, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Prior to the introduction of rotavirus vaccines in 2006, rotavirus was the leading cause of severe gastroenteritis among European children <5 years of age. We conducted a systematic review of the published literature to examine the effectiveness and impact of rotavirus vaccines in Europe following the first eight years of routine use. Four publication databases were searched, yielding 276 unique citations from February 1st, 2006 to July 31st, 2014. Twenty four studies on effectiveness (n=9) and impact (n=15) met the inclusion criteria. Across Europe, vaccine effectiveness against rotavirus-related healthcare utilisation ranged from 68% to 98%, consistent with efficacy data from clinical trials. Reductions in rotavirus hospitalisations ranged from 65% to 84%, consistent with findings from post-marketing studies from the US and Latin America. We confirm the significant public health benefit of rotavirus vaccination in Europe and provide further evidence to support implementation of universal rotavirus vaccination in all European countries.", "journal": "Vaccine", "sentences": ["Prior to the introduction of rotavirus vaccines in 2006, rotavirus was the leading cause of severe gastroenteritis among European children <5 years of age.", "We conducted a systematic review of the published literature to examine the effectiveness and impact of rotavirus vaccines in Europe following the first eight years of routine use.", "Four publication databases were searched, yielding 276 unique citations from February 1st, 2006 to July 31st, 2014.", "Twenty four studies on effectiveness (n=9) and impact (n=15) met the inclusion criteria.", "Across Europe, vaccine effectiveness against rotavirus-related healthcare utilisation ranged from 68% to 98%, consistent with efficacy data from clinical trials.", "Reductions in rotavirus hospitalisations ranged from 65% to 84%, consistent with findings from post-marketing studies from the US and Latin America.", "We confirm the significant public health benefit of rotavirus vaccination in Europe and provide further evidence to support implementation of universal rotavirus vaccination in all European countries."], "title": "Effectiveness and impact of rotavirus vaccines in Europe, 2006-2014."}
{"paper_id": 26631266, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "p53 has been shown to mediate cancer stem-like cell function by suppressing pluripotency and cellular dedifferentiation. However, there have been no studies to date that have addressed the specific effects of p53 loss in colonic adult stem cells. In this study, we investigated the consequences of conditionally ablating p53 in the highly relevant Lgr5(+) stem cell population on tumor initiation and progression in the colon. In a mouse model of carcinogen (AOM)-induced colon cancer, tamoxifen-inducible Lgr5-driven deletion of p53 reduced apoptosis and increased proliferation of crypt stem cells, but had no effect on tumor incidence or size. Conversely, in a mouse model of colitis-associated cancer, in which mice are exposed to AOM and the potent inflammation inducer DSS, stem cell-specific p53 deletion greatly enhanced tumor size and incidence in the colon. These novel findings suggest that the loss of p53 function in stem cells enables colonic tumor formation only when combined with DNA damage and chronic inflammation. Furthermore, we propose that stem cell targeting approaches are valuable for interrogating prevention and therapeutic strategies that aim to specifically eradicate genetically compromised stem cells.", "journal": "Cancer research", "sentences": ["p53 has been shown to mediate cancer stem-like cell function by suppressing pluripotency and cellular dedifferentiation.", "However, there have been no studies to date that have addressed the specific effects of p53 loss in colonic adult stem cells.", "In this study, we investigated the consequences of conditionally ablating p53 in the highly relevant Lgr5(+) stem cell population on tumor initiation and progression in the colon.", "In a mouse model of carcinogen (AOM)-induced colon cancer, tamoxifen-inducible Lgr5-driven deletion of p53 reduced apoptosis and increased proliferation of crypt stem cells, but had no effect on tumor incidence or size.", "Conversely, in a mouse model of colitis-associated cancer, in which mice are exposed to AOM and the potent inflammation inducer DSS, stem cell-specific p53 deletion greatly enhanced tumor size and incidence in the colon.", "These novel findings suggest that the loss of p53 function in stem cells enables colonic tumor formation only when combined with DNA damage and chronic inflammation.", "Furthermore, we propose that stem cell targeting approaches are valuable for interrogating prevention and therapeutic strategies that aim to specifically eradicate genetically compromised stem cells."], "title": "Targeted Deletion of p53 in Lgr5-Expressing Intestinal Stem Cells Promotes Colon Tumorigenesis in a Preclinical Model of Colitis-Associated Cancer."}
{"paper_id": 26440518, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The transport of antigen from the periphery to the draining lymph node (DLN) is critical for T-cell priming but remains poorly studied during infection with Mycobacterium bovis Bacille Calmette-Gu\u00e9rin (BCG). To address this we employed a mouse model to track the traffic of Dendritic cells (DCs) and mycobacteria from the BCG inoculation site in the skin to the DLN. Detection of BCG in the DLN was concomitant with the priming of antigen-specific CD4+ T cells at that site. We found EpCAMlow CD11bhigh migratory skin DCs to be mobilized during the transport of BCG to the DLN. Migratory skin DCs distributed to the T-cell area of the LN, co-localized with BCG and were found in close apposition to antigen-specific CD4+ T cells. Consequently, blockade of skin DC traffic into DLN dramatically reduced mycobacterial entry into DLN and muted T-cell priming. Interestingly, DC and mycobacterial entry into the DLN was dependent on IL-1R-I, MyD88, TNFR-I and IL-12p40. In addition, we found using DC adoptive transfers that the requirement for MyD88 in BCG-triggered migration was not restricted to the migrating DC itself and that hematopoietic expression of MyD88 was needed in part for full-fledged migration. Our observations thus identify a population of DCs that contribute towards the priming of CD4+ T cells to BCG infection by transporting bacilli into the DLN in an IL-1R-MyD88-dependent manner and reveal both DC-intrinsic and -extrinsic requirements for MyD88 in DC migration.", "journal": "PLoS pathogens", "sentences": ["The transport of antigen from the periphery to the draining lymph node (DLN) is critical for T-cell priming but remains poorly studied during infection with Mycobacterium bovis Bacille Calmette-Gu\u00e9rin (BCG).", "To address this we employed a mouse model to track the traffic of Dendritic cells (DCs) and mycobacteria from the BCG inoculation site in the skin to the DLN.", "Detection of BCG in the DLN was concomitant with the priming of antigen-specific CD4+ T cells at that site.", "We found EpCAMlow CD11bhigh migratory skin DCs to be mobilized during the transport of BCG to the DLN.", "Migratory skin DCs distributed to the T-cell area of the LN, co-localized with BCG and were found in close apposition to antigen-specific CD4+ T cells.", "Consequently, blockade of skin DC traffic into DLN dramatically reduced mycobacterial entry into DLN and muted T-cell priming.", "Interestingly, DC and mycobacterial entry into the DLN was dependent on IL-1R-I, MyD88, TNFR-I and IL-12p40.", "In addition, we found using DC adoptive transfers that the requirement for MyD88 in BCG-triggered migration was not restricted to the migrating DC itself and that hematopoietic expression of MyD88 was needed in part for full-fledged migration.", "Our observations thus identify a population of DCs that contribute towards the priming of CD4+ T cells to BCG infection by transporting bacilli into the DLN in an IL-1R-MyD88-dependent manner and reveal both DC-intrinsic and -extrinsic requirements for MyD88 in DC migration."], "title": "BCG Skin Infection Triggers IL-1R-MyD88-Dependent Migration of EpCAMlow CD11bhigh Skin Dendritic cells to Draining Lymph Node During CD4+ T-Cell Priming."}
{"paper_id": 23326471, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Haematococcus pluvialis is a freshwater species of green algae and is well known for its accumulation of the strong antioxidant astaxanthin, which is used in aquaculture, various pharmaceuticals, and cosmetics. High levels of astaxanthin are present in cysts, which rapidly accumulate when the environmental conditions become unfavorable for normal cell growth. It is not understood, however, how accumulation of high levels of astaxanthin, which is soluble in oil, becomes possible during encystment. Here, we performed ultrastructural 3D reconstruction based on over 350 serial sections per cell to visualize the dynamics of astaxanthin accumulation and subcellular changes during the encystment of H. pluvialis. This study showcases the marked changes in subcellular elements, such as chloroplast degeneration, in the transition from green coccoid cells to red cyst cells during encystment. In green coccoid cells, chloroplasts accounted for 41.7% of the total cell volume, whereas the relative volume of astaxanthin was very low (0.2%). In contrast, oil droplets containing astaxanthin predominated in cyst cells (52.2%), in which the total chloroplast volume was markedly decreased (9.7%). Volumetric observations also demonstrated that the relative volumes of the cell wall, starch grains, pyrenoids, mitochondria, the Golgi apparatus, and the nucleus in a cyst cell are smaller than those in green coccid cells. Our data indicated that chloroplasts are degraded, resulting in a net-like morphology, but do not completely disappear, even at the red cyst stage.", "journal": "PloS one", "sentences": ["Haematococcus pluvialis is a freshwater species of green algae and is well known for its accumulation of the strong antioxidant astaxanthin, which is used in aquaculture, various pharmaceuticals, and cosmetics.", "High levels of astaxanthin are present in cysts, which rapidly accumulate when the environmental conditions become unfavorable for normal cell growth.", "It is not understood, however, how accumulation of high levels of astaxanthin, which is soluble in oil, becomes possible during encystment.", "Here, we performed ultrastructural 3D reconstruction based on over 350 serial sections per cell to visualize the dynamics of astaxanthin accumulation and subcellular changes during the encystment of H. pluvialis.", "This study showcases the marked changes in subcellular elements, such as chloroplast degeneration, in the transition from green coccoid cells to red cyst cells during encystment.", "In green coccoid cells, chloroplasts accounted for 41.7% of the total cell volume, whereas the relative volume of astaxanthin was very low (0.2%).", "In contrast, oil droplets containing astaxanthin predominated in cyst cells (52.2%), in which the total chloroplast volume was markedly decreased (9.7%).", "Volumetric observations also demonstrated that the relative volumes of the cell wall, starch grains, pyrenoids, mitochondria, the Golgi apparatus, and the nucleus in a cyst cell are smaller than those in green coccid cells.", "Our data indicated that chloroplasts are degraded, resulting in a net-like morphology, but do not completely disappear, even at the red cyst stage."], "title": "Three-dimensional ultrastructural study of oil and astaxanthin accumulation during encystment in the green alga Haematococcus pluvialis."}
{"paper_id": 25143289, "labels": ["0", "1", "0", "1", "0"], "abstract": "UNLABELLED\nHPG Aligner applies suffix arrays for DNA read mapping. This implementation produces a highly sensitive and extremely fast mapping of DNA reads that scales up almost linearly with read length. The approach presented here is faster (over 20\u00d7 for long reads) and more sensitive (over 98% in a wide range of read lengths) than the current state-of-the-art mappers. HPG Aligner is not only an optimal alternative for current sequencers but also the only solution available to cope with longer reads and growing throughputs produced by forthcoming sequencing technologies.\n\n\nAVAILABILITY AND IMPLEMENTATION\nhttps://github.com/opencb/hpg-aligner.", "journal": "Bioinformatics (Oxford, England)", "sentences": ["UNLABELLED\nHPG Aligner applies suffix arrays for DNA read mapping.", "This implementation produces a highly sensitive and extremely fast mapping of DNA reads that scales up almost linearly with read length.", "The approach presented here is faster (over 20\u00d7 for long reads) and more sensitive (over 98% in a wide range of read lengths) than the current state-of-the-art mappers.", "HPG Aligner is not only an optimal alternative for current sequencers but also the only solution available to cope with longer reads and growing throughputs produced by forthcoming sequencing technologies.", "AVAILABILITY AND IMPLEMENTATION\nhttps://github.com/opencb/hpg-aligner."], "title": "Acceleration of short and long DNA read mapping without loss of accuracy using suffix array."}
{"paper_id": 26261509, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Clear cell renal cell carcinoma (ccRCC) is one of the most common kidney cancers; epithelial-mesenchymal transition (EMT) is associated with carcinoma invasion and metastasis. There have been several studies about the molecular regulation of EMT, but the relationship between histone demethylase and EMT is little known. Here, we reported KDM6B has high expression level in ccRCC and is positively correlated with poor ccRCC prognosis. KDM6B, also known as JMJD3, is a histone demethylase, can remove repressive histone H3K27me3 marks from chromatin, thereby activating gene expression. We found that the knockdown of KDM6B could inhibit ccRCC tumorigenesis in vitro; furthermore, KDM6B could induce EMT in ccRCC cells by activating the expression of master transcription factor SLUG. ChIP assays revealed that KDM6B stimulated SLUG expression by demethylate histone H3K27me3. The knockdown of KDM6B strongly inhibited ccRCC cell invasion in vitro, while the overexpression of KDM6B shown the opposite trend. Meanwhile, our analysis of the ccRCC tissue found that KDM6B expression was significantly corresponded with lymph node metastasis. Together, our data provide a novel epigenetic mechanism regulating tumor cell invasion and EMT, and provide a biomolecule for ccRCC diagnosis and prognosis.", "journal": "International journal of clinical and experimental pathology", "sentences": ["Clear cell renal cell carcinoma (ccRCC) is one of the most common kidney cancers; epithelial-mesenchymal transition (EMT) is associated with carcinoma invasion and metastasis.", "There have been several studies about the molecular regulation of EMT, but the relationship between histone demethylase and EMT is little known.", "Here, we reported KDM6B has high expression level in ccRCC and is positively correlated with poor ccRCC prognosis.", "KDM6B, also known as JMJD3, is a histone demethylase, can remove repressive histone H3K27me3 marks from chromatin, thereby activating gene expression.", "We found that the knockdown of KDM6B could inhibit ccRCC tumorigenesis in vitro; furthermore, KDM6B could induce EMT in ccRCC cells by activating the expression of master transcription factor SLUG.", "ChIP assays revealed that KDM6B stimulated SLUG expression by demethylate histone H3K27me3.", "The knockdown of KDM6B strongly inhibited ccRCC cell invasion in vitro, while the overexpression of KDM6B shown the opposite trend.", "Meanwhile, our analysis of the ccRCC tissue found that KDM6B expression was significantly corresponded with lymph node metastasis.", "Together, our data provide a novel epigenetic mechanism regulating tumor cell invasion and EMT, and provide a biomolecule for ccRCC diagnosis and prognosis."], "title": "KDM6B induces epithelial-mesenchymal transition and enhances clear cell renal cell carcinoma metastasis through the activation of SLUG."}
{"paper_id": 22586214, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The corticospinal tract (CST) is a major descending pathway contributing to the control of voluntary movement in mammals. During the last decades anatomical and electrophysiological studies have demonstrated significant reorganization in the CST after spinal cord injury (SCI) in animals and humans. In animal models of SCI, anatomical evidence showed corticospinal sprouts rostral and caudal to the lesion and their integration into intraspinal axonal circuits. Electrophysiological data suggested that indirect connections from the primary motor cortex to forelimb motoneurons, via brainstem nuclei and spinal cord interneurons, or direct connections from slow uninjured corticospinal axons, might contribute to the control of movement after a CST injury. In humans with SCI, post mortem spinal cord tissue revealed anatomical changes in the CST some of which were similar but others markedly different from those found in animal models of SCI. Human electrophysiological studies have provided ample evidence for corticospinal reorganization after SCI that may contribute to functional recovery. Together these studies have revealed a large plastic capacity of the CST after SCI. There is also a limited understanding of the relationship between anatomical and electrophysiological changes in the CST and control of movement after SCI. Increasing our knowledge of the role of CST plasticity in functional restoration after SCI may support the development of more effective repair strategies.", "journal": "The Journal of physiology", "sentences": ["The corticospinal tract (CST) is a major descending pathway contributing to the control of voluntary movement in mammals.", "During the last decades anatomical and electrophysiological studies have demonstrated significant reorganization in the CST after spinal cord injury (SCI) in animals and humans.", "In animal models of SCI, anatomical evidence showed corticospinal sprouts rostral and caudal to the lesion and their integration into intraspinal axonal circuits.", "Electrophysiological data suggested that indirect connections from the primary motor cortex to forelimb motoneurons, via brainstem nuclei and spinal cord interneurons, or direct connections from slow uninjured corticospinal axons, might contribute to the control of movement after a CST injury.", "In humans with SCI, post mortem spinal cord tissue revealed anatomical changes in the CST some of which were similar but others markedly different from those found in animal models of SCI.", "Human electrophysiological studies have provided ample evidence for corticospinal reorganization after SCI that may contribute to functional recovery.", "Together these studies have revealed a large plastic capacity of the CST after SCI.", "There is also a limited understanding of the relationship between anatomical and electrophysiological changes in the CST and control of movement after SCI.", "Increasing our knowledge of the role of CST plasticity in functional restoration after SCI may support the development of more effective repair strategies."], "title": "Corticospinal reorganization after spinal cord injury."}
{"paper_id": 26407240, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The missing human proteome comprises predicted protein-coding genes with no credible protein level evidence detected so far and constitutes ~18% of the human protein coding genes (neXtProt release 19/9/2014). The missing proteins may be of pharmacological interest as many of these are membrane receptors, thus requiring comprehensive characterization. In the present study, we explored various computational parameters, crucial during protein searches from tandem mass spectrometry (MS) data, for their impact on missing protein identification. Variables taken into consideration are differences in search database composition, shared peptides, semitryptic searches, post-translational modifications (PTMs), and transcriptome guided proteogenomic searches. We used a multialgorithmic approach for protein detection from publicly available mass spectra from recent studies covering diverse human tissues and cell types. Using the aforementioned approaches, we successfully detected 24 missing proteins (22-PE2, 1-PE4, and 1-PE5). Maximum of these identifications could be attributed to differences in reference proteome databases, exemplifying use of a single standard database for human protein detection from MS data. Our results suggest that search strategies with modified parameters can be rewarding alternatives for extensive profiling of missing proteins. We conclude that using complementary spectral data searches incorporating different parameters like PTMs, against a comprehensive and compact search database, might lead to discoveries of the proteins attributed so far as the missing human proteome.", "journal": "Journal of proteome research", "sentences": ["The missing human proteome comprises predicted protein-coding genes with no credible protein level evidence detected so far and constitutes ~18% of the human protein coding genes (neXtProt release 19/9/2014).", "The missing proteins may be of pharmacological interest as many of these are membrane receptors, thus requiring comprehensive characterization.", "In the present study, we explored various computational parameters, crucial during protein searches from tandem mass spectrometry (MS) data, for their impact on missing protein identification.", "Variables taken into consideration are differences in search database composition, shared peptides, semitryptic searches, post-translational modifications (PTMs), and transcriptome guided proteogenomic searches.", "We used a multialgorithmic approach for protein detection from publicly available mass spectra from recent studies covering diverse human tissues and cell types.", "Using the aforementioned approaches, we successfully detected 24 missing proteins (22-PE2, 1-PE4, and 1-PE5).", "Maximum of these identifications could be attributed to differences in reference proteome databases, exemplifying use of a single standard database for human protein detection from MS data.", "Our results suggest that search strategies with modified parameters can be rewarding alternatives for extensive profiling of missing proteins.", "We conclude that using complementary spectral data searches incorporating different parameters like PTMs, against a comprehensive and compact search database, might lead to discoveries of the proteins attributed so far as the missing human proteome."], "title": "Probing the Missing Human Proteome: A Computational Perspective."}
{"paper_id": 26263196, "labels": ["0", "0", "0", "0", "0", "0", "1", "0", "1", "1"], "abstract": "Actinobacillus pleuropneumoniae, Actinobacillus suis, and Haemophilus parasuis are bacterial pathogens from the upper respiratory tract that are responsible for a substantial burden of porcine disease. Although reduction of disease has been accomplished by intensive management practices, immunization remains an important strategy for disease prevention, particularly when intensive management practices are not feasible or suitable. An attractive target for vaccine development is the surface receptor involved in acquiring iron from host transferrin, since it is common to all three pathogenic species and has been shown to be essential for survival and disease causation. It has also recently been demonstrated that an engineered antigen derived from the lipoprotein component of the receptor, transferrin-binding protein B (TbpB), was more effective at preventing infection by H. parasuis than a commercial vaccine product. This study was initiated to explore the genetic and immunogenic diversity of the transferrin receptor system from these species. Nucleic acid sequences were obtained from a geographically and temporally diverse collection of isolates, consisting of 41 A. pleuropneumoniae strains, 30 H. parasuis strains, and 2 A. suis strains. Phylogenetic analyses demonstrated that the receptor protein sequences cluster independently of species, suggesting that there is genetic exchange between these species such that receptor-based vaccines should logically target all three species. To evaluate the cross-reactive response of TbpB-derived antigens, pigs were immunized with the intact TbpB, the TbpB N-lobe and the TbpB C-lobe from A. pleuropneumoniae strain H49 and the resulting sera were tested against a representative panel of TbpBs; demonstrating that the C-lobe induces a broadly cross-reactive response. Overall our results indicate that there is a common reservoir for transferrin receptor antigenic variation amongst these pathogens. While this could present a challenge to future vaccine development, our results suggest a rationally designed TbpB-based vaccine may provide protection against all three pathogens.", "journal": "Vaccine", "sentences": ["Actinobacillus pleuropneumoniae, Actinobacillus suis, and Haemophilus parasuis are bacterial pathogens from the upper respiratory tract that are responsible for a substantial burden of porcine disease.", "Although reduction of disease has been accomplished by intensive management practices, immunization remains an important strategy for disease prevention, particularly when intensive management practices are not feasible or suitable.", "An attractive target for vaccine development is the surface receptor involved in acquiring iron from host transferrin, since it is common to all three pathogenic species and has been shown to be essential for survival and disease causation.", "It has also recently been demonstrated that an engineered antigen derived from the lipoprotein component of the receptor, transferrin-binding protein B (TbpB), was more effective at preventing infection by H. parasuis than a commercial vaccine product.", "This study was initiated to explore the genetic and immunogenic diversity of the transferrin receptor system from these species.", "Nucleic acid sequences were obtained from a geographically and temporally diverse collection of isolates, consisting of 41 A. pleuropneumoniae strains, 30 H. parasuis strains, and 2 A. suis strains.", "Phylogenetic analyses demonstrated that the receptor protein sequences cluster independently of species, suggesting that there is genetic exchange between these species such that receptor-based vaccines should logically target all three species.", "To evaluate the cross-reactive response of TbpB-derived antigens, pigs were immunized with the intact TbpB, the TbpB N-lobe and the TbpB C-lobe from A. pleuropneumoniae strain H49 and the resulting sera were tested against a representative panel of TbpBs; demonstrating that the C-lobe induces a broadly cross-reactive response.", "Overall our results indicate that there is a common reservoir for transferrin receptor antigenic variation amongst these pathogens.", "While this could present a challenge to future vaccine development, our results suggest a rationally designed TbpB-based vaccine may provide protection against all three pathogens."], "title": "Sequence and structural diversity of transferrin receptors in Gram-negative porcine pathogens."}
{"paper_id": 22720097, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "The risk of human infection with sylvatic chikungunya (CHIKV) virus was assessed in a focus of sylvatic arbovirus circulation in Senegal by investigating distribution and abundance of anthropophilic Aedes mosquitoes, as well as the abundance and distribution of CHIKV in these mosquitoes. A 1650 km(2) area was classified into five land cover classes: forest, barren, savanna, agriculture and village. A total of 39,799 mosquitoes was sampled from all classes using human landing collections between June 2009 and January 2010. Mosquito diversity was extremely high, and overall vector abundance peaked at the start of the rainy season. CHIKV was detected in 42 mosquito pools. Our data suggest that Aedes furcifer, which occurred abundantly in all land cover classes and landed frequently on humans in villages outside of houses, is probably the major bridge vector responsible for the spillover of sylvatic CHIKV to humans.", "journal": "PLoS neglected tropical diseases", "sentences": ["The risk of human infection with sylvatic chikungunya (CHIKV) virus was assessed in a focus of sylvatic arbovirus circulation in Senegal by investigating distribution and abundance of anthropophilic Aedes mosquitoes, as well as the abundance and distribution of CHIKV in these mosquitoes.", "A 1650 km(2) area was classified into five land cover classes: forest, barren, savanna, agriculture and village.", "A total of 39,799 mosquitoes was sampled from all classes using human landing collections between June 2009 and January 2010.", "Mosquito diversity was extremely high, and overall vector abundance peaked at the start of the rainy season.", "CHIKV was detected in 42 mosquito pools.", "Our data suggest that Aedes furcifer, which occurred abundantly in all land cover classes and landed frequently on humans in villages outside of houses, is probably the major bridge vector responsible for the spillover of sylvatic CHIKV to humans."], "title": "Landscape ecology of sylvatic chikungunya virus and mosquito vectors in southeastern Senegal."}
{"paper_id": 24300855, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "Despite the damaging effect on tissues at a high concentration, it has been gradually established that oxidative stress plays a positive role during angiogenesis. In adults, physiological or pathological angiogenesis is initiated by tissue demands for oxygen and nutrients, resulting in a hypoxia/reoxygenation cycle, which, in turn promotes the formation of reactive oxygen species (ROS). The ROS can be generated either endogenously, through mitochondrial electron transport chain reactions and nicotinamide adenine dinucleotide phosphate oxidase, or exogenously, resulting from exposure to environmental agents, such as ultraviolet or ionizing radiation. In many conditions, ROS promotes angiogenesis, either directly or via the generation of active oxidation products, including peroxidized lipids. The latter lipid metabolites are generated in excess during atherosclerosis, thereby linking atherogenic processes and pathological angiogenesis. Although the main mechanism of oxidative stress-induced angiogenesis involves hypoxia-inducible factor/vascular endothelial growth factor (VEGF) signaling, recent studies have identified several pathways that are VEGF-independent. This review aims to provide a summary of the past and present views on the role of oxidative stress as a mediator and modulator of angiogenesis, and to highlight newly identified mechanisms.", "journal": "Blood", "sentences": ["Despite the damaging effect on tissues at a high concentration, it has been gradually established that oxidative stress plays a positive role during angiogenesis.", "In adults, physiological or pathological angiogenesis is initiated by tissue demands for oxygen and nutrients, resulting in a hypoxia/reoxygenation cycle, which, in turn promotes the formation of reactive oxygen species (ROS).", "The ROS can be generated either endogenously, through mitochondrial electron transport chain reactions and nicotinamide adenine dinucleotide phosphate oxidase, or exogenously, resulting from exposure to environmental agents, such as ultraviolet or ionizing radiation.", "In many conditions, ROS promotes angiogenesis, either directly or via the generation of active oxidation products, including peroxidized lipids.", "The latter lipid metabolites are generated in excess during atherosclerosis, thereby linking atherogenic processes and pathological angiogenesis.", "Although the main mechanism of oxidative stress-induced angiogenesis involves hypoxia-inducible factor/vascular endothelial growth factor (VEGF) signaling, recent studies have identified several pathways that are VEGF-independent.", "This review aims to provide a summary of the past and present views on the role of oxidative stress as a mediator and modulator of angiogenesis, and to highlight newly identified mechanisms."], "title": "Oxidative stress in angiogenesis and vascular disease."}
{"paper_id": 26553850, "labels": ["0", "0", "1", "0", "0", "1", "0", "0", "0", "1"], "abstract": "UNLABELLED\nThe GlnPQ transporter from Lactococcus lactis has the remarkable feature of having two substrate-binding domains (SBDs) fused to the N terminus of the transmembrane domain (TMD), and thus four SBDs are present in the homodimeric complex. Although X-ray structures and ligand binding data are available for both SBDs, little is known of how different amino acids compete with each other for transport via GlnPQ. Here we show GlnPQ has a broader substrate specificity than previously thought, with the ability to take up asparagine, glutamine, and glutamic acid, albeit via different routes and with different affinities. Asparagine and glutamine compete with each other at the level of binding to SBD1 and SBD2 (with differences in dissociation constant), but at the same time SBD1 and SBD2 compete with each other at the level of interaction with the translocator domain (with differences in affinity constant and rate of transport). Although glutamine transport via SBD1 is outcompeted by physiological concentrations of asparagine, SBD2 ensures high rates of import of the essential amino acid glutamine. Taken together, this study demonstrates that even in the presence of competing asparagine concentrations, GlnPQ has a high capacity to transport glutamine, which matches the high needs of the cell for glutamine and glutamate.\n\n\nIMPORTANCE\nGlnPQ is an ATP-binding cassette (ABC) transporter for glutamine, glutamic acid, and asparagine. The system is essential in various Gram-positive bacteria, including L. lactis and several pathogens. Here we show how the amino acids compete with each other for binding to the multiple SBDs of GlnPQ and how these SBDs compete with each other for substrate delivery to the transporter. Overall, our results show that GlnPQ has evolved to transport diverse substrates via different paths and to optimally acquire the abundant and essential amino acid glutamine.", "journal": "Journal of bacteriology", "sentences": ["UNLABELLED\nThe GlnPQ transporter from Lactococcus lactis has the remarkable feature of having two substrate-binding domains (SBDs) fused to the N terminus of the transmembrane domain (TMD), and thus four SBDs are present in the homodimeric complex.", "Although X-ray structures and ligand binding data are available for both SBDs, little is known of how different amino acids compete with each other for transport via GlnPQ.", "Here we show GlnPQ has a broader substrate specificity than previously thought, with the ability to take up asparagine, glutamine, and glutamic acid, albeit via different routes and with different affinities.", "Asparagine and glutamine compete with each other at the level of binding to SBD1 and SBD2 (with differences in dissociation constant), but at the same time SBD1 and SBD2 compete with each other at the level of interaction with the translocator domain (with differences in affinity constant and rate of transport).", "Although glutamine transport via SBD1 is outcompeted by physiological concentrations of asparagine, SBD2 ensures high rates of import of the essential amino acid glutamine.", "Taken together, this study demonstrates that even in the presence of competing asparagine concentrations, GlnPQ has a high capacity to transport glutamine, which matches the high needs of the cell for glutamine and glutamate.", "IMPORTANCE\nGlnPQ is an ATP-binding cassette (ABC) transporter for glutamine, glutamic acid, and asparagine.", "The system is essential in various Gram-positive bacteria, including L. lactis and several pathogens.", "Here we show how the amino acids compete with each other for binding to the multiple SBDs of GlnPQ and how these SBDs compete with each other for substrate delivery to the transporter.", "Overall, our results show that GlnPQ has evolved to transport diverse substrates via different paths and to optimally acquire the abundant and essential amino acid glutamine."], "title": "Relative Rates of Amino Acid Import via the ABC Transporter GlnPQ Determine the Growth Performance of Lactococcus lactis."}
{"paper_id": 22545086, "labels": ["0", "0", "0", "1", "1", "1", "1", "1"], "abstract": "Species that differ in their social system, and thus in traits such as group size and dispersal timing, may differ in their use of resources along spatial, temporal, or dietary dimensions. The role of sociality in creating differences in habitat use is best explored by studying closely related species or socially polymorphic species that differ in their social system, but share a common environment. Here we investigate whether five sympatric Anelosimus spider species that range from nearly solitary to highly social differ in their use of space and in their phenology as a function of their social system. By studying these species in Serra do Japi, Brazil, we find that the more social species, which form larger, longer-lived colonies, tend to live inside the forest, where sturdier, longer lasting vegetation is likely to offer better support for their nests. The less social species, which form single-family groups, in contrast, tend to occur on the forest edge where the vegetation is less robust. Within these two microhabitats, species with longer-lived colonies tend to occupy the potentially more stable positions closer to the core of the plants, while those with smaller and shorter-lived colonies build their nests towards the branch tips. The species further separate in their use of common habitat due to differences in the timing of their reproductive season. These patterns of habitat use suggest that the degree of sociality can enable otherwise similar species to differ from one another in ways that may facilitate their co-occurrence in a shared environment, a possibility that deserves further consideration.", "journal": "PloS one", "sentences": ["Species that differ in their social system, and thus in traits such as group size and dispersal timing, may differ in their use of resources along spatial, temporal, or dietary dimensions.", "The role of sociality in creating differences in habitat use is best explored by studying closely related species or socially polymorphic species that differ in their social system, but share a common environment.", "Here we investigate whether five sympatric Anelosimus spider species that range from nearly solitary to highly social differ in their use of space and in their phenology as a function of their social system.", "By studying these species in Serra do Japi, Brazil, we find that the more social species, which form larger, longer-lived colonies, tend to live inside the forest, where sturdier, longer lasting vegetation is likely to offer better support for their nests.", "The less social species, which form single-family groups, in contrast, tend to occur on the forest edge where the vegetation is less robust.", "Within these two microhabitats, species with longer-lived colonies tend to occupy the potentially more stable positions closer to the core of the plants, while those with smaller and shorter-lived colonies build their nests towards the branch tips.", "The species further separate in their use of common habitat due to differences in the timing of their reproductive season.", "These patterns of habitat use suggest that the degree of sociality can enable otherwise similar species to differ from one another in ways that may facilitate their co-occurrence in a shared environment, a possibility that deserves further consideration."], "title": "Spatio-temporal differentiation and sociality in spiders."}
{"paper_id": 24752149, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The measurement of free thyroxine concentration in serum is considered to be an essential indicator of thyroid function. Here, a novel enzyme-free sandwich electrochemical immunosensor for the detection of FT4 antigen based on the immobilization of primary antibody (Ab1) on three dimensional ordered macroporous chitosan-Au nanoparticles hybrid (3DOM CS-AuNPs) film electrode, and magnetic multiwall carbon nanotubes (MMWCNTs) were used as label of secondary antibody (Ab2). The 3DOM CS-AuNPs film electrode was constructed by one-step electrodeposition of CS-AuNPs composite onto Au electrode with silica opal template. MMWCNTs were prepared by chemical co-precipitation of Fe(2+) and Fe(3+) salts on carboxylated MWCNTs. Ru(bpy)3(2+) labeled anti-FT4 (Ru(bpy)3(2+)-Ab2) was covalently attached to MMWCNTs through the formation of amide bond between the carboxylic groups of MWCNTs and the amine groups of antibody. Under the optimal conditions, FT4 was detected in a concentration range from 0.71 fg mL(-1) to 1.15 pg mL(-1) with a correlation coefficient of 0.998 and a detection limit of 0.20 fg mL(-1). Moreover, the immunosensor showed excellent selectivity, good stability, satisfactory reproducibility and regeneration. Importantly, the developed method was used to assay clinical serum specimens, achieving a good relation with those obtained from the commercialized electrochemiluminescent method.", "journal": "Biosensors & bioelectronics", "sentences": ["The measurement of free thyroxine concentration in serum is considered to be an essential indicator of thyroid function.", "Here, a novel enzyme-free sandwich electrochemical immunosensor for the detection of FT4 antigen based on the immobilization of primary antibody (Ab1) on three dimensional ordered macroporous chitosan-Au nanoparticles hybrid (3DOM CS-AuNPs) film electrode, and magnetic multiwall carbon nanotubes (MMWCNTs) were used as label of secondary antibody (Ab2).", "The 3DOM CS-AuNPs film electrode was constructed by one-step electrodeposition of CS-AuNPs composite onto Au electrode with silica opal template.", "MMWCNTs were prepared by chemical co-precipitation of Fe(2+) and Fe(3+) salts on carboxylated MWCNTs.", "Ru(bpy)3(2+) labeled anti-FT4 (Ru(bpy)3(2+)-Ab2) was covalently attached to MMWCNTs through the formation of amide bond between the carboxylic groups of MWCNTs and the amine groups of antibody.", "Under the optimal conditions, FT4 was detected in a concentration range from 0.71 fg mL(-1) to 1.15 pg mL(-1) with a correlation coefficient of 0.998 and a detection limit of 0.20 fg mL(-1).", "Moreover, the immunosensor showed excellent selectivity, good stability, satisfactory reproducibility and regeneration.", "Importantly, the developed method was used to assay clinical serum specimens, achieving a good relation with those obtained from the commercialized electrochemiluminescent method."], "title": "Ultrasensitive enzyme-free electrochemical immunoassay for free thyroxine based on three dimensionally ordered macroporous chitosan-Au nanoparticles hybrid film."}
{"paper_id": 27145126, "labels": ["0", "0", "0", "0", "1", "0", "0", "0", "0", "1"], "abstract": "The evolutionary success of beetles and numerous other terrestrial insects is generally attributed to co-radiation with flowering plants but most studies have focused on herbivorous or pollinating insects. Non-herbivores represent a significant proportion of beetle diversity yet potential factors that influence their diversification have been largely unexamined. In the present study, we examine the factors driving diversification within the Scarabaeidae, a speciose beetle family with a range of both herbivorous and non-herbivorous ecologies. In particular, it has been long debated whether the key event in the evolution of dung beetles (Scarabaeidae: Scarabaeinae) was an adaptation to feeding on dinosaur or mammalian dung. Here we present molecular evidence to show that the origin of dung beetles occurred in the middle of the Cretaceous, likely in association with dinosaur dung, but more surprisingly the timing is consistent with the rise of the angiosperms. We hypothesize that the switch in dinosaur diet to incorporate more nutritious and less fibrous angiosperm foliage provided a palatable dung source that ultimately created a new niche for diversification. Given the well-accepted mass extinction of non-avian dinosaurs at the Cretaceous-Paleogene boundary, we examine a potential co-extinction of dung beetles due to the loss of an important evolutionary resource, i.e., dinosaur dung. The biogeography of dung beetles is also examined to explore the previously proposed \"out of Africa\" hypothesis. Given the inferred age of Scarabaeinae as originating in the Lower Cretaceous, the major radiation of dung feeders prior to the Cenomanian, and the early divergence of both African and Gondwanan lineages, we hypothesise that that faunal exchange between Africa and Gondwanaland occurred during the earliest evolution of the Scarabaeinae. Therefore we propose that both Gondwanan vicariance and dispersal of African lineages is responsible for present day distribution of scarabaeine dung beetles and provide examples.", "journal": "PloS one", "sentences": ["The evolutionary success of beetles and numerous other terrestrial insects is generally attributed to co-radiation with flowering plants but most studies have focused on herbivorous or pollinating insects.", "Non-herbivores represent a significant proportion of beetle diversity yet potential factors that influence their diversification have been largely unexamined.", "In the present study, we examine the factors driving diversification within the Scarabaeidae, a speciose beetle family with a range of both herbivorous and non-herbivorous ecologies.", "In particular, it has been long debated whether the key event in the evolution of dung beetles (Scarabaeidae: Scarabaeinae) was an adaptation to feeding on dinosaur or mammalian dung.", "Here we present molecular evidence to show that the origin of dung beetles occurred in the middle of the Cretaceous, likely in association with dinosaur dung, but more surprisingly the timing is consistent with the rise of the angiosperms.", "We hypothesize that the switch in dinosaur diet to incorporate more nutritious and less fibrous angiosperm foliage provided a palatable dung source that ultimately created a new niche for diversification.", "Given the well-accepted mass extinction of non-avian dinosaurs at the Cretaceous-Paleogene boundary, we examine a potential co-extinction of dung beetles due to the loss of an important evolutionary resource, i.e., dinosaur dung.", "The biogeography of dung beetles is also examined to explore the previously proposed \"out of Africa\" hypothesis.", "Given the inferred age of Scarabaeinae as originating in the Lower Cretaceous, the major radiation of dung feeders prior to the Cenomanian, and the early divergence of both African and Gondwanan lineages, we hypothesise that that faunal exchange between Africa and Gondwanaland occurred during the earliest evolution of the Scarabaeinae.", "Therefore we propose that both Gondwanan vicariance and dispersal of African lineages is responsible for present day distribution of scarabaeine dung beetles and provide examples."], "title": "If Dung Beetles (Scarabaeidae: Scarabaeinae) Arose in Association with Dinosaurs, Did They Also Suffer a Mass Co-Extinction at the K-Pg Boundary?"}
{"paper_id": 27225554, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Global healthcare systems are struggling with the enormous burden associated with infectious diseases, as well as the incessant rise of antimicrobial resistance. In order to adequately address these issues, there is an urgent need for rapid and accurate infectious disease diagnostics. The H2020 project DIAGORAS aims at diagnosing oral and respiratory tract infections using a fully integrated, automated and user-friendly platform for physicians' offices, schools, elderly care units, community settings, etc. Oral diseases (periodontitis, dental caries) will be detected via multiplexed, quantitative analysis of salivary markers (bacterial DNA and host response proteins) for early prevention and personalised monitoring. Respiratory Tract Infections will be diagnosed by means of DNA/RNA differentiation so as to identify their bacterial or viral nature. Together with antibiotic resistance screening on the same platform, a more efficient treatment management is expected at the point-of-care. At the heart of DIAGORAS lies a centrifugal microfluidic platform (LabDisk and associated processing device) integrating all components and assays for a fully automated analysis. The project involves an interface with a clinical algorithm for the comprehensive presentation of results to end-users, thereby increasing the platform's clinical utility. DIAGORAS' performance will be validated at clinical settings and compared with gold standards.", "journal": "Studies in health technology and informatics", "sentences": ["Global healthcare systems are struggling with the enormous burden associated with infectious diseases, as well as the incessant rise of antimicrobial resistance.", "In order to adequately address these issues, there is an urgent need for rapid and accurate infectious disease diagnostics.", "The H2020 project DIAGORAS aims at diagnosing oral and respiratory tract infections using a fully integrated, automated and user-friendly platform for physicians' offices, schools, elderly care units, community settings, etc.", "Oral diseases (periodontitis, dental caries) will be detected via multiplexed, quantitative analysis of salivary markers (bacterial DNA and host response proteins) for early prevention and personalised monitoring.", "Respiratory Tract Infections will be diagnosed by means of DNA/RNA differentiation so as to identify their bacterial or viral nature.", "Together with antibiotic resistance screening on the same platform, a more efficient treatment management is expected at the point-of-care.", "At the heart of DIAGORAS lies a centrifugal microfluidic platform (LabDisk and associated processing device) integrating all components and assays for a fully automated analysis.", "The project involves an interface with a clinical algorithm for the comprehensive presentation of results to end-users, thereby increasing the platform's clinical utility.", "DIAGORAS' performance will be validated at clinical settings and compared with gold standards."], "title": "Chair/bedside diagnosis of oral and respiratory tract infections, and identification of antibiotic resistances for personalised monitoring and treatment."}
{"paper_id": 25611573, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele =0.70; 95% CI: 0.58-0.85; ptrend \u2009=\u20092.84 \u00d7 10(-4) ; HRheterozygotes \u2009=\u20090.71; 95% CI: 0.55-0.92; HRhomozygotes \u2009=\u20090.48; 95% CI: 0.31-0.76; p2DF \u2009=\u20091.45 \u00d7 10(-3) ). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; ptrend \u2009=\u20096.6 \u00d7 10(-4) ; HRheterozygotes \u2009=\u20090.96 95% CI: 0.90-1.03; HRhomozygotes \u2009=\u20091.21; 95% CI: 1.09-1.35; p2DF =1.25 \u00d7 10(-4) ). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662.", "journal": "International journal of cancer", "sentences": ["The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status.", "However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment.", "Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival.", "We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer.", "We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations.", "In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele =0.70; 95% CI: 0.58-0.85; ptrend \u2009=\u20092.84 \u00d7 10(-4) ; HRheterozygotes \u2009=\u20090.71; 95% CI: 0.55-0.92; HRhomozygotes \u2009=\u20090.48; 95% CI: 0.31-0.76; p2DF \u2009=\u20091.45 \u00d7 10(-3) ).", "In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C).", "In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; ptrend \u2009=\u20096.6 \u00d7 10(-4) ; HRheterozygotes \u2009=\u20090.96 95% CI: 0.90-1.03; HRhomozygotes \u2009=\u20091.21; 95% CI: 1.09-1.35; p2DF =1.25 \u00d7 10(-4) ).", "In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662."], "title": "Association of breast cancer risk loci with breast cancer survival."}
{"paper_id": 26076024, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "When sounds occur with temporally structured patterns, we can feel a rhythm. To memorize a rhythm, perception of its temporal patterns and organization of them into a hierarchically structured sequence are necessary. On the other hand, rhythm perception can often cause unintentional body movements. Thus, we hypothesized that rhythm information can be manifested in two different ways; temporal and motor representations. The motor representation depends on effectors, such as the finger or foot, whereas the temporal representation is effector-independent. We tested our hypothesis with a working memory paradigm to elucidate neuronal correlates of temporal or motor representation of rhythm and to reveal the neural networks associated with these representations. We measured brain activity by fMRI while participants memorized rhythms and reproduced them by tapping with the right finger, left finger, or foot, or by articulation. The right inferior frontal gyrus and the inferior parietal lobule exhibited significant effector-independent activations during encoding and retrieval of rhythm information, whereas the left inferior parietal lobule and supplementary motor area (SMA) showed effector-dependent activations during retrieval. These results suggest that temporal sequences of rhythm are probably represented in the right fronto-parietal network, whereas motor sequences of rhythm can be represented in the SMA-parietal network.", "journal": "PloS one", "sentences": ["When sounds occur with temporally structured patterns, we can feel a rhythm.", "To memorize a rhythm, perception of its temporal patterns and organization of them into a hierarchically structured sequence are necessary.", "On the other hand, rhythm perception can often cause unintentional body movements.", "Thus, we hypothesized that rhythm information can be manifested in two different ways; temporal and motor representations.", "The motor representation depends on effectors, such as the finger or foot, whereas the temporal representation is effector-independent.", "We tested our hypothesis with a working memory paradigm to elucidate neuronal correlates of temporal or motor representation of rhythm and to reveal the neural networks associated with these representations.", "We measured brain activity by fMRI while participants memorized rhythms and reproduced them by tapping with the right finger, left finger, or foot, or by articulation.", "The right inferior frontal gyrus and the inferior parietal lobule exhibited significant effector-independent activations during encoding and retrieval of rhythm information, whereas the left inferior parietal lobule and supplementary motor area (SMA) showed effector-dependent activations during retrieval.", "These results suggest that temporal sequences of rhythm are probably represented in the right fronto-parietal network, whereas motor sequences of rhythm can be represented in the SMA-parietal network."], "title": "Temporal and Motor Representation of Rhythm in Fronto-Parietal Cortical Areas: An fMRI Study."}
{"paper_id": 24807418, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Misfolded ER proteins are retrotranslocated into the cytosol for degradation via the ubiquitin-proteasome system. The human cytomegalovirus protein US11 exploits this ER-associated protein degradation (ERAD) pathway to downregulate HLA class I molecules in virus-infected cells, thereby evading elimination by cytotoxic T-lymphocytes. US11-mediated degradation of HLA class I has been instrumental in the identification of key components of mammalian ERAD, including Derlin-1, p97, VIMP and SEL1L. Despite this, the process governing retrotranslocation of the substrate is still poorly understood. Here using a high-coverage genome-wide shRNA library, we identify the uncharacterized protein TMEM129 and the ubiquitin-conjugating E2 enzyme UBE2J2 to be essential for US11-mediated HLA class I downregulation. TMEM129 is an unconventional C4C4-type RING finger E3 ubiquitin ligase that resides within a complex containing various other ERAD components, including Derlin-1, Derlin-2, VIMP and p97, indicating that TMEM129 is an integral part of the ER-resident dislocation complex mediating US11-induced HLA class I degradation.", "journal": "Nature communications", "sentences": ["Misfolded ER proteins are retrotranslocated into the cytosol for degradation via the ubiquitin-proteasome system.", "The human cytomegalovirus protein US11 exploits this ER-associated protein degradation (ERAD) pathway to downregulate HLA class I molecules in virus-infected cells, thereby evading elimination by cytotoxic T-lymphocytes.", "US11-mediated degradation of HLA class I has been instrumental in the identification of key components of mammalian ERAD, including Derlin-1, p97, VIMP and SEL1L.", "Despite this, the process governing retrotranslocation of the substrate is still poorly understood.", "Here using a high-coverage genome-wide shRNA library, we identify the uncharacterized protein TMEM129 and the ubiquitin-conjugating E2 enzyme UBE2J2 to be essential for US11-mediated HLA class I downregulation.", "TMEM129 is an unconventional C4C4-type RING finger E3 ubiquitin ligase that resides within a complex containing various other ERAD components, including Derlin-1, Derlin-2, VIMP and p97, indicating that TMEM129 is an integral part of the ER-resident dislocation complex mediating US11-induced HLA class I degradation."], "title": "A high-coverage shRNA screen identifies TMEM129 as an E3 ligase involved in ER-associated protein degradation."}
{"paper_id": 25195135, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The molecular regulation of growth of hepatocellular carcinoma (HCC) is yet to be fully clarified. Here we found a significantly higher ratio of phosphorylated \u03b2-catenin (phos-\u03b2-cat) to \u03b2-catenin (\u03b2-cat) as an indicator of an activated Wnt signaling, with significantly higher levels of c-myc and transcription factor activating protein-4 (AP-4) and a significantly lower level of p21 in the resected HCC, compared to the paired adjacent healthy hepatic tissue from the patients. Moreover, strong correlations were detected between phos-\u03b2-cat/\u03b2-cat ratio and c-myc level, between c-myc and AP-4 levels, and between AP-4 and p21 levels. These data support the presence of a Wnt/c-myc/AP-4/p21 regulation cascade in HCC as has been reported in colorectal cancer. To prove it, we overexpressed c-myc in two HCC lines, which significantly increased AP-4 level, inhibited p21 level, and then increased cell growth. Meanwhile, c-myc inhibition in these two HCC lines significantly decreased AP-4 level, increased p21 level, and then decreased cell growth. Moreover, AP-4 inhibition in c-myc-overexpressing HCC lines abolished the inhibitory effect on p21 and abolished the increase in cell growth. In line with these findings, overexpression of AP-4 in these two HCC lines significantly decreased p21 level, and then increased cell growth, while AP-4 inhibition significantly increased p21 level, and then decreased cell growth. Our results on HCC are thus consistent with the model detected in colorectal carcinoma, suggesting that Wnt signaling activated c-myc may increase HCC growth through direct inhibitory effect of AP-4 on p21. Our study thus highlights AP-4 as a novel therapeutic target for HCC.", "journal": "Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine", "sentences": ["The molecular regulation of growth of hepatocellular carcinoma (HCC) is yet to be fully clarified.", "Here we found a significantly higher ratio of phosphorylated \u03b2-catenin (phos-\u03b2-cat) to \u03b2-catenin (\u03b2-cat) as an indicator of an activated Wnt signaling, with significantly higher levels of c-myc and transcription factor activating protein-4 (AP-4) and a significantly lower level of p21 in the resected HCC, compared to the paired adjacent healthy hepatic tissue from the patients.", "Moreover, strong correlations were detected between phos-\u03b2-cat/\u03b2-cat ratio and c-myc level, between c-myc and AP-4 levels, and between AP-4 and p21 levels.", "These data support the presence of a Wnt/c-myc/AP-4/p21 regulation cascade in HCC as has been reported in colorectal cancer.", "To prove it, we overexpressed c-myc in two HCC lines, which significantly increased AP-4 level, inhibited p21 level, and then increased cell growth.", "Meanwhile, c-myc inhibition in these two HCC lines significantly decreased AP-4 level, increased p21 level, and then decreased cell growth.", "Moreover, AP-4 inhibition in c-myc-overexpressing HCC lines abolished the inhibitory effect on p21 and abolished the increase in cell growth.", "In line with these findings, overexpression of AP-4 in these two HCC lines significantly decreased p21 level, and then increased cell growth, while AP-4 inhibition significantly increased p21 level, and then decreased cell growth.", "Our results on HCC are thus consistent with the model detected in colorectal carcinoma, suggesting that Wnt signaling activated c-myc may increase HCC growth through direct inhibitory effect of AP-4 on p21.", "Our study thus highlights AP-4 as a novel therapeutic target for HCC."], "title": "Molecular mechanism of activating protein-4 regulated growth of hepatocellular carcinoma."}
{"paper_id": 27195482, "labels": ["0", "0", "0", "0", "1", "1", "1", "1", "0"], "abstract": "Adaptation is a crucial biological function possessed by many sensory systems. Early work has shown that some influential equilibrium models can achieve accurate adaptation. However, recent studies indicate that there are close relationships between adaptation and nonequilibrium. In this paper, we provide an explanation of these two seemingly contradictory results based on Markov models with relatively simple networks. We show that as the nonequilibrium driving becomes stronger, the system under consideration will undergo a phase transition along a fixed direction: from non-adaptation to simple adaptation then to oscillatory adaptation, while the transition in the opposite direction is forbidden. This indicates that although adaptation may be observed in equilibrium systems, it tends to occur in systems far away from equilibrium. In addition, we find that nonequilibrium will improve the performance of adaptation by enhancing the adaptation efficiency. All these results provide a deeper insight into the connection between adaptation and nonequilibrium. Finally, we use a more complicated network model of bacterial chemotaxis to validate the main results of this paper.", "journal": "PloS one", "sentences": ["Adaptation is a crucial biological function possessed by many sensory systems.", "Early work has shown that some influential equilibrium models can achieve accurate adaptation.", "However, recent studies indicate that there are close relationships between adaptation and nonequilibrium.", "In this paper, we provide an explanation of these two seemingly contradictory results based on Markov models with relatively simple networks.", "We show that as the nonequilibrium driving becomes stronger, the system under consideration will undergo a phase transition along a fixed direction: from non-adaptation to simple adaptation then to oscillatory adaptation, while the transition in the opposite direction is forbidden.", "This indicates that although adaptation may be observed in equilibrium systems, it tends to occur in systems far away from equilibrium.", "In addition, we find that nonequilibrium will improve the performance of adaptation by enhancing the adaptation efficiency.", "All these results provide a deeper insight into the connection between adaptation and nonequilibrium.", "Finally, we use a more complicated network model of bacterial chemotaxis to validate the main results of this paper."], "title": "Nonequilibrium Enhances Adaptation Efficiency of Stochastic Biochemical Systems."}
{"paper_id": 21690400, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "In Trimenia moorei, an extant member of the ancient angiosperm clade Austrobaileyales, we found a remarkable pattern of female gametophyte (egg-producing structure) development that strikingly resembles that of pollen tubes and their intrasexual competition within the maternal pollen tube transmitting tissues of most flowers. In contrast with most other flowering plants, in Trimenia, multiple female gametophytes are initiated at the base (chalazal end) of each ovule. Female gametophytes grow from their tips and compete over hundreds of micrometers to reach the apex of the nucellus and the site of fertilization. Here, the successful female gametophyte will mate with a pollen tube to produce an embryo and an endosperm. Moreover, the central tissue within the ovules of Trimenia, through which the embryo sacs grow, contains starch and other carbohydrates similar to the pollen tube transmitting tissues in the styles of most flowers. The pattern of female gametophyte development found in Trimenia is rare but by no means unique in angiosperms. Importantly, it seems that multiple female gametophytes are occasionally or frequently initiated in members of other ancient angiosperm lineages. The intensification of pollen tube (male gametophyte) competition and enhanced maternal selection among competing pollen tubes are considered to have been major contributors to the rise of angiosperms. Based on insights from Trimenia, we posit that prefertilization female gametophyte (egg) competition within individual ovules in addition to male gametophyte (sperm) competition and maternal mate choice may have been key features of the earliest angiosperms.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["In Trimenia moorei, an extant member of the ancient angiosperm clade Austrobaileyales, we found a remarkable pattern of female gametophyte (egg-producing structure) development that strikingly resembles that of pollen tubes and their intrasexual competition within the maternal pollen tube transmitting tissues of most flowers.", "In contrast with most other flowering plants, in Trimenia, multiple female gametophytes are initiated at the base (chalazal end) of each ovule.", "Female gametophytes grow from their tips and compete over hundreds of micrometers to reach the apex of the nucellus and the site of fertilization.", "Here, the successful female gametophyte will mate with a pollen tube to produce an embryo and an endosperm.", "Moreover, the central tissue within the ovules of Trimenia, through which the embryo sacs grow, contains starch and other carbohydrates similar to the pollen tube transmitting tissues in the styles of most flowers.", "The pattern of female gametophyte development found in Trimenia is rare but by no means unique in angiosperms.", "Importantly, it seems that multiple female gametophytes are occasionally or frequently initiated in members of other ancient angiosperm lineages.", "The intensification of pollen tube (male gametophyte) competition and enhanced maternal selection among competing pollen tubes are considered to have been major contributors to the rise of angiosperms.", "Based on insights from Trimenia, we posit that prefertilization female gametophyte (egg) competition within individual ovules in addition to male gametophyte (sperm) competition and maternal mate choice may have been key features of the earliest angiosperms."], "title": "Female gamete competition in an ancient angiosperm lineage."}
{"paper_id": 25171170, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Neurodevelopmental disruptions caused by obstetric complications play a role in the etiology of several phenotypes associated with neuropsychiatric diseases and cognitive dysfunctions. Importantly, it has been noticed that epigenetic processes occurring early in life may mediate these associations. Here, DNA methylation signatures at IGF2 (insulin-like growth factor 2) and IGF2BP1-3 (IGF2-binding proteins 1-3) were examined in a sample consisting of 34 adult monozygotic (MZ) twins informative for obstetric complications and cognitive performance. Multivariate linear regression analysis of twin data was implemented to test for associations between methylation levels and both birth weight (BW) and adult working memory (WM) performance. Familial and unique environmental factors underlying these potential relationships were evaluated. A link was detected between DNA methylation levels of two CpG sites in the IGF2BP1 gene and both BW and adult WM performance. The BW-IGF2BP1 methylation association seemed due to non-shared environmental factors influencing BW, whereas the WM-IGF2BP1 methylation relationship seemed mediated by both genes and environment. Our data is in agreement with previous evidence indicating that DNA methylation status may be related to prenatal stress and later neurocognitive phenotypes. While former reports independently detected associations between DNA methylation and either BW or WM, current results suggest that these relationships are not confounded by each other.", "journal": "PloS one", "sentences": ["Neurodevelopmental disruptions caused by obstetric complications play a role in the etiology of several phenotypes associated with neuropsychiatric diseases and cognitive dysfunctions.", "Importantly, it has been noticed that epigenetic processes occurring early in life may mediate these associations.", "Here, DNA methylation signatures at IGF2 (insulin-like growth factor 2) and IGF2BP1-3 (IGF2-binding proteins 1-3) were examined in a sample consisting of 34 adult monozygotic (MZ) twins informative for obstetric complications and cognitive performance.", "Multivariate linear regression analysis of twin data was implemented to test for associations between methylation levels and both birth weight (BW) and adult working memory (WM) performance.", "Familial and unique environmental factors underlying these potential relationships were evaluated.", "A link was detected between DNA methylation levels of two CpG sites in the IGF2BP1 gene and both BW and adult WM performance.", "The BW-IGF2BP1 methylation association seemed due to non-shared environmental factors influencing BW, whereas the WM-IGF2BP1 methylation relationship seemed mediated by both genes and environment.", "Our data is in agreement with previous evidence indicating that DNA methylation status may be related to prenatal stress and later neurocognitive phenotypes.", "While former reports independently detected associations between DNA methylation and either BW or WM, current results suggest that these relationships are not confounded by each other."], "title": "Birth weight, working memory and epigenetic signatures in IGF2 and related genes: a MZ twin study."}
{"paper_id": 19816945, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Proteins of the lysyl oxidase (LOX) family are important modulators of the extracellular matrix. However, they have an important role in the tumour development as well as in tumour progression. To evaluate the diagnostic and prognostic value of the LOX protein in oral and oropharyngeal squamous cell carcinoma (OSCC) we performed QRT-PCR and immunohistochemical analysis on two tissue microarrays (622 tissue samples in total). Significantly higher LOX expression was detected in high grade dysplastic oral mucosa as well as in OSCC when compared to normal oral mucosa (P < 0.001). High LOX expression was correlated with clinical TNM stage (P = 0.020), lymph node metastases for the entire cohort (P < 0.001), as well as in the subgroup of small primary tumours (T1/T2, P < 0.001). Moreover, high LOX expression was correlated with poor overall survival (P = 0.004) and disease specific survival (P = 0.037). In a multivariate analysis, high LOX expression was an independent prognostic factor, predicting unfavourable overall survival. In summary, LOX expression is an independent prognostic biomarker and a predictor of lymph node metastasis in OSCC. Moreover, LOX overexpression may be an early phenomenon in the pathogenesis of OSCC and thus an attractive novel target for chemopreventive and therapeutic strategies.", "journal": "International journal of cancer", "sentences": ["Proteins of the lysyl oxidase (LOX) family are important modulators of the extracellular matrix.", "However, they have an important role in the tumour development as well as in tumour progression.", "To evaluate the diagnostic and prognostic value of the LOX protein in oral and oropharyngeal squamous cell carcinoma (OSCC) we performed QRT-PCR and immunohistochemical analysis on two tissue microarrays (622 tissue samples in total).", "Significantly higher LOX expression was detected in high grade dysplastic oral mucosa as well as in OSCC when compared to normal oral mucosa (P < 0.001).", "High LOX expression was correlated with clinical TNM stage (P = 0.020), lymph node metastases for the entire cohort (P < 0.001), as well as in the subgroup of small primary tumours (T1/T2, P < 0.001).", "Moreover, high LOX expression was correlated with poor overall survival (P = 0.004) and disease specific survival (P = 0.037).", "In a multivariate analysis, high LOX expression was an independent prognostic factor, predicting unfavourable overall survival.", "In summary, LOX expression is an independent prognostic biomarker and a predictor of lymph node metastasis in OSCC.", "Moreover, LOX overexpression may be an early phenomenon in the pathogenesis of OSCC and thus an attractive novel target for chemopreventive and therapeutic strategies."], "title": "Lysyl oxidase expression is an independent marker of prognosis and a predictor of lymph node metastasis in oral and oropharyngeal squamous cell carcinoma (OSCC)."}
{"paper_id": 26849372, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Mussel seed (Mytilusgalloprovincialis) gathered from the intertidal and subtidal environments of a Galician embayment (NW, Spain) were maintained in the laboratory during five months to select fast (F) and slow (S) growing mussels. The physiological basis underlying inter-individual growth variations were compared for F and S mussels from both origins. Fast growing seemed to be a consequence of greater energy intake (20% higher clearance and ingestion rate) and higher food absorption rate coupled with low metabolic costs. The enhanced energy absorption (around 65% higher) resulted in 3 times higher Scope for Growth in F mussels (20.5\u00b14.9 J h-1) than S individuals (7.3\u00b11.1 J h-1). The higher clearance rate of F mussels appears to be linked with larger gill filtration surface compared to S mussels. Intertidal mussels showed higher food acquisition and absorption per mg of organic weight (i.e. mass-specific standardization) than subtidal mussels under the optimal feeding conditions of the laboratory. However, the enhanced feeding and digestive rates were not enough to compensate for the initial differences in tissue weight between mussels of similar shell length collected from the intertidal and subtidal environments. At the end of the experiment, subtidal individuals had higher gill efficiency, which probably lead to higher total feeding and absorption rates relative to intertidal individuals.", "journal": "PloS one", "sentences": ["Mussel seed (Mytilusgalloprovincialis) gathered from the intertidal and subtidal environments of a Galician embayment (NW, Spain) were maintained in the laboratory during five months to select fast (F) and slow (S) growing mussels.", "The physiological basis underlying inter-individual growth variations were compared for F and S mussels from both origins.", "Fast growing seemed to be a consequence of greater energy intake (20% higher clearance and ingestion rate) and higher food absorption rate coupled with low metabolic costs.", "The enhanced energy absorption (around 65% higher) resulted in 3 times higher Scope for Growth in F mussels (20.5\u00b14.9 J h-1) than S individuals (7.3\u00b11.1 J h-1).", "The higher clearance rate of F mussels appears to be linked with larger gill filtration surface compared to S mussels.", "Intertidal mussels showed higher food acquisition and absorption per mg of organic weight (i.e.", "mass-specific standardization) than subtidal mussels under the optimal feeding conditions of the laboratory.", "However, the enhanced feeding and digestive rates were not enough to compensate for the initial differences in tissue weight between mussels of similar shell length collected from the intertidal and subtidal environments.", "At the end of the experiment, subtidal individuals had higher gill efficiency, which probably lead to higher total feeding and absorption rates relative to intertidal individuals."], "title": "Flexibility of Physiological Traits Underlying Inter-Individual Growth Differences in Intertidal and Subtidal Mussels Mytilusgalloprovincialis."}
{"paper_id": 26084911, "labels": ["0", "0", "0", "1", "0", "0", "0", "1", "1"], "abstract": "Postactivation depression (PActD) of Ia afferent excitatory postsynaptic potentials (EPSPs) in spinal motoneurons results in a long-lasting depression of the stretch reflex. This phenomenon (PActD) is of clinical interest as it has been shown to be reduced in a number of spastic disorders. Using in vivo intracellular recordings of Ia EPSPs in adult mice, we demonstrate that PActD in adult (100-220 days old) C57BL/6J mice is both qualitatively and quantitatively similar to that which has been observed in larger animals with respect to both the magnitude (with \u223c20% depression of EPSPs at 0.5 ms after a train of stimuli) and the time course (returning to almost normal amplitudes by 5 ms after the train). This validates the use of mouse models to study PActD. Changes in such excitatory inputs to spinal motoneurons may have important implications for hyperreflexia and/or glutamate-induced excitotoxicity in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). With the use of the G127X SOD1 mutant mouse, an ALS model with a prolonged asymptomatic phase and fulminant symptom onset, we observed that PActD is significantly reduced at both presymptomatic (16% depression) and symptomatic (17.3% depression) time points compared with aged-matched controls (22.4% depression). The PActD reduction was not markedly altered by symptom onset. Comparing these PActD changes at the EPSP with the known effect of the depression on the monosynaptic reflex, we conclude that this is likely to have a much larger effect on the reflex itself (a 20-40% difference). Nevertheless, it should also be accounted that in aged (580 day old) C57BL/6J mice there was also a reduction in PActD although, aging is not usually associated with spasticity.", "journal": "Journal of neurophysiology", "sentences": ["Postactivation depression (PActD) of Ia afferent excitatory postsynaptic potentials (EPSPs) in spinal motoneurons results in a long-lasting depression of the stretch reflex.", "This phenomenon (PActD) is of clinical interest as it has been shown to be reduced in a number of spastic disorders.", "Using in vivo intracellular recordings of Ia EPSPs in adult mice, we demonstrate that PActD in adult (100-220 days old) C57BL/6J mice is both qualitatively and quantitatively similar to that which has been observed in larger animals with respect to both the magnitude (with \u223c20% depression of EPSPs at 0.5 ms after a train of stimuli) and the time course (returning to almost normal amplitudes by 5 ms after the train).", "This validates the use of mouse models to study PActD.", "Changes in such excitatory inputs to spinal motoneurons may have important implications for hyperreflexia and/or glutamate-induced excitotoxicity in the neurodegenerative disease amyotrophic lateral sclerosis (ALS).", "With the use of the G127X SOD1 mutant mouse, an ALS model with a prolonged asymptomatic phase and fulminant symptom onset, we observed that PActD is significantly reduced at both presymptomatic (16% depression) and symptomatic (17.3% depression) time points compared with aged-matched controls (22.4% depression).", "The PActD reduction was not markedly altered by symptom onset.", "Comparing these PActD changes at the EPSP with the known effect of the depression on the monosynaptic reflex, we conclude that this is likely to have a much larger effect on the reflex itself (a 20-40% difference).", "Nevertheless, it should also be accounted that in aged (580 day old) C57BL/6J mice there was also a reduction in PActD although, aging is not usually associated with spasticity."], "title": "Postactivation depression of the Ia EPSP in motoneurons is reduced in both the G127X SOD1 model of amyotrophic lateral sclerosis and in aged mice."}
{"paper_id": 26615198, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "A mechanism by which control DNA elements regulate transcription over large linear genomic distances is by achieving close physical proximity with genes, and looping of the intervening chromatin paths. Alterations of such regulatory 'chromatin looping' systems are likely to play a critical role in human genetic disease at large. Here, we studied the spatial organization of a \u2248790 kb locus encompassing the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Dysregulation ofCFTRis responsible for cystic fibrosis, which is the most common lethal genetic disorder in Caucasian populations.CFTRis a relatively large gene of 189 kb with a rather complex tissue-specific and temporal expression profile. We used chromatin conformation at theCFTRlocus to identify new DNA sequences that regulate its transcription. By comparing 5C chromatin interaction maps of theCFTRlocus in expressing and non-expressing human primary cells, we identified several new contact points between theCFTRpromoter and its surroundings, in addition to regions featuring previously described regulatory elements. We demonstrate that two of these novel interacting regions cooperatively increaseCFTRexpression, and suggest that the new enhancer elements located on either side of the gene are brought together through chromatin loopingviaCTCF.", "journal": "Nucleic acids research", "sentences": ["A mechanism by which control DNA elements regulate transcription over large linear genomic distances is by achieving close physical proximity with genes, and looping of the intervening chromatin paths.", "Alterations of such regulatory 'chromatin looping' systems are likely to play a critical role in human genetic disease at large.", "Here, we studied the spatial organization of a \u2248790 kb locus encompassing the cystic fibrosis transmembrane conductance regulator (CFTR) gene.", "Dysregulation ofCFTRis responsible for cystic fibrosis, which is the most common lethal genetic disorder in Caucasian populations.CFTRis a relatively large gene of 189 kb with a rather complex tissue-specific and temporal expression profile.", "We used chromatin conformation at theCFTRlocus to identify new DNA sequences that regulate its transcription.", "By comparing 5C chromatin interaction maps of theCFTRlocus in expressing and non-expressing human primary cells, we identified several new contact points between theCFTRpromoter and its surroundings, in addition to regions featuring previously described regulatory elements.", "We demonstrate that two of these novel interacting regions cooperatively increaseCFTRexpression, and suggest that the new enhancer elements located on either side of the gene are brought together through chromatin loopingviaCTCF."], "title": "Analysis of long-range interactions in primary human cells identifies cooperative CFTR regulatory elements."}
{"paper_id": 26745023, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "The free energetics of water density fluctuations near a surface, and the rare low-density fluctuations in particular, serve as reliable indicators of surface hydrophobicity; the easier it is to displace the interfacial waters, the more hydrophobic the underlying surface is. However, characterizing the free energetics of such rare fluctuations requires computationally expensive, non-Boltzmann sampling methods like umbrella sampling. This inherent computational expense associated with umbrella sampling makes it challenging to investigate the role of polarizability or electronic structure effects in influencing interfacial fluctuations. Importantly, it also limits the size of the volume, which can be used to probe interfacial fluctuations. The latter can be particularly important in characterizing the hydrophobicity of large surfaces with molecular-level heterogeneities, such as those presented by proteins. To overcome these challenges, here we present a method for the sparse sampling of water density fluctuations, which is roughly 2 orders of magnitude more efficient than umbrella sampling. We employ thermodynamic integration to estimate the free energy differences between biased ensembles, thereby circumventing the umbrella sampling requirement of overlap between adjacent biased distributions. Further, a judicious choice of the biasing potential allows such free energy differences to be estimated using short simulations, so that the free energetics of water density fluctuations are obtained using only a few, short simulations. Leveraging the efficiency of the method, we characterize water density fluctuations in the entire hydration shell of the protein, ubiquitin, a large volume containing an average of more than 600 waters.", "journal": "Journal of chemical theory and computation", "sentences": ["The free energetics of water density fluctuations near a surface, and the rare low-density fluctuations in particular, serve as reliable indicators of surface hydrophobicity; the easier it is to displace the interfacial waters, the more hydrophobic the underlying surface is.", "However, characterizing the free energetics of such rare fluctuations requires computationally expensive, non-Boltzmann sampling methods like umbrella sampling.", "This inherent computational expense associated with umbrella sampling makes it challenging to investigate the role of polarizability or electronic structure effects in influencing interfacial fluctuations.", "Importantly, it also limits the size of the volume, which can be used to probe interfacial fluctuations.", "The latter can be particularly important in characterizing the hydrophobicity of large surfaces with molecular-level heterogeneities, such as those presented by proteins.", "To overcome these challenges, here we present a method for the sparse sampling of water density fluctuations, which is roughly 2 orders of magnitude more efficient than umbrella sampling.", "We employ thermodynamic integration to estimate the free energy differences between biased ensembles, thereby circumventing the umbrella sampling requirement of overlap between adjacent biased distributions.", "Further, a judicious choice of the biasing potential allows such free energy differences to be estimated using short simulations, so that the free energetics of water density fluctuations are obtained using only a few, short simulations.", "Leveraging the efficiency of the method, we characterize water density fluctuations in the entire hydration shell of the protein, ubiquitin, a large volume containing an average of more than 600 waters."], "title": "Sparse Sampling of Water Density Fluctuations in Interfacial Environments."}
{"paper_id": 24040333, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Exogenous proteolytic enzyme supplementation is required in certain disease conditions in humans and animals and due to compelling reasons on use of more plant protein ingredients and profitability in animal feed industry. However, limitations on their utility in diet are imposed by their pH specificity, thermolabile nature, inhibition due to a variety of factors and the possibility of intestinal damage. For enhancing the efficacy and safety of exogenous trypsin, an efficient chitosan (0.04%) nanoencapsulation-based controlled delivery system was developed. An experiment was conducted for 45 days to evaluate nanoencapsulated trypsin (0.01% and 0.02%) along with 0.02% bare trypsin and 0.4% chitosan nanoparticles against a control diet on productive efficiency (growth rate, feed conversion and protein efficiency ratio), organo-somatic indices, nutrient digestibility, tissue enzyme activities, hematic parameters and intestinal histology of the fish Labeo rohita. All the synthesized nanoparticles were of desired characteristics. Enhanced fish productive efficiency using nanoencapsulated trypsin over its bare form was noticed, which corresponded with enhanced (P<0.01) nutrient digestibility, activity of intestinal protease, liver and muscle tissue transaminases (alanine and aspartate) and dehydrogenases (lactate and malate), serum blood urea nitrogen and serum protein profile. Intestinal tissues of fish fed with 0.02% bare trypsin showed broadened, marked foamy cells with lipid vacuoles. However, villi were healthier in appearance with improved morphological features in fish fed with nanoencapsulated trypsin than with bare trypsin, and the villi were longer in fish fed with 0.01% nanoencapsulated trypsin than with 0.02% nanoencapsulated trypsin. The result of this premier experiment shows that nanoencapsulated trypsin mimics zymogen-like proteolytic activity via controlled release, and hence the use of 0.01% nanoencapsulated trypsin (in chitosan nanoparticles) over bare trypsin can be favored as a dietary supplement in animals and humans.", "journal": "PloS one", "sentences": ["Exogenous proteolytic enzyme supplementation is required in certain disease conditions in humans and animals and due to compelling reasons on use of more plant protein ingredients and profitability in animal feed industry.", "However, limitations on their utility in diet are imposed by their pH specificity, thermolabile nature, inhibition due to a variety of factors and the possibility of intestinal damage.", "For enhancing the efficacy and safety of exogenous trypsin, an efficient chitosan (0.04%) nanoencapsulation-based controlled delivery system was developed.", "An experiment was conducted for 45 days to evaluate nanoencapsulated trypsin (0.01% and 0.02%) along with 0.02% bare trypsin and 0.4% chitosan nanoparticles against a control diet on productive efficiency (growth rate, feed conversion and protein efficiency ratio), organo-somatic indices, nutrient digestibility, tissue enzyme activities, hematic parameters and intestinal histology of the fish Labeo rohita.", "All the synthesized nanoparticles were of desired characteristics.", "Enhanced fish productive efficiency using nanoencapsulated trypsin over its bare form was noticed, which corresponded with enhanced (P<0.01) nutrient digestibility, activity of intestinal protease, liver and muscle tissue transaminases (alanine and aspartate) and dehydrogenases (lactate and malate), serum blood urea nitrogen and serum protein profile.", "Intestinal tissues of fish fed with 0.02% bare trypsin showed broadened, marked foamy cells with lipid vacuoles.", "However, villi were healthier in appearance with improved morphological features in fish fed with nanoencapsulated trypsin than with bare trypsin, and the villi were longer in fish fed with 0.01% nanoencapsulated trypsin than with 0.02% nanoencapsulated trypsin.", "The result of this premier experiment shows that nanoencapsulated trypsin mimics zymogen-like proteolytic activity via controlled release, and hence the use of 0.01% nanoencapsulated trypsin (in chitosan nanoparticles) over bare trypsin can be favored as a dietary supplement in animals and humans."], "title": "Chitosan nanoencapsulated exogenous trypsin biomimics zymogen-like enzyme in fish gastrointestinal tract."}
{"paper_id": 25775402, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Corneal abrasion not only damages the epithelium but also induces stromal keratocyte death at the site of injury. While a coordinated cascade of inflammatory cell recruitment facilitates epithelial restoration, it is unclear if this cascade is necessary for keratocyte recovery. Since platelet and neutrophil (PMN) recruitment after corneal abrasion is beneficial to epithelial wound healing, we wanted to determine if these cells play a role in regulating keratocyte repopulation after epithelial abrasion. A 2 mm diameter central epithelial region was removed from the corneas of C57BL/6 wildtype (WT), P-selectin deficient (P-sel-/-), and CD18 hypomorphic (CD18hypo) mice using the Algerbrush II. Corneas were studied at 6h intervals out to 48h post-injury to evaluate platelet and PMN cell numbers; additional corneas were studied at 1, 4, 14, and 28 days post injury to evaluate keratocyte numbers. In WT mice, epithelial abrasion induced a loss of anterior central keratocytes and keratocyte recovery was rapid and incomplete, reaching ~70% of uninjured baseline values by 4 days post-injury but no further improvement at 28 days post-injury. Consistent with a beneficial role for platelets and PMNs in wound healing, keratocyte recovery was significantly depressed at 4 days post-injury (~30% of uninjured baseline) in P-sel-/- mice, which are known to have impaired platelet and PMN recruitment after corneal abrasion. Passive transfer of platelets from WT, but not P-sel-/-, into P-sel-/- mice prior to injury restored anterior central keratocyte numbers at 4 days post-injury to P-sel-/- uninjured baseline levels. While PMN infiltration in injured CD18hypo mice was similar to injured WT mice, platelet recruitment was markedly decreased and anterior central keratocyte recovery was significantly reduced (~50% of baseline) at 4-28 days post-injury. Collectively, the data suggest platelets and platelet P-selectin are critical for efficient keratocyte recovery after corneal epithelial abrasion.", "journal": "PloS one", "sentences": ["Corneal abrasion not only damages the epithelium but also induces stromal keratocyte death at the site of injury.", "While a coordinated cascade of inflammatory cell recruitment facilitates epithelial restoration, it is unclear if this cascade is necessary for keratocyte recovery.", "Since platelet and neutrophil (PMN) recruitment after corneal abrasion is beneficial to epithelial wound healing, we wanted to determine if these cells play a role in regulating keratocyte repopulation after epithelial abrasion.", "A 2 mm diameter central epithelial region was removed from the corneas of C57BL/6 wildtype (WT), P-selectin deficient (P-sel-/-), and CD18 hypomorphic (CD18hypo) mice using the Algerbrush II.", "Corneas were studied at 6h intervals out to 48h post-injury to evaluate platelet and PMN cell numbers; additional corneas were studied at 1, 4, 14, and 28 days post injury to evaluate keratocyte numbers.", "In WT mice, epithelial abrasion induced a loss of anterior central keratocytes and keratocyte recovery was rapid and incomplete, reaching ~70% of uninjured baseline values by 4 days post-injury but no further improvement at 28 days post-injury.", "Consistent with a beneficial role for platelets and PMNs in wound healing, keratocyte recovery was significantly depressed at 4 days post-injury (~30% of uninjured baseline) in P-sel-/- mice, which are known to have impaired platelet and PMN recruitment after corneal abrasion.", "Passive transfer of platelets from WT, but not P-sel-/-, into P-sel-/- mice prior to injury restored anterior central keratocyte numbers at 4 days post-injury to P-sel-/- uninjured baseline levels.", "While PMN infiltration in injured CD18hypo mice was similar to injured WT mice, platelet recruitment was markedly decreased and anterior central keratocyte recovery was significantly reduced (~50% of baseline) at 4-28 days post-injury.", "Collectively, the data suggest platelets and platelet P-selectin are critical for efficient keratocyte recovery after corneal epithelial abrasion."], "title": "Platelet recruitment promotes keratocyte repopulation following corneal epithelial abrasion in the mouse."}
{"paper_id": 23565137, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "To discover susceptibility genes of late-onset Alzheimer's disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n\u200a=\u200a1,008) and controls (n\u200a=\u200a1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values <2\u00d710(-5) were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P\u200a=\u200a7.33\u00d710(-7) in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P\u200a=\u200a1.77\u00d710(-9)) and rs3781834 (P\u200a=\u200a1.04\u00d710(-8)). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P\u200a=\u200a1.71\u00d710(-5)) and rs744373 near BIN1 (P\u200a=\u200a1.39\u00d710(-4)). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations.", "journal": "PloS one", "sentences": ["To discover susceptibility genes of late-onset Alzheimer's disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC).", "In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n\u200a=\u200a1,008) and controls (n\u200a=\u200a1,016).", "Genome-wide significance was observed with 12 SNPs in the APOE region.", "Seven SNPs from other distinct regions with p-values <2\u00d710(-5) were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P\u200a=\u200a7.33\u00d710(-7) in the combined sample).", "Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P\u200a=\u200a1.77\u00d710(-9)) and rs3781834 (P\u200a=\u200a1.04\u00d710(-8)).", "SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P\u200a=\u200a1.71\u00d710(-5)) and rs744373 near BIN1 (P\u200a=\u200a1.39\u00d710(-4)).", "The associated allele for each of these SNPs was the same as in Caucasians.", "These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese.", "Our study highlights the importance of examining associations in multiple ethnic populations."], "title": "SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and Caucasians."}
{"paper_id": 23667537, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "Phylogenomic studies based on hundreds of genes derived from expressed sequence tags libraries are increasingly used to reveal the phylogeny of taxa. A prerequisite for these studies is the assignment of genes into clusters of orthologous sequences. Sophisticated methods of orthology prediction are used in such analyses, but it is rarely assessed whether paralogous sequences have been erroneously grouped together as orthologous sequences after the prediction, and whether this had an impact on the phylogenetic reconstruction using a super-matrix approach. Herein, I tested the impact of paralogous sequences on the reconstruction of annelid relationships based on phylogenomic datasets. Using single-partition analyses, screening for bootstrap support, blast searches and pruning of sequences in the supermatrix, wrongly assigned paralogous sequences were found in eight partitions and the placement of five taxa (the annelids Owenia, Scoloplos, Sthenelais and Eurythoe and the nemertean Cerebratulus) including the robust bootstrap support could be attributed to the presence of paralogous sequences in two partitions. Excluding these sequences resulted in a different, weaker supported placement for these taxa. Moreover, the analyses revealed that paralogous sequences impacted the reconstruction when only a single taxon represented a previously supported higher taxon such as a polychaete family. One possibility of a priori detection of wrongly assigned paralogous sequences could combine 1) a screening of single-partition analyses based on criteria such as nodal support or internal branch length with 2) blast searches of suspicious cases as presented herein. Also possible are a posteriori approaches in which support for specific clades is investigated by comparing alternative hypotheses based on differences in per-site likelihoods. Increasing the sizes of EST libraries will also decrease the likelihood of wrongly assigned paralogous sequences, and in the case of orthology prediction methods like HaMStR it is likewise decreased by using more than one reference taxon.", "journal": "PloS one", "sentences": ["Phylogenomic studies based on hundreds of genes derived from expressed sequence tags libraries are increasingly used to reveal the phylogeny of taxa.", "A prerequisite for these studies is the assignment of genes into clusters of orthologous sequences.", "Sophisticated methods of orthology prediction are used in such analyses, but it is rarely assessed whether paralogous sequences have been erroneously grouped together as orthologous sequences after the prediction, and whether this had an impact on the phylogenetic reconstruction using a super-matrix approach.", "Herein, I tested the impact of paralogous sequences on the reconstruction of annelid relationships based on phylogenomic datasets.", "Using single-partition analyses, screening for bootstrap support, blast searches and pruning of sequences in the supermatrix, wrongly assigned paralogous sequences were found in eight partitions and the placement of five taxa (the annelids Owenia, Scoloplos, Sthenelais and Eurythoe and the nemertean Cerebratulus) including the robust bootstrap support could be attributed to the presence of paralogous sequences in two partitions.", "Excluding these sequences resulted in a different, weaker supported placement for these taxa.", "Moreover, the analyses revealed that paralogous sequences impacted the reconstruction when only a single taxon represented a previously supported higher taxon such as a polychaete family.", "One possibility of a priori detection of wrongly assigned paralogous sequences could combine 1) a screening of single-partition analyses based on criteria such as nodal support or internal branch length with 2) blast searches of suspicious cases as presented herein.", "Also possible are a posteriori approaches in which support for specific clades is investigated by comparing alternative hypotheses based on differences in per-site likelihoods.", "Increasing the sizes of EST libraries will also decrease the likelihood of wrongly assigned paralogous sequences, and in the case of orthology prediction methods like HaMStR it is likewise decreased by using more than one reference taxon."], "title": "The impact of paralogy on phylogenomic studies - a case study on annelid relationships."}
{"paper_id": 25852603, "labels": ["0", "0", "0", "1", "1"], "abstract": "Despite the prominent role of executive functions in children's emerging competencies, there remains debate regarding the structure and development of executive functions. In an attempt to reconcile these discrepancies, a differentiation model of executive function development was evaluated in the early years using 6-month age groupings. Specifically, 281 preschoolers completed measures of working memory, inhibition, and shifting. Results contradicted suggestions that executive functions follow a single trajectory of progressive separation in childhood, instead suggesting that these functions may undergo a period of integration in the preschool years. These results highlight potential problems with current practices and theorizing in executive function research.", "journal": "Frontiers in psychology", "sentences": ["Despite the prominent role of executive functions in children's emerging competencies, there remains debate regarding the structure and development of executive functions.", "In an attempt to reconcile these discrepancies, a differentiation model of executive function development was evaluated in the early years using 6-month age groupings.", "Specifically, 281 preschoolers completed measures of working memory, inhibition, and shifting.", "Results contradicted suggestions that executive functions follow a single trajectory of progressive separation in childhood, instead suggesting that these functions may undergo a period of integration in the preschool years.", "These results highlight potential problems with current practices and theorizing in executive function research."], "title": "Evaluation of a differentiation model of preschoolers' executive functions."}
{"paper_id": 23036890, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Neuroglobin is a member of the globin superfamily expressed in vertebrate brain and retina. The protein is thought to be involved in neuronal protection from hypoxia or oxidative stress and could represent a key element of Alzheimer disease pathogenesis. Our aim was to determine whether neuroglobin could be directly associated with mitochondrial metabolism and integrity. We identified three different forms of neuroglobin in the retina, varying in their apparent molecular masses; all forms are abundant in mitochondrial fractions. This indicates that a significant fraction of the protein localizes within the organelle either in the matrix or in the matrix side of the inner membrane. Since neuroglobin was especially abundant in the ganglion cell layer, we transduced retinal ganglion cells with an anti-neuroglobin short hairpin RNA using in vivo electroporation. Neuroglobin knockdown leads to reduced activities of respiratory chain complexes I and III, degeneration of retinal ganglion cells, and impairment of visual function. The deleterious effect on cell survival was confirmed in primary retinal ganglion cells subjected to inhibition of neuroglobin expression. Hence, neuroglobin should be considered as a novel mitochondrial protein involved in respiratory chain function which is essential for retinal ganglion cell integrity.", "journal": "Biochimica et biophysica acta", "sentences": ["Neuroglobin is a member of the globin superfamily expressed in vertebrate brain and retina.", "The protein is thought to be involved in neuronal protection from hypoxia or oxidative stress and could represent a key element of Alzheimer disease pathogenesis.", "Our aim was to determine whether neuroglobin could be directly associated with mitochondrial metabolism and integrity.", "We identified three different forms of neuroglobin in the retina, varying in their apparent molecular masses; all forms are abundant in mitochondrial fractions.", "This indicates that a significant fraction of the protein localizes within the organelle either in the matrix or in the matrix side of the inner membrane.", "Since neuroglobin was especially abundant in the ganglion cell layer, we transduced retinal ganglion cells with an anti-neuroglobin short hairpin RNA using in vivo electroporation.", "Neuroglobin knockdown leads to reduced activities of respiratory chain complexes I and III, degeneration of retinal ganglion cells, and impairment of visual function.", "The deleterious effect on cell survival was confirmed in primary retinal ganglion cells subjected to inhibition of neuroglobin expression.", "Hence, neuroglobin should be considered as a novel mitochondrial protein involved in respiratory chain function which is essential for retinal ganglion cell integrity."], "title": "Neuroglobin involvement in respiratory chain function and retinal ganglion cell integrity."}
{"paper_id": 26755577, "labels": ["0", "0", "1", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Transient Receptor Potential Canonical (TRPC) proteins form nonselective cation channels commonly known to be activated downstream from receptors that signal through phospholipase C (PLC). Although TRPC3/C6/C7 can be directly activated by diacylglycerols produced by PLC breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2), the mechanism by which the PLC pathway activates TRPC4/C5 remains unclear. We show here that TRPC4 activation requires coincident stimulation of Gi/o subgroup of G proteins and PLC\u03b4, with a preference for PLC\u03b41 over PLC\u03b43, but not necessarily the PLC\u03b2 pathway commonly thought to be involved in receptor-operated TRPC activation. In HEK293 cells coexpressing TRPC4 and Gi/o-coupled \u00b5 opioid receptor, \u00b5 agonist elicited currents biphasically, with an initial slow phase preceding a rapidly developing phase. The currents were dependent on intracellular Ca(2+) and PIP2. Reducing PIP2 through phosphatases abolished the biphasic kinetics and increased the probability of channel activation by weak Gi/o stimulation. In both HEK293 cells heterologously expressing TRPC4 and renal carcinoma-derived A-498 cells endogenously expressing TRPC4, channel activation was inhibited by knocking down PLC\u03b41 levels and almost completely eliminated by a dominant-negative PLC\u03b41 mutant and a constitutively active RhoA mutant. Conversely, the slow phase of Gi/o-mediated TRPC4 activation was diminished by inhibiting RhoA or enhancing PLC\u03b4 function. Our data reveal an integrative mechanism of TRPC4 on detection of coincident Gi/o, Ca(2+), and PLC signaling, which is further modulated by the small GTPase RhoA. This mechanism is not shared with the closely related TRPC5, implicating unique roles of TRPC4 in signal integration in brain and other systems.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Transient Receptor Potential Canonical (TRPC) proteins form nonselective cation channels commonly known to be activated downstream from receptors that signal through phospholipase C (PLC).", "Although TRPC3/C6/C7 can be directly activated by diacylglycerols produced by PLC breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2), the mechanism by which the PLC pathway activates TRPC4/C5 remains unclear.", "We show here that TRPC4 activation requires coincident stimulation of Gi/o subgroup of G proteins and PLC\u03b4, with a preference for PLC\u03b41 over PLC\u03b43, but not necessarily the PLC\u03b2 pathway commonly thought to be involved in receptor-operated TRPC activation.", "In HEK293 cells coexpressing TRPC4 and Gi/o-coupled \u00b5 opioid receptor, \u00b5 agonist elicited currents biphasically, with an initial slow phase preceding a rapidly developing phase.", "The currents were dependent on intracellular Ca(2+) and PIP2.", "Reducing PIP2 through phosphatases abolished the biphasic kinetics and increased the probability of channel activation by weak Gi/o stimulation.", "In both HEK293 cells heterologously expressing TRPC4 and renal carcinoma-derived A-498 cells endogenously expressing TRPC4, channel activation was inhibited by knocking down PLC\u03b41 levels and almost completely eliminated by a dominant-negative PLC\u03b41 mutant and a constitutively active RhoA mutant.", "Conversely, the slow phase of Gi/o-mediated TRPC4 activation was diminished by inhibiting RhoA or enhancing PLC\u03b4 function.", "Our data reveal an integrative mechanism of TRPC4 on detection of coincident Gi/o, Ca(2+), and PLC signaling, which is further modulated by the small GTPase RhoA.", "This mechanism is not shared with the closely related TRPC5, implicating unique roles of TRPC4 in signal integration in brain and other systems."], "title": "Critical roles of Gi/o proteins and phospholipase C-\u03b41 in the activation of receptor-operated TRPC4 channels."}
{"paper_id": 27420945, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The aim of the current study was to investigate survivin expression in congenital choledochal cysts (CCCs), and its associations with clinical parameters of CCCs. In total, 121 children with CCCs were included in this study as the case group, and their cysts were staged according to the Todani classification system. Additionally, 49 normal gallbladder specimens from healthy children were included as the control group. Survivin detection was conducted using immunohistochemical staining. Associations between positive survivin expression and clinical parameters of CCCs were then analyzed. Positive survivin expression was observed in the cytoplasm, and was seen as granular with yellow or dark brown staining. In the case group, positive survivin expression was detected in most tissues. Specifically, compared to that of normal tissues, the cystic-shaped and fusiform-shaped CCC tissues had significantly higher positive survivin expression rates (all P < 0.05). Importantly, positive survivin expression was also shown to be significantly associated with gender and histological type (both P < 0.05). In conclusion, increased survivin expression was observed in CCC tissues, and was correlated with certain clinical parameters of CCCs, suggesting a possible prognostic value of survivin for CCC progression.", "journal": "Genetics and molecular research : GMR", "sentences": ["The aim of the current study was to investigate survivin expression in congenital choledochal cysts (CCCs), and its associations with clinical parameters of CCCs.", "In total, 121 children with CCCs were included in this study as the case group, and their cysts were staged according to the Todani classification system.", "Additionally, 49 normal gallbladder specimens from healthy children were included as the control group.", "Survivin detection was conducted using immunohistochemical staining.", "Associations between positive survivin expression and clinical parameters of CCCs were then analyzed.", "Positive survivin expression was observed in the cytoplasm, and was seen as granular with yellow or dark brown staining.", "In the case group, positive survivin expression was detected in most tissues.", "Specifically, compared to that of normal tissues, the cystic-shaped and fusiform-shaped CCC tissues had significantly higher positive survivin expression rates (all P < 0.05).", "Importantly, positive survivin expression was also shown to be significantly associated with gender and histological type (both P < 0.05).", "In conclusion, increased survivin expression was observed in CCC tissues, and was correlated with certain clinical parameters of CCCs, suggesting a possible prognostic value of survivin for CCC progression."], "title": "Increased survivin expression and its association with clinical parameters of congenital choledochal cysts."}
{"paper_id": 21151453, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Exposure to different substances in an occupational environment is of utmost concern to global agencies such as the World Health Organization and the International Labour Organization. Interest in improving work health conditions, particularly of those employees exposed to noxious chemicals, has increased considerably and has stimulated the search for new, more specific and selective tests. Recently, the field of molecular biology has been indicated as an alternative technique for monitoring personnel while evaluating work-related pathologies. Originally, occupational exposure to environmental toxicants was assessed using biochemical techniques to determine the presence of higher concentrations of toxic compounds in blood, urine, or other fluids or tissues; results were used to evaluate potential health risk. However, this approach only estimates the presence of a noxious chemical and its effects, but does not prevent or diminish the risk. Molecular biology methods have become very useful in occupational medicine to provide more accurate and opportune diagnostics. In this review, we discuss the role of the following common techniques: (1) Use of cell cultures; (2) evaluation of gene expression; (3) the \"omic\" sciences (genomics, transcriptomics, proteomics and metabolomics) and (4) bioinformatics. We suggest that molecular biology has many applications in occupational health where the data can be applied to general environmental conditions.", "journal": "International journal of molecular sciences", "sentences": ["Exposure to different substances in an occupational environment is of utmost concern to global agencies such as the World Health Organization and the International Labour Organization.", "Interest in improving work health conditions, particularly of those employees exposed to noxious chemicals, has increased considerably and has stimulated the search for new, more specific and selective tests.", "Recently, the field of molecular biology has been indicated as an alternative technique for monitoring personnel while evaluating work-related pathologies.", "Originally, occupational exposure to environmental toxicants was assessed using biochemical techniques to determine the presence of higher concentrations of toxic compounds in blood, urine, or other fluids or tissues; results were used to evaluate potential health risk.", "However, this approach only estimates the presence of a noxious chemical and its effects, but does not prevent or diminish the risk.", "Molecular biology methods have become very useful in occupational medicine to provide more accurate and opportune diagnostics.", "In this review, we discuss the role of the following common techniques: (1) Use of cell cultures; (2) evaluation of gene expression; (3) the \"omic\" sciences (genomics, transcriptomics, proteomics and metabolomics) and (4) bioinformatics.", "We suggest that molecular biology has many applications in occupational health where the data can be applied to general environmental conditions."], "title": "The role of molecular biology in the biomonitoring of human exposure to chemicals."}
{"paper_id": 24340123, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis (PCM), the most prevalent systemic mycosis that is geographically confined to Latin America. The pro-inflammatory cytokine IL-1\u03b2 that is mainly derived from the activation of the cytoplasmic multiprotein complex inflammasome is an essential host factor against opportunistic fungal infections; however, its role in infection with a primary fungal pathogen, such as P. brasiliensis, is not well understood. In this study, we found that murine bone marrow-derived dendritic cells responded to P. brasiliensis yeast cells infection by releasing IL-1\u03b2 in a spleen tyrosine kinase (Syk), caspase-1 and NOD-like receptor (NLR) family member NLRP3 dependent manner. In addition, P. brasiliensis-induced NLRP3 inflammasome activation was dependent on potassium (K+) efflux, reactive oxygen species production, phagolysosomal acidification and cathepsin B release. Finally, using mice lacking the IL-1 receptor, we demonstrated that IL-1\u03b2 signaling has an important role in killing P. brasiliensis by murine macrophages. Altogether, our results demonstrate that the NLRP3 inflammasome senses and responds to P. brasiliensis yeast cells infection and plays an important role in host defense against this fungus.", "journal": "PLoS neglected tropical diseases", "sentences": ["Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis (PCM), the most prevalent systemic mycosis that is geographically confined to Latin America.", "The pro-inflammatory cytokine IL-1\u03b2 that is mainly derived from the activation of the cytoplasmic multiprotein complex inflammasome is an essential host factor against opportunistic fungal infections; however, its role in infection with a primary fungal pathogen, such as P. brasiliensis, is not well understood.", "In this study, we found that murine bone marrow-derived dendritic cells responded to P. brasiliensis yeast cells infection by releasing IL-1\u03b2 in a spleen tyrosine kinase (Syk), caspase-1 and NOD-like receptor (NLR) family member NLRP3 dependent manner.", "In addition, P. brasiliensis-induced NLRP3 inflammasome activation was dependent on potassium (K+) efflux, reactive oxygen species production, phagolysosomal acidification and cathepsin B release.", "Finally, using mice lacking the IL-1 receptor, we demonstrated that IL-1\u03b2 signaling has an important role in killing P. brasiliensis by murine macrophages.", "Altogether, our results demonstrate that the NLRP3 inflammasome senses and responds to P. brasiliensis yeast cells infection and plays an important role in host defense against this fungus."], "title": "NLRP3 inflammasome activation by Paracoccidioides brasiliensis."}
{"paper_id": 21813698, "labels": ["0", "0", "0", "0", "0", "1", "0", "0", "1"], "abstract": "The quiver/sleepless (qvr/sss) gene encodes a small, glycosylphosphatidylinositol-anchored protein that plays a critical role in the regulation of sleep in Drosophila. Loss-of-function mutations in qvr/sss severely suppress sleep and effect multiple changes in in situ Shaker K(+) currents, including decreased magnitude, slower time-to-peak, and cumulative inactivation. Recently, we demonstrated that SLEEPLESS (SSS) protein modulates Shaker channel activity, possibly through a direct interaction at the plasma membrane. We show here that SSS accelerates the activation of heterologously expressed Shaker channels with no effect on deactivation or fast N-type inactivation. Furthermore, this SSS-induced acceleration is sensitive to the pharmacological disruption of lipid rafts and sufficiently accounts for the slower time-to-peak of in situ Shaker currents seen in qvr/sss mutants. We also find that SSS decreases the rate of C-type inactivation of heterologously expressed Shaker channels, providing a potential mechanism for the cumulative inactivation phenotype induced by qvr/sss loss-of-function mutations. Kinetic modeling based on the in vitro results suggests that the SSS-dependent regulation of channel kinetics accounts for nearly 40% of the decrease in Shaker current magnitude in flies lacking SSS. Sleep duration in qvr/sss-null mutants is restored to normal by a qvr/sss transgene that fully rescues the Shaker kinetic phenotypes but only partially rescues the decrease in current magnitude. Together, these results suggest that the role of SSS in the regulation of sleep in Drosophila correlates more strongly with the effects of SSS on Shaker kinetics than current magnitude.", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "sentences": ["The quiver/sleepless (qvr/sss) gene encodes a small, glycosylphosphatidylinositol-anchored protein that plays a critical role in the regulation of sleep in Drosophila.", "Loss-of-function mutations in qvr/sss severely suppress sleep and effect multiple changes in in situ Shaker K(+) currents, including decreased magnitude, slower time-to-peak, and cumulative inactivation.", "Recently, we demonstrated that SLEEPLESS (SSS) protein modulates Shaker channel activity, possibly through a direct interaction at the plasma membrane.", "We show here that SSS accelerates the activation of heterologously expressed Shaker channels with no effect on deactivation or fast N-type inactivation.", "Furthermore, this SSS-induced acceleration is sensitive to the pharmacological disruption of lipid rafts and sufficiently accounts for the slower time-to-peak of in situ Shaker currents seen in qvr/sss mutants.", "We also find that SSS decreases the rate of C-type inactivation of heterologously expressed Shaker channels, providing a potential mechanism for the cumulative inactivation phenotype induced by qvr/sss loss-of-function mutations.", "Kinetic modeling based on the in vitro results suggests that the SSS-dependent regulation of channel kinetics accounts for nearly 40% of the decrease in Shaker current magnitude in flies lacking SSS.", "Sleep duration in qvr/sss-null mutants is restored to normal by a qvr/sss transgene that fully rescues the Shaker kinetic phenotypes but only partially rescues the decrease in current magnitude.", "Together, these results suggest that the role of SSS in the regulation of sleep in Drosophila correlates more strongly with the effects of SSS on Shaker kinetics than current magnitude."], "title": "Drosophila QVR/SSS modulates the activation and C-type inactivation kinetics of Shaker K(+) channels."}
{"paper_id": 22754356, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The polymorphisms of Waxy (Wx) microsatellite and G-T single-nucleotide polymorphism (SNP) in the Wx gene region were analyzed using simplified techniques in fifteen rice varieties. A rapid and reliable electrophoresis method, MetaPhor agarose gel electrophoresis (MAGE), was effectively employed as an alternative to polyacrylamide gel electrophoresis (PAGE) for separating Wx microsatellite alleles. The amplified products containing the Wx microsatellite ranged from 100 to 130 bp in length. Five Wx microsatellite alleles, namely (CT)(10), (CT)(11), (CT)(16), (CT)(17), and (CT)(18) were identified. Of these, (CT)(11) and (CT)(17) were the predominant classes among the tested varieties. All varieties with an apparent amylose content higher than 24% were associated with the shorter repeat alleles; (CT)(10) and (CT)(11), while varieties with 24% or less amylose were associated with the longer repeat alleles. All varieties with intermediate and high amylose content had the sequence AGGTATA at the 5'-leader intron splice site, while varieties with low amylose content had the sequence AGTTATA. The G-T polymorphism was further verified by the PCR-AccI cleaved amplified polymorphic sequence (CAPS) method, in which only genotypes containing the AGGTATA sequence were cleaved by AccI. Hence, varieties with desirable amylose levels can be developed rapidly using the Wx microsatellite and G-T SNP, along with MAGE.", "journal": "International journal of molecular sciences", "sentences": ["The polymorphisms of Waxy (Wx) microsatellite and G-T single-nucleotide polymorphism (SNP) in the Wx gene region were analyzed using simplified techniques in fifteen rice varieties.", "A rapid and reliable electrophoresis method, MetaPhor agarose gel electrophoresis (MAGE), was effectively employed as an alternative to polyacrylamide gel electrophoresis (PAGE) for separating Wx microsatellite alleles.", "The amplified products containing the Wx microsatellite ranged from 100 to 130 bp in length.", "Five Wx microsatellite alleles, namely (CT)(10), (CT)(11), (CT)(16), (CT)(17), and (CT)(18) were identified.", "Of these, (CT)(11) and (CT)(17) were the predominant classes among the tested varieties.", "All varieties with an apparent amylose content higher than 24% were associated with the shorter repeat alleles; (CT)(10) and (CT)(11), while varieties with 24% or less amylose were associated with the longer repeat alleles.", "All varieties with intermediate and high amylose content had the sequence AGGTATA at the 5'-leader intron splice site, while varieties with low amylose content had the sequence AGTTATA.", "The G-T polymorphism was further verified by the PCR-AccI cleaved amplified polymorphic sequence (CAPS) method, in which only genotypes containing the AGGTATA sequence were cleaved by AccI.", "Hence, varieties with desirable amylose levels can be developed rapidly using the Wx microsatellite and G-T SNP, along with MAGE."], "title": "Simple and rapid molecular techniques for identification of amylose levels in rice varieties."}
{"paper_id": 22903130, "labels": ["0", "0", "0", "1", "0"], "abstract": "The efficient clearance of amyloid-\u03b2 (A\u03b2) is essential to modulate levels of the peptide in the brain and to prevent it from accumulating in senile plaques, a hallmark of Alzheimer's disease (AD) pathology.We and others have shown that failure in A\u03b2 catabolism can produce elevations in A\u03b2 concentration similar to those observed in familial forms of AD. Based on the available evidence, it remains plausible that in late-onset AD, disturbances in the activity of A\u03b2 degrading enzymes could induce A\u03b2 accumulation, and that this increase could result in AD pathology. The following review presents a historical perspective of the parallel discovery of three vasopeptidases (neprilysin and endothelin-converting enzymes-1 and -2) as important A\u03b2 degrading enzymes. The recognition of the role of these vasopeptidases in A\u03b2 degradation, beyond bringing to light a possible explanation of how cardiovascular risk factors may influence AD risk, highlights a possible risk of the use of inhibitors of these enzymes for other clinical indications such as hypertension. We will discuss in detail the experiments conducted to assess the impact of vasopeptidase deficiency (through pharmacological inhibition or genetic mutation) on A\u03b2 accumulation, as well as the cooperative effect of multiple A\u03b2 degrading enzymes to regulate the concentration of the peptide at multiple sites, both intracellular and extracellular, throughout the brain.", "journal": "Journal of Alzheimer's disease : JAD", "sentences": ["The efficient clearance of amyloid-\u03b2 (A\u03b2) is essential to modulate levels of the peptide in the brain and to prevent it from accumulating in senile plaques, a hallmark of Alzheimer's disease (AD) pathology.We and others have shown that failure in A\u03b2 catabolism can produce elevations in A\u03b2 concentration similar to those observed in familial forms of AD.", "Based on the available evidence, it remains plausible that in late-onset AD, disturbances in the activity of A\u03b2 degrading enzymes could induce A\u03b2 accumulation, and that this increase could result in AD pathology.", "The following review presents a historical perspective of the parallel discovery of three vasopeptidases (neprilysin and endothelin-converting enzymes-1 and -2) as important A\u03b2 degrading enzymes.", "The recognition of the role of these vasopeptidases in A\u03b2 degradation, beyond bringing to light a possible explanation of how cardiovascular risk factors may influence AD risk, highlights a possible risk of the use of inhibitors of these enzymes for other clinical indications such as hypertension.", "We will discuss in detail the experiments conducted to assess the impact of vasopeptidase deficiency (through pharmacological inhibition or genetic mutation) on A\u03b2 accumulation, as well as the cooperative effect of multiple A\u03b2 degrading enzymes to regulate the concentration of the peptide at multiple sites, both intracellular and extracellular, throughout the brain."], "title": "Endothelin-converting enzymes and related metalloproteases in Alzheimer's disease."}
{"paper_id": 24904502, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "Two relatively independent lines of research have addressed the role of the prefrontal cortex in emotional processing. The first examines hemispheric asymmetries in frontal function; the second focuses on prefrontal interactions between cognition and emotion. We briefly review each perspective and highlight inconsistencies between them. We go on to describe an alternative model that integrates approaches by focusing on hemispheric asymmetry in inhibitory executive control processes. The asymmetric inhibition model proposes that right-lateralized executive control inhibits processing of positive or approach-related distractors, and left-lateralized control inhibits negative or withdrawal-related distractors. These complementary processes allow us to maintain and achieve current goals in the face of emotional distraction. We conclude with a research agenda that uses the model to generate novel experiments that will advance our understanding of both hemispheric asymmetries and cognition-emotion interactions.", "journal": "Frontiers in psychology", "sentences": ["Two relatively independent lines of research have addressed the role of the prefrontal cortex in emotional processing.", "The first examines hemispheric asymmetries in frontal function; the second focuses on prefrontal interactions between cognition and emotion.", "We briefly review each perspective and highlight inconsistencies between them.", "We go on to describe an alternative model that integrates approaches by focusing on hemispheric asymmetry in inhibitory executive control processes.", "The asymmetric inhibition model proposes that right-lateralized executive control inhibits processing of positive or approach-related distractors, and left-lateralized control inhibits negative or withdrawal-related distractors.", "These complementary processes allow us to maintain and achieve current goals in the face of emotional distraction.", "We conclude with a research agenda that uses the model to generate novel experiments that will advance our understanding of both hemispheric asymmetries and cognition-emotion interactions."], "title": "An asymmetric inhibition model of hemispheric differences in emotional processing."}
{"paper_id": 24265825, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "In eukaryotes many players in the DNA-damage response (DDR) catalyze protein sumoylation or ubiquitylation. Emphasis has been placed on how these modifications orchestrate the sequential recruitment of repair factors to sites of DNA damage or stalled replication forks. Here, we shed light on a pathway in which sumoylated factors are eliminated through the coupled action of Sumo-targeted ubiquitin ligases (STUbLs) and the ubiquitin-fusion degradation protein 1 (Ufd1). Ufd1 is a subunit of the Cdc48-Ufd1-Npl4 complex implicated in the sorting of ubiquitylated substrates for degradation by the proteasome. We find that in fission yeast, Ufd1 interacts physically and functionally with the Sumo-targeted ubiquitin ligase (STUbL) Rfp1, homologous to human RNF4, and with the Sumo E3 ligase Pli1, homologous to human PIAS1. Deleting a C-terminal domain of Ufd1 that mediates the interaction of Ufd1 with Rfp1, Pli1, and Sumo (ufd1\u0394Ct(213-342) ) lead to an accumulation of high-molecular-weight Sumo conjugates and caused severe genomic instabilities. The spectrum of sensitivity of ufd1\u0394Ct(213-342) cells to genotoxins, the epistatic relationships of ufd1\u0394Ct(213-342) with mutations in DNA repair factors, and the localization of the repair factor Rad22 in ufd1\u0394Ct(213-342) cells point to ufd1\u0394Ct(213-342) cells accumulating aberrant structures during replication that require homologous recombination (HR) for their repair. We present evidence that HR is however often not successful in ufd1\u0394Ct(213-342) cells and we identify Rad22 as one of the high-molecular-weight conjugates accumulating in the ufd1\u0394Ct(213-342) mutant consistent with Rad22 being a STUbL/Ufd1 substrate. Suggesting a direct role of Ufd1 in the processing of Sumo-conjugates, Ufd1 formed nuclear foci colocalizing with Sumo during the DDR, and Sumo-conjugates accumulated in foci in the ufd1\u0394Ct(213-342) mutant. Broader functional relationships between Ufd1 and STUbLs conceivably affect numerous cellular processes beyond the DDR.", "journal": "PloS one", "sentences": ["In eukaryotes many players in the DNA-damage response (DDR) catalyze protein sumoylation or ubiquitylation.", "Emphasis has been placed on how these modifications orchestrate the sequential recruitment of repair factors to sites of DNA damage or stalled replication forks.", "Here, we shed light on a pathway in which sumoylated factors are eliminated through the coupled action of Sumo-targeted ubiquitin ligases (STUbLs) and the ubiquitin-fusion degradation protein 1 (Ufd1).", "Ufd1 is a subunit of the Cdc48-Ufd1-Npl4 complex implicated in the sorting of ubiquitylated substrates for degradation by the proteasome.", "We find that in fission yeast, Ufd1 interacts physically and functionally with the Sumo-targeted ubiquitin ligase (STUbL) Rfp1, homologous to human RNF4, and with the Sumo E3 ligase Pli1, homologous to human PIAS1.", "Deleting a C-terminal domain of Ufd1 that mediates the interaction of Ufd1 with Rfp1, Pli1, and Sumo (ufd1\u0394Ct(213-342) ) lead to an accumulation of high-molecular-weight Sumo conjugates and caused severe genomic instabilities.", "The spectrum of sensitivity of ufd1\u0394Ct(213-342) cells to genotoxins, the epistatic relationships of ufd1\u0394Ct(213-342) with mutations in DNA repair factors, and the localization of the repair factor Rad22 in ufd1\u0394Ct(213-342) cells point to ufd1\u0394Ct(213-342) cells accumulating aberrant structures during replication that require homologous recombination (HR) for their repair.", "We present evidence that HR is however often not successful in ufd1\u0394Ct(213-342) cells and we identify Rad22 as one of the high-molecular-weight conjugates accumulating in the ufd1\u0394Ct(213-342) mutant consistent with Rad22 being a STUbL/Ufd1 substrate.", "Suggesting a direct role of Ufd1 in the processing of Sumo-conjugates, Ufd1 formed nuclear foci colocalizing with Sumo during the DDR, and Sumo-conjugates accumulated in foci in the ufd1\u0394Ct(213-342) mutant.", "Broader functional relationships between Ufd1 and STUbLs conceivably affect numerous cellular processes beyond the DDR."], "title": "Concerted action of the ubiquitin-fusion degradation protein 1 (Ufd1) and Sumo-targeted ubiquitin ligases (STUbLs) in the DNA-damage response."}
{"paper_id": 23386724, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Stabilization of virus protein structure and nucleic acid integrity is challenging yet essential to preserve the transcriptional competence of live recombinant viral vaccine vectors in the absence of a cold chain. When coupled with needle-free skin delivery, such a platform would address an unmet need in global vaccine coverage against HIV and other global pathogens. Herein, we show that a simple dissolvable microneedle array (MA) delivery system preserves the immunogenicity of vaccines encoded by live recombinant human adenovirus type 5 (rAdHu5). Specifically, dried rAdHu5 MA immunization induced CD8(+) T-cell expansion and multifunctional cytokine responses equipotent with conventional injectable routes of immunization. Intravital imaging demonstrated MA cargo distributed both in the epidermis and dermis, with acquisition by CD11c(+) dendritic cells (DCs) in the dermis. The MA immunizing properties were attributable to CD11c(+) MHCII(hi) CD8\u03b1(neg) epithelial cell adhesion molecule (EpCAM(neg)) CD11b(+) langerin (Lang; CD207)(neg) DCs, but neither Langerhans cells nor Lang(+) DCs were required for CD8(+) T-cell priming. This study demonstrates an important technical advance for viral vaccine vectors progressing to the clinic and provides insights into the mechanism of CD8(+) T-cell priming by live rAdHu5 MAs.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Stabilization of virus protein structure and nucleic acid integrity is challenging yet essential to preserve the transcriptional competence of live recombinant viral vaccine vectors in the absence of a cold chain.", "When coupled with needle-free skin delivery, such a platform would address an unmet need in global vaccine coverage against HIV and other global pathogens.", "Herein, we show that a simple dissolvable microneedle array (MA) delivery system preserves the immunogenicity of vaccines encoded by live recombinant human adenovirus type 5 (rAdHu5).", "Specifically, dried rAdHu5 MA immunization induced CD8(+) T-cell expansion and multifunctional cytokine responses equipotent with conventional injectable routes of immunization.", "Intravital imaging demonstrated MA cargo distributed both in the epidermis and dermis, with acquisition by CD11c(+) dendritic cells (DCs) in the dermis.", "The MA immunizing properties were attributable to CD11c(+) MHCII(hi) CD8\u03b1(neg) epithelial cell adhesion molecule (EpCAM(neg)) CD11b(+) langerin (Lang; CD207)(neg) DCs, but neither Langerhans cells nor Lang(+) DCs were required for CD8(+) T-cell priming.", "This study demonstrates an important technical advance for viral vaccine vectors progressing to the clinic and provides insights into the mechanism of CD8(+) T-cell priming by live rAdHu5 MAs."], "title": "Langerin negative dendritic cells promote potent CD8+ T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays."}
{"paper_id": 25695042, "labels": ["0", "0", "0", "0", "0"], "abstract": "Constitutively activated prosurvival pathways render cancer cells addicted to their effects. Consequently they turn out to be the Achilles' heels whose inhibition can be exploited in anticancer therapy. Primary effusion lymphomas (PELs) are very aggressive non-Hodgkin's B cell lymphomas, whose pathogenesis is strictly linked to Kaposi's sarcoma herpesvirus (KSHV) infection. Here we summarized previous studies from our and other laboratories exploring the cytotoxic effect of drugs inhibiting the main prosurvival pathways activated in PEL cells. Moreover, the immunogenicity of cell death, in terms of dendritic cell (DC) activation and their potential side effect on DCs, is discussed.", "journal": "BioMed research international", "sentences": ["Constitutively activated prosurvival pathways render cancer cells addicted to their effects.", "Consequently they turn out to be the Achilles' heels whose inhibition can be exploited in anticancer therapy.", "Primary effusion lymphomas (PELs) are very aggressive non-Hodgkin's B cell lymphomas, whose pathogenesis is strictly linked to Kaposi's sarcoma herpesvirus (KSHV) infection.", "Here we summarized previous studies from our and other laboratories exploring the cytotoxic effect of drugs inhibiting the main prosurvival pathways activated in PEL cells.", "Moreover, the immunogenicity of cell death, in terms of dendritic cell (DC) activation and their potential side effect on DCs, is discussed."], "title": "Targeting of prosurvival pathways as therapeutic approaches against primary effusion lymphomas: past, present, and Future."}
{"paper_id": 23101628, "labels": ["0", "0", "0", "0", "1"], "abstract": "Whereas proliferating cells enter M phase shortly after DNA replication, the first M phase of meiosis is preceded by an extended prophase in which homologous chromosomes undergo recombination. Exit from prophase I is controlled by the recombination checkpoint (RC), which, in yeast, represses the meiosis-specific transcription factor Ndt80 required for the expression of B-type cyclins and other M\u00a0phase regulators. We show that an extended prophase I additionally requires the suppression of latent, mitotic cell-cycle controls by the anaphase-promoting complex (APC/C) and its meiosis-specific activator Ama1, which trigger the degradation of M phase regulators and Ndd1, a subunit of a mitotic transcription factor. ama1\u0394 mutants exit from prophase I prematurely and independently of the RC, which results in recombination defects and chromosome missegregation. Thus, control of prophase I by meiotic mechanisms depends on the suppression of the alternative, mitotic mechanisms by a meiosis-specific form of the APC/C.", "journal": "Cell", "sentences": ["Whereas proliferating cells enter M phase shortly after DNA replication, the first M phase of meiosis is preceded by an extended prophase in which homologous chromosomes undergo recombination.", "Exit from prophase I is controlled by the recombination checkpoint (RC), which, in yeast, represses the meiosis-specific transcription factor Ndt80 required for the expression of B-type cyclins and other M\u00a0phase regulators.", "We show that an extended prophase I additionally requires the suppression of latent, mitotic cell-cycle controls by the anaphase-promoting complex (APC/C) and its meiosis-specific activator Ama1, which trigger the degradation of M phase regulators and Ndd1, a subunit of a mitotic transcription factor.", "ama1\u0394 mutants exit from prophase I prematurely and independently of the RC, which results in recombination defects and chromosome missegregation.", "Thus, control of prophase I by meiotic mechanisms depends on the suppression of the alternative, mitotic mechanisms by a meiosis-specific form of the APC/C."], "title": "Meiotic prophase requires proteolysis of M phase regulators mediated by the meiosis-specific APC/CAma1."}
{"paper_id": 26734994, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "RANK/RANKL plays a key role in metastasis of certain malignant tumors, which makes it a promising target for developing novel therapeutic strategies for cancer. However, the prognostic value and pro-metastatic activity of RANK in endometrial cancer (EC) remain to be determined. Thus, the present study investigated the effect of RANK on the prognosis of EC patients, as well as the pro-metastatic activity of EC cells. The results indicated that those with high expression of RANK showed decreased overall survival and progression-free survival. Statistical analysis revealed the positive correlations between RANK/RANKL expression and metastasis-related factors. Additionally, RANK/RANKL significantly promoted cell migration/invasion via activating AKT/\u03b2-catenin/Snail pathway in vitro. However, RANK/RANKL-induced AKT activation could be suppressed after osteoprotegerin (OPG) treatment. Furthermore, the combination of medroxyprogesterone acetate (MPA) and RANKL could in turn attenuate the effect of RANKL alone. Similarly, MPA could partially inhibit the RANK-induced metastasis in an orthotopic mouse model via suppressing AKT/\u03b2-catenin/Snail pathway. Therefore, therapeutic inhibition of MPA in RANK/RANKL-induced metastasis was mediated by AKT/\u03b2-catenin/Snail pathway both in vitro and in vivo, suggesting a potential target of RANK for gene-based therapy for EC.", "journal": "Oncotarget", "sentences": ["RANK/RANKL plays a key role in metastasis of certain malignant tumors, which makes it a promising target for developing novel therapeutic strategies for cancer.", "However, the prognostic value and pro-metastatic activity of RANK in endometrial cancer (EC) remain to be determined.", "Thus, the present study investigated the effect of RANK on the prognosis of EC patients, as well as the pro-metastatic activity of EC cells.", "The results indicated that those with high expression of RANK showed decreased overall survival and progression-free survival.", "Statistical analysis revealed the positive correlations between RANK/RANKL expression and metastasis-related factors.", "Additionally, RANK/RANKL significantly promoted cell migration/invasion via activating AKT/\u03b2-catenin/Snail pathway in vitro.", "However, RANK/RANKL-induced AKT activation could be suppressed after osteoprotegerin (OPG) treatment.", "Furthermore, the combination of medroxyprogesterone acetate (MPA) and RANKL could in turn attenuate the effect of RANKL alone.", "Similarly, MPA could partially inhibit the RANK-induced metastasis in an orthotopic mouse model via suppressing AKT/\u03b2-catenin/Snail pathway.", "Therefore, therapeutic inhibition of MPA in RANK/RANKL-induced metastasis was mediated by AKT/\u03b2-catenin/Snail pathway both in vitro and in vivo, suggesting a potential target of RANK for gene-based therapy for EC."], "title": "Clinical prognostic significance and pro-metastatic activity of RANK/RANKL via the AKT pathway in endometrial cancer."}
{"paper_id": 26445431, "labels": ["0", "0", "0", "0", "1"], "abstract": "The experiments in the Cole and Moore article in the first issue of the Biophysical Journal provided the first independent experimental confirmation of the Hodgkin-Huxley (HH) equations. A log-log plot of the K current versus time showed that raising the HH variable n to the sixth power provided the best fit to the data. Subsequent simulations using n(6) and setting the resting potential at the in vivo value simplifies the HH equations by eliminating the leakage term. Our article also reported that the K current in response to a depolarizing step to ENa was delayed if the step was preceded by a hyperpolarization. While the interpretation of this phenomenon in the article was flawed, subsequent simulations show that the effect completely arises from the original HH equations.", "journal": "Biophysical journal", "sentences": ["The experiments in the Cole and Moore article in the first issue of the Biophysical Journal provided the first independent experimental confirmation of the Hodgkin-Huxley (HH) equations.", "A log-log plot of the K current versus time showed that raising the HH variable n to the sixth power provided the best fit to the data.", "Subsequent simulations using n(6) and setting the resting potential at the in vivo value simplifies the HH equations by eliminating the leakage term.", "Our article also reported that the K current in response to a depolarizing step to ENa was delayed if the step was preceded by a hyperpolarization.", "While the interpretation of this phenomenon in the article was flawed, subsequent simulations show that the effect completely arises from the original HH equations."], "title": "Enhancing the Hodgkin-Huxley Equations: Simulations Based on the First Publication in the Biophysical Journal."}
{"paper_id": 26017223, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Fluorescence Recovery After Photobleaching (FRAP) has been a versatile tool to study transport and reaction kinetics in live cells. Since the fluorescence data generated by fluorescence microscopy are in a relative scale, a wide variety of scalings and normalizations are used in quantitative FRAP analysis. Scaling and normalization are often required to account for inherent properties of diffusing biomolecules of interest or photochemical properties of the fluorescent tag such as mobile fraction or photofading during image acquisition. In some cases, scaling and normalization are also used for computational simplicity. However, to our best knowledge, the validity of those various forms of scaling and normalization has not been studied in a rigorous manner. In this study, we investigate the validity of various scalings and normalizations that have appeared in the literature to calculate mobile fractions and correct for photofading and assess their consistency with FRAP equations. As a test case, we consider linear or affine scaling of normal or anomalous diffusion FRAP equations in combination with scaling for immobile fractions. We also consider exponential scaling of either FRAP equations or FRAP data to correct for photofading. Using a combination of theoretical and experimental approaches, we show that compatible scaling schemes should be applied in the correct sequential order; otherwise, erroneous results may be obtained. We propose a hierarchical workflow to carry out FRAP data analysis and discuss the broader implications of our findings for FRAP data analysis using a variety of kinetic models.", "journal": "PloS one", "sentences": ["Fluorescence Recovery After Photobleaching (FRAP) has been a versatile tool to study transport and reaction kinetics in live cells.", "Since the fluorescence data generated by fluorescence microscopy are in a relative scale, a wide variety of scalings and normalizations are used in quantitative FRAP analysis.", "Scaling and normalization are often required to account for inherent properties of diffusing biomolecules of interest or photochemical properties of the fluorescent tag such as mobile fraction or photofading during image acquisition.", "In some cases, scaling and normalization are also used for computational simplicity.", "However, to our best knowledge, the validity of those various forms of scaling and normalization has not been studied in a rigorous manner.", "In this study, we investigate the validity of various scalings and normalizations that have appeared in the literature to calculate mobile fractions and correct for photofading and assess their consistency with FRAP equations.", "As a test case, we consider linear or affine scaling of normal or anomalous diffusion FRAP equations in combination with scaling for immobile fractions.", "We also consider exponential scaling of either FRAP equations or FRAP data to correct for photofading.", "Using a combination of theoretical and experimental approaches, we show that compatible scaling schemes should be applied in the correct sequential order; otherwise, erroneous results may be obtained.", "We propose a hierarchical workflow to carry out FRAP data analysis and discuss the broader implications of our findings for FRAP data analysis using a variety of kinetic models."], "title": "Validation of Normalizations, Scaling, and Photofading Corrections for FRAP Data Analysis."}
{"paper_id": 21071575, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Classification image analysis is a psychophysical technique in which noise components of stimuli are analyzed to produce an image that reveals critical features of a task. Here we use classification images to gain greater understanding of perceptual learning. To achieve reasonable classification images within a single session, we developed an efficient classification image procedure that employed designer noise and a low-dimensional stimulus space. Subjects were trained across ten sessions to detect the orientation of a grating masked in noise, with an eleventh, test, session conducted using a stimulus orthogonal to the trained stimulus. As with standard perceptual learning studies, subjects showed improvements in performance metrics of accuracy, threshold, and reaction times. The clarity of the classification images and their correlation to an ideal target also improved across training sessions in an orientation-specific manner. Furthermore, image-based analyses revealed aspects of performance that could not be observed with standard performance metrics. Subjects with threshold improvements learned to use pixels across a wider area of the image, and, apposed to subjects without threshold improvements, showed improvements in both the bright and dark parts of the image. We conclude that classification image analysis is an important complement to traditional metrics of perceptual learning.", "journal": "Journal of vision", "sentences": ["Classification image analysis is a psychophysical technique in which noise components of stimuli are analyzed to produce an image that reveals critical features of a task.", "Here we use classification images to gain greater understanding of perceptual learning.", "To achieve reasonable classification images within a single session, we developed an efficient classification image procedure that employed designer noise and a low-dimensional stimulus space.", "Subjects were trained across ten sessions to detect the orientation of a grating masked in noise, with an eleventh, test, session conducted using a stimulus orthogonal to the trained stimulus.", "As with standard perceptual learning studies, subjects showed improvements in performance metrics of accuracy, threshold, and reaction times.", "The clarity of the classification images and their correlation to an ideal target also improved across training sessions in an orientation-specific manner.", "Furthermore, image-based analyses revealed aspects of performance that could not be observed with standard performance metrics.", "Subjects with threshold improvements learned to use pixels across a wider area of the image, and, apposed to subjects without threshold improvements, showed improvements in both the bright and dark parts of the image.", "We conclude that classification image analysis is an important complement to traditional metrics of perceptual learning."], "title": "Perceptual learning of oriented gratings as revealed by classification images."}
{"paper_id": 23873914, "labels": ["0", "0", "0", "0", "0", "0", "1", "0", "1"], "abstract": "DNA affinity chromatography with the promoter region of the Corynebacterium glutamicum pck gene, encoding phosphoenolpyruvate carboxykinase, led to the isolation of four transcriptional regulators, i.e., RamA, GntR1, GntR2, and IolR. Determination of the phosphoenolpyruvate carboxykinase activity of the \u0394ramA, \u0394gntR1 \u0394gntR2, and \u0394iolR deletion mutants indicated that RamA represses pck during growth on glucose about 2-fold, whereas GntR1, GntR2, and IolR activate pck expression about 2-fold irrespective of whether glucose or acetate served as the carbon source. The DNA binding sites of the four regulators in the pck promoter region were identified and their positions correlated with the predicted functions as repressor or activators. The iolR gene is located upstream and in a divergent orientation with respect to a iol gene cluster, encoding proteins involved in myo-inositol uptake and degradation. Comparative DNA microarray analysis of the \u0394iolR mutant and the parental wild-type strain revealed strongly (>100-fold) elevated mRNA levels of the iol genes in the mutant, indicating that the primary function of IolR is the repression of the iol genes. IolR binding sites were identified in the promoter regions of iolC, iolT1, and iolR. IolR therefore is presumably subject to negative autoregulation. A consensus DNA binding motif (5'-KGWCHTRACA-3') which corresponds well to those of other GntR-type regulators of the HutC family was identified. Taken together, our results disclose a complex regulation of the pck gene in C. glutamicum and identify IolR as an efficient repressor of genes involved in myo-inositol catabolism of this organism.", "journal": "Journal of bacteriology", "sentences": ["DNA affinity chromatography with the promoter region of the Corynebacterium glutamicum pck gene, encoding phosphoenolpyruvate carboxykinase, led to the isolation of four transcriptional regulators, i.e., RamA, GntR1, GntR2, and IolR.", "Determination of the phosphoenolpyruvate carboxykinase activity of the \u0394ramA, \u0394gntR1 \u0394gntR2, and \u0394iolR deletion mutants indicated that RamA represses pck during growth on glucose about 2-fold, whereas GntR1, GntR2, and IolR activate pck expression about 2-fold irrespective of whether glucose or acetate served as the carbon source.", "The DNA binding sites of the four regulators in the pck promoter region were identified and their positions correlated with the predicted functions as repressor or activators.", "The iolR gene is located upstream and in a divergent orientation with respect to a iol gene cluster, encoding proteins involved in myo-inositol uptake and degradation.", "Comparative DNA microarray analysis of the \u0394iolR mutant and the parental wild-type strain revealed strongly (>100-fold) elevated mRNA levels of the iol genes in the mutant, indicating that the primary function of IolR is the repression of the iol genes.", "IolR binding sites were identified in the promoter regions of iolC, iolT1, and iolR.", "IolR therefore is presumably subject to negative autoregulation.", "A consensus DNA binding motif (5'-KGWCHTRACA-3') which corresponds well to those of other GntR-type regulators of the HutC family was identified.", "Taken together, our results disclose a complex regulation of the pck gene in C. glutamicum and identify IolR as an efficient repressor of genes involved in myo-inositol catabolism of this organism."], "title": "Complex regulation of the phosphoenolpyruvate carboxykinase gene pck and characterization of its GntR-type regulator IolR as a repressor of myo-inositol utilization genes in Corynebacterium glutamicum."}
{"paper_id": 26872352, "labels": ["0", "0", "0", "0", "0", "1", "1", "1", "1", "1"], "abstract": "Homologous recombination provides a mechanism of DNA double-strand break repair (DSBR) that requires an intact, homologous template for DNA synthesis. When DNA synthesis associated with DSBR is convergent, the broken DNA strands are replaced and repair is accurate. However, if divergent DNA synthesis is established, over-replication of flanking DNA may occur with deleterious consequences. The RecG protein of Escherichia coli is a helicase and translocase that can re-model 3-way and 4-way DNA structures such as replication forks and Holliday junctions. However, the primary role of RecG in live cells has remained elusive. Here we show that, in the absence of RecG, attempted DSBR is accompanied by divergent DNA replication at the site of an induced chromosomal DNA double-strand break. Furthermore, DNA double-stand ends are generated in a recG mutant at sites known to block replication forks. These double-strand ends, also trigger DSBR and the divergent DNA replication characteristic of this mutant, which can explain over-replication of the terminus region of the chromosome. The loss of DNA associated with unwinding joint molecules previously observed in the absence of RuvAB and RecG, is suppressed by a helicase deficient PriA mutation (priA300), arguing that the action of RecG ensures that PriA is bound correctly on D-loops to direct DNA replication rather than to unwind joint molecules. This has led us to put forward a revised model of homologous recombination in which the re-modelling of branched intermediates by RecG plays a fundamental role in directing DNA synthesis and thus maintaining genomic stability.", "journal": "PLoS genetics", "sentences": ["Homologous recombination provides a mechanism of DNA double-strand break repair (DSBR) that requires an intact, homologous template for DNA synthesis.", "When DNA synthesis associated with DSBR is convergent, the broken DNA strands are replaced and repair is accurate.", "However, if divergent DNA synthesis is established, over-replication of flanking DNA may occur with deleterious consequences.", "The RecG protein of Escherichia coli is a helicase and translocase that can re-model 3-way and 4-way DNA structures such as replication forks and Holliday junctions.", "However, the primary role of RecG in live cells has remained elusive.", "Here we show that, in the absence of RecG, attempted DSBR is accompanied by divergent DNA replication at the site of an induced chromosomal DNA double-strand break.", "Furthermore, DNA double-stand ends are generated in a recG mutant at sites known to block replication forks.", "These double-strand ends, also trigger DSBR and the divergent DNA replication characteristic of this mutant, which can explain over-replication of the terminus region of the chromosome.", "The loss of DNA associated with unwinding joint molecules previously observed in the absence of RuvAB and RecG, is suppressed by a helicase deficient PriA mutation (priA300), arguing that the action of RecG ensures that PriA is bound correctly on D-loops to direct DNA replication rather than to unwind joint molecules.", "This has led us to put forward a revised model of homologous recombination in which the re-modelling of branched intermediates by RecG plays a fundamental role in directing DNA synthesis and thus maintaining genomic stability."], "title": "RecG Directs DNA Synthesis during Double-Strand Break Repair."}
{"paper_id": 22824796, "labels": ["0", "0", "0", "0", "1", "0", "1", "1"], "abstract": "Mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, have been reported in gliomas, myeloid leukemias, chondrosarcomas and thyroid cancer. We discovered IDH1 and IDH2 mutations in 34 of 326 (10%) intrahepatic cholangiocarcinomas. Tumor with mutations in IDH1 or IDH2 had lower 5-hydroxymethylcytosine and higher 5-methylcytosine levels, as well as increased dimethylation of histone H3 lysine 79 (H3K79). Mutations in IDH1 or IDH2 were associated with longer overall survival (P=0.028) and were independently associated with a longer time to tumor recurrence after intrahepatic cholangiocarcinoma resection in multivariate analysis (P=0.021). IDH1 and IDH2 mutations were significantly associated with increased levels of p53 in intrahepatic cholangiocarcinomas, but no mutations in the p53 gene were found, suggesting that mutations in IDH1 and IDH2 may cause a stress that leads to p53 activation. We identified 2309 genes that were significantly hypermethylated in 19 cholangiocarcinomas with mutations in IDH1 or IDH2, compared with cholangiocarcinomas without these mutations. Hypermethylated CpG sites were significantly enriched in CpG shores and upstream of transcription start sites, suggesting a global regulation of transcriptional potential. Half of the hypermethylated genes overlapped with DNA hypermethylation in IDH1-mutant gliobastomas, suggesting the existence of a common set of genes whose expression may be affected by mutations in IDH1 or IDH2 in different types of tumors.", "journal": "Oncogene", "sentences": ["Mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, have been reported in gliomas, myeloid leukemias, chondrosarcomas and thyroid cancer.", "We discovered IDH1 and IDH2 mutations in 34 of 326 (10%) intrahepatic cholangiocarcinomas.", "Tumor with mutations in IDH1 or IDH2 had lower 5-hydroxymethylcytosine and higher 5-methylcytosine levels, as well as increased dimethylation of histone H3 lysine 79 (H3K79).", "Mutations in IDH1 or IDH2 were associated with longer overall survival (P=0.028) and were independently associated with a longer time to tumor recurrence after intrahepatic cholangiocarcinoma resection in multivariate analysis (P=0.021).", "IDH1 and IDH2 mutations were significantly associated with increased levels of p53 in intrahepatic cholangiocarcinomas, but no mutations in the p53 gene were found, suggesting that mutations in IDH1 and IDH2 may cause a stress that leads to p53 activation.", "We identified 2309 genes that were significantly hypermethylated in 19 cholangiocarcinomas with mutations in IDH1 or IDH2, compared with cholangiocarcinomas without these mutations.", "Hypermethylated CpG sites were significantly enriched in CpG shores and upstream of transcription start sites, suggesting a global regulation of transcriptional potential.", "Half of the hypermethylated genes overlapped with DNA hypermethylation in IDH1-mutant gliobastomas, suggesting the existence of a common set of genes whose expression may be affected by mutations in IDH1 or IDH2 in different types of tumors."], "title": "Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas."}
{"paper_id": 24324617, "labels": ["0", "0", "0", "0", "1", "0", "1"], "abstract": "Mina is an epigenetic gene regulatory protein known to function in multiple physiological and pathological contexts, including pulmonary inflammation, cell proliferation, cancer and immunity. We showed previously that the level of Mina gene expression is subject to natural genetic variation linked to 21 SNPs occurring in the Mina 5' region. In order to explore the mechanisms regulating Mina gene expression, we set out to molecularly characterize the Mina promoter in the region encompassing these SNPs. We used three kinds of assays--reporter, gel shift and chromatin immunoprecipitation--to analyze a 2 kb genomic fragment spanning the upstream and intron 1 regions flanking exon 1. Here we discovered a pair of Mina promoters (P1 and P2) and a P1-specific enhancer element (E1). Pharmacologic inhibition and siRNA knockdown experiments suggested that Sp1/3 transcription factors trigger Mina expression through additive activity targeted to a cluster of four Sp1/3 binding sites forming the P1 promoter. These results set the stage for comprehensive analysis of Mina gene regulation from the context of tissue specificity, the impact of inherited genetic variation and the nature of upstream signaling pathways.", "journal": "PloS one", "sentences": ["Mina is an epigenetic gene regulatory protein known to function in multiple physiological and pathological contexts, including pulmonary inflammation, cell proliferation, cancer and immunity.", "We showed previously that the level of Mina gene expression is subject to natural genetic variation linked to 21 SNPs occurring in the Mina 5' region.", "In order to explore the mechanisms regulating Mina gene expression, we set out to molecularly characterize the Mina promoter in the region encompassing these SNPs.", "We used three kinds of assays--reporter, gel shift and chromatin immunoprecipitation--to analyze a 2 kb genomic fragment spanning the upstream and intron 1 regions flanking exon 1.", "Here we discovered a pair of Mina promoters (P1 and P2) and a P1-specific enhancer element (E1).", "Pharmacologic inhibition and siRNA knockdown experiments suggested that Sp1/3 transcription factors trigger Mina expression through additive activity targeted to a cluster of four Sp1/3 binding sites forming the P1 promoter.", "These results set the stage for comprehensive analysis of Mina gene regulation from the context of tissue specificity, the impact of inherited genetic variation and the nature of upstream signaling pathways."], "title": "Transcriptional activation of Mina by Sp1/3 factors."}
{"paper_id": 19403532, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "A new Homo erectus endocast, Zhoukoudian (ZKD) V, is assessed by comparing it with ZKD II, ZKD III, ZKD X, ZKD XI, ZKD XII, Hexian, Trinil II, Sambungmacan (Sm) 3, Sangiran 2, Sangiran 17, KNM-ER 3733, KNM-WT 15 000, Kabwe, Liujiang and 31 modern Chinese. The endocast of ZKD V has an estimated endocranial volume of 1140 ml. As the geological age of ZKD V is younger than the other ZKD H. erectus, evolutionary changes in brain morphology are evaluated. The brain size of the ZKD specimens increases slightly over time. Compared with the other ZKD endocasts, ZKD V shows important differences, including broader frontal and occipital lobes, some indication of fuller parietal lobes, and relatively large brain size that reflect significant trends documented in later hominin brain evolution. Bivariate and principal component analyses indicate that geographical variation does not characterize the ZKD, African and other Asian specimens. The ZKD endocasts share some common morphological and morphometric features with other H. erectus endocasts that distinguish them from Homo sapiens.", "journal": "Proceedings. Biological sciences / The Royal Society", "sentences": ["A new Homo erectus endocast, Zhoukoudian (ZKD) V, is assessed by comparing it with ZKD II, ZKD III, ZKD X, ZKD XI, ZKD XII, Hexian, Trinil II, Sambungmacan (Sm) 3, Sangiran 2, Sangiran 17, KNM-ER 3733, KNM-WT 15 000, Kabwe, Liujiang and 31 modern Chinese.", "The endocast of ZKD V has an estimated endocranial volume of 1140 ml.", "As the geological age of ZKD V is younger than the other ZKD H. erectus, evolutionary changes in brain morphology are evaluated.", "The brain size of the ZKD specimens increases slightly over time.", "Compared with the other ZKD endocasts, ZKD V shows important differences, including broader frontal and occipital lobes, some indication of fuller parietal lobes, and relatively large brain size that reflect significant trends documented in later hominin brain evolution.", "Bivariate and principal component analyses indicate that geographical variation does not characterize the ZKD, African and other Asian specimens.", "The ZKD endocasts share some common morphological and morphometric features with other H. erectus endocasts that distinguish them from Homo sapiens."], "title": "A new Homo erectus (Zhoukoudian V) brain endocast from China."}
{"paper_id": 26385968, "labels": ["0", "0", "0", "1", "0", "1", "1"], "abstract": "Contrary to the pattern seen in mammalian sex chromosomes, where most Y-linked genes have X-linked homologs, the Drosophila X and Y chromosomes appear to be unrelated. Most of the Y-linked genes have autosomal paralogs, so autosome-to-Y transposition must be the main source of Drosophila Y-linked genes. Here we show how these genes were acquired. We found a previously unidentified gene (flagrante delicto Y, FDY) that originated from a recent duplication of the autosomal gene vig2 to the Y chromosome of Drosophila melanogaster. Four contiguous genes were duplicated along with vig2, but they became pseudogenes through the accumulation of deletions and transposable element insertions, whereas FDY remained functional, acquired testis-specific expression, and now accounts for \u223c20% of the vig2-like mRNA in testis. FDY is absent in the closest relatives of D. melanogaster, and DNA sequence divergence indicates that the duplication to the Y chromosome occurred \u223c2 million years ago. Thus, FDY provides a snapshot of the early stages of the establishment of a Y-linked gene and demonstrates how the Drosophila Y has been accumulating autosomal genes.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Contrary to the pattern seen in mammalian sex chromosomes, where most Y-linked genes have X-linked homologs, the Drosophila X and Y chromosomes appear to be unrelated.", "Most of the Y-linked genes have autosomal paralogs, so autosome-to-Y transposition must be the main source of Drosophila Y-linked genes.", "Here we show how these genes were acquired.", "We found a previously unidentified gene (flagrante delicto Y, FDY) that originated from a recent duplication of the autosomal gene vig2 to the Y chromosome of Drosophila melanogaster.", "Four contiguous genes were duplicated along with vig2, but they became pseudogenes through the accumulation of deletions and transposable element insertions, whereas FDY remained functional, acquired testis-specific expression, and now accounts for \u223c20% of the vig2-like mRNA in testis.", "FDY is absent in the closest relatives of D. melanogaster, and DNA sequence divergence indicates that the duplication to the Y chromosome occurred \u223c2 million years ago.", "Thus, FDY provides a snapshot of the early stages of the establishment of a Y-linked gene and demonstrates how the Drosophila Y has been accumulating autosomal genes."], "title": "Birth of a new gene on the Y chromosome of Drosophila melanogaster."}
{"paper_id": 20494105, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The text book view of cell surface receptors depicts them at the top of a vertical chain of command that starts with ligand binding and proceeds in a lineal fashion towards the cell nucleus. Although pedagogically useful, this view is incomplete and recent findings suggest that the extracellular domain of cell surface receptors can be a transmitter as much as a receiver in intercellular communication. GFRalpha1 is a GPI-anchored receptor for GDNF (glial cell line-derived neurotrophic factor), a neuronal growth factor with widespread functions in the developing and adult nervous system. GFRalpha1 partners with transmembrane proteins, such as the receptor tyrosine kinase RET or the cell adhesion molecule NCAM, for intracellular transmission of the GDNF signal. In addition to this canonical role, GFRalpha1 can also engage in horizontal interactions and thereby modify the function of other cell surface components. GFRalpha1 can also function as a ligand-induced adhesion cell molecule, mediating homophilic cell-cell interactions in response to GDNF. Finally, GFRalpha1 can also be released from the cell surface and act at a distance as a soluble factor together with its ligand. This plethora of unconventional mechanisms is likely to be a feature common to several other receptors and considerably expands our view of cell surface receptor function.", "journal": "Biochemical and biophysical research communications", "sentences": ["The text book view of cell surface receptors depicts them at the top of a vertical chain of command that starts with ligand binding and proceeds in a lineal fashion towards the cell nucleus.", "Although pedagogically useful, this view is incomplete and recent findings suggest that the extracellular domain of cell surface receptors can be a transmitter as much as a receiver in intercellular communication.", "GFRalpha1 is a GPI-anchored receptor for GDNF (glial cell line-derived neurotrophic factor), a neuronal growth factor with widespread functions in the developing and adult nervous system.", "GFRalpha1 partners with transmembrane proteins, such as the receptor tyrosine kinase RET or the cell adhesion molecule NCAM, for intracellular transmission of the GDNF signal.", "In addition to this canonical role, GFRalpha1 can also engage in horizontal interactions and thereby modify the function of other cell surface components.", "GFRalpha1 can also function as a ligand-induced adhesion cell molecule, mediating homophilic cell-cell interactions in response to GDNF.", "Finally, GFRalpha1 can also be released from the cell surface and act at a distance as a soluble factor together with its ligand.", "This plethora of unconventional mechanisms is likely to be a feature common to several other receptors and considerably expands our view of cell surface receptor function."], "title": "Beyond the cell surface: new mechanisms of receptor function."}
{"paper_id": 27249220, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "In November and December 2013, unidentified human skeletal remains buried in a mokgwakmyo (a traditional wooden coffin) were unearthed while conducting an archaeological investigation near Gyeongju, which was the capital of the Silla Kingdom (57 BCE- 660 CE) of ancient Korea. The human skeletal remains were preserved in relatively intact condition. In an attempt to obtain biological information on the skeleton, physical anthropological, mitochondrial DNA, stable isotope and craniofacial analyses were carried out. The results indicated that the individual was a female from the Silla period, of 155 \u00b1 5 cm height, who died in her late thirties. The maternal lineage belonged to the haplogroup F1b1a, typical for East Asia, and the diet had been more C3- (wheat, rice and potatoes) than C4-based (maize, millet and other tropical grains). Finally, the face of the individual was reconstructed utilizing the skull (restored from osseous fragments) and three-dimensional computerized modeling system. This study, applying multi-dimensional approaches within an overall bio-anthropological analysis, was the first attempt to collect holistic biological information on human skeletal remains dating to the Silla Kingdom period of ancient Korea.", "journal": "PloS one", "sentences": ["In November and December 2013, unidentified human skeletal remains buried in a mokgwakmyo (a traditional wooden coffin) were unearthed while conducting an archaeological investigation near Gyeongju, which was the capital of the Silla Kingdom (57 BCE- 660 CE) of ancient Korea.", "The human skeletal remains were preserved in relatively intact condition.", "In an attempt to obtain biological information on the skeleton, physical anthropological, mitochondrial DNA, stable isotope and craniofacial analyses were carried out.", "The results indicated that the individual was a female from the Silla period, of 155 \u00b1 5 cm height, who died in her late thirties.", "The maternal lineage belonged to the haplogroup F1b1a, typical for East Asia, and the diet had been more C3- (wheat, rice and potatoes) than C4-based (maize, millet and other tropical grains).", "Finally, the face of the individual was reconstructed utilizing the skull (restored from osseous fragments) and three-dimensional computerized modeling system.", "This study, applying multi-dimensional approaches within an overall bio-anthropological analysis, was the first attempt to collect holistic biological information on human skeletal remains dating to the Silla Kingdom period of ancient Korea."], "title": "Bio-Anthropological Studies on Human Skeletons from the 6th Century Tomb of Ancient Silla Kingdom in South Korea."}
{"paper_id": 26540051, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5) were treated with SPIONs, either coated with lauric acid (SEONLA) only, or additionally with a protein corona of bovine serum albumin (BSA; SEON(LA-BSA)), or with dextran (SEON(DEX)). Both micronuclei testing and the detection of \u03b3H2A.X revealed no genotoxic effects of SEON(LA-BSA), SEON(DEX) or SEON(LA). Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system.", "journal": "International journal of molecular sciences", "sentences": ["Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics.", "According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described.", "To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on granulosa cells, which are very important for ovarian function and female fertility.", "Human granulosa cells (HLG-5) were treated with SPIONs, either coated with lauric acid (SEONLA) only, or additionally with a protein corona of bovine serum albumin (BSA; SEON(LA-BSA)), or with dextran (SEON(DEX)).", "Both micronuclei testing and the detection of \u03b3H2A.X revealed no genotoxic effects of SEON(LA-BSA), SEON(DEX) or SEON(LA).", "Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system."], "title": "Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells."}
{"paper_id": 27322858, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "In this article, an implementation of the newest iteration of the Minnesota solvation model, SM12, into the Amsterdam density functional (ADF) computational package is presented. ADF makes exclusive use of Slater-type orbitals (STO), which correctly represent the true atomic orbitals for atoms, whereas SM12 and the underlying charge model 5 (CM5) have previously only been tested on Gaussian-type orbitals (GTO). This new implementation is used to prove the basis set independence of both CM5 and SM12. A detailed comparison of the SM12 and COSMO solvation models, as implemented in ADF, is also presented. We show that this new implementation of SM12 has a mean unsigned error (MUE) of 0.68 kcal/mol for 272 molecules in water solvent, 4.10 kcal/mol MUE for 112 charged ions in water, and 0.92 kcal/mol MUE for 197 solvent calculations of various molecules. SM12 outperforms COSMO for all neutral molecules and performs as well as COSMO for cationic molecules, only falling short when anionic molecules are taken into consideration, likely due to CM5's use of Hirshfeld charges and their poor description of anionic molecules, though CM5 seems to improve upon this discrepancy.", "journal": "Journal of chemical theory and computation", "sentences": ["In this article, an implementation of the newest iteration of the Minnesota solvation model, SM12, into the Amsterdam density functional (ADF) computational package is presented.", "ADF makes exclusive use of Slater-type orbitals (STO), which correctly represent the true atomic orbitals for atoms, whereas SM12 and the underlying charge model 5 (CM5) have previously only been tested on Gaussian-type orbitals (GTO).", "This new implementation is used to prove the basis set independence of both CM5 and SM12.", "A detailed comparison of the SM12 and COSMO solvation models, as implemented in ADF, is also presented.", "We show that this new implementation of SM12 has a mean unsigned error (MUE) of 0.68 kcal/mol for 272 molecules in water solvent, 4.10 kcal/mol MUE for 112 charged ions in water, and 0.92 kcal/mol MUE for 197 solvent calculations of various molecules.", "SM12 outperforms COSMO for all neutral molecules and performs as well as COSMO for cationic molecules, only falling short when anionic molecules are taken into consideration, likely due to CM5's use of Hirshfeld charges and their poor description of anionic molecules, though CM5 seems to improve upon this discrepancy."], "title": "Implementation of the SM12 Solvation Model into ADF and Comparison with COSMO."}
{"paper_id": 23671602, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "In this study, we explore the potential contributions of a risk perception framework in understanding public perceptions of unstable ecosystems. In doing so, we characterize one type of common ecological risk- harmful algal blooms (HABs)-in four of the most seriously eutrophicated freshwater lakes in China. These lakes include Chaohu, Dianchi, Hongze, and Taihu, where a total of 2000 residents living near these sites were interviewed. Regional discrepancies existed in the pilot study regarding public perceptions of ecological changes and public concerns for ecological risk. Comparing HABs and other kinds of risks (earthquake, nuclear, and public traffic) through the psychometric paradigm method, Knowledge, Effect, and Trust were three key factors formulating the risk perception model. The results indicated that Knowledge and risk tolerance levels had significant negative correlations in the higher economic situation while correlations in the lower economic situation were significantly positive. Effect and risk tolerance levels had significant negative correlations in the high and middle education situation while correlations in the low education situation were close to zero or insignificant. For residents from Taihu with comparatively higher economic and educational levels, more investment in risk prevention measures and stronger policies are needed. And for residents from Hongze and Dianchi with comparatively low economic and educational levels, improvement of the government's credibility (Trust) was the most important factor of risk tolerance, so efforts to eliminate ecological problems with the stepwise development of economic and educational levels should be implemented and gradually strengthened. In turn, this could prevent public discontent and ensure support for ecological protection policies.", "journal": "PloS one", "sentences": ["In this study, we explore the potential contributions of a risk perception framework in understanding public perceptions of unstable ecosystems.", "In doing so, we characterize one type of common ecological risk- harmful algal blooms (HABs)-in four of the most seriously eutrophicated freshwater lakes in China.", "These lakes include Chaohu, Dianchi, Hongze, and Taihu, where a total of 2000 residents living near these sites were interviewed.", "Regional discrepancies existed in the pilot study regarding public perceptions of ecological changes and public concerns for ecological risk.", "Comparing HABs and other kinds of risks (earthquake, nuclear, and public traffic) through the psychometric paradigm method, Knowledge, Effect, and Trust were three key factors formulating the risk perception model.", "The results indicated that Knowledge and risk tolerance levels had significant negative correlations in the higher economic situation while correlations in the lower economic situation were significantly positive.", "Effect and risk tolerance levels had significant negative correlations in the high and middle education situation while correlations in the low education situation were close to zero or insignificant.", "For residents from Taihu with comparatively higher economic and educational levels, more investment in risk prevention measures and stronger policies are needed.", "And for residents from Hongze and Dianchi with comparatively low economic and educational levels, improvement of the government's credibility (Trust) was the most important factor of risk tolerance, so efforts to eliminate ecological problems with the stepwise development of economic and educational levels should be implemented and gradually strengthened.", "In turn, this could prevent public discontent and ensure support for ecological protection policies."], "title": "How do the Chinese perceive ecological risk in freshwater lakes?"}
{"paper_id": 24584461, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "We developed a sensitive quantitative assay for detecting Ralstonia solanacearum in soil by most probable number (MPN) analysis based on bio-PCR results. For development of the detection method, we optimized an elution buffer containing 5\u00a0g/L skim milk for extracting bacteria from soil and reducing contamination of polymerase inhibitors in soil extracts. Because R. solanacearum can grow in water without any added nutrients, we used a cultivation buffer in the culture step of the bio-PCR that contained only the buffer and antibiotics to suppress the growth of other soil microorganisms. To quantify the bacterial population in soil, the elution buffer was added to 10\u00a0g soil on a dry weight basis so that the combined weight of buffer, soil, and soil-water was 50\u00a0g; 5\u00a0mL of soil extract was assumed to originate from 1\u00a0g of soil. The soil extract was divided into triplicate aliquots each of 5\u00a0mL and 500, 50, and 5\u00a0\u03bcL. Each aliquot was diluted with the cultivation buffer and incubated at 35 \u00b0C for about 24\u00a0h. After incubation, 5\u00a0\u03bcL of culture was directly used for nested PCR. The number of aliquots showing positive results was collectively checked against the MPN table. The method could quantify bacterial populations in soil down to 3\u00a0cfu/10\u00a0g dried soil and was successfully applied to several types of soil. We applied the method for the quantitative detection of R. solanacearum in horticultural soils, which could quantitatively detect small populations (9.3\u00a0cfu/g), but the semiselective media were not able to detect the bacteria.", "journal": "Applied microbiology and biotechnology", "sentences": ["We developed a sensitive quantitative assay for detecting Ralstonia solanacearum in soil by most probable number (MPN) analysis based on bio-PCR results.", "For development of the detection method, we optimized an elution buffer containing 5\u00a0g/L skim milk for extracting bacteria from soil and reducing contamination of polymerase inhibitors in soil extracts.", "Because R. solanacearum can grow in water without any added nutrients, we used a cultivation buffer in the culture step of the bio-PCR that contained only the buffer and antibiotics to suppress the growth of other soil microorganisms.", "To quantify the bacterial population in soil, the elution buffer was added to 10\u00a0g soil on a dry weight basis so that the combined weight of buffer, soil, and soil-water was 50\u00a0g; 5\u00a0mL of soil extract was assumed to originate from 1\u00a0g of soil.", "The soil extract was divided into triplicate aliquots each of 5\u00a0mL and 500, 50, and 5\u00a0\u03bcL.", "Each aliquot was diluted with the cultivation buffer and incubated at 35 \u00b0C for about 24\u00a0h. After incubation, 5\u00a0\u03bcL of culture was directly used for nested PCR.", "The number of aliquots showing positive results was collectively checked against the MPN table.", "The method could quantify bacterial populations in soil down to 3\u00a0cfu/10\u00a0g dried soil and was successfully applied to several types of soil.", "We applied the method for the quantitative detection of R. solanacearum in horticultural soils, which could quantitatively detect small populations (9.3\u00a0cfu/g), but the semiselective media were not able to detect the bacteria."], "title": "Sensitive quantitative detection of Ralstonia solanacearum in soil by the most probable number-polymerase chain reaction (MPN-PCR) method."}
{"paper_id": 27042471, "labels": ["0", "0", "0", "0", "0"], "abstract": "Juvenile Granulosa Cell Tumour (JGCT) of ovary represents a small fraction of all primary ovarian malignancies. It is a subtype of granulosa cell tumour that is almost always found during the first three decades of life. Histologically, it differs from the typical adult type of granulosa cell tumour. It accounts for 5-15% of all granulosa cell tumours, majority being unilateral. Herein, we describe an unusual histopathological variant of JGCT with numerous large cystic spaces, anaplasia and focal syncytiotrophoblast like giant cells.", "journal": "Journal of clinical and diagnostic research : JCDR", "sentences": ["Juvenile Granulosa Cell Tumour (JGCT) of ovary represents a small fraction of all primary ovarian malignancies.", "It is a subtype of granulosa cell tumour that is almost always found during the first three decades of life.", "Histologically, it differs from the typical adult type of granulosa cell tumour.", "It accounts for 5-15% of all granulosa cell tumours, majority being unilateral.", "Herein, we describe an unusual histopathological variant of JGCT with numerous large cystic spaces, anaplasia and focal syncytiotrophoblast like giant cells."], "title": "Juvenile Granulosa Cell Tumour: Anaplastic Variant with Omental Deposits."}
{"paper_id": 25204196, "labels": ["0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Carboxypeptidases are important mediators of cellular behavior. Through C-terminal truncations, they alter protein functionality and participate in proteome turnover. Similarly, carboxypeptidases shape the human peptidome by targeting neuroendocrine and vasoactive peptides, thereby regulating signaling pathways in the nervous and cardiovascular systems as well as in embryonic development. Carboxypeptidases are widely connected to various pathological processes such as carcinogenesis and neurodegenerative and cardiovascular diseases. The repertoire of carboxypeptidase in vivo substrates still remains poorly defined, largely due to the lack of suitable experimental approaches. Understanding the precise role of carboxypeptidases is pivotal in the future development of diagnostic/prognostic markers in such diseases. To date, very little attention has been paid to the implication of carboxypeptidases in shaping the proteome as well as the peptidome. This review focuses on the patho-physiological function of carboxypeptidases and highlights the approaches by which proteomics-based technologies can be applied to characterize carboxypeptidases and to quantify the differential regulation of proteins by carboxypeptidases in a proteome-wide manner.", "journal": "Journal of proteome research", "sentences": ["Carboxypeptidases are important mediators of cellular behavior.", "Through C-terminal truncations, they alter protein functionality and participate in proteome turnover.", "Similarly, carboxypeptidases shape the human peptidome by targeting neuroendocrine and vasoactive peptides, thereby regulating signaling pathways in the nervous and cardiovascular systems as well as in embryonic development.", "Carboxypeptidases are widely connected to various pathological processes such as carcinogenesis and neurodegenerative and cardiovascular diseases.", "The repertoire of carboxypeptidase in vivo substrates still remains poorly defined, largely due to the lack of suitable experimental approaches.", "Understanding the precise role of carboxypeptidases is pivotal in the future development of diagnostic/prognostic markers in such diseases.", "To date, very little attention has been paid to the implication of carboxypeptidases in shaping the proteome as well as the peptidome.", "This review focuses on the patho-physiological function of carboxypeptidases and highlights the approaches by which proteomics-based technologies can be applied to characterize carboxypeptidases and to quantify the differential regulation of proteins by carboxypeptidases in a proteome-wide manner."], "title": "Carboxyterminal protein processing in health and disease: key actors and emerging technologies."}
{"paper_id": 25950761, "labels": ["0", "0", "0", "0", "1", "1", "1", "1", "1", "1"], "abstract": "Protein phosphatase 2A (PP2A) is an abundant serine/threonine phosphatase that functions as a tumor suppressor in numerous cell-cell signaling pathways, including Wnt, myc, and ras. The B56 subunit of PP2A regulates its activity, and is encoded by five genes in humans. B56 proteins share a central core domain, but have divergent amino- and carboxy-termini, which are thought to provide isoform specificity. We performed phylogenetic analyses to better understand the evolution of the B56 gene family. We found that B56 was present as a single gene in eukaryotes prior to the divergence of animals, fungi, protists, and plants, and that B56 gene duplication prior to the divergence of protostomes and deuterostomes led to the origin of two B56 subfamilies, B56\u03b1\u03b2\u03b5 and B56\u03b3\u03b4. Further duplications led to three B56\u03b1\u03b2\u03b5 genes and two B56\u03b3\u03b4 in vertebrates. Several nonvertebrate B56 gene names are based on distinct vertebrate isoform names, and would best be renamed. B56 subfamily genes lack significant divergence within primitive chordates, but each became distinct in complex vertebrates. Two vertebrate lineages have undergone B56 gene loss, Xenopus and Aves. In Xenopus, B56\u03b4 function may be compensated for by an alternatively spliced transcript, B56\u03b4/\u03b3, encoding a B56\u03b4-like amino-terminal region and a B56\u03b3 core.", "journal": "International journal of molecular sciences", "sentences": ["Protein phosphatase 2A (PP2A) is an abundant serine/threonine phosphatase that functions as a tumor suppressor in numerous cell-cell signaling pathways, including Wnt, myc, and ras.", "The B56 subunit of PP2A regulates its activity, and is encoded by five genes in humans.", "B56 proteins share a central core domain, but have divergent amino- and carboxy-termini, which are thought to provide isoform specificity.", "We performed phylogenetic analyses to better understand the evolution of the B56 gene family.", "We found that B56 was present as a single gene in eukaryotes prior to the divergence of animals, fungi, protists, and plants, and that B56 gene duplication prior to the divergence of protostomes and deuterostomes led to the origin of two B56 subfamilies, B56\u03b1\u03b2\u03b5 and B56\u03b3\u03b4.", "Further duplications led to three B56\u03b1\u03b2\u03b5 genes and two B56\u03b3\u03b4 in vertebrates.", "Several nonvertebrate B56 gene names are based on distinct vertebrate isoform names, and would best be renamed.", "B56 subfamily genes lack significant divergence within primitive chordates, but each became distinct in complex vertebrates.", "Two vertebrate lineages have undergone B56 gene loss, Xenopus and Aves.", "In Xenopus, B56\u03b4 function may be compensated for by an alternatively spliced transcript, B56\u03b4/\u03b3, encoding a B56\u03b4-like amino-terminal region and a B56\u03b3 core."], "title": "Evolutionary Analysis of the B56 Gene Family of PP2A Regulatory Subunits."}
{"paper_id": 22778413, "labels": ["0", "0", "0", "0", "1"], "abstract": "The inability to acquire protective immunity against Plasmodia is the chief obstacle to malaria control, and inadequate T-cell responses may facilitate persistent blood-stage infection. Malaria is characterized by a highly inflammatory cytokine milieu, and the lack of effective protection against infection suggests that memory T cells are not adequately formed or maintained. Using a genetically targeted strain of Plasmodium berghei, we observed that the Plasmodium ortholog of macrophage migration inhibitory factor enhanced inflammatory cytokine production and also induced antigen-experienced CD4 T cells to develop into short-lived effector cells rather than memory precursor cells. The short-lived effector CD4 T cells were more susceptible to Bcl-2-associated apoptosis, resulting in decreased CD4 T-cell recall responses against challenge infections. These findings indicate that Plasmodia actively interfere with the development of immunological memory and may account for the evolutionary conservation of parasite macrophage migration inhibitory factor orthologs.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["The inability to acquire protective immunity against Plasmodia is the chief obstacle to malaria control, and inadequate T-cell responses may facilitate persistent blood-stage infection.", "Malaria is characterized by a highly inflammatory cytokine milieu, and the lack of effective protection against infection suggests that memory T cells are not adequately formed or maintained.", "Using a genetically targeted strain of Plasmodium berghei, we observed that the Plasmodium ortholog of macrophage migration inhibitory factor enhanced inflammatory cytokine production and also induced antigen-experienced CD4 T cells to develop into short-lived effector cells rather than memory precursor cells.", "The short-lived effector CD4 T cells were more susceptible to Bcl-2-associated apoptosis, resulting in decreased CD4 T-cell recall responses against challenge infections.", "These findings indicate that Plasmodia actively interfere with the development of immunological memory and may account for the evolutionary conservation of parasite macrophage migration inhibitory factor orthologs."], "title": "A Plasmodium-encoded cytokine suppresses T-cell immunity during malaria."}
{"paper_id": 20085755, "labels": ["0", "0", "0", "0", "1", "1", "1"], "abstract": "It is well known that spinal motoneurons below a spinal transection become supersensitive to a systemic administration of serotonin (5-HT) precursors, such as 5-hydroxytryptophan. This supersensitivity has been implicated in both the process of functional recovery following chronic lesions, and also in the development of symptoms such as hyperreflexia and spasticity. However, the mechanisms of this denervation supersensitivity are still largely unknown. In this study we have investigated the changes in 5-HT2A receptor immunoreactivity following chronic spinal transections at the level of the sacrocaudal spinal cord. The results show that in the spinalized rats the immunoreactivity of 5-HT2A receptors below the lesion is dramatically increased in the motoneuron soma and its proximal dendritic territory, most likely also in their distal dendritic territory, to a level 3-5-fold higher than that of sham-operated rats. We also found a small number of intraspinal 5-HT neurons and clusters of 5-HT fibers and their varicosities in the spinal cord caudal to the lesion, which may provide an intrinsic source of 5-HT to act upon the upregulated 5-HT2A receptors. These results indicate that the upregulation of 5-HT2A receptors at least partly underlies the 5-HT denervation supersensitivity of spinal motoneurons after a complete spinal transection.", "journal": "Brain research", "sentences": ["It is well known that spinal motoneurons below a spinal transection become supersensitive to a systemic administration of serotonin (5-HT) precursors, such as 5-hydroxytryptophan.", "This supersensitivity has been implicated in both the process of functional recovery following chronic lesions, and also in the development of symptoms such as hyperreflexia and spasticity.", "However, the mechanisms of this denervation supersensitivity are still largely unknown.", "In this study we have investigated the changes in 5-HT2A receptor immunoreactivity following chronic spinal transections at the level of the sacrocaudal spinal cord.", "The results show that in the spinalized rats the immunoreactivity of 5-HT2A receptors below the lesion is dramatically increased in the motoneuron soma and its proximal dendritic territory, most likely also in their distal dendritic territory, to a level 3-5-fold higher than that of sham-operated rats.", "We also found a small number of intraspinal 5-HT neurons and clusters of 5-HT fibers and their varicosities in the spinal cord caudal to the lesion, which may provide an intrinsic source of 5-HT to act upon the upregulated 5-HT2A receptors.", "These results indicate that the upregulation of 5-HT2A receptors at least partly underlies the 5-HT denervation supersensitivity of spinal motoneurons after a complete spinal transection."], "title": "Robust upregulation of serotonin 2A receptors after chronic spinal transection of rats: an immunohistochemical study."}
{"paper_id": 25722113, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Radiotherapy and chemotherapy are targeted primarily at rapidly proliferating cancer cells and are unable to eliminate cancer stem cells in the G0 phase. Thus, these treatments cannot prevent the recurrence and metastasis of cancer. Understanding the mechanisms by which cancer stem cells are maintained in the dormant G0 phase, and how they become active is key to developing new cancer therapies. The current study found that the anti-cancer drug 5-fluorouracil, acting on the oral squamous cell carcinoma KB cell line, selectively killed proliferating cells while sparing cells in the G0 phase. Bisulfite sequencing PCR showed that demethylation of the Sox2 promoter led to the expression of Sox2. This then resulted in the transformation of cancer stem cells from the G0 phase to the division stage and suggested that the transformation of cancer stem cells from the G0 phase to the division stage is closely related to an epigenetic modification of the cell.", "journal": "Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine", "sentences": ["Radiotherapy and chemotherapy are targeted primarily at rapidly proliferating cancer cells and are unable to eliminate cancer stem cells in the G0 phase.", "Thus, these treatments cannot prevent the recurrence and metastasis of cancer.", "Understanding the mechanisms by which cancer stem cells are maintained in the dormant G0 phase, and how they become active is key to developing new cancer therapies.", "The current study found that the anti-cancer drug 5-fluorouracil, acting on the oral squamous cell carcinoma KB cell line, selectively killed proliferating cells while sparing cells in the G0 phase.", "Bisulfite sequencing PCR showed that demethylation of the Sox2 promoter led to the expression of Sox2.", "This then resulted in the transformation of cancer stem cells from the G0 phase to the division stage and suggested that the transformation of cancer stem cells from the G0 phase to the division stage is closely related to an epigenetic modification of the cell."], "title": "Dormancy activation mechanism of oral cavity cancer stem cells."}
{"paper_id": 26696987, "labels": ["0", "0", "0", "1", "1", "0", "1", "1"], "abstract": "Recent years have seen significant progress in understanding basic bacterial cell cycle properties such as cell growth and cell division. While characterization and regulation of bacterial cell cycle is quite well-documented in the case of fast growing aerobic model organisms, no data has been so far reported for anaerobic bacteria. This lack of information in anaerobic microorganisms can mainly be explained by the absence of molecular and cellular tools such as single cell microscopy and fluorescent probes usable for anaerobes and essential to study cellular events and/or subcellular localization of the actors involved in cell cycle. In this study, single-cell microscopy has been adapted to study for the first time, in real time, the cell cycle of a bacterial anaerobe, Desulfovibrio vulgaris Hildenborough (DvH). This single-cell analysis provides mechanistic insights into the cell division cycle of DvH, which seems to be governed by the recently discussed so-called incremental model that generates remarkably homogeneous cell sizes. Furthermore, cell division was reversibly blocked during oxygen exposure. This may constitute a strategy for anaerobic cells to cope with transient exposure to oxygen that they may encounter in their natural environment, thereby contributing to their aerotolerance. This study lays the foundation for the first molecular, single-cell assay that will address factors that cannot otherwise be resolved in bulk assays and that will allow visualization of a wide range of molecular mechanisms within living anaerobic cells.", "journal": "Frontiers in microbiology", "sentences": ["Recent years have seen significant progress in understanding basic bacterial cell cycle properties such as cell growth and cell division.", "While characterization and regulation of bacterial cell cycle is quite well-documented in the case of fast growing aerobic model organisms, no data has been so far reported for anaerobic bacteria.", "This lack of information in anaerobic microorganisms can mainly be explained by the absence of molecular and cellular tools such as single cell microscopy and fluorescent probes usable for anaerobes and essential to study cellular events and/or subcellular localization of the actors involved in cell cycle.", "In this study, single-cell microscopy has been adapted to study for the first time, in real time, the cell cycle of a bacterial anaerobe, Desulfovibrio vulgaris Hildenborough (DvH).", "This single-cell analysis provides mechanistic insights into the cell division cycle of DvH, which seems to be governed by the recently discussed so-called incremental model that generates remarkably homogeneous cell sizes.", "Furthermore, cell division was reversibly blocked during oxygen exposure.", "This may constitute a strategy for anaerobic cells to cope with transient exposure to oxygen that they may encounter in their natural environment, thereby contributing to their aerotolerance.", "This study lays the foundation for the first molecular, single-cell assay that will address factors that cannot otherwise be resolved in bulk assays and that will allow visualization of a wide range of molecular mechanisms within living anaerobic cells."], "title": "Single-Cell Analysis of Growth and Cell Division of the Anaerobe Desulfovibrio vulgaris Hildenborough."}
{"paper_id": 26512617, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Adult onset asthma and periocular xanthogranuloma (AAPOX) is a rare non-Langerhans histiocytosis characterized histopathologically by a periocular infiltration of foamy histiocytes and Touton giant cells. Benign hyperplasia with plasma cell infiltration is classically described in eyelids or lymph nodes of AAPOX patients. It is also a characteristic feature of IgG4-related disease (IgG4-RD), a new entity defined by an IgG4-bearing plasma cell infiltration of organs.To determine if AAPOX syndrome shares clinical, biological, and histopathological characteristics with IgG4-RD, we used the comprehensive clinical diagnostic criteria for IgG4-RD in a retrospective case series of three consecutive patients with histologically-proven AAPOX. Patients who were diagnosed with AAPOX at a French academic referral center for orbital inflammation between November 1996 and March 2013 were enrolled. Biopsies from ocular adnexa or other organs were systematically reexamined. For each patient, clinical and serological data, radiologic findings, and treatment were retrospectively analyzed.Two AAPOX patients fulfilled all of the diagnostic criteria for a definite IgG4-RD. One patient who lacked the serological criteria fulfilled the criteria of a probable IgG4-RD.These 3 cases of AAPOX patients fulfilled the IgG4-RD comprehensive clinical diagnostic criteria. To our knowledge, this is the first observational case report study to clearly show a strong relationship between IgG4-RD and AAPOX syndrome.", "journal": "Medicine", "sentences": ["Adult onset asthma and periocular xanthogranuloma (AAPOX) is a rare non-Langerhans histiocytosis characterized histopathologically by a periocular infiltration of foamy histiocytes and Touton giant cells.", "Benign hyperplasia with plasma cell infiltration is classically described in eyelids or lymph nodes of AAPOX patients.", "It is also a characteristic feature of IgG4-related disease (IgG4-RD), a new entity defined by an IgG4-bearing plasma cell infiltration of organs.To determine if AAPOX syndrome shares clinical, biological, and histopathological characteristics with IgG4-RD, we used the comprehensive clinical diagnostic criteria for IgG4-RD in a retrospective case series of three consecutive patients with histologically-proven AAPOX.", "Patients who were diagnosed with AAPOX at a French academic referral center for orbital inflammation between November 1996 and March 2013 were enrolled.", "Biopsies from ocular adnexa or other organs were systematically reexamined.", "For each patient, clinical and serological data, radiologic findings, and treatment were retrospectively analyzed.Two AAPOX patients fulfilled all of the diagnostic criteria for a definite IgG4-RD.", "One patient who lacked the serological criteria fulfilled the criteria of a probable IgG4-RD.These 3 cases of AAPOX patients fulfilled the IgG4-RD comprehensive clinical diagnostic criteria.", "To our knowledge, this is the first observational case report study to clearly show a strong relationship between IgG4-RD and AAPOX syndrome."], "title": "Adult Onset Asthma and Periocular Xanthogranuloma (AAPOX), a Rare Entity With a Strong Link to IgG4-Related Disease: An Observational Case Report Study."}
{"paper_id": 22980979, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Ubiquitin-dependent signaling during the DNA damage response (DDR) to double-strand breaks (DSBs) is initiated by two E3 ligases, RNF8 and RNF168, targeting histone H2A and H2AX. RNF8 is the first ligase recruited to the damage site, and RNF168 follows RNF8-dependent ubiquitination. This suggests that RNF8 initiates H2A/H2AX ubiquitination with K63-linked ubiquitin chains and RNF168 extends them. Here, we show that RNF8 is inactive toward nucleosomal H2A, whereas RNF168 catalyzes the monoubiquitination of the histones specifically on K13-15. Structure-based mutagenesis of RNF8 and RNF168 RING domains shows that\u00a0a charged residue determines whether nucleosomal proteins are recognized. We find that K63 ubiquitin chains are conjugated to RNF168-dependent H2A/H2AX monoubiquitination at K13-15 and not on K118-119. Using a mutant of RNF168 unable to target histones but still catalyzing ubiquitin chains at DSBs, we show that ubiquitin chains per se are insufficient for signaling, but RNF168 target ubiquitination is required for DDR.", "journal": "Cell", "sentences": ["Ubiquitin-dependent signaling during the DNA damage response (DDR) to double-strand breaks (DSBs) is initiated by two E3 ligases, RNF8 and RNF168, targeting histone H2A and H2AX.", "RNF8 is the first ligase recruited to the damage site, and RNF168 follows RNF8-dependent ubiquitination.", "This suggests that RNF8 initiates H2A/H2AX ubiquitination with K63-linked ubiquitin chains and RNF168 extends them.", "Here, we show that RNF8 is inactive toward nucleosomal H2A, whereas RNF168 catalyzes the monoubiquitination of the histones specifically on K13-15.", "Structure-based mutagenesis of RNF8 and RNF168 RING domains shows that\u00a0a charged residue determines whether nucleosomal proteins are recognized.", "We find that K63 ubiquitin chains are conjugated to RNF168-dependent H2A/H2AX monoubiquitination at K13-15 and not on K118-119.", "Using a mutant of RNF168 unable to target histones but still catalyzing ubiquitin chains at DSBs, we show that ubiquitin chains per se are insufficient for signaling, but RNF168 target ubiquitination is required for DDR."], "title": "RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling."}
{"paper_id": 20421471, "labels": ["0", "0", "1", "0", "0", "0", "1"], "abstract": "Two contrasting theories have emerged that attempt to describe T-cell ligand potency, one based on the t(1/2) of the interaction and the other based on the equilibrium affinity (K(D)). Here, we have identified and studied an extensive set of T-cell receptor (TCR)-peptide-MHC (pMHC) interactions for CD4(+) cells that have differential K(D)s and kinetics of binding. Our data indicate that ligands with a short t(1/2) can be highly stimulatory if they have fast on-rates. Simple models suggest these fast kinetic ligands are stimulatory because the pMHCs bind and rebind the same TCR several times. Rebinding occurs when the TCR-pMHC on-rate outcompetes TCR-pMHC diffusion within the cell membrane, creating an aggregate t(1/2) (t(a)) that can be significantly longer than a single TCR-pMHC encounter. Accounting for t(a), ligand potency is K(D)-based when ligands have fast on-rates (k(on)) and t(1/2)-dependent when they have slow k(on). Thus, TCR-pMHC k(on) allow high-affinity short t(1/2) ligands to follow a kinetic proofreading model.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Two contrasting theories have emerged that attempt to describe T-cell ligand potency, one based on the t(1/2) of the interaction and the other based on the equilibrium affinity (K(D)).", "Here, we have identified and studied an extensive set of T-cell receptor (TCR)-peptide-MHC (pMHC) interactions for CD4(+) cells that have differential K(D)s and kinetics of binding.", "Our data indicate that ligands with a short t(1/2) can be highly stimulatory if they have fast on-rates.", "Simple models suggest these fast kinetic ligands are stimulatory because the pMHCs bind and rebind the same TCR several times.", "Rebinding occurs when the TCR-pMHC on-rate outcompetes TCR-pMHC diffusion within the cell membrane, creating an aggregate t(1/2) (t(a)) that can be significantly longer than a single TCR-pMHC encounter.", "Accounting for t(a), ligand potency is K(D)-based when ligands have fast on-rates (k(on)) and t(1/2)-dependent when they have slow k(on).", "Thus, TCR-pMHC k(on) allow high-affinity short t(1/2) ligands to follow a kinetic proofreading model."], "title": "Fast on-rates allow short dwell time ligands to activate T cells."}
{"paper_id": 21446470, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "Reported herein are the effects of the fabrication variables and surface capping of nanocrystal quantum dots (NQDs) on the characteristics of NQDs-based light-emitting diodes (LEDs). The molecular weight of the hole transport layer (HTL) material and the annealing conditions of the NQDs layer were chosen as fabrication process variables. Their effects on the layer characteristics and device efficiency were characterized. The maximum brightness varied over 50% according to the molecular weight of the HTL material. The optimized annealing temperature was shown to improve the maximum brightness by 20%. The surface-capping molecules of the NQDs were changed from conventional trioctyl phosphine/trioctyl phosphine oxide (TOPO/TOP) to pyridine and were incorporated into LEDs, and its effects on the device characteristics were discussed.", "journal": "Journal of nanoscience and nanotechnology", "sentences": ["Reported herein are the effects of the fabrication variables and surface capping of nanocrystal quantum dots (NQDs) on the characteristics of NQDs-based light-emitting diodes (LEDs).", "The molecular weight of the hole transport layer (HTL) material and the annealing conditions of the NQDs layer were chosen as fabrication process variables.", "Their effects on the layer characteristics and device efficiency were characterized.", "The maximum brightness varied over 50% according to the molecular weight of the HTL material.", "The optimized annealing temperature was shown to improve the maximum brightness by 20%.", "The surface-capping molecules of the NQDs were changed from conventional trioctyl phosphine/trioctyl phosphine oxide (TOPO/TOP) to pyridine and were incorporated into LEDs, and its effects on the device characteristics were discussed."], "title": "Improved performance of nanocrystal quantum dots-based LEDs by modifying hole transport layer."}
{"paper_id": 25006905, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "0"], "abstract": "The purpose of this retrospective study was to evaluate the long-term outcomes of using the microscopic minimally invasive approach for the treatment of nonsyndromic craniosynostosis. During the last 10 years, 180 consecutive patients with nonsyndromic craniosynostosis were treated: 67 patients were treated with microscopic minimally invasive approach, and 113 were treated with the open approach. In the microscopic group, there was 1 intraoperative complication (1.5%). There were 10 postoperative complications (14.9%), of which 9 required major reoperations and 1 required a minor procedure. The major complications occurred in 7 unicoronal patients (58.3%) and 2 metopic patients (25.0%). In the open-approach group, there were 8 complications (7.1%), 2 patients required major reoperations and 6 required minor procedures. Chi-squared test showed that there was no statistically significant difference in the overall complication rate between the microscopic and open approaches. However, in the unicoronal patients, the complication rate was significantly higher in the microscopic group (P < 0.001). In conclusion, the microscopic approach is our treatment of choice in nonsyndromic patients with sagittal and lambdoidal craniosynostosis. We no longer use the microscopic approach in patients with unicoronal or metopic craniosynostosis because of the high complication rate.", "journal": "The Journal of craniofacial surgery", "sentences": ["The purpose of this retrospective study was to evaluate the long-term outcomes of using the microscopic minimally invasive approach for the treatment of nonsyndromic craniosynostosis.", "During the last 10 years, 180 consecutive patients with nonsyndromic craniosynostosis were treated: 67 patients were treated with microscopic minimally invasive approach, and 113 were treated with the open approach.", "In the microscopic group, there was 1 intraoperative complication (1.5%).", "There were 10 postoperative complications (14.9%), of which 9 required major reoperations and 1 required a minor procedure.", "The major complications occurred in 7 unicoronal patients (58.3%) and 2 metopic patients (25.0%).", "In the open-approach group, there were 8 complications (7.1%), 2 patients required major reoperations and 6 required minor procedures.", "Chi-squared test showed that there was no statistically significant difference in the overall complication rate between the microscopic and open approaches.", "However, in the unicoronal patients, the complication rate was significantly higher in the microscopic group (P < 0.001).", "In conclusion, the microscopic approach is our treatment of choice in nonsyndromic patients with sagittal and lambdoidal craniosynostosis.", "We no longer use the microscopic approach in patients with unicoronal or metopic craniosynostosis because of the high complication rate."], "title": "Microscopic versus open approach to craniosynostosis: a long-term outcomes comparison."}
{"paper_id": 26151378, "labels": ["0", "0", "0", "0", "0", "1", "1", "1", "1"], "abstract": "Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of high-risk atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using (18)F-sodium fluoride ((18)F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of (18)F-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse (18)F-NaF binding. We show that (18)F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. (18)F-NaF PET/CT imaging can distinguish between areas of macro- and microcalcification. This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis. The use of (18)F-NaF may foster new approaches to developing treatments for vascular calcification.", "journal": "Nature communications", "sentences": ["Vascular calcification is a complex biological process that is a hallmark of atherosclerosis.", "While macrocalcification confers plaque stability, microcalcification is a key feature of high-risk atheroma and is associated with increased morbidity and mortality.", "Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using (18)F-sodium fluoride ((18)F-NaF) has the potential to identify pathologically high-risk nascent microcalcification.", "However, the precise molecular mechanism of (18)F-NaF vascular uptake is still unknown.", "Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse (18)F-NaF binding.", "We show that (18)F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific.", "(18)F-NaF PET/CT imaging can distinguish between areas of macro- and microcalcification.", "This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis.", "The use of (18)F-NaF may foster new approaches to developing treatments for vascular calcification."], "title": "Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography."}
{"paper_id": 22942703, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "The mechanisms underlying the pathogenesis of idiopathic pulmonary fibrosis (IPF) involve multiple pathways, such as inflammation, epithelial mesenchymal transition, coagulation, oxidative stress, and developmental processes. The small GTPase, RhoA, and its target protein, Rho-kinase (ROCK), may interact with other signaling pathways known to contribute to pulmonary fibrosis. This study aimed to determine the beneficial effects and mechanisms of fasudil, a selective ROCK inhibitor, on bleomycin-induced pulmonary fibrosis in mice. Our results showed that the Aschcroft score and hydroxyproline content of the bleomycin-treated mouse lung decreased in response to fasudil treatment. The number of infiltrated inflammatory cells in the bronchoalveolar lavage fluid (BALF) was attenuated by fasudil. In addition, fasudil reduced the production of transforming growth factor-\u03b21 (TGF-\u03b21), connective tissue growth factor (CTGF), alpha-smooth muscle actin (\u03b1-SMA), and plasminogen activator inhibitor-1 (PAI-1) mRNA and protein expression in bleomycin-induced pulmonary fibrosis. These findings suggest that fasudil may be a potential therapeutic candidate for the treatment of pulmonary fibrosis.", "journal": "International journal of molecular sciences", "sentences": ["The mechanisms underlying the pathogenesis of idiopathic pulmonary fibrosis (IPF) involve multiple pathways, such as inflammation, epithelial mesenchymal transition, coagulation, oxidative stress, and developmental processes.", "The small GTPase, RhoA, and its target protein, Rho-kinase (ROCK), may interact with other signaling pathways known to contribute to pulmonary fibrosis.", "This study aimed to determine the beneficial effects and mechanisms of fasudil, a selective ROCK inhibitor, on bleomycin-induced pulmonary fibrosis in mice.", "Our results showed that the Aschcroft score and hydroxyproline content of the bleomycin-treated mouse lung decreased in response to fasudil treatment.", "The number of infiltrated inflammatory cells in the bronchoalveolar lavage fluid (BALF) was attenuated by fasudil.", "In addition, fasudil reduced the production of transforming growth factor-\u03b21 (TGF-\u03b21), connective tissue growth factor (CTGF), alpha-smooth muscle actin (\u03b1-SMA), and plasminogen activator inhibitor-1 (PAI-1) mRNA and protein expression in bleomycin-induced pulmonary fibrosis.", "These findings suggest that fasudil may be a potential therapeutic candidate for the treatment of pulmonary fibrosis."], "title": "Fasudil, a Rho-kinase inhibitor, attenuates bleomycin-induced pulmonary fibrosis in mice."}
{"paper_id": 21881560, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The current picture of galaxy evolution advocates co-evolution of galaxies and their nuclear massive black holes, through accretion and galactic merging. Pairs of quasars, each with a massive black hole at the centre of its galaxy, have separations of 6,000 to 300,000 light years (refs 2 and 3; 1 parsec = 3.26 light years) and exemplify the first stages of this gravitational interaction. The final stages of the black-hole merging process, through binary black holes and final collapse into a single black hole with gravitational wave emission, are consistent with the sub-light-year separation inferred from the optical spectra and light-variability of two such quasars. The double active nuclei of a few nearby galaxies with disrupted morphology and intense star formation (such as NGC 6240 with a separation of about 2,600 light years and Mrk 463 with a separation of about 13,000 light years between the nuclei) demonstrate the importance of major mergers of equal-mass spiral galaxies in this evolution; such mergers lead to an elliptical galaxy, as in the case of the double-radio-nucleus elliptical galaxy 0402+379 (with a separation of about 24 light years between the nuclei). Minor mergers of a spiral galaxy with a smaller companion should be a more common occurrence, evolving into spiral galaxies with active massive black-hole pairs, but have hitherto not been seen. Here we report the presence of two active massive black holes, separated by about 490 light years, in the Seyfert galaxy NGC 3393 (50 Mpc, about 160 million light years). The regular spiral morphology and predominantly old circum-nuclear stellar population of this galaxy, and the closeness of the black holes embedded in the bulge, provide a hitherto missing observational point to the study of galaxy/black hole evolution. Comparison of our observations with current theoretical models of mergers suggests that they are the result of minor merger evolution.", "journal": "Nature", "sentences": ["The current picture of galaxy evolution advocates co-evolution of galaxies and their nuclear massive black holes, through accretion and galactic merging.", "Pairs of quasars, each with a massive black hole at the centre of its galaxy, have separations of 6,000 to 300,000 light years (refs 2 and 3; 1 parsec = 3.26 light years) and exemplify the first stages of this gravitational interaction.", "The final stages of the black-hole merging process, through binary black holes and final collapse into a single black hole with gravitational wave emission, are consistent with the sub-light-year separation inferred from the optical spectra and light-variability of two such quasars.", "The double active nuclei of a few nearby galaxies with disrupted morphology and intense star formation (such as NGC 6240 with a separation of about 2,600 light years and Mrk 463 with a separation of about 13,000 light years between the nuclei) demonstrate the importance of major mergers of equal-mass spiral galaxies in this evolution; such mergers lead to an elliptical galaxy, as in the case of the double-radio-nucleus elliptical galaxy 0402+379 (with a separation of about 24 light years between the nuclei).", "Minor mergers of a spiral galaxy with a smaller companion should be a more common occurrence, evolving into spiral galaxies with active massive black-hole pairs, but have hitherto not been seen.", "Here we report the presence of two active massive black holes, separated by about 490 light years, in the Seyfert galaxy NGC 3393 (50 Mpc, about 160 million light years).", "The regular spiral morphology and predominantly old circum-nuclear stellar population of this galaxy, and the closeness of the black holes embedded in the bulge, provide a hitherto missing observational point to the study of galaxy/black hole evolution.", "Comparison of our observations with current theoretical models of mergers suggests that they are the result of minor merger evolution."], "title": "A close nuclear black-hole pair in the spiral galaxy NGC 3393."}
{"paper_id": 27310556, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Lyme borreliosis is caused by the spirochete Borrelia burgdorferi sensu lato, a fastidious bacterium that replicates slowly and requires special conditions to grow in the laboratory. Borrelia isolation from clinical material is a golden standard for microbiological diagnosis of borrelial infection. Important factors that affect in vitro borrelia growth are temperature of incubation and number of borrelia cells in the sample. The aim of the study was to assess the influence of temperature on borrelia growth and survival by evaluation and comparison of growth of 31 different borrelia strains at five different temperatures and to determine the influence of different inoculums on borrelia growth at different temperatures. Borreliae were cultured in the MKP medium; the initial and final number of spirochetes was determined by dark field microscopy using Neubauer counting chamber. The growth of borrelia was defined as final number of cells/mL after three days of incubation. For all three Borrelia species, the best growth was found at 33\u00b0C, followed by 37, 28, and 23\u00b0C, while no growth was detected at 4\u00b0C (P<0.05). The growth of B. afzelii species was weaker in comparison to the other two species at 23, 28, 33 and 37\u00b0C (P<0.05), respectively. There was no statistically significant difference between the growth of B. garinii and B. burgdorferi sensu stricto at 28, 33, and 37\u00b0C (P>0.05), respectively. Inoculum had statistically significant influence on growth of all three Borrelia species at all tested temperatures except at 4\u00b0C.", "journal": "PloS one", "sentences": ["Lyme borreliosis is caused by the spirochete Borrelia burgdorferi sensu lato, a fastidious bacterium that replicates slowly and requires special conditions to grow in the laboratory.", "Borrelia isolation from clinical material is a golden standard for microbiological diagnosis of borrelial infection.", "Important factors that affect in vitro borrelia growth are temperature of incubation and number of borrelia cells in the sample.", "The aim of the study was to assess the influence of temperature on borrelia growth and survival by evaluation and comparison of growth of 31 different borrelia strains at five different temperatures and to determine the influence of different inoculums on borrelia growth at different temperatures.", "Borreliae were cultured in the MKP medium; the initial and final number of spirochetes was determined by dark field microscopy using Neubauer counting chamber.", "The growth of borrelia was defined as final number of cells/mL after three days of incubation.", "For all three Borrelia species, the best growth was found at 33\u00b0C, followed by 37, 28, and 23\u00b0C, while no growth was detected at 4\u00b0C (P<0.05).", "The growth of B. afzelii species was weaker in comparison to the other two species at 23, 28, 33 and 37\u00b0C (P<0.05), respectively.", "There was no statistically significant difference between the growth of B. garinii and B. burgdorferi sensu stricto at 28, 33, and 37\u00b0C (P>0.05), respectively.", "Inoculum had statistically significant influence on growth of all three Borrelia species at all tested temperatures except at 4\u00b0C."], "title": "Comparison of Growth of Borrelia afzelii, Borrelia garinii, and Borrelia burgdorferi Sensu Stricto at Five Different Temperatures."}
{"paper_id": 23591073, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "0", "1"], "abstract": "In the present fMRI study we investigated the responses of the anterior supramarginal gyrus (aSMG) to the observation of tool and hand actions. Three experiments were carried out. In the first, we studied the specificity of the aSMG region for tool action observation, relative to the observation of hand action, and compared it with that of neighboring parietal regions. This experiment showed that there is a clear difference between aSMG and other posterior parietal regions, i.e. the putative homologue of anterior intraparietal (phAIP) area, and the dorsal intraparietal anterior (DIPSA) area. These regions are also activated by tool action observation, but in a way not significantly different from that due to hand action observation. The second experiment revealed that aSMG is equally activated by observing a tool action and a hand action carried out without the typical finger movements, but in a rigid way, imitating a tool. This indicates that aSMG uses, as visual cues, specific tool-related kinematics parameters. The third experiment showed that aSMG is strongly influenced by a concomitant attention-demanding acuity task. Taken together, the three experiments clearly show that human anterior IPL includes a specific, high-level aSMG region devoted to tool-action observation, distinct from the biological hand-action observation circuit.", "journal": "NeuroImage", "sentences": ["In the present fMRI study we investigated the responses of the anterior supramarginal gyrus (aSMG) to the observation of tool and hand actions.", "Three experiments were carried out.", "In the first, we studied the specificity of the aSMG region for tool action observation, relative to the observation of hand action, and compared it with that of neighboring parietal regions.", "This experiment showed that there is a clear difference between aSMG and other posterior parietal regions, i.e.", "the putative homologue of anterior intraparietal (phAIP) area, and the dorsal intraparietal anterior (DIPSA) area.", "These regions are also activated by tool action observation, but in a way not significantly different from that due to hand action observation.", "The second experiment revealed that aSMG is equally activated by observing a tool action and a hand action carried out without the typical finger movements, but in a rigid way, imitating a tool.", "This indicates that aSMG uses, as visual cues, specific tool-related kinematics parameters.", "The third experiment showed that aSMG is strongly influenced by a concomitant attention-demanding acuity task.", "Taken together, the three experiments clearly show that human anterior IPL includes a specific, high-level aSMG region devoted to tool-action observation, distinct from the biological hand-action observation circuit."], "title": "Functional properties of the left parietal tool use region."}
{"paper_id": 27486413, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "The aim with the present study was to examine the relationship between the subcomponents in working memory (WM) and mathematical performance, as measured by the National tests in a sample of 597 Swedish third-grade pupils. In line with compelling evidence of other studies, individual differences in WM capacity significantly predicted mathematical performance. Dividing the sample into four groups, based on their mathematical performance, revealed that mathematical ability can be conceptualized in terms of different WM profiles. Pupils categorized as High-math performers particularly differed from the other three groups in having a significant higher phonological ability. In contrast, pupils categorized as Low-math performers were particularly characterized by having a significant lower visuo-spatial ability. Findings suggest that it is important for educators to recognize and acknowledge individual differences in WM to support mathematical achievement at an individual level.", "journal": "Frontiers in psychology", "sentences": ["The aim with the present study was to examine the relationship between the subcomponents in working memory (WM) and mathematical performance, as measured by the National tests in a sample of 597 Swedish third-grade pupils.", "In line with compelling evidence of other studies, individual differences in WM capacity significantly predicted mathematical performance.", "Dividing the sample into four groups, based on their mathematical performance, revealed that mathematical ability can be conceptualized in terms of different WM profiles.", "Pupils categorized as High-math performers particularly differed from the other three groups in having a significant higher phonological ability.", "In contrast, pupils categorized as Low-math performers were particularly characterized by having a significant lower visuo-spatial ability.", "Findings suggest that it is important for educators to recognize and acknowledge individual differences in WM to support mathematical achievement at an individual level."], "title": "Untangling the Contribution of the Subcomponents of Working Memory to Mathematical Proficiency as Measured by the National Tests: A Study among Swedish Third Graders."}
{"paper_id": 24724590, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "In the past few years, the focus of phosphoproteomics has shifted from merely qualitative to quantitative and targeted studies. Tryptic digestion is a critical step that directly affects quantification and that can be impaired by phosphorylation. Therefore, we systematically characterized the digestion efficiency of 19 nonmodified and phosphorylated model peptides. Whereas we quantified a strong reduction of tryptic cleavage within phosphorylated PKA motifs (R)-R-X-pS/pT and also R-X-X-pT sequences, (R)-R-X-pY sequences were almost unaffected. Structural prediction implied the formation of salt bridges between R/K cleavage sites and phosphoamino acids pS/pT as the main reason for impaired tryptic digestion. We evaluated different conditions to optimize the digestion of such \"resistant\" phosphopeptides, yielding a substantial improvement of digestion efficiency. We performed a quantitative large-scale phosphoproteomic analysis of human platelets to validate our findings in a complex biological sample. Here, increasing trypsin concentrations up to a trypsin to peptide ratio of 1:10 led to a significant gain (i) in the overall number of phosphorylation sites (up to 9%) and (ii) in the intensities of individual phosphopeptides, thereby improving the sensitivity of phosphopeptide quantification. Still, for certain sequences, the negative impact of phosphorylation on digestion efficiency will further complicate the analysis of phosphorylation stoichiometry.", "journal": "Journal of proteome research", "sentences": ["In the past few years, the focus of phosphoproteomics has shifted from merely qualitative to quantitative and targeted studies.", "Tryptic digestion is a critical step that directly affects quantification and that can be impaired by phosphorylation.", "Therefore, we systematically characterized the digestion efficiency of 19 nonmodified and phosphorylated model peptides.", "Whereas we quantified a strong reduction of tryptic cleavage within phosphorylated PKA motifs (R)-R-X-pS/pT and also R-X-X-pT sequences, (R)-R-X-pY sequences were almost unaffected.", "Structural prediction implied the formation of salt bridges between R/K cleavage sites and phosphoamino acids pS/pT as the main reason for impaired tryptic digestion.", "We evaluated different conditions to optimize the digestion of such \"resistant\" phosphopeptides, yielding a substantial improvement of digestion efficiency.", "We performed a quantitative large-scale phosphoproteomic analysis of human platelets to validate our findings in a complex biological sample.", "Here, increasing trypsin concentrations up to a trypsin to peptide ratio of 1:10 led to a significant gain (i) in the overall number of phosphorylation sites (up to 9%) and (ii) in the intensities of individual phosphopeptides, thereby improving the sensitivity of phosphopeptide quantification.", "Still, for certain sequences, the negative impact of phosphorylation on digestion efficiency will further complicate the analysis of phosphorylation stoichiometry."], "title": "Impact of digestion conditions on phosphoproteomics."}
{"paper_id": 26328315, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "To investigate the possibility of drug targeting via the transferrin receptor-mediated pathway, iron-saturated transferrin was conjugated with chitosan (Tr-chitosan) and complexed with doxorubicin-conjugated methoxy poly(ethylene glycol)-b-dextran succinate (DEX-DOX). DEX-DOX nanoparticles have spherical morphologies with less than 150 nm particle sizes. When Tr-chitosan was complexed with DEX-DOX nanoparticles (TR nanoparticle), particle sizes were increased to higher than 200 nm. Viability of 9L cells with treatment of doxorubicin (DOX) or DEX-DOX nanoparticle was dose-dependently decreased regardless of transferrin receptor blocking. However, cytotoxicity of TR nanoparticles was reduced by blocking of transferrin receptor. Flow cytometric analysis and confocal microscopic observation showed that fluorescence intensity of tumor cells with treatment of TR nanoparticles was significantly decreased by blocking of transferring receptor while DEX-DOX nanoparticles were not affected by blocking of transferring receptor. These results indicated that TR nanoparticles are promising candidates for brain tumor drug delivery.", "journal": "Journal of nanoscience and nanotechnology", "sentences": ["To investigate the possibility of drug targeting via the transferrin receptor-mediated pathway, iron-saturated transferrin was conjugated with chitosan (Tr-chitosan) and complexed with doxorubicin-conjugated methoxy poly(ethylene glycol)-b-dextran succinate (DEX-DOX).", "DEX-DOX nanoparticles have spherical morphologies with less than 150 nm particle sizes.", "When Tr-chitosan was complexed with DEX-DOX nanoparticles (TR nanoparticle), particle sizes were increased to higher than 200 nm.", "Viability of 9L cells with treatment of doxorubicin (DOX) or DEX-DOX nanoparticle was dose-dependently decreased regardless of transferrin receptor blocking.", "However, cytotoxicity of TR nanoparticles was reduced by blocking of transferrin receptor.", "Flow cytometric analysis and confocal microscopic observation showed that fluorescence intensity of tumor cells with treatment of TR nanoparticles was significantly decreased by blocking of transferring receptor while DEX-DOX nanoparticles were not affected by blocking of transferring receptor.", "These results indicated that TR nanoparticles are promising candidates for brain tumor drug delivery."], "title": "Delivery of Transferrin-Conjugated Polysaccharide Nanoparticles in 9L Gliosacoma Cells."}
{"paper_id": 22238671, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "The directed forgetting paradigm is frequently used to determine the ability to voluntarily suppress information. However, little is known about brain areas associated with information to forget. The present study used functional magnetic resonance imaging to determine brain activity during the encoding and retrieval phases of an item-method directed forgetting recognition task with neutral verbal material in order to apprehend all processing stages that information to forget and to remember undergoes. We hypothesized that regions supporting few selective processes, namely recollection and familiarity memory processes, working memory, inhibitory and selection processes should be differentially activated during the processing of to-be-remembered and to-be-forgotten items. Successful encoding and retrieval of items to remember engaged the entorhinal cortex, the hippocampus, the anterior medial prefrontal cortex, the left inferior parietal cortex, the posterior cingulate cortex and the precuneus; this set of regions is well known to support deep and associative encoding and retrieval processes in episodic memory. For items to forget, encoding was associated with higher activation in the right middle frontal and posterior parietal cortex, regions known to intervene in attentional control. Items to forget but nevertheless correctly recognized at retrieval yielded activation in the dorsomedial thalamus, associated with familiarity-based memory processes and in the posterior intraparietal sulcus and the anterior cingulate cortex, involved in attentional processes.", "journal": "PloS one", "sentences": ["The directed forgetting paradigm is frequently used to determine the ability to voluntarily suppress information.", "However, little is known about brain areas associated with information to forget.", "The present study used functional magnetic resonance imaging to determine brain activity during the encoding and retrieval phases of an item-method directed forgetting recognition task with neutral verbal material in order to apprehend all processing stages that information to forget and to remember undergoes.", "We hypothesized that regions supporting few selective processes, namely recollection and familiarity memory processes, working memory, inhibitory and selection processes should be differentially activated during the processing of to-be-remembered and to-be-forgotten items.", "Successful encoding and retrieval of items to remember engaged the entorhinal cortex, the hippocampus, the anterior medial prefrontal cortex, the left inferior parietal cortex, the posterior cingulate cortex and the precuneus; this set of regions is well known to support deep and associative encoding and retrieval processes in episodic memory.", "For items to forget, encoding was associated with higher activation in the right middle frontal and posterior parietal cortex, regions known to intervene in attentional control.", "Items to forget but nevertheless correctly recognized at retrieval yielded activation in the dorsomedial thalamus, associated with familiarity-based memory processes and in the posterior intraparietal sulcus and the anterior cingulate cortex, involved in attentional processes."], "title": "The neural substrates of memory suppression: a FMRI exploration of directed forgetting."}
{"paper_id": 21199792, "labels": ["0", "0", "0", "0", "0"], "abstract": "The process of cancer metastasis involves a series of sequential and complex steps. Here we give a perspective on recent results regarding noncoding transcription in cancer progression, focusing on the emerging role of long intergenic noncoding RNAs (lincRNAs). LincRNAs target chromatin modification complexes or RNA-binding proteins to alter gene expression programs. Similarly to miRNAs, lincRNAs exhibit distinct gene expression patterns in primary tumors and metastases. We discuss how lincRNAs can be used for cancer diagnosis and prognosis and serve as potential therapeutic targets.", "journal": "Cancer research", "sentences": ["The process of cancer metastasis involves a series of sequential and complex steps.", "Here we give a perspective on recent results regarding noncoding transcription in cancer progression, focusing on the emerging role of long intergenic noncoding RNAs (lincRNAs).", "LincRNAs target chromatin modification complexes or RNA-binding proteins to alter gene expression programs.", "Similarly to miRNAs, lincRNAs exhibit distinct gene expression patterns in primary tumors and metastases.", "We discuss how lincRNAs can be used for cancer diagnosis and prognosis and serve as potential therapeutic targets."], "title": "Long intergenic noncoding RNAs: new links in cancer progression."}
{"paper_id": 22902414, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Boys faced with future sterility as a result of the need of a sterilizing cancer therapy might avoid this fate by engraftment of cryopreserved immature testicular tissue after therapy is completed. Efforts to address this important survivorship issue have been encouraged by reports of the long-term survival and proliferation of human spermatogonia after xenotransplant of cryopreserved immature testicular tissue into immunocompromised murine hosts. However, spermatogenic arrest at the pachytene spermatocyte stage that occurs in this situation has been associated with a failure in sperm production. In this study, we used a prepubescent simian model to address the possibility that testicular tissue engraftment is insufficiently supported in the model to allow suitable maturation of germ cells. Briefly, we carried out autologous orthotopic grafting of cryopreserved testicular tissue from four prepubescent monkeys and one pubescent rhesus monkey after testicular irradiation and castration of the host animal. Five months after implantation of scrotal grafts, we determined that 3% to 7% of the autografts could be recovered with spermatogenesis proceeding through spermatozoa formation in 13% to 17% of the seminiferous tubules formed in the grafts. In contrast, Sertoli cell-only tubules were detected in parallel xenografts transplanted into immunocompromised mice. Our results show that cryopreservation of testicular tissue from prepubescent primates can maintain the fully functional capacity of spermatogonia to produce sperm, but that host conditions are critical for spermatogenic maturation. Furthermore, our results establish an initial perspective on the quantity of cryopreserved material needed to ensure success in preserving fertility through testicular tissue grafts.", "journal": "Cancer research", "sentences": ["Boys faced with future sterility as a result of the need of a sterilizing cancer therapy might avoid this fate by engraftment of cryopreserved immature testicular tissue after therapy is completed.", "Efforts to address this important survivorship issue have been encouraged by reports of the long-term survival and proliferation of human spermatogonia after xenotransplant of cryopreserved immature testicular tissue into immunocompromised murine hosts.", "However, spermatogenic arrest at the pachytene spermatocyte stage that occurs in this situation has been associated with a failure in sperm production.", "In this study, we used a prepubescent simian model to address the possibility that testicular tissue engraftment is insufficiently supported in the model to allow suitable maturation of germ cells.", "Briefly, we carried out autologous orthotopic grafting of cryopreserved testicular tissue from four prepubescent monkeys and one pubescent rhesus monkey after testicular irradiation and castration of the host animal.", "Five months after implantation of scrotal grafts, we determined that 3% to 7% of the autografts could be recovered with spermatogenesis proceeding through spermatozoa formation in 13% to 17% of the seminiferous tubules formed in the grafts.", "In contrast, Sertoli cell-only tubules were detected in parallel xenografts transplanted into immunocompromised mice.", "Our results show that cryopreservation of testicular tissue from prepubescent primates can maintain the fully functional capacity of spermatogonia to produce sperm, but that host conditions are critical for spermatogenic maturation.", "Furthermore, our results establish an initial perspective on the quantity of cryopreserved material needed to ensure success in preserving fertility through testicular tissue grafts."], "title": "Autologous ectopic grafting of cryopreserved testicular tissue preserves the fertility of prepubescent monkeys that receive sterilizing cytotoxic therapy."}
{"paper_id": 23149917, "labels": ["0", "0", "0", "0", "1", "1", "0", "1", "1", "0"], "abstract": "The angiopoietins Ang1 (ANGPT1) and Ang2 (ANGPT2) are secreted factors that bind to the endothelial cell-specific receptor tyrosine kinase Tie2 (TEK) and regulate angiogenesis. Ang1 activates Tie2 to promote blood vessel maturation and stabilization. In contrast, Ang2, which is highly expressed by tumor endothelial cells, is thought to inhibit Tie2 activity and destabilize blood vessels, thereby facilitating VEGF-dependent vessel growth. Here, we show that the inhibition of tumor xenograft growth caused by an Ang2-specific antibody (REGN910) is reversed by systemic administration of the Tie2 agonist Ang1. These results indicate that Ang2 blockade inhibits tumor growth by decreasing Tie2 activity, showing that Ang2 is a Tie2 activator. REGN910 treatment of tumors resulted in increased expression of genes that are repressed by Tie2 activation, providing further evidence that REGN910 inhibits Tie2 signaling. Combination treatment with REGN910 plus the VEGF blocker aflibercept reduced tumor vascularity and tumor perfusion more dramatically than either single agent, resulting in more extensive tumor cell death and more potent inhibition of tumor growth. Challenging the prevailing model of Ang2 as a destabilizing factor, our findings indicate that Ang2 plays a protective role in tumor endothelial cells by activating Tie2, thereby limiting the antivascular effects of VEGF inhibition. Thus, blockade of Ang2 might enhance the clinical benefits currently provided by anti-VEGF agents. .", "journal": "Cancer research", "sentences": ["The angiopoietins Ang1 (ANGPT1) and Ang2 (ANGPT2) are secreted factors that bind to the endothelial cell-specific receptor tyrosine kinase Tie2 (TEK) and regulate angiogenesis.", "Ang1 activates Tie2 to promote blood vessel maturation and stabilization.", "In contrast, Ang2, which is highly expressed by tumor endothelial cells, is thought to inhibit Tie2 activity and destabilize blood vessels, thereby facilitating VEGF-dependent vessel growth.", "Here, we show that the inhibition of tumor xenograft growth caused by an Ang2-specific antibody (REGN910) is reversed by systemic administration of the Tie2 agonist Ang1.", "These results indicate that Ang2 blockade inhibits tumor growth by decreasing Tie2 activity, showing that Ang2 is a Tie2 activator.", "REGN910 treatment of tumors resulted in increased expression of genes that are repressed by Tie2 activation, providing further evidence that REGN910 inhibits Tie2 signaling.", "Combination treatment with REGN910 plus the VEGF blocker aflibercept reduced tumor vascularity and tumor perfusion more dramatically than either single agent, resulting in more extensive tumor cell death and more potent inhibition of tumor growth.", "Challenging the prevailing model of Ang2 as a destabilizing factor, our findings indicate that Ang2 plays a protective role in tumor endothelial cells by activating Tie2, thereby limiting the antivascular effects of VEGF inhibition.", "Thus, blockade of Ang2 might enhance the clinical benefits currently provided by anti-VEGF agents.", "."], "title": "Angiopoietin-2 functions as a Tie2 agonist in tumor models, where it limits the effects of VEGF inhibition."}
{"paper_id": 26342031, "labels": ["0", "0", "1", "0", "0", "0", "0", "1"], "abstract": "Elevated serum concentrations of the vasoactive protein endothelin-1 (ET-1) occur in the setting of systemic inflammatory response syndrome and contribute to distal organ hypoperfusion and pulmonary hypertension. Thus, understanding the cellular source and transcriptional regulation of systemic inflammatory stress-induced ET-1 expression may reveal therapeutic targets. Using a murine model of LPS-induced septic shock, we demonstrate that the hepatic macrophage is the primary source of elevated circulating ET-1, rather than the endothelium as previously proposed. Using pharmacologic inhibitors, ET-1 promoter luciferase assays, and by silencing and overexpressing NF-\u03baB inhibitory protein I\u03baB expression, we demonstrate that LPS-induced ET-1 expression occurs via an NF-\u03baB-dependent pathway. Finally, the specific role of the cRel/p65 inhibitory protein I\u03baB\u03b2 was evaluated. Although cytoplasmic I\u03baB\u03b2 inhibits activity of cRel-containing NF-\u03baB dimers, nuclear I\u03baB\u03b2 stabilizes NF-\u03baB/DNA binding and enhances gene expression. Using targeted pharmacologic therapies to specifically prevent I\u03baB\u03b2/NF-\u03baB signaling, as well as mice genetically modified to overexpress I\u03baB\u03b2, we show that nuclear I\u03baB\u03b2 is both necessary and sufficient to drive LPS-induced ET-1 expression. Together, these results mechanistically link the innate immune response mediated by I\u03baB\u03b2/NF-\u03baB to ET-1 expression and potentially reveal therapeutic targets for patients with Gram-negative septic shock.", "journal": "Journal of immunology (Baltimore, Md. : 1950)", "sentences": ["Elevated serum concentrations of the vasoactive protein endothelin-1 (ET-1) occur in the setting of systemic inflammatory response syndrome and contribute to distal organ hypoperfusion and pulmonary hypertension.", "Thus, understanding the cellular source and transcriptional regulation of systemic inflammatory stress-induced ET-1 expression may reveal therapeutic targets.", "Using a murine model of LPS-induced septic shock, we demonstrate that the hepatic macrophage is the primary source of elevated circulating ET-1, rather than the endothelium as previously proposed.", "Using pharmacologic inhibitors, ET-1 promoter luciferase assays, and by silencing and overexpressing NF-\u03baB inhibitory protein I\u03baB expression, we demonstrate that LPS-induced ET-1 expression occurs via an NF-\u03baB-dependent pathway.", "Finally, the specific role of the cRel/p65 inhibitory protein I\u03baB\u03b2 was evaluated.", "Although cytoplasmic I\u03baB\u03b2 inhibits activity of cRel-containing NF-\u03baB dimers, nuclear I\u03baB\u03b2 stabilizes NF-\u03baB/DNA binding and enhances gene expression.", "Using targeted pharmacologic therapies to specifically prevent I\u03baB\u03b2/NF-\u03baB signaling, as well as mice genetically modified to overexpress I\u03baB\u03b2, we show that nuclear I\u03baB\u03b2 is both necessary and sufficient to drive LPS-induced ET-1 expression.", "Together, these results mechanistically link the innate immune response mediated by I\u03baB\u03b2/NF-\u03baB to ET-1 expression and potentially reveal therapeutic targets for patients with Gram-negative septic shock."], "title": "Endotoxemia Induces I\u03baB\u03b2/NF-\u03baB-Dependent Endothelin-1 Expression in Hepatic Macrophages."}
{"paper_id": 21378196, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "A reservoir of pseudogene alleles encoding the primary adhesin VlhA occurs in the avian pathogen Mycoplasma synoviae. Recombination between this reservoir and its single expression site was predicted to result in lineages of M. synoviae that each express a different vlhA allele as a consequence of host immune responses to those antigens. Such interstrain diversity at the vlhA expression site, including major differences in the predicted secondary structures of their expressed adhesins, was confirmed in 14 specimens of M. synoviae. Corresponding functional differences in the extent to which they agglutinated erythrocytes, a quantitative proxy for VlhA-mediated cytadherence, were also evident. There was a >20-fold difference between the highest- and lowest-agglutinating strains and a rheostatic distribution of intermediate phenotypes among the others (Tukey-Kramer honestly significant difference [HSD], P < 0.001). Coincubation with the sialic acid analog 2-deoxy-2,3-didehydro-N-acetylneuraminate inhibited hemagglutination in a pattern correlated with endogenous sialidase activity (r = 0.91, P < 0.001), although not consistently to the same extent that erythrocyte pretreatment with sialidase purified from Clostridium perfringens did (P < 0.05). The striking correlation between the ranked hemagglutination and endogenous sialidase activities of these strains (Spearman's r = 0.874, P < 0.001) is evidence that host-induced vlhA allele switching indirectly drives sequence diversity in the passenger sialidase gene of M. synoviae.", "journal": "Journal of bacteriology", "sentences": ["A reservoir of pseudogene alleles encoding the primary adhesin VlhA occurs in the avian pathogen Mycoplasma synoviae.", "Recombination between this reservoir and its single expression site was predicted to result in lineages of M. synoviae that each express a different vlhA allele as a consequence of host immune responses to those antigens.", "Such interstrain diversity at the vlhA expression site, including major differences in the predicted secondary structures of their expressed adhesins, was confirmed in 14 specimens of M. synoviae.", "Corresponding functional differences in the extent to which they agglutinated erythrocytes, a quantitative proxy for VlhA-mediated cytadherence, were also evident.", "There was a >20-fold difference between the highest- and lowest-agglutinating strains and a rheostatic distribution of intermediate phenotypes among the others (Tukey-Kramer honestly significant difference [HSD], P < 0.001).", "Coincubation with the sialic acid analog 2-deoxy-2,3-didehydro-N-acetylneuraminate inhibited hemagglutination in a pattern correlated with endogenous sialidase activity (r = 0.91, P < 0.001), although not consistently to the same extent that erythrocyte pretreatment with sialidase purified from Clostridium perfringens did (P < 0.05).", "The striking correlation between the ranked hemagglutination and endogenous sialidase activities of these strains (Spearman's r = 0.874, P < 0.001) is evidence that host-induced vlhA allele switching indirectly drives sequence diversity in the passenger sialidase gene of M. synoviae."], "title": "Diversity of expressed vlhA adhesin sequences and intermediate hemagglutination phenotypes in Mycoplasma synoviae."}
{"paper_id": 26249173, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "The tumor-promoting chemokine CCL5 has been implicated in malignant transformation of breast epithelial cells, with studies to date focusing mainly on basal-type breast cancers. In this study, we investigated the consequences of CCL5 deletion in the MMTV-PyMT transgenic mouse model of luminal breast cancer. In this model, primary tumor burden and pulmonary metastases were reduced significantly in CCL5-deficient subjects, an effect found to be associated with a deficit of Th2 (IL4\u207aCD4\u207a T) cells. Mechanistic investigations revealed that CCL5 activates CCR3, a highly expressed chemokine receptor on CD4\u207a T cells, and also boosts Gfi1 expression to promote the differentiation of Th2 cells, which enhance the prometastatic activity of tumor-associated myeloid cells. Clinically, polarization toward this immunosuppressive Th2 phenotype was also evident in patients with advanced luminal breast cancer. Thus, our findings showed that CCL5/CCR3 signaling promotes metastasis by inducing Th2 polarization of CD4\u207a T cells, with implications for prognosis and immunotherapy of luminal breast cancer.", "journal": "Cancer research", "sentences": ["The tumor-promoting chemokine CCL5 has been implicated in malignant transformation of breast epithelial cells, with studies to date focusing mainly on basal-type breast cancers.", "In this study, we investigated the consequences of CCL5 deletion in the MMTV-PyMT transgenic mouse model of luminal breast cancer.", "In this model, primary tumor burden and pulmonary metastases were reduced significantly in CCL5-deficient subjects, an effect found to be associated with a deficit of Th2 (IL4\u207aCD4\u207a T) cells.", "Mechanistic investigations revealed that CCL5 activates CCR3, a highly expressed chemokine receptor on CD4\u207a T cells, and also boosts Gfi1 expression to promote the differentiation of Th2 cells, which enhance the prometastatic activity of tumor-associated myeloid cells.", "Clinically, polarization toward this immunosuppressive Th2 phenotype was also evident in patients with advanced luminal breast cancer.", "Thus, our findings showed that CCL5/CCR3 signaling promotes metastasis by inducing Th2 polarization of CD4\u207a T cells, with implications for prognosis and immunotherapy of luminal breast cancer."], "title": "CCL5-Mediated Th2 Immune Polarization Promotes Metastasis in Luminal Breast Cancer."}
{"paper_id": 26688816, "labels": ["0", "0", "0", "1", "0", "0", "1"], "abstract": "In the recent decade, disease classification and biomarker discovery have become increasingly important in modern biological and medical research. ECGs are comparatively low-cost and noninvasive in screening and diagnosing heart diseases. With the development of personal ECG monitors, large amounts of ECGs are recorded and stored; therefore, fast and efficient algorithms are called for to analyze the data and make diagnosis. In this paper, an efficient and easy-to-interpret procedure of cardiac disease classification is developed through novel feature extraction methods and comparison of classifiers. Motivated by the observation that the distributions of various measures on ECGs of the diseased group are often skewed, heavy-tailed, or multimodal, we characterize the distributions by sample quantiles which outperform sample means. Three classifiers are compared in application both to all features and to dimension-reduced features by PCA: stepwise discriminant analysis (SDA), SVM, and LASSO logistic regression. It is found that SDA applied to dimension-reduced features by PCA is the most stable and effective procedure, with sensitivity, specificity, and accuracy being 89.68%, 84.62%, and 88.52%, respectively.", "journal": "BioMed research international", "sentences": ["In the recent decade, disease classification and biomarker discovery have become increasingly important in modern biological and medical research.", "ECGs are comparatively low-cost and noninvasive in screening and diagnosing heart diseases.", "With the development of personal ECG monitors, large amounts of ECGs are recorded and stored; therefore, fast and efficient algorithms are called for to analyze the data and make diagnosis.", "In this paper, an efficient and easy-to-interpret procedure of cardiac disease classification is developed through novel feature extraction methods and comparison of classifiers.", "Motivated by the observation that the distributions of various measures on ECGs of the diseased group are often skewed, heavy-tailed, or multimodal, we characterize the distributions by sample quantiles which outperform sample means.", "Three classifiers are compared in application both to all features and to dimension-reduced features by PCA: stepwise discriminant analysis (SDA), SVM, and LASSO logistic regression.", "It is found that SDA applied to dimension-reduced features by PCA is the most stable and effective procedure, with sensitivity, specificity, and accuracy being 89.68%, 84.62%, and 88.52%, respectively."], "title": "Disease Classification and Biomarker Discovery Using ECG Data."}
{"paper_id": 20219648, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Progressive dysfunction of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons during normal aging is associated in the female rat with chronic hyperprolactinemia. We assessed the effectiveness of glial cell line-derived neurotrophic factor (GDNF) gene therapy to restore TIDA neuron function in senile female rats and reverse their chronic hyperprolactinemia. Young (2.5 months) and senile (29 months) rats received a bilateral intrahypothalamic injection (10(10) pfu) of either an adenoviral vector expressing the gene for beta-galactosidase; (Y-betagal and S-betagal, respectively) or a vector expressing rat GDNF (Y-GDNF and S-GDNF, respectively). Transgenic GDNF levels in supernatants of GDNF adenovector-transduced N2a neuronal cell cultures were 25+/-4 ng/ml, as determined by bioassay. In the rats, serum prolactin (PRL) was measured at regular intervals. On day 17 animals were sacrificed and neuronal nuclear antigen (NeuN) and tyrosine hydroxylase (TH) immunoreactive cells counted in the arcuate-periventricular hypothalamic region. The S-GDNF but not the S-betagal rats, showed a significant reduction in body weight. The chronic hyperprolactinemia of the senile females was significantly ameliorated in the S-GDNF rats (P<0.05) but not in the S-betagal rats. Neither age nor GDNF induced significant changes in the number of NeuN and TH neurons. We conclude that transgenic GDNF ameliorates chronic hyperprolactinemia in aging female rats, probably by restoring TIDA neuron function.", "journal": "Neuroscience", "sentences": ["Progressive dysfunction of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons during normal aging is associated in the female rat with chronic hyperprolactinemia.", "We assessed the effectiveness of glial cell line-derived neurotrophic factor (GDNF) gene therapy to restore TIDA neuron function in senile female rats and reverse their chronic hyperprolactinemia.", "Young (2.5 months) and senile (29 months) rats received a bilateral intrahypothalamic injection (10(10) pfu) of either an adenoviral vector expressing the gene for beta-galactosidase; (Y-betagal and S-betagal, respectively) or a vector expressing rat GDNF (Y-GDNF and S-GDNF, respectively).", "Transgenic GDNF levels in supernatants of GDNF adenovector-transduced N2a neuronal cell cultures were 25+/-4 ng/ml, as determined by bioassay.", "In the rats, serum prolactin (PRL) was measured at regular intervals.", "On day 17 animals were sacrificed and neuronal nuclear antigen (NeuN) and tyrosine hydroxylase (TH) immunoreactive cells counted in the arcuate-periventricular hypothalamic region.", "The S-GDNF but not the S-betagal rats, showed a significant reduction in body weight.", "The chronic hyperprolactinemia of the senile females was significantly ameliorated in the S-GDNF rats (P<0.05) but not in the S-betagal rats.", "Neither age nor GDNF induced significant changes in the number of NeuN and TH neurons.", "We conclude that transgenic GDNF ameliorates chronic hyperprolactinemia in aging female rats, probably by restoring TIDA neuron function."], "title": "Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats."}
{"paper_id": 21304931, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "The F region downstream of the mecI gene in the SCCmec element in hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) contains two bidirectionally overlapping open reading frames (ORFs), the fudoh ORF and the psm-mec ORF. The psm-mec ORF encodes a cytolysin, phenol-soluble modulin (PSM)-mec. Transformation of the F region into the Newman strain, which is a methicillin-sensitive S. aureus (MSSA) strain, or into the MW2 (USA400) and FRP3757 (USA300) strains, which are community-acquired MRSA (CA-MRSA) strains that lack the F region, attenuated their virulence in a mouse systemic infection model. Introducing the F region to these strains suppressed colony-spreading activity and PSM\u03b1 production, and promoted biofilm formation. By producing mutations into the psm-mec ORF, we revealed that (i) both the transcription and translation products of the psm-mec ORF suppressed colony-spreading activity and promoted biofilm formation; and (ii) the transcription product of the psm-mec ORF, but not its translation product, decreased PSM\u03b1 production. These findings suggest that both the psm-mec transcript, acting as a regulatory RNA, and the PSM-mec protein encoded by the gene on the mobile genetic element SCCmec regulate the virulence of Staphylococcus aureus.", "journal": "PLoS pathogens", "sentences": ["The F region downstream of the mecI gene in the SCCmec element in hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) contains two bidirectionally overlapping open reading frames (ORFs), the fudoh ORF and the psm-mec ORF.", "The psm-mec ORF encodes a cytolysin, phenol-soluble modulin (PSM)-mec.", "Transformation of the F region into the Newman strain, which is a methicillin-sensitive S. aureus (MSSA) strain, or into the MW2 (USA400) and FRP3757 (USA300) strains, which are community-acquired MRSA (CA-MRSA) strains that lack the F region, attenuated their virulence in a mouse systemic infection model.", "Introducing the F region to these strains suppressed colony-spreading activity and PSM\u03b1 production, and promoted biofilm formation.", "By producing mutations into the psm-mec ORF, we revealed that (i) both the transcription and translation products of the psm-mec ORF suppressed colony-spreading activity and promoted biofilm formation; and (ii) the transcription product of the psm-mec ORF, but not its translation product, decreased PSM\u03b1 production.", "These findings suggest that both the psm-mec transcript, acting as a regulatory RNA, and the PSM-mec protein encoded by the gene on the mobile genetic element SCCmec regulate the virulence of Staphylococcus aureus."], "title": "Transcription and translation products of the cytolysin gene psm-mec on the mobile genetic element SCCmec regulate Staphylococcus aureus virulence."}
{"paper_id": 26863540, "labels": ["0", "0", "0", "0", "1", "0", "0", "0", "0"], "abstract": "Extensive interdisciplinary literatures have built on the seminal spatial dilemmas model, which depicts the evolution of cooperation on regular lattices, with strategies propagating locally by relative fitness. In this model agents may cooperate with neighbors, paying an individual cost to enhance their collective welfare, or they may exploit cooperative neighbors and diminish collective welfare. Recent research has extended the model in numerous ways, incorporating behavioral noise, implementing other network topologies or adaptive networks, and employing alternative dynamics of replication. Although the underlying dilemma arises from two distinct dimensions-the gains for exploiting cooperative partners (Greed) and the cost of cooperating with exploitative partners (Fear)-most work following from the spatial dilemmas model has argued or assumed that the dilemma can be represented with a single parameter: This research has typically examined Greed or Fear in isolation, or a composite such as the K-index of Cooperation or the ratio of the benefit to cost of cooperation. We challenge this claim on theoretical grounds-showing that embedding interaction in networks generally leads Greed and Fear to have divergent, interactive, and highly nonlinear effects on cooperation at the macro level, even when individuals respond identically to Greed and Fear. Using computational experiments, we characterize both dynamic local behavior and long run outcomes across regions of this space. We also simulate interventions to investigate changes of Greed and Fear over time, showing how model behavior changes asymmetrically as boundaries in payoff space are crossed, leading some interventions to have irreversible effects on cooperation. We then replicate our experiments on inter-organizational network data derived from links through shared directors among 2,400 large US corporations, thus demonstrating our findings for Greed and Fear on a naturally-occurring network. In closing, we discuss implications of our main findings regarding Greed and Fear for the problem of cooperation on inter-organizational networks.", "journal": "PloS one", "sentences": ["Extensive interdisciplinary literatures have built on the seminal spatial dilemmas model, which depicts the evolution of cooperation on regular lattices, with strategies propagating locally by relative fitness.", "In this model agents may cooperate with neighbors, paying an individual cost to enhance their collective welfare, or they may exploit cooperative neighbors and diminish collective welfare.", "Recent research has extended the model in numerous ways, incorporating behavioral noise, implementing other network topologies or adaptive networks, and employing alternative dynamics of replication.", "Although the underlying dilemma arises from two distinct dimensions-the gains for exploiting cooperative partners (Greed) and the cost of cooperating with exploitative partners (Fear)-most work following from the spatial dilemmas model has argued or assumed that the dilemma can be represented with a single parameter: This research has typically examined Greed or Fear in isolation, or a composite such as the K-index of Cooperation or the ratio of the benefit to cost of cooperation.", "We challenge this claim on theoretical grounds-showing that embedding interaction in networks generally leads Greed and Fear to have divergent, interactive, and highly nonlinear effects on cooperation at the macro level, even when individuals respond identically to Greed and Fear.", "Using computational experiments, we characterize both dynamic local behavior and long run outcomes across regions of this space.", "We also simulate interventions to investigate changes of Greed and Fear over time, showing how model behavior changes asymmetrically as boundaries in payoff space are crossed, leading some interventions to have irreversible effects on cooperation.", "We then replicate our experiments on inter-organizational network data derived from links through shared directors among 2,400 large US corporations, thus demonstrating our findings for Greed and Fear on a naturally-occurring network.", "In closing, we discuss implications of our main findings regarding Greed and Fear for the problem of cooperation on inter-organizational networks."], "title": "Greed and Fear in Network Reciprocity: Implications for Cooperation among Organizations."}
{"paper_id": 25550916, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Hyperbaric oxygen therapy (HBOT) protects brain tissue from inflammatory injury by suppressing mitochondrial apoptotic pathways. However, its neuroprotective mechanism via anti-apoptosis in spinal cord injury (SCI) is still unclear. In our study, Male Sprague-Dawley rats were randomly divided into three groups: sham-operated (SH), SCI model, and SCI + HBOT. Rats in each group were randomly divided into four sub-groups in a time-dependent manner (1 day, 3 days, 7 days and 14 days after surgery). Expression of adaptor molecule apoptosis-associated speck-like protein (ASC) and caspase-3 was evaluated at the indicated time after injury. Our data showed that HBOT downregulated expression of ASC in SCI rats at the mRNA and protein levels. HBOT mitigated caspase-3 release in injured spinal cord tissue. We conclude that HBOT prevents inflammation apoptosis after SCI, likely through suppression of ASC and caspase-3.", "journal": "International journal of clinical and experimental medicine", "sentences": ["Hyperbaric oxygen therapy (HBOT) protects brain tissue from inflammatory injury by suppressing mitochondrial apoptotic pathways.", "However, its neuroprotective mechanism via anti-apoptosis in spinal cord injury (SCI) is still unclear.", "In our study, Male Sprague-Dawley rats were randomly divided into three groups: sham-operated (SH), SCI model, and SCI + HBOT.", "Rats in each group were randomly divided into four sub-groups in a time-dependent manner (1 day, 3 days, 7 days and 14 days after surgery).", "Expression of adaptor molecule apoptosis-associated speck-like protein (ASC) and caspase-3 was evaluated at the indicated time after injury.", "Our data showed that HBOT downregulated expression of ASC in SCI rats at the mRNA and protein levels.", "HBOT mitigated caspase-3 release in injured spinal cord tissue.", "We conclude that HBOT prevents inflammation apoptosis after SCI, likely through suppression of ASC and caspase-3."], "title": "Hyperbaric oxygen therapy reduces apoptosis after spinal cord injury in rats."}
{"paper_id": 20888373, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "Apoptosis is an active and tightly regulated form of cell death, which can also be considered a stress-induced process of cellular communication. Recent studies reveal that the lipid network within cells is involved in the regulation and propagation of death signalling. Despite the vast growth of our current knowledge on apoptosis, little is known of the specific role played by lipid molecules in the central event of apoptosis-the piercing of mitochondrial membranes. Here we review the information regarding changes in mitochondrial lipids that are associated with apoptosis and discuss whether they may be involved in the permeabilization of mitochondria to release their apoptogenic factors, or just lie downstream of this permeabilization leading to the amplification of caspase activation. We focus on the earliest changes that physiological apoptosis induces in mitochondrial membranes, which may derive from an upstream alteration of phospholipid metabolism that reverberates on the mitochondrial re-modelling of their characteristic lipid, cardiolipin. Hopefully, this review will lead to an increased understanding of the role of mitochondrial lipids in apoptosis and also help revealing new stress sensing mechanisms in cells. This article is part of a Special Issue entitled Mitochondria: the deadly organelle.", "journal": "Biochimica et biophysica acta", "sentences": ["Apoptosis is an active and tightly regulated form of cell death, which can also be considered a stress-induced process of cellular communication.", "Recent studies reveal that the lipid network within cells is involved in the regulation and propagation of death signalling.", "Despite the vast growth of our current knowledge on apoptosis, little is known of the specific role played by lipid molecules in the central event of apoptosis-the piercing of mitochondrial membranes.", "Here we review the information regarding changes in mitochondrial lipids that are associated with apoptosis and discuss whether they may be involved in the permeabilization of mitochondria to release their apoptogenic factors, or just lie downstream of this permeabilization leading to the amplification of caspase activation.", "We focus on the earliest changes that physiological apoptosis induces in mitochondrial membranes, which may derive from an upstream alteration of phospholipid metabolism that reverberates on the mitochondrial re-modelling of their characteristic lipid, cardiolipin.", "Hopefully, this review will lead to an increased understanding of the role of mitochondrial lipids in apoptosis and also help revealing new stress sensing mechanisms in cells.", "This article is part of a Special Issue entitled Mitochondria: the deadly organelle."], "title": "Apoptosis-induced changes in mitochondrial lipids."}
{"paper_id": 22972994, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Humans take into account their own movement variability as well as potential consequences of different movement outcomes in planning movement trajectories. When variability increases, planned movements are altered so as to optimize expected consequences of the movement. Past research has focused on the steady-state responses to changing conditions of movement under risk. Here, we study the dynamics of such strategy adjustment in a visuomotor decision task in which subjects reach toward a display with regions that lead to rewards and penalties, under conditions of changing uncertainty. In typical reinforcement learning tasks, subjects should base subsequent strategy by computing an estimate of the mean outcome (e.g., reward) in recent trials. In contrast, in our task, strategy should be based on a dynamic estimate of recent outcome uncertainty (i.e., squared error). We find that subjects respond to increased movement uncertainty by aiming movements more conservatively with respect to penalty regions, and that the estimate of uncertainty they use is well characterized by a weighted average of recent squared errors, with higher weights given to more recent trials.", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "sentences": ["Humans take into account their own movement variability as well as potential consequences of different movement outcomes in planning movement trajectories.", "When variability increases, planned movements are altered so as to optimize expected consequences of the movement.", "Past research has focused on the steady-state responses to changing conditions of movement under risk.", "Here, we study the dynamics of such strategy adjustment in a visuomotor decision task in which subjects reach toward a display with regions that lead to rewards and penalties, under conditions of changing uncertainty.", "In typical reinforcement learning tasks, subjects should base subsequent strategy by computing an estimate of the mean outcome (e.g., reward) in recent trials.", "In contrast, in our task, strategy should be based on a dynamic estimate of recent outcome uncertainty (i.e., squared error).", "We find that subjects respond to increased movement uncertainty by aiming movements more conservatively with respect to penalty regions, and that the estimate of uncertainty they use is well characterized by a weighted average of recent squared errors, with higher weights given to more recent trials."], "title": "Dynamic estimation of task-relevant variance in movement under risk."}
{"paper_id": 24260747, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Human life and activity depends on microorganisms, as they are responsible for providing basic elements of life. Although microbes have such a key role in sustaining basic functions for all living organisms, very little is known about their biology since only a small fraction (average 1%) can be cultured under laboratory conditions. This is even more evident when considering that >88% of all bacterial isolates belong to four bacterial phyla, the Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. Advanced technologies, developed in the last years, promise to revolutionise the way that we characterize, identify, and study microbial communities. In this review, we present the most advanced tools that microbial ecologists can use for the study of microbial communities. Innovative microbial ecological DNA microarrays such as PhyloChip and GeoChip that have been developed for investigating the composition and function of microbial communities are presented, along with an overview of the next generation sequencing technologies. Finally, the Single Cell Genomics approach, which can be used for obtaining genomes from uncultured phyla, is outlined. This tool enables the amplification and sequencing of DNA from single cells obtained directly from environmental samples and is promising to revolutionise microbiology.", "journal": "BioMed research international", "sentences": ["Human life and activity depends on microorganisms, as they are responsible for providing basic elements of life.", "Although microbes have such a key role in sustaining basic functions for all living organisms, very little is known about their biology since only a small fraction (average 1%) can be cultured under laboratory conditions.", "This is even more evident when considering that >88% of all bacterial isolates belong to four bacterial phyla, the Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes.", "Advanced technologies, developed in the last years, promise to revolutionise the way that we characterize, identify, and study microbial communities.", "In this review, we present the most advanced tools that microbial ecologists can use for the study of microbial communities.", "Innovative microbial ecological DNA microarrays such as PhyloChip and GeoChip that have been developed for investigating the composition and function of microbial communities are presented, along with an overview of the next generation sequencing technologies.", "Finally, the Single Cell Genomics approach, which can be used for obtaining genomes from uncultured phyla, is outlined.", "This tool enables the amplification and sequencing of DNA from single cells obtained directly from environmental samples and is promising to revolutionise microbiology."], "title": "Microbial diversity in the era of omic technologies."}
{"paper_id": 24189395, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "A water soluble branched \u03b2-D-glucan (PS-I) with an average molecular weight ~2.1\u00d710(5) Da was isolated from alkaline extract of the fruit bodies of the edible mushroom Entoloma lividoalbum (K\u00fchner & Romagn) Kubi\u010dka which consists of terminal \u03b2-D-glucopyranosyl, (1\u21923)-\u03b2-D-glucopyranosyl, (1\u21926)-\u03b2-D-glucopyranosyl, and (1\u21923,6)-\u03b2-D-glucopyranosyl moieties in a molar ratio of nearly 1:3:2:1. The structure of PS-I was elucidated using acid hydrolysis, methylation analysis, periodate oxidation study, partial hydrolysis, and 1D/2D NMR experiments. The repeating unit of the polysaccharide (PS-I) contains a backbone chain of three (1\u21926)-\u03b2-D-glucopyranosyl residues, one of which was branched at O-3 position with the side chain consisting of three (1\u21923)-\u03b2-D-glucopyranosyl and a terminal \u03b2-D-glucopyranosyl residues. Total antioxidant capacity of 1mg PS-I was measured and found equivalent to 70\u00b115 \u03bcg of ascorbic acid. The PS-I was found to possess hydroxyl and superoxide radical-scavenging activities with EC50 values of 480 and 150 \u03bcg/mL, respectively. The reducing power of PS-I was determined 0.5 at 480 \u03bcg/mL.", "journal": "International journal of biological macromolecules", "sentences": ["A water soluble branched \u03b2-D-glucan (PS-I) with an average molecular weight ~2.1\u00d710(5) Da was isolated from alkaline extract of the fruit bodies of the edible mushroom Entoloma lividoalbum (K\u00fchner & Romagn) Kubi\u010dka which consists of terminal \u03b2-D-glucopyranosyl, (1\u21923)-\u03b2-D-glucopyranosyl, (1\u21926)-\u03b2-D-glucopyranosyl, and (1\u21923,6)-\u03b2-D-glucopyranosyl moieties in a molar ratio of nearly 1:3:2:1.", "The structure of PS-I was elucidated using acid hydrolysis, methylation analysis, periodate oxidation study, partial hydrolysis, and 1D/2D NMR experiments.", "The repeating unit of the polysaccharide (PS-I) contains a backbone chain of three (1\u21926)-\u03b2-D-glucopyranosyl residues, one of which was branched at O-3 position with the side chain consisting of three (1\u21923)-\u03b2-D-glucopyranosyl and a terminal \u03b2-D-glucopyranosyl residues.", "Total antioxidant capacity of 1mg PS-I was measured and found equivalent to 70\u00b115 \u03bcg of ascorbic acid.", "The PS-I was found to possess hydroxyl and superoxide radical-scavenging activities with EC50 values of 480 and 150 \u03bcg/mL, respectively.", "The reducing power of PS-I was determined 0.5 at 480 \u03bcg/mL."], "title": "Structure elucidation and antioxidant properties of a soluble \u03b2-D-glucan from mushroom Entoloma lividoalbum."}
{"paper_id": 25274368, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Evolutionary biologists have often assumed that ecological generalism comes at the expense of less intense exploitation of specific resources and that this trade-off will promote the evolution of ecologically specialized daughter species. Using a phylogenetic comparative approach with butterflies as a model system, we test hypotheses that incorporate changes in niche breadth and location into explanations of the taxonomic diversification of insect herbivores. Specifically, we compare the oscillation hypothesis, where speciation is driven by host-plant generalists giving rise to specialist daughter species, to the musical chairs hypothesis, where speciation is driven by host-plant switching, without changes in niche breadth. Contrary to the predictions of the oscillation hypothesis, we recover a negative relationship between host-plant breadth and diversification rate and find that changes in host breadth are seldom coupled to speciation events. By contrast, we present evidence for a positive relationship between rates of host switching and butterfly diversification, consonant with the musical chairs hypothesis. These results suggest that the costs of trophic generalism in plant-feeding insects may have been overvalued and that transitions from generalists to ecological specialists may not be an important driver of speciation in general.", "journal": "Proceedings. Biological sciences / The Royal Society", "sentences": ["Evolutionary biologists have often assumed that ecological generalism comes at the expense of less intense exploitation of specific resources and that this trade-off will promote the evolution of ecologically specialized daughter species.", "Using a phylogenetic comparative approach with butterflies as a model system, we test hypotheses that incorporate changes in niche breadth and location into explanations of the taxonomic diversification of insect herbivores.", "Specifically, we compare the oscillation hypothesis, where speciation is driven by host-plant generalists giving rise to specialist daughter species, to the musical chairs hypothesis, where speciation is driven by host-plant switching, without changes in niche breadth.", "Contrary to the predictions of the oscillation hypothesis, we recover a negative relationship between host-plant breadth and diversification rate and find that changes in host breadth are seldom coupled to speciation events.", "By contrast, we present evidence for a positive relationship between rates of host switching and butterfly diversification, consonant with the musical chairs hypothesis.", "These results suggest that the costs of trophic generalism in plant-feeding insects may have been overvalued and that transitions from generalists to ecological specialists may not be an important driver of speciation in general."], "title": "Specialization and generalization in the diversification of phytophagous insects: tests of the musical chairs and oscillation hypotheses."}
{"paper_id": 24042114, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Innate immune recognition of malaria parasites is the critical first step in the development of the host response. At present, Toll-like receptor 9 (TLR9) is thought to play a central role in sensing malaria infection. However, we and others have observed that Tlr9(-/-) mice, in contrast to mice deficient in the downstream adaptor, Myeloid differentiation primary response gene 88 (MYD88), exhibit few deficiencies in immune function during early infection with the malaria parasite Plasmodium chabaudi, implying that another MYD88-dependent receptor also contributes to the antimalarial response. Here we use candidate-based screening to identify TLR7 as a key sensor of early P. chabaudi infection. We show that TLR7 mediates a rapid systemic response to infection through induction of cytokines such as type I interferons (IFN-I), interleukin 12, and gamma interferon. TLR7 is also required for induction of IFN-I by other species and strains of Plasmodium, including an etiological agent of human disease, P. falciparum, suggesting that malaria parasites harbor a common pathogen-associated molecular pattern (PAMP) recognized by TLR7. In contrast to the nonredundant requirement for TLR7 in early immune activation, sensing through both TLR7 and TLR9 was required for proinflammatory cytokine production and immune cell activation during the peak of parasitemia. Our findings indicate that TLR7 plays a central role in early immune activation during malaria infection, whereas TLR7 and TLR9 contribute combinatorially to immune responses as infection progresses.", "journal": "Infection and immunity", "sentences": ["Innate immune recognition of malaria parasites is the critical first step in the development of the host response.", "At present, Toll-like receptor 9 (TLR9) is thought to play a central role in sensing malaria infection.", "However, we and others have observed that Tlr9(-/-) mice, in contrast to mice deficient in the downstream adaptor, Myeloid differentiation primary response gene 88 (MYD88), exhibit few deficiencies in immune function during early infection with the malaria parasite Plasmodium chabaudi, implying that another MYD88-dependent receptor also contributes to the antimalarial response.", "Here we use candidate-based screening to identify TLR7 as a key sensor of early P. chabaudi infection.", "We show that TLR7 mediates a rapid systemic response to infection through induction of cytokines such as type I interferons (IFN-I), interleukin 12, and gamma interferon.", "TLR7 is also required for induction of IFN-I by other species and strains of Plasmodium, including an etiological agent of human disease, P. falciparum, suggesting that malaria parasites harbor a common pathogen-associated molecular pattern (PAMP) recognized by TLR7.", "In contrast to the nonredundant requirement for TLR7 in early immune activation, sensing through both TLR7 and TLR9 was required for proinflammatory cytokine production and immune cell activation during the peak of parasitemia.", "Our findings indicate that TLR7 plays a central role in early immune activation during malaria infection, whereas TLR7 and TLR9 contribute combinatorially to immune responses as infection progresses."], "title": "Toll-like receptor 7 mediates early innate immune responses to malaria."}
{"paper_id": 26098625, "labels": ["0", "0", "0", "1", "1", "0", "1", "1"], "abstract": "Mycobacterium tuberculosis (Mtb) is well-established to be one of the most important bacterial pathogens for which new antimicrobial therapies are needed. Herein, we describe the development of a high throughput screening assay for the identification of molecules that are bactericidal against Mycobacteria. The assay utilizes the release of the intracellular enzyme adenylate kinase into the culture medium as a reporter of mycobacterial cell death. We demonstrate that the assay is selective for mycobactericidal molecules and detects anti-mycobacterial activity at concentrations below the minimum inhibitory concentration of many molecules. Thus, the AK assay is more sensitive than traditional growth assays. We have validated the AK assay in the HTS setting using the Mtb surrogate organism M. smegmatis and libraries of FDA approved drugs as well as a commercially available Diversity set. The screen of the FDA-approved library demonstrated that the AK assay is able to identify the vast majority of drugs with known mycobactericidal activity. Importantly, our screen of the Diversity set revealed that the increased sensitivity of the AK assay increases the ability of M. smegmatis-based screens to detect molecules with relatively poor activity against M. smegmatis but good to excellent activity against Mtb.", "journal": "PloS one", "sentences": ["Mycobacterium tuberculosis (Mtb) is well-established to be one of the most important bacterial pathogens for which new antimicrobial therapies are needed.", "Herein, we describe the development of a high throughput screening assay for the identification of molecules that are bactericidal against Mycobacteria.", "The assay utilizes the release of the intracellular enzyme adenylate kinase into the culture medium as a reporter of mycobacterial cell death.", "We demonstrate that the assay is selective for mycobactericidal molecules and detects anti-mycobacterial activity at concentrations below the minimum inhibitory concentration of many molecules.", "Thus, the AK assay is more sensitive than traditional growth assays.", "We have validated the AK assay in the HTS setting using the Mtb surrogate organism M. smegmatis and libraries of FDA approved drugs as well as a commercially available Diversity set.", "The screen of the FDA-approved library demonstrated that the AK assay is able to identify the vast majority of drugs with known mycobactericidal activity.", "Importantly, our screen of the Diversity set revealed that the increased sensitivity of the AK assay increases the ability of M. smegmatis-based screens to detect molecules with relatively poor activity against M. smegmatis but good to excellent activity against Mtb."], "title": "A High Throughput Screening Assay for Anti-Mycobacterial Small Molecules Based on Adenylate Kinase Release as a Reporter of Cell Lysis."}
{"paper_id": 26392563, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Most therapeutic agents are excluded from entering the central nervous system by the blood-brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf-TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Most therapeutic agents are excluded from entering the central nervous system by the blood-brain barrier (BBB).", "Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB.", "Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB.", "These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf-TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain.", "These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf.", "In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR.", "With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones.", "These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium.", "In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis."], "title": "Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core."}
{"paper_id": 26766068, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Xanthomonas fragariae is a bacterium that causes angular leaf spot of strawberry. Asymptomatic infection is common and contributes to the difficulties in disease management. The aim of this study was to develop a loop-mediated isothermal amplification (LAMP) assay as an efficient method for detection of asymptomatic infections of X. fragariae. In addition, a new method of sample preparation was developed that allows sampling of a larger amount of plant tissue, hence increasing the detection rate in real-life samples. The sample preparation procedure includes an overnight incubation of strawberry tissues in phosphate-buffered saline (PBS), followed by a quick sample concentration and a boiling step to extract DNA for amplification. The detection limit of the LAMP assay was approximately 2\u00d7103 CFU/mL for pure bacteria culture and 300 CFU/mL for bacteria spiked strawberry leaf and petiole samples. LAMP provided a 2-3 fold lower detection limit than the standard qPCR assay but was faster, and more user-friendly. The LAMP assay should serve as a rapid, sensitive and cost-effective tool for detecting asymptomatic infections of X. fragariae in strawberry nursery stock and contribute to improved disease management.", "journal": "PloS one", "sentences": ["Xanthomonas fragariae is a bacterium that causes angular leaf spot of strawberry.", "Asymptomatic infection is common and contributes to the difficulties in disease management.", "The aim of this study was to develop a loop-mediated isothermal amplification (LAMP) assay as an efficient method for detection of asymptomatic infections of X. fragariae.", "In addition, a new method of sample preparation was developed that allows sampling of a larger amount of plant tissue, hence increasing the detection rate in real-life samples.", "The sample preparation procedure includes an overnight incubation of strawberry tissues in phosphate-buffered saline (PBS), followed by a quick sample concentration and a boiling step to extract DNA for amplification.", "The detection limit of the LAMP assay was approximately 2\u00d7103 CFU/mL for pure bacteria culture and 300 CFU/mL for bacteria spiked strawberry leaf and petiole samples.", "LAMP provided a 2-3 fold lower detection limit than the standard qPCR assay but was faster, and more user-friendly.", "The LAMP assay should serve as a rapid, sensitive and cost-effective tool for detecting asymptomatic infections of X. fragariae in strawberry nursery stock and contribute to improved disease management."], "title": "A Loop-Mediated Isothermal Amplification Assay and Sample Preparation Procedure for Sensitive Detection of Xanthomonas fragariae in Strawberry."}
{"paper_id": 21788520, "labels": ["0", "0", "0", "0", "1", "1", "1", "1", "1"], "abstract": "The suprachiasmatic nucleus (SCN) is the principal circadian pacemaker of mammals, coordinating daily rhythms of behavior and metabolism. Circadian timekeeping in SCN neurons revolves around transcriptional/posttranslational feedback loops, in which Period (Per) and Cryptochrome (Cry) genes are negatively regulated by their protein products. Recent studies have revealed, however, that these \"core loops\" also rely upon cytosolic and circuit-level properties for sustained oscillation. To characterize interneuronal signals responsible for robust pacemaking in SCN cells and circuits, we have developed a unique coculture technique using wild-type (WT) \"graft\" SCN to drive pacemaking (reported by PER2::LUCIFERASE bioluminescence) in \"host\" SCN deficient either in elements of neuropeptidergic signaling or in elements of the core feedback loop. We demonstrate that paracrine signaling is sufficient to restore cellular synchrony and amplitude of pacemaking in SCN circuits lacking vasoactive intestinal peptide (VIP). By using grafts with mutant circadian periods we show that pacemaking in the host SCN is specified by the genotype of the graft, confirming graft-derived factors as determinants of the host rhythm. By combining pharmacological with genetic manipulations, we show that a hierarchy of neuropeptidergic signals underpins this paracrine regulation, with a preeminent role for VIP augmented by contributions from arginine vasopressin (AVP) and gastrin-releasing peptide (GRP). Finally, we show that interneuronal signaling is sufficiently powerful to maintain circadian pacemaking in arrhythmic Cry-null SCN, deficient in essential elements of the transcriptional negative feedback loops. Thus, a hierarchy of paracrine neuropeptidergic signals determines cell- and circuit-level circadian pacemaking in the SCN.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["The suprachiasmatic nucleus (SCN) is the principal circadian pacemaker of mammals, coordinating daily rhythms of behavior and metabolism.", "Circadian timekeeping in SCN neurons revolves around transcriptional/posttranslational feedback loops, in which Period (Per) and Cryptochrome (Cry) genes are negatively regulated by their protein products.", "Recent studies have revealed, however, that these \"core loops\" also rely upon cytosolic and circuit-level properties for sustained oscillation.", "To characterize interneuronal signals responsible for robust pacemaking in SCN cells and circuits, we have developed a unique coculture technique using wild-type (WT) \"graft\" SCN to drive pacemaking (reported by PER2::LUCIFERASE bioluminescence) in \"host\" SCN deficient either in elements of neuropeptidergic signaling or in elements of the core feedback loop.", "We demonstrate that paracrine signaling is sufficient to restore cellular synchrony and amplitude of pacemaking in SCN circuits lacking vasoactive intestinal peptide (VIP).", "By using grafts with mutant circadian periods we show that pacemaking in the host SCN is specified by the genotype of the graft, confirming graft-derived factors as determinants of the host rhythm.", "By combining pharmacological with genetic manipulations, we show that a hierarchy of neuropeptidergic signals underpins this paracrine regulation, with a preeminent role for VIP augmented by contributions from arginine vasopressin (AVP) and gastrin-releasing peptide (GRP).", "Finally, we show that interneuronal signaling is sufficiently powerful to maintain circadian pacemaking in arrhythmic Cry-null SCN, deficient in essential elements of the transcriptional negative feedback loops.", "Thus, a hierarchy of paracrine neuropeptidergic signals determines cell- and circuit-level circadian pacemaking in the SCN."], "title": "A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits."}
{"paper_id": 26273609, "labels": ["0", "0", "0", "0", "1"], "abstract": "Microbial Fuel cells (MFCs) have been proposed for nutrient removal and energy recovery from different wastes. In this study the anaerobic digestate was used to feed H-type MFC reactors, one with a graphite anode preconditioned with Geobacter sulfurreducens and the other with an unconditioned graphite anode. The data demonstrate that the digestate acts as a carbon source, and even in the absence of anode preconditioning, electroactive bacteria colonise the anodic chamber, producing a maximum power density of 172.2 mW/m(2). The carbon content was also reduced by up to 60%, while anaerobic ammonium oxidation (anammox) bacteria, which were found in the anodic compartment of the reactors, contributed to nitrogen removal from the digestate. Overall, these results demonstrate that MFCs can be used to recover anammox bacteria from natural sources, and it may represent a promising bioremediation unit in anaerobic digestor plants for the simultaneous nitrogen removal and electricity generation using digestate as substrate.", "journal": "BioMed research international", "sentences": ["Microbial Fuel cells (MFCs) have been proposed for nutrient removal and energy recovery from different wastes.", "In this study the anaerobic digestate was used to feed H-type MFC reactors, one with a graphite anode preconditioned with Geobacter sulfurreducens and the other with an unconditioned graphite anode.", "The data demonstrate that the digestate acts as a carbon source, and even in the absence of anode preconditioning, electroactive bacteria colonise the anodic chamber, producing a maximum power density of 172.2 mW/m(2).", "The carbon content was also reduced by up to 60%, while anaerobic ammonium oxidation (anammox) bacteria, which were found in the anodic compartment of the reactors, contributed to nitrogen removal from the digestate.", "Overall, these results demonstrate that MFCs can be used to recover anammox bacteria from natural sources, and it may represent a promising bioremediation unit in anaerobic digestor plants for the simultaneous nitrogen removal and electricity generation using digestate as substrate."], "title": "Development of Electroactive and Anaerobic Ammonium-Oxidizing (Anammox) Biofilms from Digestate in Microbial Fuel Cells."}
{"paper_id": 27598259, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "The ventromedial nucleus of the hypothalamus (VMH) is important for the regulation of whole body energy homeostasis and lesions in the VMH are reported to result in massive weight gain. The nuclear receptor steroidogenic factor 1 (SF-1) is a known VMH marker as it is exclusively expressed in the VMH region of the brain. SF-1 plays a critical role not only in the development of VMH but also in its physiological functions. In this study, we generated prenatal VMH-specific SF-1 KO mice and investigated age-dependent energy homeostasis regulation by SF-1. Deletion of SF-1 in the VMH resulted in dysregulated insulin and leptin homeostasis and late onset obesity due to increased food intake under normal chow and high fat diet conditions. In addition, SF-1 ablation was accompanied by a marked reduction in energy expenditure and physical activity and this effect was significantly pronounced in the aged mice. Taken together, our data indicates that SF-1 is a key component in the VMH-mediated regulation of energy homeostasis and implies that SF-1 plays a protective role against metabolic stressors including aging and high fat diet.", "journal": "PloS one", "sentences": ["The ventromedial nucleus of the hypothalamus (VMH) is important for the regulation of whole body energy homeostasis and lesions in the VMH are reported to result in massive weight gain.", "The nuclear receptor steroidogenic factor 1 (SF-1) is a known VMH marker as it is exclusively expressed in the VMH region of the brain.", "SF-1 plays a critical role not only in the development of VMH but also in its physiological functions.", "In this study, we generated prenatal VMH-specific SF-1 KO mice and investigated age-dependent energy homeostasis regulation by SF-1.", "Deletion of SF-1 in the VMH resulted in dysregulated insulin and leptin homeostasis and late onset obesity due to increased food intake under normal chow and high fat diet conditions.", "In addition, SF-1 ablation was accompanied by a marked reduction in energy expenditure and physical activity and this effect was significantly pronounced in the aged mice.", "Taken together, our data indicates that SF-1 is a key component in the VMH-mediated regulation of energy homeostasis and implies that SF-1 plays a protective role against metabolic stressors including aging and high fat diet."], "title": "Steroidogenic Factor 1 in the Ventromedial Nucleus of the Hypothalamus Regulates Age-Dependent Obesity."}
{"paper_id": 25952963, "labels": ["0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "Many previous behavioral inhibition studies have employed the classic Stroop and reverse-Stroop paradigm. Although an experimental dissociation has been demonstrated between Stroop interference (SI) and reverse-Stroop interference (RI), the mechanisms that underlie these phenomena remain unclear. In this study, we used functional magnetic resonance imaging (fMRI) to compare the functional mechanisms of SI and RI. We identified the brain regions activated by the Stroop word-color matching task using four tests: the Stroop control test (Test 1), Stroop test (Test 2), reverse-Stroop control test (Test 3), and reverse-Stroop test (Test 4). Neuroimaging results revealed that SI elicited activation in the bilateral middle frontal gyrus (BA9). In contrast, a number of other regions, including the bilateral middle frontal gyrus (BA 9 and BA10), medial frontal gyrus (BA 8), and cingulate gyrus (BA6 and BA 32) exhibited significant activation during RI. Our results indicate that there is a dissociation between the types of interference and brain activation. These findings suggest that SI and RI interference can be attributable to different neural mechanisms. It also suggests that the prefrontal cortex and the cingulate cortex are differentially sensitive to various types of interference, and that the reverse-Stroop task may be more useful than the Stroop task for evaluating interference control in psychiatric patients with frontal dysfunction.", "journal": "Behavioural brain research", "sentences": ["Many previous behavioral inhibition studies have employed the classic Stroop and reverse-Stroop paradigm.", "Although an experimental dissociation has been demonstrated between Stroop interference (SI) and reverse-Stroop interference (RI), the mechanisms that underlie these phenomena remain unclear.", "In this study, we used functional magnetic resonance imaging (fMRI) to compare the functional mechanisms of SI and RI.", "We identified the brain regions activated by the Stroop word-color matching task using four tests: the Stroop control test (Test 1), Stroop test (Test 2), reverse-Stroop control test (Test 3), and reverse-Stroop test (Test 4).", "Neuroimaging results revealed that SI elicited activation in the bilateral middle frontal gyrus (BA9).", "In contrast, a number of other regions, including the bilateral middle frontal gyrus (BA 9 and BA10), medial frontal gyrus (BA 8), and cingulate gyrus (BA6 and BA 32) exhibited significant activation during RI.", "Our results indicate that there is a dissociation between the types of interference and brain activation.", "These findings suggest that SI and RI interference can be attributable to different neural mechanisms.", "It also suggests that the prefrontal cortex and the cingulate cortex are differentially sensitive to various types of interference, and that the reverse-Stroop task may be more useful than the Stroop task for evaluating interference control in psychiatric patients with frontal dysfunction."], "title": "An fMRI study of the functional mechanisms of Stroop/reverse-Stroop effects."}
{"paper_id": 26856261, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1\u2009Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing \u223c57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing', prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent.", "journal": "Nature communications", "sentences": ["Ticks transmit more pathogens to humans and animals than any other arthropod.", "We describe the 2.1\u2009Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases.", "The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans.", "Annotation of scaffolds representing \u223c57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions.", "We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing', prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival.", "We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent."], "title": "Genomic insights into the Ixodes scapularis tick vector of Lyme disease."}
{"paper_id": 23424630, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Cytoplasmic inclusion bodies formed in reovirus-infected cells are the sites of viral replication and assembly. Previous studies have suggested that the NS80 protein of aquareovirus may be involved in the formation of viral inclusion bodies. However, it remains unknown whether other viral proteins are involved in the process, and what regions of NS80 may act coordinately in mediating inclusion formation. Here, we observed that globular cytoplasmic inclusions were formed in virus-infected cells and viral proteins NS80 and NS38 colocalized in the inclusions. During transfection, singly expressed NS80 could form cytoplasmic inclusions and recruit NS38 and GFP-tagged VP4 to these structures. Further treatment of cells with nocodazole, a microtubule inhibitor, did not disrupt the inclusion, suggesting that inclusion formation does not rely on microtubule network. Besides, we identified that the region 530-742 of NS80 was likely the minimal region required for inclusion formation, and the C-tail, coiled-coil region as well as the conserved linker region were essential for inclusion phenotype. Moreover, with series deletions from the N-terminus, a stepwise conversion occurred from large condensed cytoplasmic to small nuclear inclusions, then to a diffused intracellular distribution. Notablely, we found that the nuclear inclusions, formed by NS80 truncations (471 to 513-742), colocalized with cellular protein \u03b2-catenin. These data indicated that NS80 could be a major mediator in recruiting NS38 and VP4 into inclusion structures, and the C-terminus of NS80 is responsible for inclusion formation.", "journal": "PloS one", "sentences": ["Cytoplasmic inclusion bodies formed in reovirus-infected cells are the sites of viral replication and assembly.", "Previous studies have suggested that the NS80 protein of aquareovirus may be involved in the formation of viral inclusion bodies.", "However, it remains unknown whether other viral proteins are involved in the process, and what regions of NS80 may act coordinately in mediating inclusion formation.", "Here, we observed that globular cytoplasmic inclusions were formed in virus-infected cells and viral proteins NS80 and NS38 colocalized in the inclusions.", "During transfection, singly expressed NS80 could form cytoplasmic inclusions and recruit NS38 and GFP-tagged VP4 to these structures.", "Further treatment of cells with nocodazole, a microtubule inhibitor, did not disrupt the inclusion, suggesting that inclusion formation does not rely on microtubule network.", "Besides, we identified that the region 530-742 of NS80 was likely the minimal region required for inclusion formation, and the C-tail, coiled-coil region as well as the conserved linker region were essential for inclusion phenotype.", "Moreover, with series deletions from the N-terminus, a stepwise conversion occurred from large condensed cytoplasmic to small nuclear inclusions, then to a diffused intracellular distribution.", "Notablely, we found that the nuclear inclusions, formed by NS80 truncations (471 to 513-742), colocalized with cellular protein \u03b2-catenin.", "These data indicated that NS80 could be a major mediator in recruiting NS38 and VP4 into inclusion structures, and the C-terminus of NS80 is responsible for inclusion formation."], "title": "Aquareovirus NS80 recruits viral proteins to its inclusions, and its C-terminal domain is the primary driving force for viral inclusion formation."}
{"paper_id": 22860072, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Top marine predators present high mercury concentrations in their tissues as consequence of biomagnification of the most toxic form of this metal, methylmercury (MeHg). The present study concerns mercury accumulation by Guiana dolphins (Sotalia guianensis), highlighting the selenium-mediated methylmercury detoxification process. Liver samples from 19 dolphins incidentally captured within Guanabara Bay (Rio de Janeiro State, Brazil) from 1994 to 2006 were analyzed for total mercury (THg), methylmercury (MeHg), total organic mercury (TOrgHg) and selenium (Se). X-ray microanalyses were also performed. The specimens, including from fetuses to 30-year-old dolphins, comprising 8 females and 11 males, presented high THg (0.53-132 \u00b5g/g wet wt.) and Se concentrations (0.17-74.8 \u00b5g/g wet wt.). Correlations between THg, MeHg, TOrgHg and Se were verified with age (p<0.05), as well as a high and positive correlation was observed between molar concentrations of Hg and Se (p<0.05). Negative correlations were observed between THg and the percentage of MeHg contribution to THg (p<0.05), which represents a consequence of the selenium-mediated methylmercury detoxification process. Accumulation of Se-Hg amorphous crystals in Kupffer Cells was demonstrated through ultra-structural analysis, which shows that Guiana dolphin is capable of carrying out the demethylation process via mercury selenide formation.", "journal": "PloS one", "sentences": ["Top marine predators present high mercury concentrations in their tissues as consequence of biomagnification of the most toxic form of this metal, methylmercury (MeHg).", "The present study concerns mercury accumulation by Guiana dolphins (Sotalia guianensis), highlighting the selenium-mediated methylmercury detoxification process.", "Liver samples from 19 dolphins incidentally captured within Guanabara Bay (Rio de Janeiro State, Brazil) from 1994 to 2006 were analyzed for total mercury (THg), methylmercury (MeHg), total organic mercury (TOrgHg) and selenium (Se).", "X-ray microanalyses were also performed.", "The specimens, including from fetuses to 30-year-old dolphins, comprising 8 females and 11 males, presented high THg (0.53-132 \u00b5g/g wet wt.)", "and Se concentrations (0.17-74.8 \u00b5g/g wet wt.).", "Correlations between THg, MeHg, TOrgHg and Se were verified with age (p<0.05), as well as a high and positive correlation was observed between molar concentrations of Hg and Se (p<0.05).", "Negative correlations were observed between THg and the percentage of MeHg contribution to THg (p<0.05), which represents a consequence of the selenium-mediated methylmercury detoxification process.", "Accumulation of Se-Hg amorphous crystals in Kupffer Cells was demonstrated through ultra-structural analysis, which shows that Guiana dolphin is capable of carrying out the demethylation process via mercury selenide formation."], "title": "Mercury-selenium relationships in liver of Guiana dolphin: the possible role of Kupffer cells in the detoxification process by tiemannite formation."}
{"paper_id": 24829448, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "Identifying functionally significant microRNAs (miRs) and their correspondingly most important messenger RNA targets (mRNAs) in specific biological contexts is a critical task to improve our understanding of molecular mechanisms underlying organismal development, physiology and disease. However, current miR-mRNA target prediction platforms rank miR targets based on estimated strength of physical interactions and lack the ability to rank interactants as a function of their potential to impact a given biological system. To address this, we have developed ToppMiR (http://toppmir.cchmc.org), a web-based analytical workbench that allows miRs and mRNAs to be co-analyzed via biologically centered approaches in which gene function associated annotations are used to train a machine learning-based analysis engine. ToppMiR learns about biological contexts based on gene associated information from expression data or from a user-specified set of genes that relate to context-relevant knowledge or hypotheses. Within the biological framework established by the genes in the training set, its associated information content is then used to calculate a features association matrix composed of biological functions, protein interactions and other features. This scoring matrix is then used to jointly rank both the test/candidate miRs and mRNAs. Results of these analyses are provided as downloadable tables or network file formats usable in Cytoscape.", "journal": "Nucleic acids research", "sentences": ["Identifying functionally significant microRNAs (miRs) and their correspondingly most important messenger RNA targets (mRNAs) in specific biological contexts is a critical task to improve our understanding of molecular mechanisms underlying organismal development, physiology and disease.", "However, current miR-mRNA target prediction platforms rank miR targets based on estimated strength of physical interactions and lack the ability to rank interactants as a function of their potential to impact a given biological system.", "To address this, we have developed ToppMiR (http://toppmir.cchmc.org), a web-based analytical workbench that allows miRs and mRNAs to be co-analyzed via biologically centered approaches in which gene function associated annotations are used to train a machine learning-based analysis engine.", "ToppMiR learns about biological contexts based on gene associated information from expression data or from a user-specified set of genes that relate to context-relevant knowledge or hypotheses.", "Within the biological framework established by the genes in the training set, its associated information content is then used to calculate a features association matrix composed of biological functions, protein interactions and other features.", "This scoring matrix is then used to jointly rank both the test/candidate miRs and mRNAs.", "Results of these analyses are provided as downloadable tables or network file formats usable in Cytoscape."], "title": "ToppMiR: ranking microRNAs and their mRNA targets based on biological functions and context."}
{"paper_id": 22970286, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "This study was undertaken to decipher the interdependent roles of (i) methylation within E2 binding site I and II (E2BS-I/II) and replication origin (nt 7862) in the long control region (LCR), (ii) expression of viral oncogene E7, (iii) expression of the transcript (E7-E1/E4) that encodes E2 repressor protein and (iv) viral load, in human papillomavirus 16 (HPV16) related cervical cancer (CaCx) pathogenesis. The results revealed over-representation (p<0.001) of methylation at nucleotide 58 of E2BS-I among E2-intact CaCx cases compared to E2-disrupted cases. Bisulphite sequencing of LCR revealed overrepresentation of methylation at nucleotide 58 or other CpGs in E2BS-I/II, among E2-intact cases than E2-disrupted cases and lack of methylation at replication origin in case of both. The viral transcript (E7-E1/E4) that produces the repressor E2 was analyzed by APOT (amplification of papillomavirus oncogenic transcript)-coupled-quantitative-RT-PCR (of E7 and E4 genes) to distinguish episomal (pure or concomitant with integrated) from purely integrated viral genomes based on the ratio, E7 C(T)/E4 C(T). Relative quantification based on comparative C(T) (threshold cycle) method revealed 75.087 folds higher E7 mRNA expression in episomal cases over purely integrated cases. Viral load and E2 gene copy numbers were negatively correlated with E7 C(T) (p = 0.007) and E2 C(T) (p<0.0001), respectively, each normalized with ACTB C(T), among episomal cases only. The k-means clustering analysis considering E7 C(T) from APOT-coupled-quantitative-RT-PCR assay, in conjunction with viral load, revealed immense heterogeneity among the HPV16 positive CaCx cases portraying integrated viral genomes. The findings provide novel insights into HPV16 related CaCx pathogenesis and highlight that CaCx cases that harbour episomal HPV16 genomes with intact E2 are likely to be distinct biologically, from the purely integrated viral genomes in terms of host genes and/or pathways involved in cervical carcinogenesis.", "journal": "PloS one", "sentences": ["This study was undertaken to decipher the interdependent roles of (i) methylation within E2 binding site I and II (E2BS-I/II) and replication origin (nt 7862) in the long control region (LCR), (ii) expression of viral oncogene E7, (iii) expression of the transcript (E7-E1/E4) that encodes E2 repressor protein and (iv) viral load, in human papillomavirus 16 (HPV16) related cervical cancer (CaCx) pathogenesis.", "The results revealed over-representation (p<0.001) of methylation at nucleotide 58 of E2BS-I among E2-intact CaCx cases compared to E2-disrupted cases.", "Bisulphite sequencing of LCR revealed overrepresentation of methylation at nucleotide 58 or other CpGs in E2BS-I/II, among E2-intact cases than E2-disrupted cases and lack of methylation at replication origin in case of both.", "The viral transcript (E7-E1/E4) that produces the repressor E2 was analyzed by APOT (amplification of papillomavirus oncogenic transcript)-coupled-quantitative-RT-PCR (of E7 and E4 genes) to distinguish episomal (pure or concomitant with integrated) from purely integrated viral genomes based on the ratio, E7 C(T)/E4 C(T).", "Relative quantification based on comparative C(T) (threshold cycle) method revealed 75.087 folds higher E7 mRNA expression in episomal cases over purely integrated cases.", "Viral load and E2 gene copy numbers were negatively correlated with E7 C(T) (p = 0.007) and E2 C(T) (p<0.0001), respectively, each normalized with ACTB C(T), among episomal cases only.", "The k-means clustering analysis considering E7 C(T) from APOT-coupled-quantitative-RT-PCR assay, in conjunction with viral load, revealed immense heterogeneity among the HPV16 positive CaCx cases portraying integrated viral genomes.", "The findings provide novel insights into HPV16 related CaCx pathogenesis and highlight that CaCx cases that harbour episomal HPV16 genomes with intact E2 are likely to be distinct biologically, from the purely integrated viral genomes in terms of host genes and/or pathways involved in cervical carcinogenesis."], "title": "Some novel insights on HPV16 related cervical cancer pathogenesis based on analyses of LCR methylation, viral load, E7 and E2/E4 expressions."}
{"paper_id": 25023366, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Individuals suffering from schizophrenia are frequently considered to be dangerous. The current longitudinal chart review was carried out to investigate the diagnostic mix of patients who were admitted to the Department of Psychiatry and Psychotherapy at the Medical University Innsbruck due to risk of harm to others. The sample consisted of all adult inpatients admitted to psychiatric acute care units in the years 1992, 1997, 2002, and 2007. Data collection included diagnoses, criteria for risk of harm to others, and the use of mechanical restraint. Altogether, 7222 admissions were reviewed. Of these, 529 patients had to be admitted to a locked unit because of risk of harm to others. Among those mechanical restraint was more often used in patients with organic mental disorders, Cluster B personality disorders, and mania than in patients with schizophrenia. Patients suffering from schizophrenia with comorbid psychoactive substance use constitute a potentially harmful population and are therefore frequently admitted to locked units due to risk of harm to others. However, in the current study additional coercive measures were more commonly applied in patients suffering from personality disorders and organic mental disorders.", "journal": "Psychiatry research", "sentences": ["Individuals suffering from schizophrenia are frequently considered to be dangerous.", "The current longitudinal chart review was carried out to investigate the diagnostic mix of patients who were admitted to the Department of Psychiatry and Psychotherapy at the Medical University Innsbruck due to risk of harm to others.", "The sample consisted of all adult inpatients admitted to psychiatric acute care units in the years 1992, 1997, 2002, and 2007.", "Data collection included diagnoses, criteria for risk of harm to others, and the use of mechanical restraint.", "Altogether, 7222 admissions were reviewed.", "Of these, 529 patients had to be admitted to a locked unit because of risk of harm to others.", "Among those mechanical restraint was more often used in patients with organic mental disorders, Cluster B personality disorders, and mania than in patients with schizophrenia.", "Patients suffering from schizophrenia with comorbid psychoactive substance use constitute a potentially harmful population and are therefore frequently admitted to locked units due to risk of harm to others.", "However, in the current study additional coercive measures were more commonly applied in patients suffering from personality disorders and organic mental disorders."], "title": "Risk of violence of inpatients with severe mental illness--do patients with schizophrenia pose harm to others?"}
{"paper_id": 27573816, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "The development of sophisticated experimental means to control nanoscale systems has motivated efforts to design driving protocols that minimize the energy dissipated to the environment. Computational models are a crucial tool in this practical challenge. We describe a general method for sampling an ensemble of finite-time, nonequilibrium protocols biased toward a low average dissipation. We show that this scheme can be carried out very efficiently in several limiting cases. As an application, we sample the ensemble of low-dissipation protocols that invert the magnetization of a 2D Ising model and explore how the diversity of the protocols varies in response to constraints on the average dissipation. In this example, we find that there is a large set of protocols with average dissipation close to the optimal value, which we argue is a general phenomenon.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["The development of sophisticated experimental means to control nanoscale systems has motivated efforts to design driving protocols that minimize the energy dissipated to the environment.", "Computational models are a crucial tool in this practical challenge.", "We describe a general method for sampling an ensemble of finite-time, nonequilibrium protocols biased toward a low average dissipation.", "We show that this scheme can be carried out very efficiently in several limiting cases.", "As an application, we sample the ensemble of low-dissipation protocols that invert the magnetization of a 2D Ising model and explore how the diversity of the protocols varies in response to constraints on the average dissipation.", "In this example, we find that there is a large set of protocols with average dissipation close to the optimal value, which we argue is a general phenomenon."], "title": "Near-optimal protocols in complex nonequilibrium transformations."}
{"paper_id": 25335848, "labels": ["0", "0", "1", "0", "0", "1"], "abstract": "In many green electrochemical energy devices, the conversion between oxygen and water suffers from high potential loss due to the difficulty in decreasing activation energy. Overcoming this issue requires full understanding of global reactions and development of strategies in efficient catalyst design. Here we report an active copper nanocomposite, inspired by natural coordination environments of catalytic sites in an enzyme, which catalyzes oxygen reduction/evolution at potentials closely approaching standard potential. Such performances are related to the imperfect coordination configuration of the copper(II) active site whose electron density is tuned by neighbouring copper(0) and nitrogen ligands incorporated in graphene. The electron transfer number of oxygen reduction is estimated by monitoring the redox of hydrogen peroxide, which is determined by the overpotential and electrolyte pH. An in situ fluorescence spectroelectrochemistry reveals that hydroxyl radical is the common intermediate for the electrochemical conversion between oxygen and water.", "journal": "Nature communications", "sentences": ["In many green electrochemical energy devices, the conversion between oxygen and water suffers from high potential loss due to the difficulty in decreasing activation energy.", "Overcoming this issue requires full understanding of global reactions and development of strategies in efficient catalyst design.", "Here we report an active copper nanocomposite, inspired by natural coordination environments of catalytic sites in an enzyme, which catalyzes oxygen reduction/evolution at potentials closely approaching standard potential.", "Such performances are related to the imperfect coordination configuration of the copper(II) active site whose electron density is tuned by neighbouring copper(0) and nitrogen ligands incorporated in graphene.", "The electron transfer number of oxygen reduction is estimated by monitoring the redox of hydrogen peroxide, which is determined by the overpotential and electrolyte pH.", "An in situ fluorescence spectroelectrochemistry reveals that hydroxyl radical is the common intermediate for the electrochemical conversion between oxygen and water."], "title": "Bioinspired copper catalyst effective for both reduction and evolution of oxygen."}
{"paper_id": 24626393, "labels": ["0", "0", "0", "0", "1", "0", "0"], "abstract": "We examine bidirectional brain-machine interfaces that control external devices in a closed loop by decoding motor cortical activity to command the device and by encoding the state of the device by delivering electrical stimuli to sensory areas. Although it is possible to design this artificial sensory-motor interaction while maintaining two independent channels of communication, here we propose a rule that closes the loop between flows of sensory and motor information in a way that approximates a desired dynamical policy expressed as a field of forces acting upon the controlled external device. We previously developed a first implementation of this approach based on linear decoding of neural activity recorded from the motor cortex into a set of forces (a force field) applied to a point mass, and on encoding of position of the point mass into patterns of electrical stimuli delivered to somatosensory areas. However, this previous algorithm had the limitation that it only worked in situations when the position-to-force map to be implemented is invertible. Here we overcome this limitation by developing a new non-linear form of the bidirectional interface that can approximate a virtually unlimited family of continuous fields. The new algorithm bases both the encoding of position information and the decoding of motor cortical activity on an explicit map between spike trains and the state space of the device computed with Multi-Dimensional-Scaling. We present a detailed computational analysis of the performance of the interface and a validation of its robustness by using synthetic neural responses in a simulated sensory-motor loop.", "journal": "PloS one", "sentences": ["We examine bidirectional brain-machine interfaces that control external devices in a closed loop by decoding motor cortical activity to command the device and by encoding the state of the device by delivering electrical stimuli to sensory areas.", "Although it is possible to design this artificial sensory-motor interaction while maintaining two independent channels of communication, here we propose a rule that closes the loop between flows of sensory and motor information in a way that approximates a desired dynamical policy expressed as a field of forces acting upon the controlled external device.", "We previously developed a first implementation of this approach based on linear decoding of neural activity recorded from the motor cortex into a set of forces (a force field) applied to a point mass, and on encoding of position of the point mass into patterns of electrical stimuli delivered to somatosensory areas.", "However, this previous algorithm had the limitation that it only worked in situations when the position-to-force map to be implemented is invertible.", "Here we overcome this limitation by developing a new non-linear form of the bidirectional interface that can approximate a virtually unlimited family of continuous fields.", "The new algorithm bases both the encoding of position information and the decoding of motor cortical activity on an explicit map between spike trains and the state space of the device computed with Multi-Dimensional-Scaling.", "We present a detailed computational analysis of the performance of the interface and a validation of its robustness by using synthetic neural responses in a simulated sensory-motor loop."], "title": "A bidirectional brain-machine interface algorithm that approximates arbitrary force-fields."}
{"paper_id": 26075820, "labels": ["0", "0", "0", "0", "1", "0", "1"], "abstract": "Type 2 diabetes mellitus (T2DM) is a worldwide heath problem that is characterized by insulin resistance and the eventual loss of \u03b2 cell function. As recent studies have shown that loss of ribosomal protein (RP) S6 kinase 1 (S6K1) increases systemic insulin sensitivity, S6K1 inhibitors are being pursued as potential agents for improving insulin resistance. Here we found that S6K1 deficiency in mice also leads to decreased \u03b2 cell growth, intrauterine growth restriction (IUGR), and impaired placental development. IUGR is a common complication of human pregnancy that limits the supply of oxygen and nutrients to the developing fetus, leading to diminished embryonic \u03b2 cell growth and the onset of T2DM later in life. However, restoration of placental development and the rescue of IUGR by tetraploid embryo complementation did not restore \u03b2 cell size or insulin levels in S6K1-/- embryos, suggesting that loss of S6K1 leads to an intrinsic \u03b2 cell lesion. Consistent with this hypothesis, reexpression of S6K1 in \u03b2 cells of S6K1-/- mice restored embryonic \u03b2 cell size, insulin levels, glucose tolerance, and RPS6 phosphorylation, without rescuing IUGR. Together, these data suggest that a nutrient-mediated reduction in intrinsic \u03b2 cell S6K1 signaling, rather than IUGR, during fetal development may underlie reduced \u03b2 cell growth and eventual development of T2DM later in life.", "journal": "The Journal of clinical investigation", "sentences": ["Type 2 diabetes mellitus (T2DM) is a worldwide heath problem that is characterized by insulin resistance and the eventual loss of \u03b2 cell function.", "As recent studies have shown that loss of ribosomal protein (RP) S6 kinase 1 (S6K1) increases systemic insulin sensitivity, S6K1 inhibitors are being pursued as potential agents for improving insulin resistance.", "Here we found that S6K1 deficiency in mice also leads to decreased \u03b2 cell growth, intrauterine growth restriction (IUGR), and impaired placental development.", "IUGR is a common complication of human pregnancy that limits the supply of oxygen and nutrients to the developing fetus, leading to diminished embryonic \u03b2 cell growth and the onset of T2DM later in life.", "However, restoration of placental development and the rescue of IUGR by tetraploid embryo complementation did not restore \u03b2 cell size or insulin levels in S6K1-/- embryos, suggesting that loss of S6K1 leads to an intrinsic \u03b2 cell lesion.", "Consistent with this hypothesis, reexpression of S6K1 in \u03b2 cells of S6K1-/- mice restored embryonic \u03b2 cell size, insulin levels, glucose tolerance, and RPS6 phosphorylation, without rescuing IUGR.", "Together, these data suggest that a nutrient-mediated reduction in intrinsic \u03b2 cell S6K1 signaling, rather than IUGR, during fetal development may underlie reduced \u03b2 cell growth and eventual development of T2DM later in life."], "title": "S6K1 controls pancreatic \u03b2 cell size independently of intrauterine growth restriction."}
{"paper_id": 23678172, "labels": ["0", "0", "1", "0", "1", "1", "1", "1", "0", "1"], "abstract": "The latent-to-lytic switch of Epstein-Barr virus (EBV) is mediated by the immediate early protein BZLF1 (Z). However, the cellular factors regulating this process remain incompletely characterized. In this report, we show that the B-cell-specific transcription factor Pax5 helps to promote viral latency in B cells by blocking Z function. Although Z was previously shown to directly interact with Pax5 and inhibit its activity, the effect of Pax5 on Z function has not been investigated. Here, we demonstrate that Pax5 inhibits Z-mediated lytic viral gene expression and the release of infectious viral particles in latently infected epithelial cell lines. Conversely, we found that shRNA-mediated knockdown of endogenous Pax5 in a Burkitt lymphoma B-cell line leads to viral reactivation. Furthermore, we show that Pax5 reduces Z activation of early lytic viral promoters in reporter gene assays and inhibits Z binding to lytic viral promoters in vivo. We confirm that Pax5 and Z directly interact and show that this interaction requires the carboxy-terminal DNA-binding/dimerization domain of Z and the amino-terminal DNA-binding domain of Pax5. A Pax5 DNA-binding mutant (V26G/P80R) that interacts with Z retains the ability to inhibit Z function, whereas a Pax5 mutant (\u0394106-110) that is deficient for interaction with Z does not inhibit Z-mediated lytic viral reactivation. Since the B-cell-specific transcription factor Oct-2 also directly interacts with Z and inhibits its function, these results suggest that EBV uses multiple redundant mechanisms to establish and maintain viral latency in B cells.", "journal": "Journal of virology", "sentences": ["The latent-to-lytic switch of Epstein-Barr virus (EBV) is mediated by the immediate early protein BZLF1 (Z).", "However, the cellular factors regulating this process remain incompletely characterized.", "In this report, we show that the B-cell-specific transcription factor Pax5 helps to promote viral latency in B cells by blocking Z function.", "Although Z was previously shown to directly interact with Pax5 and inhibit its activity, the effect of Pax5 on Z function has not been investigated.", "Here, we demonstrate that Pax5 inhibits Z-mediated lytic viral gene expression and the release of infectious viral particles in latently infected epithelial cell lines.", "Conversely, we found that shRNA-mediated knockdown of endogenous Pax5 in a Burkitt lymphoma B-cell line leads to viral reactivation.", "Furthermore, we show that Pax5 reduces Z activation of early lytic viral promoters in reporter gene assays and inhibits Z binding to lytic viral promoters in vivo.", "We confirm that Pax5 and Z directly interact and show that this interaction requires the carboxy-terminal DNA-binding/dimerization domain of Z and the amino-terminal DNA-binding domain of Pax5.", "A Pax5 DNA-binding mutant (V26G/P80R) that interacts with Z retains the ability to inhibit Z function, whereas a Pax5 mutant (\u0394106-110) that is deficient for interaction with Z does not inhibit Z-mediated lytic viral reactivation.", "Since the B-cell-specific transcription factor Oct-2 also directly interacts with Z and inhibits its function, these results suggest that EBV uses multiple redundant mechanisms to establish and maintain viral latency in B cells."], "title": "The B-cell-specific transcription factor and master regulator Pax5 promotes Epstein-Barr virus latency by negatively regulating the viral immediate early protein BZLF1."}
{"paper_id": 26452079, "labels": ["0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "The nematode Caenorhabditis elegans has become an essential model organism in neuroscience research because of its stereotyped anatomy, relevance to human biology, and capacity for genetic manipulation. To solve the intrinsic challenges associated with performing manual operations on C. elegans, many automated chip designs based on immobilization-imaging-release approaches have been proposed. These designs are prone to limitations such as the exertion of physical stress on the worms and limited throughput. In this work, a continuous-flow, high-throughput, automated C. elegans analyzer based on droplet encapsulation and real-time image processing was developed to analyze fluorescence expression in worms. To demonstrate its capabilities, two strains of C. elegans nematodes with different levels of expression of green fluorescent protein (GFP) were first mixed in a buffer solution. The worms were encapsulated in water-in-oil droplets to restrict random locomotion. The droplets were closely packed in a two-layer polydimethylsiloxane (PDMS) platform and were flowed through a narrow straight channel, in which a region of interest (ROI) was defined and continuously recorded by a frame acquisition device. Based on the number of pixels counted in the selected color range, our custom software analyzed GFP expression to differentiate between two strains with nearly 100% accuracy and a throughput of 0.5 seconds/worm.", "journal": "Biosensors & bioelectronics", "sentences": ["The nematode Caenorhabditis elegans has become an essential model organism in neuroscience research because of its stereotyped anatomy, relevance to human biology, and capacity for genetic manipulation.", "To solve the intrinsic challenges associated with performing manual operations on C. elegans, many automated chip designs based on immobilization-imaging-release approaches have been proposed.", "These designs are prone to limitations such as the exertion of physical stress on the worms and limited throughput.", "In this work, a continuous-flow, high-throughput, automated C. elegans analyzer based on droplet encapsulation and real-time image processing was developed to analyze fluorescence expression in worms.", "To demonstrate its capabilities, two strains of C. elegans nematodes with different levels of expression of green fluorescent protein (GFP) were first mixed in a buffer solution.", "The worms were encapsulated in water-in-oil droplets to restrict random locomotion.", "The droplets were closely packed in a two-layer polydimethylsiloxane (PDMS) platform and were flowed through a narrow straight channel, in which a region of interest (ROI) was defined and continuously recorded by a frame acquisition device.", "Based on the number of pixels counted in the selected color range, our custom software analyzed GFP expression to differentiate between two strains with nearly 100% accuracy and a throughput of 0.5 seconds/worm."], "title": "Continuous-flow C. elegans fluorescence expression analysis with real-time image processing through microfluidics."}
{"paper_id": 23954636, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Mammalian ghrelin is a stomach-derived peptide that stimulates secretion of growth hormone and food intake. Zebrafish is an excellent model system for forward genetic studies, and many aspects of energy homeostasis characterized in mammals appear to be conserved in the zebrafish. In this study, we investigated the expression and regulation of zebrafish ghrelin by metabolic status. Quantitative RT-PCR revealed that zebrafish ghrelin is highly enriched in anterior gut associated tissues. Using in situ hybridization with adult zebrafish tissues, we found that zebrafish ghrelin mRNA was not expressed in intestine tissue, but rather in clusters of endocrine pancreas cells distinct from insulin-expressing islets. Fasting specifically upregulated pancreatic ghrelin but not brain ghrelin expression by 3- to 4-fold and refeeding restored ghrelin transcript to control levels seen in the fed group within 5 h. These results demonstrate that although ghrelin is expressed in a different site in zebrafish, it is responsive to metabolic state in a similar manner as mammalian ghrelin, suggesting a role in the regulation of feeding in teleosts, and thus validate the utility of zebrafish as a genetic model system for the analysis of the ghrelin system and energy homeostasis.", "journal": "Biochemical and biophysical research communications", "sentences": ["Mammalian ghrelin is a stomach-derived peptide that stimulates secretion of growth hormone and food intake.", "Zebrafish is an excellent model system for forward genetic studies, and many aspects of energy homeostasis characterized in mammals appear to be conserved in the zebrafish.", "In this study, we investigated the expression and regulation of zebrafish ghrelin by metabolic status.", "Quantitative RT-PCR revealed that zebrafish ghrelin is highly enriched in anterior gut associated tissues.", "Using in situ hybridization with adult zebrafish tissues, we found that zebrafish ghrelin mRNA was not expressed in intestine tissue, but rather in clusters of endocrine pancreas cells distinct from insulin-expressing islets.", "Fasting specifically upregulated pancreatic ghrelin but not brain ghrelin expression by 3- to 4-fold and refeeding restored ghrelin transcript to control levels seen in the fed group within 5 h. These results demonstrate that although ghrelin is expressed in a different site in zebrafish, it is responsive to metabolic state in a similar manner as mammalian ghrelin, suggesting a role in the regulation of feeding in teleosts, and thus validate the utility of zebrafish as a genetic model system for the analysis of the ghrelin system and energy homeostasis."], "title": "Zebrafish ghrelin is expressed in pancreatic endocrine cells and regulated by metabolic state."}
{"paper_id": 27196735, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "A key feature of multicellular systems is the ability of cells to function collectively in response to external stimuli. However, the mechanisms of intercellular cell signaling and their functional implications in diverse vascular structures are poorly understood. Using a combination of computational modeling and plasma lithography micropatterning, we investigate the roles of structural arrangement of endothelial cells in collective calcium signaling and cell contractility. Under histamine stimulation, endothelial cells in self-assembled and microengineered networks, but not individual cells and monolayers, exhibit calcium oscillations. Micropatterning, pharmacological inhibition, and computational modeling reveal that the calcium oscillation depends on the number of neighboring cells coupled via gap junctional intercellular communication, providing a mechanistic basis of the architecture-dependent calcium signaling. Furthermore, the calcium oscillation attenuates the histamine-induced cytoskeletal reorganization and cell contraction, resulting in differential cell responses in an architecture-dependent manner. Taken together, our results suggest that endothelial cells can sense and respond to chemical stimuli according to the vascular architecture via collective calcium signaling.", "journal": "PLoS computational biology", "sentences": ["A key feature of multicellular systems is the ability of cells to function collectively in response to external stimuli.", "However, the mechanisms of intercellular cell signaling and their functional implications in diverse vascular structures are poorly understood.", "Using a combination of computational modeling and plasma lithography micropatterning, we investigate the roles of structural arrangement of endothelial cells in collective calcium signaling and cell contractility.", "Under histamine stimulation, endothelial cells in self-assembled and microengineered networks, but not individual cells and monolayers, exhibit calcium oscillations.", "Micropatterning, pharmacological inhibition, and computational modeling reveal that the calcium oscillation depends on the number of neighboring cells coupled via gap junctional intercellular communication, providing a mechanistic basis of the architecture-dependent calcium signaling.", "Furthermore, the calcium oscillation attenuates the histamine-induced cytoskeletal reorganization and cell contraction, resulting in differential cell responses in an architecture-dependent manner.", "Taken together, our results suggest that endothelial cells can sense and respond to chemical stimuli according to the vascular architecture via collective calcium signaling."], "title": "Cellular Architecture Regulates Collective Calcium Signaling and Cell Contractility."}
{"paper_id": 26505393, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Compared to other placental mammals, humans have unique thinking and cognitive abilities because of their developed cerebral cortex composed of billions of neurons and synaptic connections. As the primary effectors of the mechanisms of life, proteins and their interactions form the basis of cellular and molecular functions in the living body. In this paper, we developed a pipeline for mining topological structures, identifying functional modules, and analyzing their functions from publically available datasets. A human brain-specific protein-protein interaction network with 1482 nodes and 3105 edges was built using a MapReduce based shortest path algorithm. Within this, 7 functional cliques were identified using a network clustering method, 98 hub proteins were obtained by the calculation of betweenness and connectivity, and 5 closest relationship to clique connector proteins were recognized by the combination scores of topological distance and gene ontology similarity. Furthermore, we discovered functional modules interacting with TP53 protein, which involves several fragmented research study conclusions and might be an important clue for further in vivo or in silico experiments to confirm these associations.", "journal": "Genetics and molecular research : GMR", "sentences": ["Compared to other placental mammals, humans have unique thinking and cognitive abilities because of their developed cerebral cortex composed of billions of neurons and synaptic connections.", "As the primary effectors of the mechanisms of life, proteins and their interactions form the basis of cellular and molecular functions in the living body.", "In this paper, we developed a pipeline for mining topological structures, identifying functional modules, and analyzing their functions from publically available datasets.", "A human brain-specific protein-protein interaction network with 1482 nodes and 3105 edges was built using a MapReduce based shortest path algorithm.", "Within this, 7 functional cliques were identified using a network clustering method, 98 hub proteins were obtained by the calculation of betweenness and connectivity, and 5 closest relationship to clique connector proteins were recognized by the combination scores of topological distance and gene ontology similarity.", "Furthermore, we discovered functional modules interacting with TP53 protein, which involves several fragmented research study conclusions and might be an important clue for further in vivo or in silico experiments to confirm these associations."], "title": "Mining topological structures of protein-protein interaction networks for human brain-specific genes."}
{"paper_id": 26080425, "labels": ["0", "0", "1", "0", "0", "1", "1"], "abstract": "TRAIL (TNF-related apoptosis-inducing ligand) is a promising anticancer agent that can be potentially used as an alternative or complementary therapy because of its specific antitumor activity. However, TRAIL can also stimulate the proliferation of cancer cells through the activation of NF-\u03baB, but the exact mechanism is still poorly understood. In this study, we show that chronic exposure to subtoxic concentrations of TRAIL results in acquired resistance. This resistance is associated with the increase in miR-21, miR-30c, and miR-100 expression, which target tumor-suppressor genes fundamental in the response to TRAIL. Importantly, down-regulation of caspase-8 by miR-21 blocks receptor interacting protein-1 cleavage and induces the activation of NF-\u03baB, which regulates these miRNAs. Thus, TRAIL activates a positive feedback loop that sustains the acquired resistance and causes an aggressive phenotype. Finally, we prove that combinatory treatment of NF-\u03baB inhibitors and TRAIL is able to revert resistance and reduce tumor growth, with important consequences for the clinical practice.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["TRAIL (TNF-related apoptosis-inducing ligand) is a promising anticancer agent that can be potentially used as an alternative or complementary therapy because of its specific antitumor activity.", "However, TRAIL can also stimulate the proliferation of cancer cells through the activation of NF-\u03baB, but the exact mechanism is still poorly understood.", "In this study, we show that chronic exposure to subtoxic concentrations of TRAIL results in acquired resistance.", "This resistance is associated with the increase in miR-21, miR-30c, and miR-100 expression, which target tumor-suppressor genes fundamental in the response to TRAIL.", "Importantly, down-regulation of caspase-8 by miR-21 blocks receptor interacting protein-1 cleavage and induces the activation of NF-\u03baB, which regulates these miRNAs.", "Thus, TRAIL activates a positive feedback loop that sustains the acquired resistance and causes an aggressive phenotype.", "Finally, we prove that combinatory treatment of NF-\u03baB inhibitors and TRAIL is able to revert resistance and reduce tumor growth, with important consequences for the clinical practice."], "title": "A set of NF-\u03baB-regulated microRNAs induces acquired TRAIL resistance in lung cancer."}
{"paper_id": 22993187, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "In clinical microbiology, bacterial identification is labor-intensive and time-consuming. A solution for this problem is the use of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). In this study, we evaluated a modified protein extraction method of identification performed on target plates (on-plate extraction method) with MALDI-TOF (Bruker Microflex LT with Biotyper version 3.0) and compared it to 2 previously described methods: the direct colony method and a standard protein extraction method (standard extraction method). We evaluated the species of 273 clinical strains and 14 reference strains of staphylococci. All isolates were characterized using the superoxide dismutase A sequence as a reference. For the species identification, the on-plate, standard extraction, and direct colony methods identified 257 isolates (89.5%), 232 isolates (80.8%), and 173 isolates (60.2%), respectively, with statistically significant differences among the three methods (P < 0.05). In conclusion, the on-plate extraction method is at least as good as standard extraction in identification rate and has the advantage of a shorter processing time.", "journal": "Journal of clinical microbiology", "sentences": ["In clinical microbiology, bacterial identification is labor-intensive and time-consuming.", "A solution for this problem is the use of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).", "In this study, we evaluated a modified protein extraction method of identification performed on target plates (on-plate extraction method) with MALDI-TOF (Bruker Microflex LT with Biotyper version 3.0) and compared it to 2 previously described methods: the direct colony method and a standard protein extraction method (standard extraction method).", "We evaluated the species of 273 clinical strains and 14 reference strains of staphylococci.", "All isolates were characterized using the superoxide dismutase A sequence as a reference.", "For the species identification, the on-plate, standard extraction, and direct colony methods identified 257 isolates (89.5%), 232 isolates (80.8%), and 173 isolates (60.2%), respectively, with statistically significant differences among the three methods (P < 0.05).", "In conclusion, the on-plate extraction method is at least as good as standard extraction in identification rate and has the advantage of a shorter processing time."], "title": "Evaluation of a simple protein extraction method for species identification of clinically relevant staphylococci by matrix-assisted laser desorption ionization-time of flight mass spectrometry."}
{"paper_id": 26520441, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Activation of AMP-activated protein kinase (AMPK) suppressed mammalian target of rapamycin (mTOR) pathway, resulting in impaired cancer cell proliferation. Two cohorts (50 and 1072 cases) of patients with resected gastric adenocarcinoma were enrolled in the study. Immunohistochemical staining for p-AMPKa, p-ACC, p-mTOR, p-S6, and p-4EBP1 was performed on the 50-patient cohort. Tissue microarray blocks containing samples from 1072 patients of Chinese ethnicity were used for the immunohistochemical detection of p-AMPKa and p-S6 levels. p-AMPK and p-ACC were frequently inactivated in both cohorts of gastric cancer samples, while p-mTOR, p-S6, and p-4EBP1 were frequently activated in the small cohort of gastric cancer. However, only levels of p-AMPKa and p-S6 were associated with the overall survival of gastric cancer patients. In the larger 1072-patient cohort, downregulation of p-AMPKa and upregulation of p-S6 were associated with tumor progression and were independent predictors of survival after resection of primary gastric cancer. Therefore, reciprocal expression of p-AMPKa and p-S6 may be promising prognostic biomarkers in patients with gastric cancer.", "journal": "Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine", "sentences": ["Activation of AMP-activated protein kinase (AMPK) suppressed mammalian target of rapamycin (mTOR) pathway, resulting in impaired cancer cell proliferation.", "Two cohorts (50 and 1072 cases) of patients with resected gastric adenocarcinoma were enrolled in the study.", "Immunohistochemical staining for p-AMPKa, p-ACC, p-mTOR, p-S6, and p-4EBP1 was performed on the 50-patient cohort.", "Tissue microarray blocks containing samples from 1072 patients of Chinese ethnicity were used for the immunohistochemical detection of p-AMPKa and p-S6 levels.", "p-AMPK and p-ACC were frequently inactivated in both cohorts of gastric cancer samples, while p-mTOR, p-S6, and p-4EBP1 were frequently activated in the small cohort of gastric cancer.", "However, only levels of p-AMPKa and p-S6 were associated with the overall survival of gastric cancer patients.", "In the larger 1072-patient cohort, downregulation of p-AMPKa and upregulation of p-S6 were associated with tumor progression and were independent predictors of survival after resection of primary gastric cancer.", "Therefore, reciprocal expression of p-AMPKa and p-S6 may be promising prognostic biomarkers in patients with gastric cancer."], "title": "Reciprocal expression of p-AMPKa and p-S6 is strongly associated with the prognosis of gastric cancer."}
{"paper_id": 23638033, "labels": ["0", "0", "0", "0", "1", "1", "1"], "abstract": "We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo. Here we interrogated the mechanism by which these novel compounds activate AMPK, a leading anti-diabetic drug target. BMTs did not activate AMPK directly in an allosteric manner as AMP or the Abbott compound (A-769662) does, nor did they activate AMPK by inhibiting cellular respiration like many commonly used anti-diabetic medications. BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20-35%. Incubation with the CaMKK\u03b2 inhibitor, STO-609, completely attenuated this effect suggesting a key role for CaMKK\u03b2 in this activation. Incubation of L6 myotubes with the calcium chelator EGTA-AM did not alter this activation suggesting that the BMT-dependent activation was Ca(2+)-independent. We therefore propose that CaMKK\u03b2 is a key upstream kinase for BMT-induced activation of AMPK.", "journal": "PloS one", "sentences": ["We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo.", "Here we interrogated the mechanism by which these novel compounds activate AMPK, a leading anti-diabetic drug target.", "BMTs did not activate AMPK directly in an allosteric manner as AMP or the Abbott compound (A-769662) does, nor did they activate AMPK by inhibiting cellular respiration like many commonly used anti-diabetic medications.", "BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20-35%.", "Incubation with the CaMKK\u03b2 inhibitor, STO-609, completely attenuated this effect suggesting a key role for CaMKK\u03b2 in this activation.", "Incubation of L6 myotubes with the calcium chelator EGTA-AM did not alter this activation suggesting that the BMT-dependent activation was Ca(2+)-independent.", "We therefore propose that CaMKK\u03b2 is a key upstream kinase for BMT-induced activation of AMPK."], "title": "Activation of AMPK by bitter melon triterpenoids involves CaMKK\u03b2."}
{"paper_id": 26478367, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "To obtain a kind of light-curable fiber-reinforced composite for dental restoration, an excellent interfacial adhesion between the fiber and the acrylate resin matrix is quite essential. Herein, surface modification on glass fibers were carried out by coating them with poly(methyl methacrylate) (PMMA), polydopamine (PDA), or both. The PMMA or PDA coating was performed by soaking fibers in PMMA/acetone solution or dopamine aqueous solution. PDA/PMMA co-coated glass fibers were obtained by further soaking PDA-coated fibers in PMMA/acetone solution. These modified fibers were impregnated with bisphenol A glycidyl methacrylate (Bis-GMA)/triethylene glycol dimethacrylate (TEGDMA) (5:5, w/w) dental resin at a volume fraction of 75%, using unmodified fibers as reference. Light-cured specimens were submitted to evaluations including flexural properties, morphological observation, dynamic mechanical thermal analysis (DMTA) and pull-out test. In comparison with unmodified glass fibers, all the modified glass fibers showed enhancements in flexural strength and modulus of Bis-GMA/TEGDMA resin composites. Results of DMTA and pull-out tests confirmed that surface modification had significantly improved the interfacial adhesion between the glass fiber and the resin matrix. Particularly, the PDA/PMMA co-coated glass fibers displayed the most efficient reinforcement and the strongest interfacial adhesion due to the synergetic effects of PDA and PMMA. It indicated that co-coating method was a promising approach in modifying the interfacial compatibility between inorganic glass fiber and organic resin matrix.", "journal": "Materials science & engineering. C, Materials for biological applications", "sentences": ["To obtain a kind of light-curable fiber-reinforced composite for dental restoration, an excellent interfacial adhesion between the fiber and the acrylate resin matrix is quite essential.", "Herein, surface modification on glass fibers were carried out by coating them with poly(methyl methacrylate) (PMMA), polydopamine (PDA), or both.", "The PMMA or PDA coating was performed by soaking fibers in PMMA/acetone solution or dopamine aqueous solution.", "PDA/PMMA co-coated glass fibers were obtained by further soaking PDA-coated fibers in PMMA/acetone solution.", "These modified fibers were impregnated with bisphenol A glycidyl methacrylate (Bis-GMA)/triethylene glycol dimethacrylate (TEGDMA) (5:5, w/w) dental resin at a volume fraction of 75%, using unmodified fibers as reference.", "Light-cured specimens were submitted to evaluations including flexural properties, morphological observation, dynamic mechanical thermal analysis (DMTA) and pull-out test.", "In comparison with unmodified glass fibers, all the modified glass fibers showed enhancements in flexural strength and modulus of Bis-GMA/TEGDMA resin composites.", "Results of DMTA and pull-out tests confirmed that surface modification had significantly improved the interfacial adhesion between the glass fiber and the resin matrix.", "Particularly, the PDA/PMMA co-coated glass fibers displayed the most efficient reinforcement and the strongest interfacial adhesion due to the synergetic effects of PDA and PMMA.", "It indicated that co-coating method was a promising approach in modifying the interfacial compatibility between inorganic glass fiber and organic resin matrix."], "title": "Flexible fiber-reinforced composites with improved interfacial adhesion by mussel-inspired polydopamine and poly(methyl methacrylate) coating."}
{"paper_id": 24107963, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "NMDA receptors (NMDARs) expressed by cerebellar molecular layer interneurons (MLIs) are not activated by single exocytotic events but can respond to glutamate spillover following coactivation of adjacent parallel fibers (PFs), indicating that NMDARs are perisynaptic. Several types of synaptic plasticity rely on these receptors but whether they are activated at isolated synapses is not known. Using a combination of electrophysiological and optical recording techniques in acute slices of rat cerebellum, along with modeling, we find that repetitive activation of single PF-MLI synapses can activate NMDARs in MLIs. High-frequency stimulation, multivesicular release (MVR), or asynchronous release can each activate NMDARs. Frequency facilitation was found at all PF-MLI synapses but, while some showed robust MVR with increased release probability, most were limited to univesicular release. Together, these results reveal a functional diversity of PF synapses, which use different mechanisms to activate NMDARs.", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "sentences": ["NMDA receptors (NMDARs) expressed by cerebellar molecular layer interneurons (MLIs) are not activated by single exocytotic events but can respond to glutamate spillover following coactivation of adjacent parallel fibers (PFs), indicating that NMDARs are perisynaptic.", "Several types of synaptic plasticity rely on these receptors but whether they are activated at isolated synapses is not known.", "Using a combination of electrophysiological and optical recording techniques in acute slices of rat cerebellum, along with modeling, we find that repetitive activation of single PF-MLI synapses can activate NMDARs in MLIs.", "High-frequency stimulation, multivesicular release (MVR), or asynchronous release can each activate NMDARs.", "Frequency facilitation was found at all PF-MLI synapses but, while some showed robust MVR with increased release probability, most were limited to univesicular release.", "Together, these results reveal a functional diversity of PF synapses, which use different mechanisms to activate NMDARs."], "title": "Activation of extrasynaptic NMDARs at individual parallel fiber-molecular layer interneuron synapses in cerebellum."}
{"paper_id": 25493918, "labels": ["0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Statistical analysis is error prone. A best practice for researchers using statistics would therefore be to share data among co-authors, allowing double-checking of executed tasks just as co-pilots do in aviation. To document the extent to which this 'co-piloting' currently occurs in psychology, we surveyed the authors of 697 articles published in six top psychology journals and asked them whether they had collaborated on four aspects of analyzing data and reporting results, and whether the described data had been shared between the authors. We acquired responses for 49.6% of the articles and found that co-piloting on statistical analysis and reporting results is quite uncommon among psychologists, while data sharing among co-authors seems reasonably but not completely standard. We then used an automated procedure to study the prevalence of statistical reporting errors in the articles in our sample and examined the relationship between reporting errors and co-piloting. Overall, 63% of the articles contained at least one p-value that was inconsistent with the reported test statistic and the accompanying degrees of freedom, and 20% of the articles contained at least one p-value that was inconsistent to such a degree that it may have affected decisions about statistical significance. Overall, the probability that a given p-value was inconsistent was over 10%. Co-piloting was not found to be associated with reporting errors.", "journal": "PloS one", "sentences": ["Statistical analysis is error prone.", "A best practice for researchers using statistics would therefore be to share data among co-authors, allowing double-checking of executed tasks just as co-pilots do in aviation.", "To document the extent to which this 'co-piloting' currently occurs in psychology, we surveyed the authors of 697 articles published in six top psychology journals and asked them whether they had collaborated on four aspects of analyzing data and reporting results, and whether the described data had been shared between the authors.", "We acquired responses for 49.6% of the articles and found that co-piloting on statistical analysis and reporting results is quite uncommon among psychologists, while data sharing among co-authors seems reasonably but not completely standard.", "We then used an automated procedure to study the prevalence of statistical reporting errors in the articles in our sample and examined the relationship between reporting errors and co-piloting.", "Overall, 63% of the articles contained at least one p-value that was inconsistent with the reported test statistic and the accompanying degrees of freedom, and 20% of the articles contained at least one p-value that was inconsistent to such a degree that it may have affected decisions about statistical significance.", "Overall, the probability that a given p-value was inconsistent was over 10%.", "Co-piloting was not found to be associated with reporting errors."], "title": "Statistical Reporting Errors and Collaboration on Statistical Analyses in Psychological Science."}
{"paper_id": 23516598, "labels": ["0", "0", "1", "0", "0", "0", "1", "0", "1"], "abstract": "NOA36/ZNF330 is an evolutionarily well-preserved protein present in the nucleolus and mitochondria of mammalian cells. We have previously reported that the pro-apoptotic activity of this protein is mediated by a characteristic cysteine-rich domain. We now demonstrate that the nucleolar localization of NOA36 is due to a highly-conserved nucleolar localization signal (NoLS) present in residues 1-33. This NoLS is a sequence containing three clusters of two or three basic amino acids. We fused the amino terminal of NOA36 to eGFP in order to characterize this putative NoLS. We show that a cluster of three lysine residues at positions 3 to 5 within this sequence is critical for the nucleolar localization. We also demonstrate that the sequence as found in human is capable of directing eGFP to the nucleolus in several mammal, fish and insect cells. Moreover, this NoLS is capable of specifically directing the cytosolic yeast enzyme polyphosphatase to the target of the nucleolus of HeLa cells, wherein its enzymatic activity was detected. This NoLS could therefore serve as a very useful tool as a nucleolar marker and for directing particular proteins to the nucleolus in distant animal species.", "journal": "PloS one", "sentences": ["NOA36/ZNF330 is an evolutionarily well-preserved protein present in the nucleolus and mitochondria of mammalian cells.", "We have previously reported that the pro-apoptotic activity of this protein is mediated by a characteristic cysteine-rich domain.", "We now demonstrate that the nucleolar localization of NOA36 is due to a highly-conserved nucleolar localization signal (NoLS) present in residues 1-33.", "This NoLS is a sequence containing three clusters of two or three basic amino acids.", "We fused the amino terminal of NOA36 to eGFP in order to characterize this putative NoLS.", "We show that a cluster of three lysine residues at positions 3 to 5 within this sequence is critical for the nucleolar localization.", "We also demonstrate that the sequence as found in human is capable of directing eGFP to the nucleolus in several mammal, fish and insect cells.", "Moreover, this NoLS is capable of specifically directing the cytosolic yeast enzyme polyphosphatase to the target of the nucleolus of HeLa cells, wherein its enzymatic activity was detected.", "This NoLS could therefore serve as a very useful tool as a nucleolar marker and for directing particular proteins to the nucleolus in distant animal species."], "title": "NOA36 protein contains a highly conserved nucleolar localization signal capable of directing functional proteins to the nucleolus, in mammalian cells."}
{"paper_id": 23185343, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The dopamine D(1), D(2), D(3) receptors, vesicular monoamine transporter type-2 (VMAT2), and dopamine transporter (DAT) densities were measured in 11 aged human brains (aged 77-107.8, mean: 91 years) by quantitative autoradiography. The density of D(1) receptors, VMAT2, and DAT was measured using [(3)H]SCH23390, [(3)H]dihydrotetrabenazine, and [(3)H]WIN35428, respectively. The density of D(2) and D(3) receptors was calculated using the D(3)-preferring radioligand, [(3)H]WC-10 and the D(2)-preferring radioligand [(3)H]raclopride using a mathematical model developed previously by our group. Dopamine D(1), D(2), and D(3) receptors are extensively distributed throughout striatum; the highest density of D(3) receptors occurred in the nucleus accumbens (NAc). The density of the DAT is 10-20-fold lower than that of VMAT2 in striatal regions. Dopamine D(3) receptor density exceeded D(2) receptor densities in extrastriatal regions, and thalamus contained a high level of D(3) receptors with negligible D(2) receptors. The density of dopamine D(1) linearly correlated with D(3) receptor density in the thalamus. The density of the DAT was negligible in the extrastriatal regions whereas the VMAT2 was expressed in moderate density. D(3) receptor and VMAT2 densities were in similar level between the aged human and aged rhesus brain samples, whereas aged human brain samples had lower range of densities of D(1) and D(2) receptors and DAT compared with the aged rhesus monkey brain. The differential density of D(3) and D(2) receptors in human brain will be useful in the interpretation of PET imaging studies in human subjects with existing radiotracers, and assist in the validation of newer PET radiotracers having a higher selectivity for dopamine D(2) or D(3) receptors.", "journal": "PloS one", "sentences": ["The dopamine D(1), D(2), D(3) receptors, vesicular monoamine transporter type-2 (VMAT2), and dopamine transporter (DAT) densities were measured in 11 aged human brains (aged 77-107.8, mean: 91 years) by quantitative autoradiography.", "The density of D(1) receptors, VMAT2, and DAT was measured using [(3)H]SCH23390, [(3)H]dihydrotetrabenazine, and [(3)H]WIN35428, respectively.", "The density of D(2) and D(3) receptors was calculated using the D(3)-preferring radioligand, [(3)H]WC-10 and the D(2)-preferring radioligand [(3)H]raclopride using a mathematical model developed previously by our group.", "Dopamine D(1), D(2), and D(3) receptors are extensively distributed throughout striatum; the highest density of D(3) receptors occurred in the nucleus accumbens (NAc).", "The density of the DAT is 10-20-fold lower than that of VMAT2 in striatal regions.", "Dopamine D(3) receptor density exceeded D(2) receptor densities in extrastriatal regions, and thalamus contained a high level of D(3) receptors with negligible D(2) receptors.", "The density of dopamine D(1) linearly correlated with D(3) receptor density in the thalamus.", "The density of the DAT was negligible in the extrastriatal regions whereas the VMAT2 was expressed in moderate density.", "D(3) receptor and VMAT2 densities were in similar level between the aged human and aged rhesus brain samples, whereas aged human brain samples had lower range of densities of D(1) and D(2) receptors and DAT compared with the aged rhesus monkey brain.", "The differential density of D(3) and D(2) receptors in human brain will be useful in the interpretation of PET imaging studies in human subjects with existing radiotracers, and assist in the validation of newer PET radiotracers having a higher selectivity for dopamine D(2) or D(3) receptors."], "title": "Dopamine D1, D2, D3 receptors, vesicular monoamine transporter type-2 (VMAT2) and dopamine transporter (DAT) densities in aged human brain."}
{"paper_id": 21772079, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) involves the acquisition of images before, during and after the injection of a contrast agent. In order to perform quantitative modeling on the resulting signal intensity time course, data must be acquired rapidly, which compromises spatial resolution, signal to noise and/or field of view. One approach that may allow for gains in temporal or spatial resolution or signal to noise of an individual image is to use compressed sensing (CS) MRI. In this study, we demonstrate the accuracy of extracted pharmacokinetic parameters from DCE-MRI data obtained as part of pre-clinical and clinical studies in which fully sampled acquisitions have been retrospectively undersampled by factors of 2, 3 and 4 in Fourier space and then reconstructed with CS. The mean voxel-level concordance correlation coefficient for K(trans) (i.e. the volume transfer constant) obtained from the 2\u00d7 accelerated and the fully sampled data is 0.92 and 0.90 for mouse and human data, respectively; for 3\u00d7, the results are 0.79 and 0.79, respectively; for 4\u00d7, the results are 0.64 and 0.70, respectively. The mean error in the tumor mean K(trans) for the mouse and human data at 2\u00d7 acceleration is 1.8% and -4.2%, respectively; at 3\u00d7, 3.6% and -10%, respectively; at 4\u00d7, 7.8% and -12%, respectively. These results suggest that CS combined with appropriate reduced acquisitions may be an effective approach to improving image quality in DCE-MRI.", "journal": "Physics in medicine and biology", "sentences": ["Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) involves the acquisition of images before, during and after the injection of a contrast agent.", "In order to perform quantitative modeling on the resulting signal intensity time course, data must be acquired rapidly, which compromises spatial resolution, signal to noise and/or field of view.", "One approach that may allow for gains in temporal or spatial resolution or signal to noise of an individual image is to use compressed sensing (CS) MRI.", "In this study, we demonstrate the accuracy of extracted pharmacokinetic parameters from DCE-MRI data obtained as part of pre-clinical and clinical studies in which fully sampled acquisitions have been retrospectively undersampled by factors of 2, 3 and 4 in Fourier space and then reconstructed with CS.", "The mean voxel-level concordance correlation coefficient for K(trans) (i.e.", "the volume transfer constant) obtained from the 2\u00d7 accelerated and the fully sampled data is 0.92 and 0.90 for mouse and human data, respectively; for 3\u00d7, the results are 0.79 and 0.79, respectively; for 4\u00d7, the results are 0.64 and 0.70, respectively.", "The mean error in the tumor mean K(trans) for the mouse and human data at 2\u00d7 acceleration is 1.8% and -4.2%, respectively; at 3\u00d7, 3.6% and -10%, respectively; at 4\u00d7, 7.8% and -12%, respectively.", "These results suggest that CS combined with appropriate reduced acquisitions may be an effective approach to improving image quality in DCE-MRI."], "title": "Quantitative effects of using compressed sensing in dynamic contrast enhanced MRI."}
{"paper_id": 24991573, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "We evaluated the association between the expression of myeloid antigens on neoplastic plasma cells and patient prognosis. The expression status of CD13, CD19, CD20, CD33, CD38, CD56, and CD117 was analyzed on myeloma cells from 55 newly diagnosed patients, including 36 men (65%), of median age 61 years (range: 38-78). Analyzed clinical characteristics and laboratory parameters were as follows: serum \u03b2 2-microglobulin, lactate dehydrogenase, calcium, albumin, hemoglobin, serum creatinine concentrations, bone marrow histology, and cytogenetic findings. CD13+ and CD33+ were detected in 53% and 18%, respectively. Serum calcium (P = 0.049) and LDH (P = 0.018) concentrations were significantly higher and morphologic subtype of immature or plasmablastic was more frequent in CD33+ than in CD33- patients (P = 0.022). CD33 and CD13 expression demonstrate a potential prognostic impact and were associated with lower overall survival (OS; P = 0.001 and P = 0.025) in Kaplan-Meier analysis. Multivariate analysis showed that CD33 was independently prognostic of shorter progression free survival (PFS; P = 0.037) and OS (P = 0.001) with correction of clinical prognostic factors. This study showed that CD13 and CD33 expression associated with poor prognosis in patients with MM implicating the need of analysis of these markers in MM diagnosis.", "journal": "BioMed research international", "sentences": ["We evaluated the association between the expression of myeloid antigens on neoplastic plasma cells and patient prognosis.", "The expression status of CD13, CD19, CD20, CD33, CD38, CD56, and CD117 was analyzed on myeloma cells from 55 newly diagnosed patients, including 36 men (65%), of median age 61 years (range: 38-78).", "Analyzed clinical characteristics and laboratory parameters were as follows: serum \u03b2 2-microglobulin, lactate dehydrogenase, calcium, albumin, hemoglobin, serum creatinine concentrations, bone marrow histology, and cytogenetic findings.", "CD13+ and CD33+ were detected in 53% and 18%, respectively.", "Serum calcium (P = 0.049) and LDH (P = 0.018) concentrations were significantly higher and morphologic subtype of immature or plasmablastic was more frequent in CD33+ than in CD33- patients (P = 0.022).", "CD33 and CD13 expression demonstrate a potential prognostic impact and were associated with lower overall survival (OS; P = 0.001 and P = 0.025) in Kaplan-Meier analysis.", "Multivariate analysis showed that CD33 was independently prognostic of shorter progression free survival (PFS; P = 0.037) and OS (P = 0.001) with correction of clinical prognostic factors.", "This study showed that CD13 and CD33 expression associated with poor prognosis in patients with MM implicating the need of analysis of these markers in MM diagnosis."], "title": "Expression of myeloid antigen in neoplastic plasma cells is related to adverse prognosis in patients with multiple myeloma."}
{"paper_id": 21152317, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "Zinc-fingers play crucial roles in regulating gene expression and mediating protein-protein interactions. In this article, two different proteins (Sp1f2 and FSD-1) are investigated using the Gaussian network model and anisotropy elastic network model. By using these simple coarse-grained methods, we analyze the structural stabilization and establish the unfolding pathway of the two different proteins, in good agreement with related experimental and molecular dynamics simulation data. From the analysis, it is also found that the folding process of the zinc-finger motif is predominated by several factors. Both the zinc ion and C-terminal loop affect the folding pathway of the zinc-finger motif. Knowledge about the stability and folding behavior of zinc-fingers may help in understanding the folding mechanisms of the zinc-finger motif and in designing new zinc-fingers. Meanwhile, these simple coarse-grained analyses can be used as a general and quick method for mechanistic studies of metalloproteins.", "journal": "International journal of molecular sciences", "sentences": ["Zinc-fingers play crucial roles in regulating gene expression and mediating protein-protein interactions.", "In this article, two different proteins (Sp1f2 and FSD-1) are investigated using the Gaussian network model and anisotropy elastic network model.", "By using these simple coarse-grained methods, we analyze the structural stabilization and establish the unfolding pathway of the two different proteins, in good agreement with related experimental and molecular dynamics simulation data.", "From the analysis, it is also found that the folding process of the zinc-finger motif is predominated by several factors.", "Both the zinc ion and C-terminal loop affect the folding pathway of the zinc-finger motif.", "Knowledge about the stability and folding behavior of zinc-fingers may help in understanding the folding mechanisms of the zinc-finger motif and in designing new zinc-fingers.", "Meanwhile, these simple coarse-grained analyses can be used as a general and quick method for mechanistic studies of metalloproteins."], "title": "Stability and folding behavior analysis of zinc-finger using simple models."}
{"paper_id": 26612863, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "Viral -1 programmed ribosomal frameshifting (PRF) as a potential antiviral target has attracted interest because many human viral pathogens, including human immunodeficiency virus (HIV) and coronaviruses, rely on -1 PRF for optimal propagation. Efficient eukaryotic -1 PRF requires an optimally placed stimulator structure downstream of the frameshifting site and different strategies targeting viral -1 PRF stimulators have been developed. However, accessing particular -1 PRF stimulator information represents a bottle-neck in combating the emerging epidemic viral pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV). Recently, an RNA hairpin upstream of frameshifting site was shown to act as a cis-element to attenuate -1 PRF with mechanism unknown. Here, we show that an upstream duplex formed in-trans, by annealing an antisense to its complementary mRNA sequence upstream of frameshifting site, can replace an upstream hairpin to attenuate -1 PRF efficiently. This finding indicates that the formation of a proximal upstream duplex is the main determining factor responsible for -1 PRF attenuation and provides mechanistic insight. Additionally, the antisense-mediated upstream duplex approach downregulates -1 PRF stimulated by distinct -1 PRF stimulators, including those of MERS-CoV, suggesting its general application potential as a robust means to evaluating viral -1 PRF inhibition as soon as the sequence information of an emerging human coronavirus is available.", "journal": "Nucleic acids research", "sentences": ["Viral -1 programmed ribosomal frameshifting (PRF) as a potential antiviral target has attracted interest because many human viral pathogens, including human immunodeficiency virus (HIV) and coronaviruses, rely on -1 PRF for optimal propagation.", "Efficient eukaryotic -1 PRF requires an optimally placed stimulator structure downstream of the frameshifting site and different strategies targeting viral -1 PRF stimulators have been developed.", "However, accessing particular -1 PRF stimulator information represents a bottle-neck in combating the emerging epidemic viral pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV).", "Recently, an RNA hairpin upstream of frameshifting site was shown to act as a cis-element to attenuate -1 PRF with mechanism unknown.", "Here, we show that an upstream duplex formed in-trans, by annealing an antisense to its complementary mRNA sequence upstream of frameshifting site, can replace an upstream hairpin to attenuate -1 PRF efficiently.", "This finding indicates that the formation of a proximal upstream duplex is the main determining factor responsible for -1 PRF attenuation and provides mechanistic insight.", "Additionally, the antisense-mediated upstream duplex approach downregulates -1 PRF stimulated by distinct -1 PRF stimulators, including those of MERS-CoV, suggesting its general application potential as a robust means to evaluating viral -1 PRF inhibition as soon as the sequence information of an emerging human coronavirus is available."], "title": "A general strategy to inhibiting viral -1 frameshifting based on upstream attenuation duplex formation."}
{"paper_id": 26363028, "labels": ["0", "0", "0", "1", "1", "0"], "abstract": "UNLABELLED\n: Large resequencing projects require a significant amount of storage for raw sequences, as well as alignment files. Because the raw sequences are redundant once the alignment has been generated, it is possible to keep only the alignment files. We present BamHash, a checksum based method to ensure that the read pairs in FASTQ files match exactly the read pairs stored in BAM files, regardless of the ordering of reads. BamHash can be used to verify the integrity of the files stored and discover any discrepancies. Thus, BamHash can be used to determine if it is safe to delete the FASTQ files storing raw sequencing read after alignment, without the loss of data.\n\n\nAVAILABILITY AND IMPLEMENTATION\nThe software is implemented in C++, GPL licensed and available at https://github.com/DecodeGenetics/BamHashContact: pmelsted@hi.is.", "journal": "Bioinformatics (Oxford, England)", "sentences": ["UNLABELLED\n: Large resequencing projects require a significant amount of storage for raw sequences, as well as alignment files.", "Because the raw sequences are redundant once the alignment has been generated, it is possible to keep only the alignment files.", "We present BamHash, a checksum based method to ensure that the read pairs in FASTQ files match exactly the read pairs stored in BAM files, regardless of the ordering of reads.", "BamHash can be used to verify the integrity of the files stored and discover any discrepancies.", "Thus, BamHash can be used to determine if it is safe to delete the FASTQ files storing raw sequencing read after alignment, without the loss of data.", "AVAILABILITY AND IMPLEMENTATION\nThe software is implemented in C++, GPL licensed and available at https://github.com/DecodeGenetics/BamHashContact: pmelsted@hi.is."], "title": "BamHash: a checksum program for verifying the integrity of sequence data."}
{"paper_id": 23372167, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Recombinant canine B-domain deleted (BDD) factor VIII (FVIII) is predominantly expressed as a single-chain protein and exhibits greater stability after activation compared with human FVIII-BDD. We generated a novel BDD-FVIII variant (FVIII-RH) with an amino acid change at the furin cleavage site within the B domain (position R1645H) that mimics the canine sequence (HHQR vs human RHQR). Compared with human FVIII-BDD, expression of FVIII-RH protein revealed a 2.5-fold increase in the single-chain form. Notably, FVIII-RH exhibited a twofold increase in biological activity compared with FVIII-BDD, likely due to its slower dissociation of the A2-domain upon thrombin activation. Injection of FVIII-RH protein in hemophilia A (HA) mice resulted in more efficacious hemostasis following vascular injury in both the macro- and microcirculation. These findings were successfully translated to adeno-associated viral (AAV)-based liver gene transfer in HA mice. Expression of circulating FVIII-RH was approximately twofold higher compared with AAV-FVIII-BDD-injected mice. Moreover, FVIII-RH exhibits superior procoagulant effects compared with FVIII-BDD following a series of hemostatic challenges. Notably, the immunogenicity of FVIII-RH did not differ from FVIII-BDD. Thus, FVIII-RH is an attractive bioengineered molecule for improving efficacy without increased immunogenicity and may be suitable for both protein- and gene-based strategies for HA.", "journal": "Blood", "sentences": ["Recombinant canine B-domain deleted (BDD) factor VIII (FVIII) is predominantly expressed as a single-chain protein and exhibits greater stability after activation compared with human FVIII-BDD.", "We generated a novel BDD-FVIII variant (FVIII-RH) with an amino acid change at the furin cleavage site within the B domain (position R1645H) that mimics the canine sequence (HHQR vs human RHQR).", "Compared with human FVIII-BDD, expression of FVIII-RH protein revealed a 2.5-fold increase in the single-chain form.", "Notably, FVIII-RH exhibited a twofold increase in biological activity compared with FVIII-BDD, likely due to its slower dissociation of the A2-domain upon thrombin activation.", "Injection of FVIII-RH protein in hemophilia A (HA) mice resulted in more efficacious hemostasis following vascular injury in both the macro- and microcirculation.", "These findings were successfully translated to adeno-associated viral (AAV)-based liver gene transfer in HA mice.", "Expression of circulating FVIII-RH was approximately twofold higher compared with AAV-FVIII-BDD-injected mice.", "Moreover, FVIII-RH exhibits superior procoagulant effects compared with FVIII-BDD following a series of hemostatic challenges.", "Notably, the immunogenicity of FVIII-RH did not differ from FVIII-BDD.", "Thus, FVIII-RH is an attractive bioengineered molecule for improving efficacy without increased immunogenicity and may be suitable for both protein- and gene-based strategies for HA."], "title": "Minimal modification in the factor VIII B-domain sequence ameliorates the murine hemophilia A phenotype."}
{"paper_id": 26762204, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "The results from the randomized phase II BELOB trial provided evidence for a potential benefit of bevacizumab (beva), a humanized monoclonal antibody against circulating VEGF-A, when added to CCNU chemotherapy in patients with recurrent glioblastoma (GBM). In this study, we performed gene expression profiling (DASL and RNA-seq) of formalin-fixed, paraffin-embedded tumor material from participants of the BELOB trial to identify patients with recurrent GBM who benefitted most from beva+CCNU treatment. We demonstrate that tumors assigned to the IGS-18 or \"classical\" subtype and treated with beva+CCNU showed a significant benefit in progression-free survival and a trend toward benefit in overall survival, whereas other subtypes did not exhibit such benefit. In particular, expression of FMO4 and OSBPL3 was associated with treatment response. Importantly, the improved outcome in the beva+CCNU treatment arm was not explained by an uneven distribution of prognostically favorable subtypes as all molecular glioma subtypes were evenly distributed along the different study arms. The RNA-seq analysis also highlighted genetic alterations, including mutations, gene fusions, and copy number changes, within this well-defined cohort of tumors that may serve as useful predictive or prognostic biomarkers of patient outcome. Further validation of the identified molecular markers may enable the future stratification of recurrent GBM patients into appropriate treatment regimens.", "journal": "Cancer research", "sentences": ["The results from the randomized phase II BELOB trial provided evidence for a potential benefit of bevacizumab (beva), a humanized monoclonal antibody against circulating VEGF-A, when added to CCNU chemotherapy in patients with recurrent glioblastoma (GBM).", "In this study, we performed gene expression profiling (DASL and RNA-seq) of formalin-fixed, paraffin-embedded tumor material from participants of the BELOB trial to identify patients with recurrent GBM who benefitted most from beva+CCNU treatment.", "We demonstrate that tumors assigned to the IGS-18 or \"classical\" subtype and treated with beva+CCNU showed a significant benefit in progression-free survival and a trend toward benefit in overall survival, whereas other subtypes did not exhibit such benefit.", "In particular, expression of FMO4 and OSBPL3 was associated with treatment response.", "Importantly, the improved outcome in the beva+CCNU treatment arm was not explained by an uneven distribution of prognostically favorable subtypes as all molecular glioma subtypes were evenly distributed along the different study arms.", "The RNA-seq analysis also highlighted genetic alterations, including mutations, gene fusions, and copy number changes, within this well-defined cohort of tumors that may serve as useful predictive or prognostic biomarkers of patient outcome.", "Further validation of the identified molecular markers may enable the future stratification of recurrent GBM patients into appropriate treatment regimens."], "title": "Identification of Patients with Recurrent Glioblastoma Who May Benefit from Combined Bevacizumab and CCNU Therapy: A Report from the BELOB Trial."}
{"paper_id": 22517894, "labels": ["0", "0", "0", "1", "0"], "abstract": "Inorganic polyphosphate is widespread in biology and exhibits striking prohemostatic, prothrombotic, and proinflammatory effects in vivo. Long-chain polyphosphate (of the size present in infectious microorganisms) is a potent, natural pathophysiologic activator of the contact pathway of blood clotting. Medium-chain polyphosphate (of the size secreted from activated human platelets) accelerates factor V activation, completely abrogates the anticoagulant function of tissue factor pathway inhibitor, enhances fibrin clot structure, and greatly accelerates factor XI activation by thrombin. Polyphosphate may have utility as a hemostatic agent, whereas antagonists of polyphosphate may function as novel antithrombotic/anti-inflammatory agents. The detailed molecular mechanisms by which polyphosphate modulates blood clotting reactions remain to be elucidated.", "journal": "Blood", "sentences": ["Inorganic polyphosphate is widespread in biology and exhibits striking prohemostatic, prothrombotic, and proinflammatory effects in vivo.", "Long-chain polyphosphate (of the size present in infectious microorganisms) is a potent, natural pathophysiologic activator of the contact pathway of blood clotting.", "Medium-chain polyphosphate (of the size secreted from activated human platelets) accelerates factor V activation, completely abrogates the anticoagulant function of tissue factor pathway inhibitor, enhances fibrin clot structure, and greatly accelerates factor XI activation by thrombin.", "Polyphosphate may have utility as a hemostatic agent, whereas antagonists of polyphosphate may function as novel antithrombotic/anti-inflammatory agents.", "The detailed molecular mechanisms by which polyphosphate modulates blood clotting reactions remain to be elucidated."], "title": "Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation."}
{"paper_id": 22359497, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "To investigate the stability and functional role of long-residence water molecules in the Q61H variant of the signaling protein K-ras, we analyzed all available Ras crystal structures and conformers derived from a series of independent explicit solvent molecular dynamics (MD) simulations totaling 1.76 \u00b5s. We show that the protein samples a different region of phase space in the presence and absence of several crystallographically conserved and buried water molecules. The dynamics of these waters is coupled with the local as well as the global motions of the protein, in contrast to less buried waters whose exchange with bulk is only loosely coupled with the motion of loops in their vicinity. Aided by two novel reaction coordinates involving the distance (d) between the C(\u03b1) atoms of G60 at switch 2 and G10 at the P-loop and the N-C(\u03b1)-C-O dihedral (\u03be) of G60, we further show that three water molecules located in lobe1, at the interface between the lobes and at lobe2, are involved in the relative motion of residues at the two lobes of Q61H K-ras. Moreover, a d/\u03be plot classifies the available Ras x-ray structures and MD-derived K-ras conformers into active GTP-, intermediate GTP-, inactive GDP-bound, and nucleotide-free conformational states. The population of these states and the transition between them is modulated by water-mediated correlated motions involving the functionally critical switch 2, P-loop and helix 3. These results suggest that water molecules act as allosteric ligands to induce a population shift among distinct switch 2 conformations that differ in effector recognition.", "journal": "PLoS computational biology", "sentences": ["To investigate the stability and functional role of long-residence water molecules in the Q61H variant of the signaling protein K-ras, we analyzed all available Ras crystal structures and conformers derived from a series of independent explicit solvent molecular dynamics (MD) simulations totaling 1.76 \u00b5s.", "We show that the protein samples a different region of phase space in the presence and absence of several crystallographically conserved and buried water molecules.", "The dynamics of these waters is coupled with the local as well as the global motions of the protein, in contrast to less buried waters whose exchange with bulk is only loosely coupled with the motion of loops in their vicinity.", "Aided by two novel reaction coordinates involving the distance (d) between the C(\u03b1) atoms of G60 at switch 2 and G10 at the P-loop and the N-C(\u03b1)-C-O dihedral (\u03be) of G60, we further show that three water molecules located in lobe1, at the interface between the lobes and at lobe2, are involved in the relative motion of residues at the two lobes of Q61H K-ras.", "Moreover, a d/\u03be plot classifies the available Ras x-ray structures and MD-derived K-ras conformers into active GTP-, intermediate GTP-, inactive GDP-bound, and nucleotide-free conformational states.", "The population of these states and the transition between them is modulated by water-mediated correlated motions involving the functionally critical switch 2, P-loop and helix 3.", "These results suggest that water molecules act as allosteric ligands to induce a population shift among distinct switch 2 conformations that differ in effector recognition."], "title": "The role of conserved waters in conformational transitions of Q61H K-ras."}
{"paper_id": 20719951, "labels": ["0", "0", "0", "0", "1", "1", "1"], "abstract": "Culturing newly identified human lung pathogens from clinical sample isolates can represent a daunting task, with problems ranging from low levels of pathogens to the presence of growth suppressive factors in the specimens, compounded by the lack of a suitable tissue culture system. However, it is critical to develop suitable in vitro platforms to isolate and characterize the replication kinetics and pathogenesis of recently identified human pathogens. HCoV-HKU1, a human coronavirus identified in a clinical sample from a patient with severe pneumonia, has been a major challenge for successful propagation on all immortalized cells tested to date. To determine if HCoV-HKU1 could replicate in in vitro models of human ciliated airway epithelial cell cultures (HAE) that recapitulate the morphology, biochemistry, and physiology of the human airway epithelium, the apical surfaces of HAE were inoculated with a clinical sample of HCoV-HKU1 (Cean1 strain). High virus yields were found for several days postinoculation and electron micrograph, Northern blot, and immunofluorescence data confirmed that HCoV-HKU1 replicated efficiently within ciliated cells, demonstrating that this cell type is infected by all human coronaviruses identified to date. Antiserum directed against human leukocyte antigen C (HLA-C) failed to attenuate HCoV-HKU1 infection and replication in HAE, suggesting that HLA-C is not required for HCoV-HKU1 infection of the human ciliated airway epithelium. We propose that the HAE model provides a ready platform for molecular studies and characterization of HCoV-HKU1 and in general serves as a robust technology for the recovery, amplification, adaptation, and characterization of novel coronaviruses and other respiratory viruses from clinical material.", "journal": "Journal of virology", "sentences": ["Culturing newly identified human lung pathogens from clinical sample isolates can represent a daunting task, with problems ranging from low levels of pathogens to the presence of growth suppressive factors in the specimens, compounded by the lack of a suitable tissue culture system.", "However, it is critical to develop suitable in vitro platforms to isolate and characterize the replication kinetics and pathogenesis of recently identified human pathogens.", "HCoV-HKU1, a human coronavirus identified in a clinical sample from a patient with severe pneumonia, has been a major challenge for successful propagation on all immortalized cells tested to date.", "To determine if HCoV-HKU1 could replicate in in vitro models of human ciliated airway epithelial cell cultures (HAE) that recapitulate the morphology, biochemistry, and physiology of the human airway epithelium, the apical surfaces of HAE were inoculated with a clinical sample of HCoV-HKU1 (Cean1 strain).", "High virus yields were found for several days postinoculation and electron micrograph, Northern blot, and immunofluorescence data confirmed that HCoV-HKU1 replicated efficiently within ciliated cells, demonstrating that this cell type is infected by all human coronaviruses identified to date.", "Antiserum directed against human leukocyte antigen C (HLA-C) failed to attenuate HCoV-HKU1 infection and replication in HAE, suggesting that HLA-C is not required for HCoV-HKU1 infection of the human ciliated airway epithelium.", "We propose that the HAE model provides a ready platform for molecular studies and characterization of HCoV-HKU1 and in general serves as a robust technology for the recovery, amplification, adaptation, and characterization of novel coronaviruses and other respiratory viruses from clinical material."], "title": "Culturing the unculturable: human coronavirus HKU1 infects, replicates, and produces progeny virions in human ciliated airway epithelial cell cultures."}
{"paper_id": 26444777, "labels": ["0", "0", "0", "0", "1"], "abstract": "We present the effects of Targretin\u00ae (bexarotene) on cognition and biomarkers in a patient with mild Alzheimer's disease (AD). Targretin\u00ae is a Retinoic X Receptor (RXR) agonist shown to improve synaptic and cognitive functions in animal models of AD by increasing neuronal cholesterol efflux. After 6 months of treatment with Targretin\u00ae 300\u200amg/day, memory improved by about 40% and the tau protein in the cerebrospinal fluid decreased by about 20% . No significant side effects were noticed. This observation in a single patient indicates that Targretin\u00ae may improve memory performance and biological markers at an early stage of AD.", "journal": "Journal of Alzheimer's disease : JAD", "sentences": ["We present the effects of Targretin\u00ae (bexarotene) on cognition and biomarkers in a patient with mild Alzheimer's disease (AD).", "Targretin\u00ae is a Retinoic X Receptor (RXR) agonist shown to improve synaptic and cognitive functions in animal models of AD by increasing neuronal cholesterol efflux.", "After 6 months of treatment with Targretin\u00ae 300\u200amg/day, memory improved by about 40% and the tau protein in the cerebrospinal fluid decreased by about 20% .", "No significant side effects were noticed.", "This observation in a single patient indicates that Targretin\u00ae may improve memory performance and biological markers at an early stage of AD."], "title": "Targretin Improves Cognitive and Biological Markers in a Patient with Alzheimer's Disease."}
{"paper_id": 23716606, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "The Francisella tularensis pathogenicity island (FPI) encodes many proteins that are required for virulence. Expression of these genes depends upon the FevR (PigR) regulator and its interactions with the MglA/SspA and RNA polymerase transcriptional complex. Experiments to identify how transcription of the FPI genes is activated have led to identification of mutations within the migR, trmE, and cphA genes that decrease FPI expression. Recent data demonstrated that the small alarmone ppGpp, produced by RelA and SpoT, is important for stabilizing MglA/SspA and FevR (PigR) interactions in Francisella. Production of ppGpp is commonly known to be activated by cellular and nutritional stress in bacteria, which indicates that cellular and nutritional stresses act as important signals for FPI activation. In this work, we demonstrate that mutations in migR, trmE, or cphA significantly reduce ppGpp accumulation. The reduction in ppGpp levels was similar for each of the mutants and correlated with a corresponding reduction in iglA reporter expression. In addition, we observed that there were differences in the ability of each of these mutants to replicate within various mammalian cells, indicating that the migR, trmE, and cphA genes are likely parts of different cellular stress response pathways in Francisella. These results also indicate that different nutritional and cellular stresses exist in different mammalian cells. This work provides new information to help understand how Francisella regulates its virulence genes in response to host cell environments, and it contributes to our growing knowledge of this highly successful bacterial pathogen.", "journal": "Infection and immunity", "sentences": ["The Francisella tularensis pathogenicity island (FPI) encodes many proteins that are required for virulence.", "Expression of these genes depends upon the FevR (PigR) regulator and its interactions with the MglA/SspA and RNA polymerase transcriptional complex.", "Experiments to identify how transcription of the FPI genes is activated have led to identification of mutations within the migR, trmE, and cphA genes that decrease FPI expression.", "Recent data demonstrated that the small alarmone ppGpp, produced by RelA and SpoT, is important for stabilizing MglA/SspA and FevR (PigR) interactions in Francisella.", "Production of ppGpp is commonly known to be activated by cellular and nutritional stress in bacteria, which indicates that cellular and nutritional stresses act as important signals for FPI activation.", "In this work, we demonstrate that mutations in migR, trmE, or cphA significantly reduce ppGpp accumulation.", "The reduction in ppGpp levels was similar for each of the mutants and correlated with a corresponding reduction in iglA reporter expression.", "In addition, we observed that there were differences in the ability of each of these mutants to replicate within various mammalian cells, indicating that the migR, trmE, and cphA genes are likely parts of different cellular stress response pathways in Francisella.", "These results also indicate that different nutritional and cellular stresses exist in different mammalian cells.", "This work provides new information to help understand how Francisella regulates its virulence genes in response to host cell environments, and it contributes to our growing knowledge of this highly successful bacterial pathogen."], "title": "The Francisella tularensis migR, trmE, and cphA genes contribute to F. tularensis pathogenicity island gene regulation and intracellular growth by modulation of the stress alarmone ppGpp."}
{"paper_id": 27028864, "labels": ["0", "0", "0", "0", "0", "1", "0", "1"], "abstract": "The SRC kinase has pivotal roles in multiple developmental processes and in tumor progression. An inverse relationship has been observed between androgen receptor (AR) activity and SRC signaling in advanced prostate cancer (PCa); however, the modulation of AR/SRC crosstalk that leads to metastatic PCa is unclear. Here, we showed that patients with high SRC levels displayed correspondingly low canonical AR gene signatures. Our results demonstrated that activated AR induced miR-203 and reduced SRC levels in PCa model systems. miR-203 directly binds to the 3' UTR of SRC and regulates the stability of SRC mRNA upon AR activation. Moreover, we found that progressive PCa cell migration and growth were associated with a decrease in AR-regulated miR-203 and an increase in SRC. Relationships among AR, miR-203, and SRC were also confirmed in clinical datasets and specimens. We suggest that the induction of SRC results in increased PCa metastasis that is linked to the dysregulation of the AR signaling pathway through the inactivation of miR-203.", "journal": "Oncotarget", "sentences": ["The SRC kinase has pivotal roles in multiple developmental processes and in tumor progression.", "An inverse relationship has been observed between androgen receptor (AR) activity and SRC signaling in advanced prostate cancer (PCa); however, the modulation of AR/SRC crosstalk that leads to metastatic PCa is unclear.", "Here, we showed that patients with high SRC levels displayed correspondingly low canonical AR gene signatures.", "Our results demonstrated that activated AR induced miR-203 and reduced SRC levels in PCa model systems.", "miR-203 directly binds to the 3' UTR of SRC and regulates the stability of SRC mRNA upon AR activation.", "Moreover, we found that progressive PCa cell migration and growth were associated with a decrease in AR-regulated miR-203 and an increase in SRC.", "Relationships among AR, miR-203, and SRC were also confirmed in clinical datasets and specimens.", "We suggest that the induction of SRC results in increased PCa metastasis that is linked to the dysregulation of the AR signaling pathway through the inactivation of miR-203."], "title": "Androgen receptor regulates SRC expression through microRNA-203."}
{"paper_id": 27112299, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "The ability to shift between multiple decision-making strategies during natural behavior allows animals to\u00a0strike a balance between flexibility and efficiency. We investigated odor-guided navigation by mice to\u00a0understand how decision-making strategies are balanced during a complex natural behavior. Mice navigated to odor sources in an open arena using naturally fluctuating airborne odor cues as their positions were recorded precisely in real time. When mice had limited prior experience of source locations, their\u00a0search behavior was consistent with\u00a0a gradient ascent algorithm that utilized directional cues in the\u00a0plume to navigate to the odor source. Gradient climbing was effective because the arena size allowed animals to conduct their search mainly within the odor plume, with frequent odor contacts.\u00a0With increased experience, mice shifted their strategy from this flexible, sensory-driven search behavior to a more efficient and stereotyped foraging approach that varied little in response to odor plumes. This study demonstrates that mice use prior knowledge to adaptively balance flexibility and efficiency during complex behavior guided by dynamic natural stimuli.", "journal": "Current biology : CB", "sentences": ["The ability to shift between multiple decision-making strategies during natural behavior allows animals to\u00a0strike a balance between flexibility and efficiency.", "We investigated odor-guided navigation by mice to\u00a0understand how decision-making strategies are balanced during a complex natural behavior.", "Mice navigated to odor sources in an open arena using naturally fluctuating airborne odor cues as their positions were recorded precisely in real time.", "When mice had limited prior experience of source locations, their\u00a0search behavior was consistent with\u00a0a gradient ascent algorithm that utilized directional cues in the\u00a0plume to navigate to the odor source.", "Gradient climbing was effective because the arena size allowed animals to conduct their search mainly within the odor plume, with frequent odor contacts.", "With increased experience, mice shifted their strategy from this flexible, sensory-driven search behavior to a more efficient and stereotyped foraging approach that varied little in response to odor plumes.", "This study demonstrates that mice use prior knowledge to adaptively balance flexibility and efficiency during complex behavior guided by dynamic natural stimuli."], "title": "Mice Develop Efficient Strategies for Foraging and Navigation Using Complex Natural Stimuli."}
{"paper_id": 26812546, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Autophagy is required for the homeostasis of cellular material and is proposed to be involved in many aspects of health. Defects in the autophagy pathway have been observed in neurodegenerative disorders; however, no genetically-inherited pathogenic mutations in any of the core autophagy-related (ATG) genes have been reported in human patients to date. We identified a homozygous missense mutation, changing a conserved amino acid, in ATG5 in two siblings with congenital ataxia, mental retardation, and developmental delay. The subjects' cells display a decrease in autophagy flux and defects in conjugation of ATG12 to ATG5. The homologous mutation in yeast demonstrates a 30-50% reduction of induced autophagy. Flies in which Atg5 is substituted with the mutant human ATG5 exhibit severe movement disorder, in contrast to flies expressing the wild-type human protein. Our results demonstrate the critical role of autophagy in preventing neurological diseases and maintaining neuronal health.", "journal": "eLife", "sentences": ["Autophagy is required for the homeostasis of cellular material and is proposed to be involved in many aspects of health.", "Defects in the autophagy pathway have been observed in neurodegenerative disorders; however, no genetically-inherited pathogenic mutations in any of the core autophagy-related (ATG) genes have been reported in human patients to date.", "We identified a homozygous missense mutation, changing a conserved amino acid, in ATG5 in two siblings with congenital ataxia, mental retardation, and developmental delay.", "The subjects' cells display a decrease in autophagy flux and defects in conjugation of ATG12 to ATG5.", "The homologous mutation in yeast demonstrates a 30-50% reduction of induced autophagy.", "Flies in which Atg5 is substituted with the mutant human ATG5 exhibit severe movement disorder, in contrast to flies expressing the wild-type human protein.", "Our results demonstrate the critical role of autophagy in preventing neurological diseases and maintaining neuronal health."], "title": "Mutation in ATG5 reduces autophagy and leads to ataxia with developmental delay."}
{"paper_id": 27093059, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep. Neurons active during behavior reactivate in both structures during sleep, in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation. In the hippocampus, replay occurs within sharp wave-ripples: short bouts of high-frequency activity in area CA1 caused by excitatory activation from area CA3. In this work, we develop a computational model of ripple generation, motivated by in vivo rat data showing that ripples have a broad frequency distribution, exponential inter-arrival times and yet highly non-variable durations. Our study predicts that ripples are not persistent oscillations but result from a transient network behavior, induced by input from CA3, in which the high frequency synchronous firing of perisomatic interneurons does not depend on the time scale of synaptic inhibition. We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration. Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network.", "journal": "PLoS computational biology", "sentences": ["Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep.", "Neurons active during behavior reactivate in both structures during sleep, in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation.", "In the hippocampus, replay occurs within sharp wave-ripples: short bouts of high-frequency activity in area CA1 caused by excitatory activation from area CA3.", "In this work, we develop a computational model of ripple generation, motivated by in vivo rat data showing that ripples have a broad frequency distribution, exponential inter-arrival times and yet highly non-variable durations.", "Our study predicts that ripples are not persistent oscillations but result from a transient network behavior, induced by input from CA3, in which the high frequency synchronous firing of perisomatic interneurons does not depend on the time scale of synaptic inhibition.", "We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration.", "Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network."], "title": "Hippocampal CA1 Ripples as Inhibitory Transients."}
{"paper_id": 26076722, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "UNLABELLED\nHere, we present REDEMPTION ( RE: duced D: imension E: nsemble M: odeling and P: arameter estima TION: ), a toolbox for parameter estimation and ensemble modeling of ordinary differential equations (ODEs) using time-series data. For models with more reactions than measured species, a common scenario in biological modeling, the parameter estimation is formulated as a nested optimization problem based on incremental parameter estimation strategy. REDEMPTION also includes a tool for the identification of an ensemble of parameter combinations that provide satisfactory goodness-of-fit to the data. The functionalities of REDEMPTION are accessible through a MATLAB user interface (UI), as well as through programming script. For computational speed-up, REDEMPTION provides a numerical parallelization option using MATLAB Parallel Computing toolbox.\n\n\nAVAILABILITY AND IMPLEMENTATION\nREDEMPTION can be downloaded from http://www.cabsel.ethz.ch/tools/redemption.\n\n\nCONTACT\nrudi.gunawan@chem.ethz.ch.", "journal": "Bioinformatics (Oxford, England)", "sentences": ["UNLABELLED\nHere, we present REDEMPTION ( RE: duced D: imension E: nsemble M: odeling and P: arameter estima TION: ), a toolbox for parameter estimation and ensemble modeling of ordinary differential equations (ODEs) using time-series data.", "For models with more reactions than measured species, a common scenario in biological modeling, the parameter estimation is formulated as a nested optimization problem based on incremental parameter estimation strategy.", "REDEMPTION also includes a tool for the identification of an ensemble of parameter combinations that provide satisfactory goodness-of-fit to the data.", "The functionalities of REDEMPTION are accessible through a MATLAB user interface (UI), as well as through programming script.", "For computational speed-up, REDEMPTION provides a numerical parallelization option using MATLAB Parallel Computing toolbox.", "AVAILABILITY AND IMPLEMENTATION\nREDEMPTION can be downloaded from http://www.cabsel.ethz.ch/tools/redemption.", "CONTACT\nrudi.gunawan@chem.ethz.ch."], "title": "REDEMPTION: reduced dimension ensemble modeling and parameter estimation."}
{"paper_id": 26462176, "labels": ["0", "1", "0", "0", "0", "0", "0", "1"], "abstract": "Recent evidence has shown that the level of 5-hydroxymethylcytosine (5 hmC) in chromosomal DNA is aberrantly decreased in a variety of cancers, but whether this decrease is a cause or a consequence of tumorigenesis is unclear. Here we show that, in gastric cancers, the 5 hmC decrease correlates with a decrease in ten-eleven translocation 1 (TET1) expression, which is strongly associated with metastasis and poor survival in patients with gastric cancer. In gastric cancer cells, TET1-targeted siRNA induced a decrease in 5 hmC, whereas TET1 overexpression induced an increase in 5 hmC and reduced cell proliferation, thus correlating decreased 5 hmC with gastric carcinogenesis. We also report the epigenetic signatures responsible for regulating TET1 transcription. Methyl-CpG Binding Domain Sequencing and Reduced Representation Bisulfite Sequencing identified unique CpG methylation signatures at the CpG island 3'-shore region located 1.3 kb from the transcription start site of TET1 in gastric tumor cells but not in normal mucosa. The luciferase activity of constructs with a methylated 3'-shore sequence was greatly decreased compared with that of an unmethylated sequence in transformed gastric cancer cells. In gastric cancer cells, dense CpG methylation in the 3'-shore was strongly associated with TET1 silencing and bivalent histone marks. Thus, a decrease in 5 hmC may be a cause of gastric tumorigenesis owing to a decrease in TET1 expression through DNA methylation coupled with bivalent marks in the 3'-shore of TET1.", "journal": "Oncotarget", "sentences": ["Recent evidence has shown that the level of 5-hydroxymethylcytosine (5 hmC) in chromosomal DNA is aberrantly decreased in a variety of cancers, but whether this decrease is a cause or a consequence of tumorigenesis is unclear.", "Here we show that, in gastric cancers, the 5 hmC decrease correlates with a decrease in ten-eleven translocation 1 (TET1) expression, which is strongly associated with metastasis and poor survival in patients with gastric cancer.", "In gastric cancer cells, TET1-targeted siRNA induced a decrease in 5 hmC, whereas TET1 overexpression induced an increase in 5 hmC and reduced cell proliferation, thus correlating decreased 5 hmC with gastric carcinogenesis.", "We also report the epigenetic signatures responsible for regulating TET1 transcription.", "Methyl-CpG Binding Domain Sequencing and Reduced Representation Bisulfite Sequencing identified unique CpG methylation signatures at the CpG island 3'-shore region located 1.3 kb from the transcription start site of TET1 in gastric tumor cells but not in normal mucosa.", "The luciferase activity of constructs with a methylated 3'-shore sequence was greatly decreased compared with that of an unmethylated sequence in transformed gastric cancer cells.", "In gastric cancer cells, dense CpG methylation in the 3'-shore was strongly associated with TET1 silencing and bivalent histone marks.", "Thus, a decrease in 5 hmC may be a cause of gastric tumorigenesis owing to a decrease in TET1 expression through DNA methylation coupled with bivalent marks in the 3'-shore of TET1."], "title": "Decrease of 5hmC in gastric cancers is associated with TET1 silencing due to with DNA methylation and bivalent histone marks at TET1 CpG island 3'-shore."}
{"paper_id": 25080347, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The homodimeric transmembrane receptor endoglin (CD105) plays an important role in angiogenesis. This is highlighted by mutations in its gene, causing the vascular disorder HHT1. The main role of endoglin function has been assigned to the modulation of transforming growth factor \u03b2 and bone morphogenetic protein signalling in endothelial cells. Nevertheless, other functions of endoglin have been revealed to be involved in different cellular functions and in other cell types than endothelial cells. Compared to the exploration of its natural function, little experimental data have been gathered about the mode of action of endoglin HHT mutations at the cellular level, especially missense mutations, and to what degree these might interfere with normal endoglin function. In this paper, we have used fluorescence-based microscopic techniques, such as bimolecular fluorescence complementation (BiFC), immunofluorescence staining with the endoglin specific monoclonal antibody SN6, and protein interaction studies by F\u00f6rster Resonance Energy Transfer (FRET) to investigate the formation and cellular localisation of possible homo- and heterodimers composed of endoglin wild-type and endoglin missense mutant proteins. The results show that all of the investigated missense mutants dimerise with themselves, as well as with wild-type endoglin, and localise, depending on the position of the affected amino acid, either in the rough endoplasmic reticulum (rER) or in the plasma membrane of the cells. We show that the rER retained mutants reduce the amount of endogenous wild-type endoglin on the plasma membrane through interception in the rER when transiently or stably expressed in HMEC-1 endothelial cells. As a result of this, endoglin modulated TGF-\u03b21 signal transduction is also abrogated, which is not due to TGF-\u03b2 receptor ER trafficking interference. Protein interaction analyses by FRET show that rER located endoglin missense mutants do not perturb protein processing of other membrane receptors, such as T\u03b2RII, ALK5 or ALK1.", "journal": "PloS one", "sentences": ["The homodimeric transmembrane receptor endoglin (CD105) plays an important role in angiogenesis.", "This is highlighted by mutations in its gene, causing the vascular disorder HHT1.", "The main role of endoglin function has been assigned to the modulation of transforming growth factor \u03b2 and bone morphogenetic protein signalling in endothelial cells.", "Nevertheless, other functions of endoglin have been revealed to be involved in different cellular functions and in other cell types than endothelial cells.", "Compared to the exploration of its natural function, little experimental data have been gathered about the mode of action of endoglin HHT mutations at the cellular level, especially missense mutations, and to what degree these might interfere with normal endoglin function.", "In this paper, we have used fluorescence-based microscopic techniques, such as bimolecular fluorescence complementation (BiFC), immunofluorescence staining with the endoglin specific monoclonal antibody SN6, and protein interaction studies by F\u00f6rster Resonance Energy Transfer (FRET) to investigate the formation and cellular localisation of possible homo- and heterodimers composed of endoglin wild-type and endoglin missense mutant proteins.", "The results show that all of the investigated missense mutants dimerise with themselves, as well as with wild-type endoglin, and localise, depending on the position of the affected amino acid, either in the rough endoplasmic reticulum (rER) or in the plasma membrane of the cells.", "We show that the rER retained mutants reduce the amount of endogenous wild-type endoglin on the plasma membrane through interception in the rER when transiently or stably expressed in HMEC-1 endothelial cells.", "As a result of this, endoglin modulated TGF-\u03b21 signal transduction is also abrogated, which is not due to TGF-\u03b2 receptor ER trafficking interference.", "Protein interaction analyses by FRET show that rER located endoglin missense mutants do not perturb protein processing of other membrane receptors, such as T\u03b2RII, ALK5 or ALK1."], "title": "Investigation of endoglin wild-type and missense mutant protein heterodimerisation using fluorescence microscopy based IF, BiFC and FRET analyses."}
{"paper_id": 25608591, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The effect of different sources of nitrogen as well as their concentrations on the bioconversion of carbon monoxide to metabolic products such as acetic acid and ethanol by Clostridium autoethanogenum was studied. In a first set of assays, under batch conditions, either NH4Cl, trypticase soy broth or yeast extract (YE) were used as sources of nitrogen. The use of YE was found statistically significant (p < 0.05) on the product spectrum in such batch assays. In another set of experiments, three bioreactors were operated with continuous CO supply, in order to estimate the effect of running conditions on products and biomass formation. The bioreactors were operated under different conditions, i.e., EXP1 (pH = 5.75, YE 1g/L), EXP2 (pH = 4.75, YE 1 g/L) and EXP3 (pH = 5.75, YE 0.2 g/L). When compared to EXP2 and EXP3, it was found that EXP1 yielded the maximum biomass accumulation (302.4 mg/L) and products concentrations, i.e., acetic acid (2147.1 mg/L) and ethanol (352.6 mg/L). This can be attributed to the fact that the higher pH and higher YE concentration used in EXP1 stimulated cell growth and did, consequently, also enhance metabolite production. However, when ethanol is the desired end-product, as a biofuel, the lower pH used in EXP2 was more favourable for solventogenesis and yielded the highest ethanol/acetic acid ratio, reaching a value of 0.54.", "journal": "International journal of environmental research and public health", "sentences": ["The effect of different sources of nitrogen as well as their concentrations on the bioconversion of carbon monoxide to metabolic products such as acetic acid and ethanol by Clostridium autoethanogenum was studied.", "In a first set of assays, under batch conditions, either NH4Cl, trypticase soy broth or yeast extract (YE) were used as sources of nitrogen.", "The use of YE was found statistically significant (p < 0.05) on the product spectrum in such batch assays.", "In another set of experiments, three bioreactors were operated with continuous CO supply, in order to estimate the effect of running conditions on products and biomass formation.", "The bioreactors were operated under different conditions, i.e., EXP1 (pH = 5.75, YE 1g/L), EXP2 (pH = 4.75, YE 1 g/L) and EXP3 (pH = 5.75, YE 0.2 g/L).", "When compared to EXP2 and EXP3, it was found that EXP1 yielded the maximum biomass accumulation (302.4 mg/L) and products concentrations, i.e., acetic acid (2147.1 mg/L) and ethanol (352.6 mg/L).", "This can be attributed to the fact that the higher pH and higher YE concentration used in EXP1 stimulated cell growth and did, consequently, also enhance metabolite production.", "However, when ethanol is the desired end-product, as a biofuel, the lower pH used in EXP2 was more favourable for solventogenesis and yielded the highest ethanol/acetic acid ratio, reaching a value of 0.54."], "title": "Ethanol and acetic acid production from carbon monoxide in a Clostridium strain in batch and continuous gas-fed bioreactors."}
{"paper_id": 26824266, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "CD8(+) T cell anergy is a critical mechanism of peripheral tolerance, poorly investigated in response to immunotherapy. Here, using a pancreatic islet allograft model and CD3 antibody therapy, we showed, by single cell gene profiling, that intragraft CD8(+) lymphocytes coexpressing granzyme B and perforin were selectively depleted through the Fas/FasL pathway. This step led to long-standing anergy of the remaining CD8(+) T cells marked by the absence of cytotoxic/inflammatory gene expression also confirmed by transcriptome analysis. This sustained unresponsiveness required the presence of the alloantigens. Furthermore, tissue-resident CD8(+) lymphocytes produced TGF\u03b2 and expressed the inhibitory receptors PD-1 and PD-L1. Blockade of TGF\u03b2 downregulated PD-1 and PD-L1 expression and precipitated graft rejection. Neutralizing PD-1, PD-L1 or TGF\u03b2RII signaling in T cells also abrogated CD3 antibody-induced tolerance. These studies unravel novel mechanisms underlying CD8(+) T cell anergy and reveal a cell intrinsic regulatory link between the TGF\u03b2 and the PD-1/PD-L1 pathways.", "journal": "eLife", "sentences": ["CD8(+) T cell anergy is a critical mechanism of peripheral tolerance, poorly investigated in response to immunotherapy.", "Here, using a pancreatic islet allograft model and CD3 antibody therapy, we showed, by single cell gene profiling, that intragraft CD8(+) lymphocytes coexpressing granzyme B and perforin were selectively depleted through the Fas/FasL pathway.", "This step led to long-standing anergy of the remaining CD8(+) T cells marked by the absence of cytotoxic/inflammatory gene expression also confirmed by transcriptome analysis.", "This sustained unresponsiveness required the presence of the alloantigens.", "Furthermore, tissue-resident CD8(+) lymphocytes produced TGF\u03b2 and expressed the inhibitory receptors PD-1 and PD-L1.", "Blockade of TGF\u03b2 downregulated PD-1 and PD-L1 expression and precipitated graft rejection.", "Neutralizing PD-1, PD-L1 or TGF\u03b2RII signaling in T cells also abrogated CD3 antibody-induced tolerance.", "These studies unravel novel mechanisms underlying CD8(+) T cell anergy and reveal a cell intrinsic regulatory link between the TGF\u03b2 and the PD-1/PD-L1 pathways."], "title": "TGF\u03b2-dependent expression of PD-1 and PD-L1 controls CD8(+) T cell anergy in transplant tolerance."}
{"paper_id": 26503655, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Tenofovir alafenamide fumarate (TAF) is an oral phosphonoamidate prodrug of the HIV reverse transcriptase nucleotide inhibitor tenofovir (TFV). Previous studies suggested a principal role for the lysosomal serine protease cathepsin A (CatA) in the intracellular activation of TAF. Here we further investigated the role of CatA and other human hydrolases in the metabolism of TAF. Overexpression of CatA or liver carboxylesterase 1 (Ces1) in HEK293T cells increased intracellular TAF hydrolysis 2- and 5-fold, respectively. Knockdown of CatA expression with RNA interference (RNAi) in HeLa cells reduced intracellular TAF metabolism 5-fold. Additionally, the anti-HIV activity and the rate of CatA hydrolysis showed good correlation within a large set of TFV phosphonoamidate prodrugs. The covalent hepatitis C virus (HCV) protease inhibitors (PIs) telaprevir and boceprevir potently inhibited CatA-mediated TAF activation (50% inhibitory concentration [IC50] = 0.27 and 0.16 \u03bcM, respectively) in vitro and also reduced its anti-HIV activity in primary human CD4(+) T lymphocytes (21- and 3-fold, respectively) at pharmacologically relevant concentrations. In contrast, there was no inhibition of CatA or any significant effect on anti-HIV activity of TAF observed with cobicistat, noncovalent HIV and HCV PIs, or various prescribed inhibitors of host serine proteases. Collectively, these studies confirm that CatA plays a pivotal role in the intracellular metabolism of TAF, whereas the liver esterase Ces1 likely contributes to the hepatic activation of TAF. Moreover, this work demonstrates that a wide range of viral and host PIs, with the exception of telaprevir and boceprevir, do not interfere with the antiretroviral activity of TAF.", "journal": "Antimicrobial agents and chemotherapy", "sentences": ["Tenofovir alafenamide fumarate (TAF) is an oral phosphonoamidate prodrug of the HIV reverse transcriptase nucleotide inhibitor tenofovir (TFV).", "Previous studies suggested a principal role for the lysosomal serine protease cathepsin A (CatA) in the intracellular activation of TAF.", "Here we further investigated the role of CatA and other human hydrolases in the metabolism of TAF.", "Overexpression of CatA or liver carboxylesterase 1 (Ces1) in HEK293T cells increased intracellular TAF hydrolysis 2- and 5-fold, respectively.", "Knockdown of CatA expression with RNA interference (RNAi) in HeLa cells reduced intracellular TAF metabolism 5-fold.", "Additionally, the anti-HIV activity and the rate of CatA hydrolysis showed good correlation within a large set of TFV phosphonoamidate prodrugs.", "The covalent hepatitis C virus (HCV) protease inhibitors (PIs) telaprevir and boceprevir potently inhibited CatA-mediated TAF activation (50% inhibitory concentration [IC50] = 0.27 and 0.16 \u03bcM, respectively) in vitro and also reduced its anti-HIV activity in primary human CD4(+) T lymphocytes (21- and 3-fold, respectively) at pharmacologically relevant concentrations.", "In contrast, there was no inhibition of CatA or any significant effect on anti-HIV activity of TAF observed with cobicistat, noncovalent HIV and HCV PIs, or various prescribed inhibitors of host serine proteases.", "Collectively, these studies confirm that CatA plays a pivotal role in the intracellular metabolism of TAF, whereas the liver esterase Ces1 likely contributes to the hepatic activation of TAF.", "Moreover, this work demonstrates that a wide range of viral and host PIs, with the exception of telaprevir and boceprevir, do not interfere with the antiretroviral activity of TAF."], "title": "Intracellular Activation of Tenofovir Alafenamide and the Effect of Viral and Host Protease Inhibitors."}
{"paper_id": 26458101, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Inositol-1,4,5-trisphosphate receptors (InsP3Rs) are ubiquitous ion channels responsible for cytosolic Ca(2+) signalling and essential for a broad array of cellular processes ranging from contraction to secretion, and from proliferation to cell death. Despite decades of research on InsP3Rs, a mechanistic understanding of their structure-function relationship is lacking. Here we present the first, to our knowledge, near-atomic (4.7 \u00c5) resolution electron cryomicroscopy structure of the tetrameric mammalian type 1 InsP3R channel in its apo-state. At this resolution, we are able to trace unambiguously \u223c85% of the protein backbone, allowing us to identify the structural elements involved in gating and modulation of this 1.3-megadalton channel. Although the central Ca(2+)-conduction pathway is similar to other ion channels, including the closely related ryanodine receptor, the cytosolic carboxy termini are uniquely arranged in a left-handed \u03b1-helical bundle, directly interacting with the amino-terminal domains of adjacent subunits. This configuration suggests a molecular mechanism for allosteric regulation of channel gating by intracellular signals.", "journal": "Nature", "sentences": ["Inositol-1,4,5-trisphosphate receptors (InsP3Rs) are ubiquitous ion channels responsible for cytosolic Ca(2+) signalling and essential for a broad array of cellular processes ranging from contraction to secretion, and from proliferation to cell death.", "Despite decades of research on InsP3Rs, a mechanistic understanding of their structure-function relationship is lacking.", "Here we present the first, to our knowledge, near-atomic (4.7 \u00c5) resolution electron cryomicroscopy structure of the tetrameric mammalian type 1 InsP3R channel in its apo-state.", "At this resolution, we are able to trace unambiguously \u223c85% of the protein backbone, allowing us to identify the structural elements involved in gating and modulation of this 1.3-megadalton channel.", "Although the central Ca(2+)-conduction pathway is similar to other ion channels, including the closely related ryanodine receptor, the cytosolic carboxy termini are uniquely arranged in a left-handed \u03b1-helical bundle, directly interacting with the amino-terminal domains of adjacent subunits.", "This configuration suggests a molecular mechanism for allosteric regulation of channel gating by intracellular signals."], "title": "Gating machinery of InsP3R channels revealed by electron cryomicroscopy."}
{"paper_id": 27029645, "labels": ["0", "0", "1", "1", "1"], "abstract": "Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer's disease and Huntington's disease). These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane. Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders.", "journal": "Nature communications", "sentences": ["Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies.", "Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food.", "We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer's disease and Huntington's disease).", "These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane.", "Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders."], "title": "Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration."}
{"paper_id": 27031697, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Long-term manure application is recognized as an efficient management practice to enhance soil organic carbon (SOC) accumulation and nitrogen (N) mineralization capacity. A field study was established in 1979 to understand the impact of long-term manure and/or chemical fertilizer application on soil fertility in a continuous maize cropping system. Soil samples were collected from field plots in 2012 from 9 fertilization treatments (M0CK, M0N, M0NPK, M30CK, M30N, M30NPK, M60CK, M60N, and M60NPK) where M0, M30, and M60 refer to manure applied at rates of 0, 30, and 60 t ha-1 yr-1, respectively; CK indicates no fertilizer; N and NPK refer to chemical fertilizer in the forms of either N or N plus phosphorus (P) and potassium (K). Soils were separated into three particle-size fractions (2000-250, 250-53, and <53 \u03bcm) by dry- and wet-sieving. A laboratory incubation study of these separated particle-size fractions was used to evaluate the effect of long-term manure, in combination with/without chemical fertilization application, on the accumulation and mineralization of SOC and total N in each fraction. Results showed that long-term manure application significantly increased SOC and total N content and enhanced C and N mineralization in the three particle-size fractions. The content of SOC and total N followed the order 2000-250 \u03bcm > 250-53\u03bcm > 53 \u03bcm fraction, whereas the amount of C and N mineralization followed the reverse order. In the <53 \u03bcm fraction, the M60NPK treatment significantly increased the amount of C and N mineralized (7.0 and 10.1 times, respectively) compared to the M0CK treatment. Long-term manure application, especially when combined with chemical fertilizers, resulted in increased soil microbial biomass C and N, and a decreased microbial metabolic quotient. Consequently, long-term manure fertilization was beneficial to both soil C and N turnover and microbial activity, and had significant effect on the microbial metabolic quotient.", "journal": "PloS one", "sentences": ["Long-term manure application is recognized as an efficient management practice to enhance soil organic carbon (SOC) accumulation and nitrogen (N) mineralization capacity.", "A field study was established in 1979 to understand the impact of long-term manure and/or chemical fertilizer application on soil fertility in a continuous maize cropping system.", "Soil samples were collected from field plots in 2012 from 9 fertilization treatments (M0CK, M0N, M0NPK, M30CK, M30N, M30NPK, M60CK, M60N, and M60NPK) where M0, M30, and M60 refer to manure applied at rates of 0, 30, and 60 t ha-1 yr-1, respectively; CK indicates no fertilizer; N and NPK refer to chemical fertilizer in the forms of either N or N plus phosphorus (P) and potassium (K).", "Soils were separated into three particle-size fractions (2000-250, 250-53, and <53 \u03bcm) by dry- and wet-sieving.", "A laboratory incubation study of these separated particle-size fractions was used to evaluate the effect of long-term manure, in combination with/without chemical fertilization application, on the accumulation and mineralization of SOC and total N in each fraction.", "Results showed that long-term manure application significantly increased SOC and total N content and enhanced C and N mineralization in the three particle-size fractions.", "The content of SOC and total N followed the order 2000-250 \u03bcm > 250-53\u03bcm > 53 \u03bcm fraction, whereas the amount of C and N mineralization followed the reverse order.", "In the <53 \u03bcm fraction, the M60NPK treatment significantly increased the amount of C and N mineralized (7.0 and 10.1 times, respectively) compared to the M0CK treatment.", "Long-term manure application, especially when combined with chemical fertilizers, resulted in increased soil microbial biomass C and N, and a decreased microbial metabolic quotient.", "Consequently, long-term manure fertilization was beneficial to both soil C and N turnover and microbial activity, and had significant effect on the microbial metabolic quotient."], "title": "Carbon and Nitrogen Mineralization in Relation to Soil Particle-Size Fractions after 32 Years of Chemical and Manure Application in a Continuous Maize Cropping System."}
{"paper_id": 25658744, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Lipoxygenases (LOXs) are key enzymes to regulate the production of hormones and defensive metabolites in plants, animals and algae. In this research, a full length LOX gene has been cloned and expressed from the red alga Pyropia haitanensis (Bangiales, Rhodophyta) gametophyte (PhLOX2). Subsequent phylogenetic analysis showed that such LOX enzymes are separated at the early stage of evolution, establishing an independent branch. The LOX activity was investigated at the optimal pH of 8.0. It appears that PhLOX2 is a multifunctional enzyme featuring both lipoxygenase and hydroperoxidase activities. Additionally, PhLOX2 exhibits remarkable substrate and position flexibility, and it can catalyze an array of chemical reactions involving various polyunsaturated fatty acids, ranging from C18 to C22. As a matter of fact, mono-hydroperoxy, di-hydroperoxy and hydroxyl products have been obtained from such transformations, and eicosapentaenoic acid seem to be the most preferred substrate. It was found that at least triple ethylenic bonds are required for PhLOX2 to function as a LOX, and the resulting hydroxy products should be originated from the PhLOX2 mediated reduction of mono-hydroperoxides, in which the hydrogen abstraction occurs on the carbon atom between the second and third double bond. Most of the di-hydroperoxides observed seem to be missing their mono-position precursors. The substrate and position flexibility, as well as the function versatility of PhLOXs represent the ancient enzymatic pathway for organisms to control intracellular oxylipins.", "journal": "PloS one", "sentences": ["Lipoxygenases (LOXs) are key enzymes to regulate the production of hormones and defensive metabolites in plants, animals and algae.", "In this research, a full length LOX gene has been cloned and expressed from the red alga Pyropia haitanensis (Bangiales, Rhodophyta) gametophyte (PhLOX2).", "Subsequent phylogenetic analysis showed that such LOX enzymes are separated at the early stage of evolution, establishing an independent branch.", "The LOX activity was investigated at the optimal pH of 8.0.", "It appears that PhLOX2 is a multifunctional enzyme featuring both lipoxygenase and hydroperoxidase activities.", "Additionally, PhLOX2 exhibits remarkable substrate and position flexibility, and it can catalyze an array of chemical reactions involving various polyunsaturated fatty acids, ranging from C18 to C22.", "As a matter of fact, mono-hydroperoxy, di-hydroperoxy and hydroxyl products have been obtained from such transformations, and eicosapentaenoic acid seem to be the most preferred substrate.", "It was found that at least triple ethylenic bonds are required for PhLOX2 to function as a LOX, and the resulting hydroxy products should be originated from the PhLOX2 mediated reduction of mono-hydroperoxides, in which the hydrogen abstraction occurs on the carbon atom between the second and third double bond.", "Most of the di-hydroperoxides observed seem to be missing their mono-position precursors.", "The substrate and position flexibility, as well as the function versatility of PhLOXs represent the ancient enzymatic pathway for organisms to control intracellular oxylipins."], "title": "A lipoxygenase from red alga Pyropia haitanensis, a unique enzyme catalyzing the free radical reactions of polyunsaturated fatty acids with triple ethylenic bonds."}
{"paper_id": 24121109, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Severe hypoxic and ischemic injury leads to primary graft dysfunction after lung transplantation. Arginine methylation, which is responsible for the regulation of a variety of biological functions, is mediated by protein arginine methylation transferases (PRMTs). This study examined the role of hypoxia in PRMT activation in A549 human lung epithelial cells, as well as the role of ischemia in PRMT activation in the lung of miniature pigs. In A459 cells, hypoxia increased the expression of PRMT1 and PRMT5, and overexpression of PRMT1 and PRMT5 induced apoptosis. The transfection of PRMT1 and PRMT5 small interfering RNA (siRNA) prevented hypoxia-inducible factor (HIF)-1\u03b1 expression and apoptosis in A549 cells. Hypoxia-induced expression of PRMT1 and PRMT5 was blocked by p38 and JNK mitogen-activated protein kinase (MAPK) inhibitors, but not by an inhibitor of extracellular signal-regulated kinases (ERK) 1/2. In the lungs of miniature pigs, ischemia stimulated PRMT1 and PRMT5 expression and induced phosphorylation of p38 MAPK (p-p38), phosphorylation of JNK (p-JNK), and apoptotic molecules. These results demonstrate that PRMT1 and PRMT5 are involved in hypoxia and ischemia-induced apoptosis via p-p38 MAPK and p-JNK in in vitro and in vivo models.", "journal": "Biochemical and biophysical research communications", "sentences": ["Severe hypoxic and ischemic injury leads to primary graft dysfunction after lung transplantation.", "Arginine methylation, which is responsible for the regulation of a variety of biological functions, is mediated by protein arginine methylation transferases (PRMTs).", "This study examined the role of hypoxia in PRMT activation in A549 human lung epithelial cells, as well as the role of ischemia in PRMT activation in the lung of miniature pigs.", "In A459 cells, hypoxia increased the expression of PRMT1 and PRMT5, and overexpression of PRMT1 and PRMT5 induced apoptosis.", "The transfection of PRMT1 and PRMT5 small interfering RNA (siRNA) prevented hypoxia-inducible factor (HIF)-1\u03b1 expression and apoptosis in A549 cells.", "Hypoxia-induced expression of PRMT1 and PRMT5 was blocked by p38 and JNK mitogen-activated protein kinase (MAPK) inhibitors, but not by an inhibitor of extracellular signal-regulated kinases (ERK) 1/2.", "In the lungs of miniature pigs, ischemia stimulated PRMT1 and PRMT5 expression and induced phosphorylation of p38 MAPK (p-p38), phosphorylation of JNK (p-JNK), and apoptotic molecules.", "These results demonstrate that PRMT1 and PRMT5 are involved in hypoxia and ischemia-induced apoptosis via p-p38 MAPK and p-JNK in in vitro and in vivo models."], "title": "Activation of PRMT1 and PRMT5 mediates hypoxia- and ischemia-induced apoptosis in human lung epithelial cells and the lung of miniature pigs: the role of p38 and JNK mitogen-activated protein kinases."}
{"paper_id": 26061495, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "Autism spectrum disorder (ASD) comprise a group of neurodevelopmental disorders characterized by deficits in social and communication capacities and repetitive behaviors. Increasing neuroscientific evidence indicates that the neuropathology of ASD is widespread and involves epigenetic regulation in the brain. Differentially expressed miRNAs in the peripheral blood from autism patients were identified by high-throughput miRNA microarray analyses. Five of these miRNAs were confirmed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. A search for candidate target genes of the five confirmed miRNAs was performed through a Kyoto encyclopedia of genes and genomes (KEGG) biological pathways and Gene Ontology enrichment analysis of gene function to identify gene regulatory networks. To the best of our knowledge, this study provides the first global miRNA expression profile of ASD in China. The differentially expressed miR-34b may potentially explain the higher percentage of male ASD patients, and the aberrantly expressed miR-103a-3p may contribute to the abnormal ubiquitin-mediated proteolysis observed in ASD.", "journal": "PloS one", "sentences": ["Autism spectrum disorder (ASD) comprise a group of neurodevelopmental disorders characterized by deficits in social and communication capacities and repetitive behaviors.", "Increasing neuroscientific evidence indicates that the neuropathology of ASD is widespread and involves epigenetic regulation in the brain.", "Differentially expressed miRNAs in the peripheral blood from autism patients were identified by high-throughput miRNA microarray analyses.", "Five of these miRNAs were confirmed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis.", "A search for candidate target genes of the five confirmed miRNAs was performed through a Kyoto encyclopedia of genes and genomes (KEGG) biological pathways and Gene Ontology enrichment analysis of gene function to identify gene regulatory networks.", "To the best of our knowledge, this study provides the first global miRNA expression profile of ASD in China.", "The differentially expressed miR-34b may potentially explain the higher percentage of male ASD patients, and the aberrantly expressed miR-103a-3p may contribute to the abnormal ubiquitin-mediated proteolysis observed in ASD."], "title": "Investigation of Gene Regulatory Networks Associated with Autism Spectrum Disorder Based on MiRNA Expression in China."}
{"paper_id": 24795877, "labels": ["0", "0", "0", "0", "0", "0"], "abstract": "nAG (newt-Anterrior Gradient) protein is the key mediator of regrowth of amputated limbs in salamanders. In a previous work in our lab, a new nAG gene (suitable for humans) was designed and cloned. The cloned vector was transfected into primary human fibroblasts. The expression of nAG in human primary fibroblasts was found to suppress collagen expression. The current study shows that local injection of recombinant nAG reduces scar hypertrophy in the rabbit ear model. This is associated with lower scar elevation index (SEI), lower levels of collagen I & III, higher levels of MMP1, and a higher degree of scar maturation in experimental wounds compared to controls.", "journal": "BioMed research international", "sentences": ["nAG (newt-Anterrior Gradient) protein is the key mediator of regrowth of amputated limbs in salamanders.", "In a previous work in our lab, a new nAG gene (suitable for humans) was designed and cloned.", "The cloned vector was transfected into primary human fibroblasts.", "The expression of nAG in human primary fibroblasts was found to suppress collagen expression.", "The current study shows that local injection of recombinant nAG reduces scar hypertrophy in the rabbit ear model.", "This is associated with lower scar elevation index (SEI), lower levels of collagen I & III, higher levels of MMP1, and a higher degree of scar maturation in experimental wounds compared to controls."], "title": "Recombinant nAG (a salamander-derived protein) decreases the formation of hypertrophic scarring in the rabbit ear model."}
{"paper_id": 25185712, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "0"], "abstract": "First-line therapy of severe aplastic anemia (SAA) with high-dose cyclophosphamide causes toxicity and increased short-term mortality. We investigated cyclophosphamide at a lower, more moderate dose in combination with aggressive supportive care to determine whether severe infections might be avoided and hematologic outcomes defined for this regimen. From 2010 to 2012, 22 patients received cyclophosphamide at 120 mg/kg plus cyclosporine and antibacterial, antiviral, and antifungal prophylaxis. Toxicity was considerable, mainly due to prolonged absolute neutropenia, which occurred regardless of pretherapy blood counts, and persisted an average of 2 months. Granulocyte transfusions for uncontrolled infection were required in 5 patients, confirmed fungal infections were documented in 6, and 9 patients died. Nine patients (41%) responded at 6 months. After a median follow-up of 2.2 years, relapse occurred in 2 patients, and cytogenetic abnormalities (including monosomy 7) were observed in 4 patients. Although cyclophosphamide has activity in SAA, its toxicity is not justified when far less dangerous alternatives are available. This trial was registered at www.clinicaltrials.gov as #NCT01193283.", "journal": "Blood", "sentences": ["First-line therapy of severe aplastic anemia (SAA) with high-dose cyclophosphamide causes toxicity and increased short-term mortality.", "We investigated cyclophosphamide at a lower, more moderate dose in combination with aggressive supportive care to determine whether severe infections might be avoided and hematologic outcomes defined for this regimen.", "From 2010 to 2012, 22 patients received cyclophosphamide at 120 mg/kg plus cyclosporine and antibacterial, antiviral, and antifungal prophylaxis.", "Toxicity was considerable, mainly due to prolonged absolute neutropenia, which occurred regardless of pretherapy blood counts, and persisted an average of 2 months.", "Granulocyte transfusions for uncontrolled infection were required in 5 patients, confirmed fungal infections were documented in 6, and 9 patients died.", "Nine patients (41%) responded at 6 months.", "After a median follow-up of 2.2 years, relapse occurred in 2 patients, and cytogenetic abnormalities (including monosomy 7) were observed in 4 patients.", "Although cyclophosphamide has activity in SAA, its toxicity is not justified when far less dangerous alternatives are available.", "This trial was registered at www.clinicaltrials.gov as #NCT01193283."], "title": "Moderate-dose cyclophosphamide for severe aplastic anemia has significant toxicity and does not prevent relapse and clonal evolution."}
{"paper_id": 24324720, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Teleost fish, as with all vertebrates, are capable of synthesizing cholesterol and as such have no dietary requirement for it. Thus, limited research has addressed the potential effects of dietary cholesterol in fish, even if fish meal and fish oil are increasingly replaced by vegetable alternatives in modern aquafeeds, resulting in progressively reduced dietary cholesterol content. The objective of this study was to determine if dietary cholesterol fortification in a vegetable oil-based diet can manifest any effects on growth and feed utilization performance in the salmonid fish, the rainbow trout. In addition, given a series of studies in mammals have shown that dietary cholesterol can directly affect the fatty acid metabolism, the apparent in vivo fatty acid metabolism of fish fed the experimental diets was assessed. Triplicate groups of juvenile fish were fed one of two identical vegetable oil-based diets, with additional cholesterol fortification (high cholesterol; H-Chol) or without (low cholesterol; L-Chol), for 12 weeks. No effects were observed on growth and feed efficiency, however, in fish fed H-Col no biosynthesis of cholesterol, and a remarkably decreased apparent in vivo fatty acid \u03b2-oxidation were recorded, whilst in L-Chol fed fish, cholesterol was abundantly biosynthesised and an increased apparent in vivo fatty acid \u03b2-oxidation was observed. Only minor effects were observed on the activity of stearyl-CoA desaturase, but a significant increase was observed for both the transcription rate in liver and the apparent in vivo activity of the fatty acid \u0394-6 desaturase and elongase, with increasing dietary cholesterol. This study showed that the possible effects of reduced dietary cholesterol in current aquafeeds can be significant and warrant future investigations.", "journal": "PloS one", "sentences": ["Teleost fish, as with all vertebrates, are capable of synthesizing cholesterol and as such have no dietary requirement for it.", "Thus, limited research has addressed the potential effects of dietary cholesterol in fish, even if fish meal and fish oil are increasingly replaced by vegetable alternatives in modern aquafeeds, resulting in progressively reduced dietary cholesterol content.", "The objective of this study was to determine if dietary cholesterol fortification in a vegetable oil-based diet can manifest any effects on growth and feed utilization performance in the salmonid fish, the rainbow trout.", "In addition, given a series of studies in mammals have shown that dietary cholesterol can directly affect the fatty acid metabolism, the apparent in vivo fatty acid metabolism of fish fed the experimental diets was assessed.", "Triplicate groups of juvenile fish were fed one of two identical vegetable oil-based diets, with additional cholesterol fortification (high cholesterol; H-Chol) or without (low cholesterol; L-Chol), for 12 weeks.", "No effects were observed on growth and feed efficiency, however, in fish fed H-Col no biosynthesis of cholesterol, and a remarkably decreased apparent in vivo fatty acid \u03b2-oxidation were recorded, whilst in L-Chol fed fish, cholesterol was abundantly biosynthesised and an increased apparent in vivo fatty acid \u03b2-oxidation was observed.", "Only minor effects were observed on the activity of stearyl-CoA desaturase, but a significant increase was observed for both the transcription rate in liver and the apparent in vivo activity of the fatty acid \u0394-6 desaturase and elongase, with increasing dietary cholesterol.", "This study showed that the possible effects of reduced dietary cholesterol in current aquafeeds can be significant and warrant future investigations."], "title": "Fish oil replacement in current aquaculture feed: is cholesterol a hidden treasure for fish nutrition?"}
{"paper_id": 25740514, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "The endocannabinoid system negatively regulates the release of various neurotransmitters in an activity-dependent manner, thereby influencing the excitability of neuronal circuits. In the hippocampus, cannabinoid type 1 (CB1) receptor is present on both GABAergic and glutamatergic axon terminals. CB1 receptor-deficient mice were previously shown to have increased hippocampal long-term potentiation (LTP). In this study, we have investigated the consequences of cell-type-specific deletion of the CB1 receptor on the induction of hippocampal LTP and on CA1 pyramidal cell morphology. Deletion of CB1 receptor in GABAergic neurons in GABA-CB1-KO mice leads to a significantly decreased hippocampal LTP compared with WT controls. Concomitantly, CA1 pyramidal neurons have a significantly reduced dendritic branching both on the apical and on the basal dendrites. Moreover, the average spine density on the apical dendrites of CA1 pyramidal neurons is significantly diminished. In contrast, in mice lacking CB1 receptor in glutamatergic cells (Glu-CB1-KO), hippocampal LTP is significantly enhanced and CA1 pyramidal neurons show an increased branching and an increased spine density in the apical dendritic region. Together, these results indicate that the CB1 receptor signaling system both on inhibitory and excitatory neurons controls functional and structural synaptic plasticity of pyramidal neurons in the hippocampal CA1 region to maintain an appropriate homeostatic state upon neuronal activation. Consequently, if the CB1 receptor is lost in either neuronal population, an allostatic shift will occur leading to a long-term dysregulation of neuronal functions.", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "sentences": ["The endocannabinoid system negatively regulates the release of various neurotransmitters in an activity-dependent manner, thereby influencing the excitability of neuronal circuits.", "In the hippocampus, cannabinoid type 1 (CB1) receptor is present on both GABAergic and glutamatergic axon terminals.", "CB1 receptor-deficient mice were previously shown to have increased hippocampal long-term potentiation (LTP).", "In this study, we have investigated the consequences of cell-type-specific deletion of the CB1 receptor on the induction of hippocampal LTP and on CA1 pyramidal cell morphology.", "Deletion of CB1 receptor in GABAergic neurons in GABA-CB1-KO mice leads to a significantly decreased hippocampal LTP compared with WT controls.", "Concomitantly, CA1 pyramidal neurons have a significantly reduced dendritic branching both on the apical and on the basal dendrites.", "Moreover, the average spine density on the apical dendrites of CA1 pyramidal neurons is significantly diminished.", "In contrast, in mice lacking CB1 receptor in glutamatergic cells (Glu-CB1-KO), hippocampal LTP is significantly enhanced and CA1 pyramidal neurons show an increased branching and an increased spine density in the apical dendritic region.", "Together, these results indicate that the CB1 receptor signaling system both on inhibitory and excitatory neurons controls functional and structural synaptic plasticity of pyramidal neurons in the hippocampal CA1 region to maintain an appropriate homeostatic state upon neuronal activation.", "Consequently, if the CB1 receptor is lost in either neuronal population, an allostatic shift will occur leading to a long-term dysregulation of neuronal functions."], "title": "Cannabinoid CB1 receptor calibrates excitatory synaptic balance in the mouse hippocampus."}
{"paper_id": 25911324, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Our previous study showed that Octamer-binding transcription factor 4 (OCT4) expression was upregulated and significantly associated with histological grade through the analysis of OCT4 expression in 159 ovarian cancer tissue samples, and OCT4 mediated follicle-stimulating hormone (FSH)-induced anti-apoptosis in epithelial ovarian cancer. Nevertheless, whether OCT4 participates in FSH-induced invasion in ovarian cancer is still unknown. Therefore, the present study aimed to define whether FSH-induced ovarian cancer invasion is mediated by OCT4. In present study, we showed that FSH induced not only the epithelial-mesenchymal transition (EMT) and invasive phenotype but also the upregulation of OCT4 expression in a dose- and time-dependent manner in epithelial ovarian cancer cells. In addition, the expression of FSH receptor (FSHR) was upregulated by FSH induction, and knockdown of FSHR inhibited FSH-stimulated OCT4 expression. ERK1/2 signaling pathway participated in the enhanced expression of OCT4 and Snail induced by FSH. We further showed that the activated expression of Snail and N-cadherin, the suppressed expression of E-cadherin and the morphological change of the cells stimulated by FSH were blocked by OCT4-specific small interfering RNA. Moreover, our results showed that OCT4 mediated the increase in invasive capacity induced by FSH in ovarian cancer cells. Taken together, our work reveals that OCT4 is an essential mediator in FSH-induced EMT and invasion in epithelial ovarian cancer and may act as a potential therapeutic target.", "journal": "Biochemical and biophysical research communications", "sentences": ["Our previous study showed that Octamer-binding transcription factor 4 (OCT4) expression was upregulated and significantly associated with histological grade through the analysis of OCT4 expression in 159 ovarian cancer tissue samples, and OCT4 mediated follicle-stimulating hormone (FSH)-induced anti-apoptosis in epithelial ovarian cancer.", "Nevertheless, whether OCT4 participates in FSH-induced invasion in ovarian cancer is still unknown.", "Therefore, the present study aimed to define whether FSH-induced ovarian cancer invasion is mediated by OCT4.", "In present study, we showed that FSH induced not only the epithelial-mesenchymal transition (EMT) and invasive phenotype but also the upregulation of OCT4 expression in a dose- and time-dependent manner in epithelial ovarian cancer cells.", "In addition, the expression of FSH receptor (FSHR) was upregulated by FSH induction, and knockdown of FSHR inhibited FSH-stimulated OCT4 expression.", "ERK1/2 signaling pathway participated in the enhanced expression of OCT4 and Snail induced by FSH.", "We further showed that the activated expression of Snail and N-cadherin, the suppressed expression of E-cadherin and the morphological change of the cells stimulated by FSH were blocked by OCT4-specific small interfering RNA.", "Moreover, our results showed that OCT4 mediated the increase in invasive capacity induced by FSH in ovarian cancer cells.", "Taken together, our work reveals that OCT4 is an essential mediator in FSH-induced EMT and invasion in epithelial ovarian cancer and may act as a potential therapeutic target."], "title": "OCT4 mediates FSH-induced epithelial-mesenchymal transition and invasion through the ERK1/2 signaling pathway in epithelial ovarian cancer."}
{"paper_id": 25402442, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Nitrification plays a central role in the nitrogen cycle by determining the oxidation state of nitrogen and its subsequent bioavailability and cycling. However, relatively little is known about the underlying ecology of the microbial communities that carry out nitrification in freshwater ecosystems--and particularly within high-altitude oligotrophic lakes, where nitrogen is frequently a limiting nutrient. We quantified ammonia-oxidizing archaea (AOA) and bacteria (AOB) in 9 high-altitude lakes (2289-3160 m) in the Sierra Nevada, California, USA, in relation to spatial and biogeochemical data. Based on their ammonia monooxygenase (amoA) genes, AOB and AOA were frequently detected. AOB were present in 88% of samples and were more abundant than AOA in all samples. Both groups showed >100 fold variation in abundance between different lakes, and were also variable through time within individual lakes. Nutrient concentrations (ammonium, nitrite, nitrate, and phosphate) were generally low but also varied across and within lakes, suggestive of active internal nutrient cycling; AOB abundance was significantly correlated with phosphate (r(2) = 0.32, p<0.1), whereas AOA abundance was inversely correlated with lake elevation (r(2) = 0.43, p<0.05). We also measured low rates of ammonia oxidation--indicating that AOB, AOA, or both, may be biogeochemically active in these oligotrophic ecosystems. Our data indicate that dynamic populations of AOB and AOA are found in oligotrophic, high-altitude, freshwater lakes.", "journal": "PloS one", "sentences": ["Nitrification plays a central role in the nitrogen cycle by determining the oxidation state of nitrogen and its subsequent bioavailability and cycling.", "However, relatively little is known about the underlying ecology of the microbial communities that carry out nitrification in freshwater ecosystems--and particularly within high-altitude oligotrophic lakes, where nitrogen is frequently a limiting nutrient.", "We quantified ammonia-oxidizing archaea (AOA) and bacteria (AOB) in 9 high-altitude lakes (2289-3160 m) in the Sierra Nevada, California, USA, in relation to spatial and biogeochemical data.", "Based on their ammonia monooxygenase (amoA) genes, AOB and AOA were frequently detected.", "AOB were present in 88% of samples and were more abundant than AOA in all samples.", "Both groups showed >100 fold variation in abundance between different lakes, and were also variable through time within individual lakes.", "Nutrient concentrations (ammonium, nitrite, nitrate, and phosphate) were generally low but also varied across and within lakes, suggestive of active internal nutrient cycling; AOB abundance was significantly correlated with phosphate (r(2) = 0.32, p<0.1), whereas AOA abundance was inversely correlated with lake elevation (r(2) = 0.43, p<0.05).", "We also measured low rates of ammonia oxidation--indicating that AOB, AOA, or both, may be biogeochemically active in these oligotrophic ecosystems.", "Our data indicate that dynamic populations of AOB and AOA are found in oligotrophic, high-altitude, freshwater lakes."], "title": "High abundances of potentially active ammonia-oxidizing bacteria and archaea in oligotrophic, high-altitude lakes of the Sierra Nevada, California, USA."}
{"paper_id": 22735540, "labels": ["0", "0", "0", "0", "0", "1", "0", "1", "1", "1"], "abstract": "The aggregation of alpha-synuclein (\u03b1-syn) and huntingtin (htt) into fibrillar assemblies in nerve and glial cells is a molecular hallmark of Parkinson's and Huntington's diseases. Within the aggregation process, prefibrillar and fibrillar oligomeric species form. Prefibrillar assemblies rather than fibrils are nowadays considered cytotoxic. However, recent reports describing spreading of fibrillar assemblies from one cell to another, in cell cultures, animal models, and brains of grafted patients suggest a critical role for fibrillar assemblies in pathogenesis. Here we compare the cytotoxic effect of defined and comparable particle concentrations of on-assembly pathway oligomeric and fibrillar \u03b1-syn and Htt fragment corresponding to the first exon of the protein (HttEx1). We show that homogeneous populations of \u03b1-syn and HttEx1 fibrils, rather than their precursor on-assembly pathway oligomers, are highly toxic to cultured cells and induce apoptotic cell death. We document the reasons that make fibrils toxic. We show that \u03b1-syn and HttEx1 fibrils bind and permeabilize lipid vesicles. We also show that fibrils binding to the plasma membrane in cultured cells alter Ca(2+) homeostasis. Overall, our data indicate that fibrillar \u03b1-syn and HttEx1, rather than their precursor oligomers, are highly cytotoxic, the toxicity being associated to their ability to bind and permeabilize the cell membranes.", "journal": "Biophysical journal", "sentences": ["The aggregation of alpha-synuclein (\u03b1-syn) and huntingtin (htt) into fibrillar assemblies in nerve and glial cells is a molecular hallmark of Parkinson's and Huntington's diseases.", "Within the aggregation process, prefibrillar and fibrillar oligomeric species form.", "Prefibrillar assemblies rather than fibrils are nowadays considered cytotoxic.", "However, recent reports describing spreading of fibrillar assemblies from one cell to another, in cell cultures, animal models, and brains of grafted patients suggest a critical role for fibrillar assemblies in pathogenesis.", "Here we compare the cytotoxic effect of defined and comparable particle concentrations of on-assembly pathway oligomeric and fibrillar \u03b1-syn and Htt fragment corresponding to the first exon of the protein (HttEx1).", "We show that homogeneous populations of \u03b1-syn and HttEx1 fibrils, rather than their precursor on-assembly pathway oligomers, are highly toxic to cultured cells and induce apoptotic cell death.", "We document the reasons that make fibrils toxic.", "We show that \u03b1-syn and HttEx1 fibrils bind and permeabilize lipid vesicles.", "We also show that fibrils binding to the plasma membrane in cultured cells alter Ca(2+) homeostasis.", "Overall, our data indicate that fibrillar \u03b1-syn and HttEx1, rather than their precursor oligomers, are highly cytotoxic, the toxicity being associated to their ability to bind and permeabilize the cell membranes."], "title": "Fibrillar \u03b1-synuclein and huntingtin exon 1 assemblies are toxic to the cells."}
{"paper_id": 25411970, "labels": ["0", "0", "0", "0", "1"], "abstract": "Visual illusions and other perceptual phenomena can be used as tools to uncover the otherwise hidden constructive processes that give rise to perception. Although many perceptual processes are assumed to be universal, variable susceptibility to certain illusions and perceptual effects across populations suggests a role for factors that vary culturally. One striking phenomenon is seen with two-tone images-photos reduced to two tones: black and white. Deficient recognition is observed in young children under conditions that trigger automatic recognition in adults. Here we show a similar lack of cue-triggered perceptual reorganization in the Pirah\u00e3, a hunter-gatherer tribe with limited exposure to modern visual media, suggesting such recognition is experience- and culture-specific.", "journal": "PloS one", "sentences": ["Visual illusions and other perceptual phenomena can be used as tools to uncover the otherwise hidden constructive processes that give rise to perception.", "Although many perceptual processes are assumed to be universal, variable susceptibility to certain illusions and perceptual effects across populations suggests a role for factors that vary culturally.", "One striking phenomenon is seen with two-tone images-photos reduced to two tones: black and white.", "Deficient recognition is observed in young children under conditions that trigger automatic recognition in adults.", "Here we show a similar lack of cue-triggered perceptual reorganization in the Pirah\u00e3, a hunter-gatherer tribe with limited exposure to modern visual media, suggesting such recognition is experience- and culture-specific."], "title": "Cultural differences in perceptual reorganization in US and Pirah\u00e3 adults."}
{"paper_id": 21949374, "labels": ["0", "0", "0", "0", "1"], "abstract": "Microphthalmia-associated transcription factor (MITF) regulates normal melanocyte development and is also a lineage-selective oncogene implicated in melanoma and clear-cell sarcoma (i.e., melanoma of soft parts). We have observed that MITF expression is potently reduced under hypoxic conditions in primary melanocytes and melanoma and clear cell sarcoma cells through hypoxia inducible factor 1 (HIF1)-mediated induction of the transcriptional repressor differentially expressed in chondrocytes protein 1 (DEC1) (BHLHE40), which subsequently binds and suppresses the promoter of M-MITF (melanocyte-restricted MITF isoform). Correspondingly, hypoxic conditions or HIF1\u03b1 stabilization achieved by using small-molecule prolyl-hydroxylase inhibitors reduced M-MITF expression, leading to melanoma cell growth arrest that was rescued by ectopic expression of M-MITF in vitro. Prolyl hydroxylase inhibition also potently suppressed melanoma growth in a mouse xenograft model. These studies illuminate a physiologic hypoxia response in pigment cells leading to M-MITF suppression, one that suggests a potential survival advantage mechanism for MITF amplification in metastatic melanoma and offers a small-molecule strategy for suppression of the MITF oncogene in vivo.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Microphthalmia-associated transcription factor (MITF) regulates normal melanocyte development and is also a lineage-selective oncogene implicated in melanoma and clear-cell sarcoma (i.e., melanoma of soft parts).", "We have observed that MITF expression is potently reduced under hypoxic conditions in primary melanocytes and melanoma and clear cell sarcoma cells through hypoxia inducible factor 1 (HIF1)-mediated induction of the transcriptional repressor differentially expressed in chondrocytes protein 1 (DEC1) (BHLHE40), which subsequently binds and suppresses the promoter of M-MITF (melanocyte-restricted MITF isoform).", "Correspondingly, hypoxic conditions or HIF1\u03b1 stabilization achieved by using small-molecule prolyl-hydroxylase inhibitors reduced M-MITF expression, leading to melanoma cell growth arrest that was rescued by ectopic expression of M-MITF in vitro.", "Prolyl hydroxylase inhibition also potently suppressed melanoma growth in a mouse xenograft model.", "These studies illuminate a physiologic hypoxia response in pigment cells leading to M-MITF suppression, one that suggests a potential survival advantage mechanism for MITF amplification in metastatic melanoma and offers a small-molecule strategy for suppression of the MITF oncogene in vivo."], "title": "Hypoxia-induced transcriptional repression of the melanoma-associated oncogene MITF."}
{"paper_id": 23071301, "labels": ["0", "0", "0", "0", "0", "1", "1", "1", "1"], "abstract": "Predators must ignore unhelpful background \"noise\" within information-rich environments and focus on useful cues of prey activity to forage efficiently. Learning to disregard unrewarding cues should happen quickly, weakening future interest in the cue. Prey odor, which is rapidly investigated by predators, may be particularly appropriate for testing whether consistently unrewarded cues are ignored, and whether such behavior can be exploited to benefit prey. Using wild free-ranging populations of black rats, Rattus rattus, an alien predator of global concern, we tested whether the application of bird-nesting odors before the introduction of artificial nests (odor preexposure), enhanced the survival of birds eggs (prey) compared with areas where prey and nesting odors were introduced concurrently. In areas where predators had encountered prey odor before prey being available, the subsequently introduced eggs showed 62% greater survival than in areas where prey and odor were introduced together. We suggest that black rats preexposed to prey odor learned to ignore the unrewarding cue, leading to a significant improvement in prey survival that held for the 7-d monitoring period. Exploiting rapid learning that underpins foraging decisions by manipulating sensory contexts offers a nonlethal, but effective approach to reducing undesirable predatory impacts. Techniques based on olfactory preexposure may provide prey with protection during critical periods of vulnerability, such as immediately following a prey reintroduction. These results also highlight the potential benefits to species conservation to be gained from a greater understanding of the cognitive mechanisms driving alien predator behavior within ecological contexts.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Predators must ignore unhelpful background \"noise\" within information-rich environments and focus on useful cues of prey activity to forage efficiently.", "Learning to disregard unrewarding cues should happen quickly, weakening future interest in the cue.", "Prey odor, which is rapidly investigated by predators, may be particularly appropriate for testing whether consistently unrewarded cues are ignored, and whether such behavior can be exploited to benefit prey.", "Using wild free-ranging populations of black rats, Rattus rattus, an alien predator of global concern, we tested whether the application of bird-nesting odors before the introduction of artificial nests (odor preexposure), enhanced the survival of birds eggs (prey) compared with areas where prey and nesting odors were introduced concurrently.", "In areas where predators had encountered prey odor before prey being available, the subsequently introduced eggs showed 62% greater survival than in areas where prey and odor were introduced together.", "We suggest that black rats preexposed to prey odor learned to ignore the unrewarding cue, leading to a significant improvement in prey survival that held for the 7-d monitoring period.", "Exploiting rapid learning that underpins foraging decisions by manipulating sensory contexts offers a nonlethal, but effective approach to reducing undesirable predatory impacts.", "Techniques based on olfactory preexposure may provide prey with protection during critical periods of vulnerability, such as immediately following a prey reintroduction.", "These results also highlight the potential benefits to species conservation to be gained from a greater understanding of the cognitive mechanisms driving alien predator behavior within ecological contexts."], "title": "Exploiting olfactory learning in alien rats to protect birds' eggs."}
{"paper_id": 21654681, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Non-small-cell lung cancer (NSCLC) remains by far the major cause of cancer-related death in the Western world in both men and women. The majority of patients will be diagnosed with metastatic disease, and chemotherapy doublets remain the cornerstone of treatment for these patients. However, chemotherapy has a minimal impact on long-term survival and prognosis remains poor for these patients. Further improvement in treatment is likely to require incorporation of novel targeted therapies. Among these agents, inhibitors of the epidermal growth factor receptor (EGFR) have demonstrated significant activity in the first-, second- or third-line treatment of NSCLC. The purpose of current paper is to present the evidence for using several proposed molecular biomarkers as a tool for selection of NSCLC patients for anti-EGFR treatment. According to current data, EGFR mutation status appears to be the strongest predictor for the selection of NSCLC patients to first-line treatment with EGFR tyrosine kinase inhibitors vs chemotherapy. Use of other biomarkers remains investigational.", "journal": "British journal of cancer", "sentences": ["Non-small-cell lung cancer (NSCLC) remains by far the major cause of cancer-related death in the Western world in both men and women.", "The majority of patients will be diagnosed with metastatic disease, and chemotherapy doublets remain the cornerstone of treatment for these patients.", "However, chemotherapy has a minimal impact on long-term survival and prognosis remains poor for these patients.", "Further improvement in treatment is likely to require incorporation of novel targeted therapies.", "Among these agents, inhibitors of the epidermal growth factor receptor (EGFR) have demonstrated significant activity in the first-, second- or third-line treatment of NSCLC.", "The purpose of current paper is to present the evidence for using several proposed molecular biomarkers as a tool for selection of NSCLC patients for anti-EGFR treatment.", "According to current data, EGFR mutation status appears to be the strongest predictor for the selection of NSCLC patients to first-line treatment with EGFR tyrosine kinase inhibitors vs chemotherapy.", "Use of other biomarkers remains investigational."], "title": "Biomarkers of clinical benefit for anti-epidermal growth factor receptor agents in patients with non-small-cell lung cancer."}
{"paper_id": 20538768, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Enhancements in the strength of corticospinal projections to muscles are induced in conscious humans by paired associative stimulation (PAS) to the motor cortex. Although most of the previous studies support the hypothesis that the increase of the amplitude of motor evoked potentials (MEPs) by PAS involves long-term potentiation (LTP)-like mechanism in cortical synapses, changes in spinal excitability after PAS have been reported, suggestive of parallel modifications in both cortical and spinal excitability. In a first series of experiments (experiment 1), we confirmed that both flexor carpi radialis (FCR) MEPs and FCR H reflex recruitment curves are enhanced by PAS. To elucidate the mechanism responsible for this change in the H reflex amplitude, we tested, using the same subjects, the hypothesis that enhanced H reflexes are caused by a down-regulation of the efficacy of mechanisms controlling Ia afferent discharge, including presynaptic Ia inhibition and postactivation depression. To address this question, amounts of both presynaptic Ia inhibition of FCR Ia terminals (D1 and D2 inhibitions methods; experiment 2) and postactivation depression (experiment 3) were determined before and after PAS. Results showed that PAS induces a significant decrease of presynaptic Ia inhibition of FCR terminals, which was concomitant with the facilitation of the H reflex. Postactivation depression was unaffected by PAS. It is argued that enhancement of segmental excitation by PAS relies on a selective effect of PAS on the interneurons controlling presynaptic inhibition of Ia terminals.", "journal": "Journal of neurophysiology", "sentences": ["Enhancements in the strength of corticospinal projections to muscles are induced in conscious humans by paired associative stimulation (PAS) to the motor cortex.", "Although most of the previous studies support the hypothesis that the increase of the amplitude of motor evoked potentials (MEPs) by PAS involves long-term potentiation (LTP)-like mechanism in cortical synapses, changes in spinal excitability after PAS have been reported, suggestive of parallel modifications in both cortical and spinal excitability.", "In a first series of experiments (experiment 1), we confirmed that both flexor carpi radialis (FCR) MEPs and FCR H reflex recruitment curves are enhanced by PAS.", "To elucidate the mechanism responsible for this change in the H reflex amplitude, we tested, using the same subjects, the hypothesis that enhanced H reflexes are caused by a down-regulation of the efficacy of mechanisms controlling Ia afferent discharge, including presynaptic Ia inhibition and postactivation depression.", "To address this question, amounts of both presynaptic Ia inhibition of FCR Ia terminals (D1 and D2 inhibitions methods; experiment 2) and postactivation depression (experiment 3) were determined before and after PAS.", "Results showed that PAS induces a significant decrease of presynaptic Ia inhibition of FCR terminals, which was concomitant with the facilitation of the H reflex.", "Postactivation depression was unaffected by PAS.", "It is argued that enhancement of segmental excitation by PAS relies on a selective effect of PAS on the interneurons controlling presynaptic inhibition of Ia terminals."], "title": "Paired associative stimulation induces change in presynaptic inhibition of Ia terminals in wrist flexors in humans."}
{"paper_id": 23827606, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Tissue engineering with chondrogenic cell based therapies is an expanding field with the intention of treating cartilage defects. It has been suggested that scaffolds used in cartilage tissue engineering influence cellular behavior and thus the long-term clinical outcome. The objective of this study was to assess whether chondrocyte attachment, proliferation and post-expansion re-differentiation could be influenced by the size of the fibers presented to the cells in a scaffold. Polylactic acid (PLA) scaffolds with different fiber morphologies were produced, i.e. microfiber (MS) scaffolds as well as nanofiber-coated microfiber scaffold (NMS). Adult human articular chondrocytes were cultured in the scaffolds in vitro up to 28 days, and the resulting constructs were assessed histologically, immunohistochemically, and biochemically. Attachment of cells and serum proteins to the scaffolds was affected by the architecture. The results point toward nano-patterning onto the microfibers influencing proliferation of the chondrocytes, and the overall 3D environment having a greater influence on the re-differentiation. In the efforts of finding the optimal scaffold for cartilage tissue engineering, studies as the current contribute to the knowledge of how to affect and control chondrocytes behavior.", "journal": "Materials science & engineering. C, Materials for biological applications", "sentences": ["Tissue engineering with chondrogenic cell based therapies is an expanding field with the intention of treating cartilage defects.", "It has been suggested that scaffolds used in cartilage tissue engineering influence cellular behavior and thus the long-term clinical outcome.", "The objective of this study was to assess whether chondrocyte attachment, proliferation and post-expansion re-differentiation could be influenced by the size of the fibers presented to the cells in a scaffold.", "Polylactic acid (PLA) scaffolds with different fiber morphologies were produced, i.e.", "microfiber (MS) scaffolds as well as nanofiber-coated microfiber scaffold (NMS).", "Adult human articular chondrocytes were cultured in the scaffolds in vitro up to 28 days, and the resulting constructs were assessed histologically, immunohistochemically, and biochemically.", "Attachment of cells and serum proteins to the scaffolds was affected by the architecture.", "The results point toward nano-patterning onto the microfibers influencing proliferation of the chondrocytes, and the overall 3D environment having a greater influence on the re-differentiation.", "In the efforts of finding the optimal scaffold for cartilage tissue engineering, studies as the current contribute to the knowledge of how to affect and control chondrocytes behavior."], "title": "Nanosized fibers' effect on adult human articular chondrocytes behavior."}
{"paper_id": 25302234, "labels": ["0", "0", "0", "0", "0"], "abstract": "Vanishing testis syndrome or Testicular regression syndrome (TRS) is defined as the absence or an incomplete development of the testis of varying degrees in 46XY patients with normal external genitalia.TRS or vanishing testis syndrome may be seen in less than 5% of all patients of cryptorchidism. We report two cases of TRS who underwent surgical exploration with an initial diagnosis of cryptorchidism with impalpable testis. Grossly testicular tissue was not identified and the vas deferens was ending into a nubbin in both the cases. The presumed testicular remnants were sent for histological examination. The histological sections in both the cases showed vascularised fibrous nodule, structure of the spermatic cord and calcification, supporting the diagnosis of TRS.", "journal": "Journal of clinical and diagnostic research : JCDR", "sentences": ["Vanishing testis syndrome or Testicular regression syndrome (TRS) is defined as the absence or an incomplete development of the testis of varying degrees in 46XY patients with normal external genitalia.TRS or vanishing testis syndrome may be seen in less than 5% of all patients of cryptorchidism.", "We report two cases of TRS who underwent surgical exploration with an initial diagnosis of cryptorchidism with impalpable testis.", "Grossly testicular tissue was not identified and the vas deferens was ending into a nubbin in both the cases.", "The presumed testicular remnants were sent for histological examination.", "The histological sections in both the cases showed vascularised fibrous nodule, structure of the spermatic cord and calcification, supporting the diagnosis of TRS."], "title": "Vanishing testis syndrome: report of two cases."}
{"paper_id": 25575943, "labels": ["0", "0", "0", "1", "0", "0", "0"], "abstract": "Decision making can be defined as the flexible integration and transformation of information from the external world into action. Recently, the development of novel genetic tools and new behavioral paradigms has made it attractive to study behavior of all kinds in rodents. By some perspectives, rodents are not an acceptable model for the study of decision making due to their simpler behavior often attributed to their less extensive cortical development when compared to non-human primates. We argue that decision making can be approached with a common framework across species. We review insights from comparative anatomy that suggest the expansion of cortical-striatal connectivity is a key development in evolutionary increases in behavioral flexibility. We briefly review studies that establish a role for corticostriatal circuits in integrative decision making. Finally, we provide an overview of a few recent, highly complementary rodent decision making studies using genetic tools, revealing with new cellular and temporal resolution how, when and where information can be integrated and compared in striatal circuits to influence choice.", "journal": "Neuroscience", "sentences": ["Decision making can be defined as the flexible integration and transformation of information from the external world into action.", "Recently, the development of novel genetic tools and new behavioral paradigms has made it attractive to study behavior of all kinds in rodents.", "By some perspectives, rodents are not an acceptable model for the study of decision making due to their simpler behavior often attributed to their less extensive cortical development when compared to non-human primates.", "We argue that decision making can be approached with a common framework across species.", "We review insights from comparative anatomy that suggest the expansion of cortical-striatal connectivity is a key development in evolutionary increases in behavioral flexibility.", "We briefly review studies that establish a role for corticostriatal circuits in integrative decision making.", "Finally, we provide an overview of a few recent, highly complementary rodent decision making studies using genetic tools, revealing with new cellular and temporal resolution how, when and where information can be integrated and compared in striatal circuits to influence choice."], "title": "Between the primate and 'reptilian' brain: Rodent models demonstrate the role of corticostriatal circuits in decision making."}
{"paper_id": 24714063, "labels": ["0", "0", "0", "0", "1", "1"], "abstract": "Salp15, a 15-kDa tick salivary gland protein, is both essential for ticks to successfully obtain host blood and also facilitates transmission of Lyme borreliosis. To determine whether the Salp15 gene is expressed in Ixodes persulcatus and Ixodes sinensis, principle vectors of Lyme borreliosis in China, we studied transcriptions of this gene in semi-engorged larvae, nymph and adults of these two species. A total of eight Salp15 homologues, five in I. persulcatus and three in I. sinensis, were identified by reverse transcriptase-polymerase chain reaction (RT-PCR). Interestingly, the intra-species similarity of Salp15 is approximately equal to its interspecies similarity and more than one Salp15 protein is expressed in a certain tick developmental stage. Comparison of DNA and proteins with other available tick Salp15 homologues suggests that the Salp15 superfamily is genetically conserved and diverse in the Ixodes ricinus complex. These findings indicate that Salp15 proteins in the I. ricinus complex may play an essential role in interacting with the host immune system and transmission of Borrelia genospecies.", "journal": "PloS one", "sentences": ["Salp15, a 15-kDa tick salivary gland protein, is both essential for ticks to successfully obtain host blood and also facilitates transmission of Lyme borreliosis.", "To determine whether the Salp15 gene is expressed in Ixodes persulcatus and Ixodes sinensis, principle vectors of Lyme borreliosis in China, we studied transcriptions of this gene in semi-engorged larvae, nymph and adults of these two species.", "A total of eight Salp15 homologues, five in I. persulcatus and three in I. sinensis, were identified by reverse transcriptase-polymerase chain reaction (RT-PCR).", "Interestingly, the intra-species similarity of Salp15 is approximately equal to its interspecies similarity and more than one Salp15 protein is expressed in a certain tick developmental stage.", "Comparison of DNA and proteins with other available tick Salp15 homologues suggests that the Salp15 superfamily is genetically conserved and diverse in the Ixodes ricinus complex.", "These findings indicate that Salp15 proteins in the I. ricinus complex may play an essential role in interacting with the host immune system and transmission of Borrelia genospecies."], "title": "Genetic diversity of Salp15 in the Ixodes ricinus complex (Acari: Ixodidae)."}
{"paper_id": 24966607, "labels": ["0", "0", "0", "1", "0", "0", "1", "0", "1"], "abstract": "Non-alcoholic fatty liver disease covers a wide spectrum of liver pathologies which range from simple steatosis to non-alcoholic steatohepatitis. Polyphenols are members of a very large family of plant-derived compounds that can have beneficial effects on human health, and thus their study has become an increasingly important area of human nutrition research. The aim of the present review is to compile published data concerning the effects of both isolated polyphenols as well as polyphenol extracts, on hepatocyte and liver fat accumulation under different steatosis-inducing conditions. The results reported clearly show that this group of biomolecules is able to reduce fat accumulation, but further studies are needed to establish the optimal dose and treatment period length. With regard to the potential mechanisms of action, there is a good consensus. The anti-lipidogenic effect of polyphenols is mainly due to reduced fatty acid and triacylglycerol synthesis, increased in fatty acid oxidation, and reduced of oxidative stress and inflammation. As a general conclusion, it can be stated that polyphenols are biomolecules which produce hepatoprotective effects. To date, these beneficial effects have been demonstrated in cultured cells and animal models. Thus, studies performed in humans are needed before these molecules can be considered as truly useful tools in the prevention of liver steatosis.", "journal": "World journal of gastroenterology", "sentences": ["Non-alcoholic fatty liver disease covers a wide spectrum of liver pathologies which range from simple steatosis to non-alcoholic steatohepatitis.", "Polyphenols are members of a very large family of plant-derived compounds that can have beneficial effects on human health, and thus their study has become an increasingly important area of human nutrition research.", "The aim of the present review is to compile published data concerning the effects of both isolated polyphenols as well as polyphenol extracts, on hepatocyte and liver fat accumulation under different steatosis-inducing conditions.", "The results reported clearly show that this group of biomolecules is able to reduce fat accumulation, but further studies are needed to establish the optimal dose and treatment period length.", "With regard to the potential mechanisms of action, there is a good consensus.", "The anti-lipidogenic effect of polyphenols is mainly due to reduced fatty acid and triacylglycerol synthesis, increased in fatty acid oxidation, and reduced of oxidative stress and inflammation.", "As a general conclusion, it can be stated that polyphenols are biomolecules which produce hepatoprotective effects.", "To date, these beneficial effects have been demonstrated in cultured cells and animal models.", "Thus, studies performed in humans are needed before these molecules can be considered as truly useful tools in the prevention of liver steatosis."], "title": "Effects of resveratrol and other polyphenols in hepatic steatosis."}
{"paper_id": 25401150, "labels": ["0", "0", "0", "0", "1"], "abstract": "In order to investigate the change rules and response characteristics of growth status on each component of poplar seedling followed by continuous cropping generations and growth period, we clear the biomass distribution pattern of poplar seedling, adapt continuous cropping, and provide theoretical foundation and technical reference on cultivation management of poplar seedling, the first generation, second generation, and third generation continuous cropping poplar seedlings were taken as study objects, and the whole poplar seedling was harvested to measure and analyze the change of each component biomass on different growth period poplar leaves, newly emerging branches, trunks and root system, and so forth. The results showed that the whole biomass of poplar seedling decreased significantly with the leaf area and its ratio increased, and the growth was inhibited obviously. The biomass aboveground was more than that underground. The ratios of leaf biomass and newly emerging branches biomass of first continuous cropping poplar seedling were relatively high. With the continuous cropping generations and growth cycle increasing, poplar seedling had a growth strategy to improve the ratio of root-shoot and root-leaf to adapt the limited soil nutrient of continuous cropping.", "journal": "TheScientificWorldJournal", "sentences": ["In order to investigate the change rules and response characteristics of growth status on each component of poplar seedling followed by continuous cropping generations and growth period, we clear the biomass distribution pattern of poplar seedling, adapt continuous cropping, and provide theoretical foundation and technical reference on cultivation management of poplar seedling, the first generation, second generation, and third generation continuous cropping poplar seedlings were taken as study objects, and the whole poplar seedling was harvested to measure and analyze the change of each component biomass on different growth period poplar leaves, newly emerging branches, trunks and root system, and so forth.", "The results showed that the whole biomass of poplar seedling decreased significantly with the leaf area and its ratio increased, and the growth was inhibited obviously.", "The biomass aboveground was more than that underground.", "The ratios of leaf biomass and newly emerging branches biomass of first continuous cropping poplar seedling were relatively high.", "With the continuous cropping generations and growth cycle increasing, poplar seedling had a growth strategy to improve the ratio of root-shoot and root-leaf to adapt the limited soil nutrient of continuous cropping."], "title": "Effect of continuous cropping generations on each component biomass of poplar seedlings during different growth periods."}
{"paper_id": 24587014, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Cancer cells breach the endothelium not only through cell-cell junctions but also via individual endothelial cells (ECs), or transcellular invasion. The underlying EC forms a circular structure around the transcellular invasion pore that is dependent on myosin light chain kinase (MLCK) and myosin II regulatory light chain (RLC) phosphorylation. Here we offer mechanistic insights into transcellular invasive array formation amid persistent tensile force from activated EC myosin. Fluorescence recovery after photobleaching (FRAP) experiments, sarcomeric distance measurements using super-resolution microscopy and electron microscopy provide details about the nature of the myosin II invasion array. To probe the relationship between biomechanical forces and the tension required to maintain the curvature of contractile filaments, we targeted individual actin-myosin fibers at the invasion site for photoablation. We showed that adjacent filaments rapidly replace the ablat11ed structures. We propose that the transcellular circumferential invasion array (TCIA) provides the necessary constraint within the EC to blunt the radial compression from the invading cancer cell.", "journal": "PloS one", "sentences": ["Cancer cells breach the endothelium not only through cell-cell junctions but also via individual endothelial cells (ECs), or transcellular invasion.", "The underlying EC forms a circular structure around the transcellular invasion pore that is dependent on myosin light chain kinase (MLCK) and myosin II regulatory light chain (RLC) phosphorylation.", "Here we offer mechanistic insights into transcellular invasive array formation amid persistent tensile force from activated EC myosin.", "Fluorescence recovery after photobleaching (FRAP) experiments, sarcomeric distance measurements using super-resolution microscopy and electron microscopy provide details about the nature of the myosin II invasion array.", "To probe the relationship between biomechanical forces and the tension required to maintain the curvature of contractile filaments, we targeted individual actin-myosin fibers at the invasion site for photoablation.", "We showed that adjacent filaments rapidly replace the ablat11ed structures.", "We propose that the transcellular circumferential invasion array (TCIA) provides the necessary constraint within the EC to blunt the radial compression from the invading cancer cell."], "title": "Structure and biomechanics of the endothelial transcellular circumferential invasion array in tumor invasion."}
{"paper_id": 26837049, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Aquaporin (AQP) 9, a member of the transmembrane water channel family, is defined as a water/glycerol transporting protein. Some AQPs including AQP3 and AQP8 have been recently found to transport hydrogen peroxide (H2O2). Here we show that AQP9 facilitates the membrane transport of H2O2 in human and mice cells. Enforced expression of human AQP9 in Chinese hamster ovary-K1 potentiated the increase in cellular H2O2 after adding exogenous H2O2. In contrast, AQP9 knockdown by siRNA in human hepatoma HepG2 cells reduced the import of extracellular H2O2. In addition, the uptake of extracellular H2O2 was suppressed in erythrocytes and bone marrow-derived mast cells from AQP9 knockout mice compared with wild-type cells. Coincidentally, H2O2-induced cytotoxicity was attenuated by AQP9 deficiency in human and mice cells. Our findings implicate the involvement of AQP9 in H2O2 transport in human and mice cells.", "journal": "Biochemical and biophysical research communications", "sentences": ["Aquaporin (AQP) 9, a member of the transmembrane water channel family, is defined as a water/glycerol transporting protein.", "Some AQPs including AQP3 and AQP8 have been recently found to transport hydrogen peroxide (H2O2).", "Here we show that AQP9 facilitates the membrane transport of H2O2 in human and mice cells.", "Enforced expression of human AQP9 in Chinese hamster ovary-K1 potentiated the increase in cellular H2O2 after adding exogenous H2O2.", "In contrast, AQP9 knockdown by siRNA in human hepatoma HepG2 cells reduced the import of extracellular H2O2.", "In addition, the uptake of extracellular H2O2 was suppressed in erythrocytes and bone marrow-derived mast cells from AQP9 knockout mice compared with wild-type cells.", "Coincidentally, H2O2-induced cytotoxicity was attenuated by AQP9 deficiency in human and mice cells.", "Our findings implicate the involvement of AQP9 in H2O2 transport in human and mice cells."], "title": "Aquaporin-9 facilitates membrane transport of hydrogen peroxide in mammalian cells."}
{"paper_id": 21170962, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The study investigated the role of factors considered related to the early stimulation of the immune system in the aetiology of childhood lymphoma. The national registry-based case-control study, Escale, was carried out in France over the period 2003-2004. Population controls were frequency matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders. Data from 128 cases of Hodgkin's lymphoma (HL) aged 5-14 years, 164 cases of non-Hodgkin's lymphoma (NHL) aged 2-14 years and 1,312 controls were analyzed. Negative associations were observed between HL and day care attendance [OR = 0.5 (0.2-1.2)] and between HL and repeated early common infections among non-breastfed children [OR = 0.3 (.2-0.7), p = 0.003] [OR for breastfed children: 1.0 (.5-2.1)], but not for the other factors investigated. Negative associations were observed between NHL and birth order 3 or more [OR = 0.7 (0.4-1.1)], prolonged breastfeeding [OR = 0.5 (0.3-1.0)], regular contact with farm animals [OR = 0.5 (0.3-1.0)], frequent farm visits in early life [OR = 0.6 (0.4-1.1)] and history of asthma [OR = 0.6 (0.3-1.1)]. In conclusion, the results partly support the hypothesis that an abnormal maturation of the immune system may play a role in childhood HL or NHL, and call for further investigations.", "journal": "International journal of cancer", "sentences": ["The study investigated the role of factors considered related to the early stimulation of the immune system in the aetiology of childhood lymphoma.", "The national registry-based case-control study, Escale, was carried out in France over the period 2003-2004.", "Population controls were frequency matched with the cases on age and gender.", "Data were obtained from structured telephone questionnaires administered to mothers.", "Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders.", "Data from 128 cases of Hodgkin's lymphoma (HL) aged 5-14 years, 164 cases of non-Hodgkin's lymphoma (NHL) aged 2-14 years and 1,312 controls were analyzed.", "Negative associations were observed between HL and day care attendance [OR = 0.5 (0.2-1.2)] and between HL and repeated early common infections among non-breastfed children [OR = 0.3 (.2-0.7), p = 0.003] [OR for breastfed children: 1.0 (.5-2.1)], but not for the other factors investigated.", "Negative associations were observed between NHL and birth order 3 or more [OR = 0.7 (0.4-1.1)], prolonged breastfeeding [OR = 0.5 (0.3-1.0)], regular contact with farm animals [OR = 0.5 (0.3-1.0)], frequent farm visits in early life [OR = 0.6 (0.4-1.1)] and history of asthma [OR = 0.6 (0.3-1.1)].", "In conclusion, the results partly support the hypothesis that an abnormal maturation of the immune system may play a role in childhood HL or NHL, and call for further investigations."], "title": "Childhood Hodgkin's lymphoma, non-Hodgkin's lymphoma and factors related to the immune system: the Escale Study (SFCE)."}
{"paper_id": 26365256, "labels": ["0", "0", "0", "1", "0", "0", "0", "1"], "abstract": "People prefer to move in ways that minimize their energetic cost. For example, people tend to walk at a speed that minimizes energy use per unit distance and, for that speed, they select a step frequency that makes walking less costly. Although aspects of this preference appear to be established over both evolutionary and developmental timescales, it remains unclear whether people can also optimize energetic cost in real time. Here we show that during walking, people readily adapt established motor programs to minimize energy use. To accomplish this, we used robotic exoskeletons to shift people's energetically optimal step frequency to frequencies higher and lower than normally preferred. In response, we found that subjects adapted their step frequency to converge on the new energetic optima within minutes and in response to relatively small savings in cost (<5%). When transiently perturbed from their new optimal gait, subjects relied on an updated prediction to rapidly re-converge within seconds. Our collective findings indicate that energetic cost is not just an outcome of movement, but also plays a central role in continuously shaping it.", "journal": "Current biology : CB", "sentences": ["People prefer to move in ways that minimize their energetic cost.", "For example, people tend to walk at a speed that minimizes energy use per unit distance and, for that speed, they select a step frequency that makes walking less costly.", "Although aspects of this preference appear to be established over both evolutionary and developmental timescales, it remains unclear whether people can also optimize energetic cost in real time.", "Here we show that during walking, people readily adapt established motor programs to minimize energy use.", "To accomplish this, we used robotic exoskeletons to shift people's energetically optimal step frequency to frequencies higher and lower than normally preferred.", "In response, we found that subjects adapted their step frequency to converge on the new energetic optima within minutes and in response to relatively small savings in cost (<5%).", "When transiently perturbed from their new optimal gait, subjects relied on an updated prediction to rapidly re-converge within seconds.", "Our collective findings indicate that energetic cost is not just an outcome of movement, but also plays a central role in continuously shaping it."], "title": "Humans Can Continuously Optimize Energetic Cost during Walking."}
{"paper_id": 24876878, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Natural products have long gained wide acceptance among the public and scientific community in the gastrointestinal ulcerative field. The present study explore the potential effects of aged garlic extract (AGE) on indomethacin-(IN-) induced gastric inflammation in male rats. Animals were divided into six groups (n = 8) control group, IN-induced gastric inflammation group via oral single dose (30\u2009mg/kg to fasted rats) two AGE orally administered groups (100 and 200\u2009mg/kg for 30 consecutive days) two AGE orally administered groups to rats pretreated with IN at the same aforementioned doses. The results declared the more potent effect of the higher AGE dose (200\u2009mg/kg) as compared to that of the 100\u2009mg/kg dose in the gastroprotective effects reflected by significant gastric mucosal healing of damage and reduction in the total microbial induced due to indomethacin administration. In addition to the significant effect to normalize the significant increase in malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor- \u03b1 (TNF- \u03b1 ) values, and the significant decrease in the total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) values induced by indomethacin. The results support AGE antioxidant, anti-inflammatory, and antimicrobial potency reflected by the healing of the gastric tissue damage induced by indomethacin.", "journal": "Evidence-based complementary and alternative medicine : eCAM", "sentences": ["Natural products have long gained wide acceptance among the public and scientific community in the gastrointestinal ulcerative field.", "The present study explore the potential effects of aged garlic extract (AGE) on indomethacin-(IN-) induced gastric inflammation in male rats.", "Animals were divided into six groups (n = 8) control group, IN-induced gastric inflammation group via oral single dose (30\u2009mg/kg to fasted rats) two AGE orally administered groups (100 and 200\u2009mg/kg for 30 consecutive days) two AGE orally administered groups to rats pretreated with IN at the same aforementioned doses.", "The results declared the more potent effect of the higher AGE dose (200\u2009mg/kg) as compared to that of the 100\u2009mg/kg dose in the gastroprotective effects reflected by significant gastric mucosal healing of damage and reduction in the total microbial induced due to indomethacin administration.", "In addition to the significant effect to normalize the significant increase in malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor- \u03b1 (TNF- \u03b1 ) values, and the significant decrease in the total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) values induced by indomethacin.", "The results support AGE antioxidant, anti-inflammatory, and antimicrobial potency reflected by the healing of the gastric tissue damage induced by indomethacin."], "title": "The protective effect of aged garlic extract on nonsteroidal anti-inflammatory drug-induced gastric inflammations in male albino rats."}
{"paper_id": 25874581, "labels": ["0", "0", "1", "1", "1"], "abstract": "Combined with neural language models, distributed word representations achieve significant advantages in computational linguistics and text mining. Most existing models estimate distributed word vectors from large-scale data in an unsupervised fashion, which, however, do not take rich linguistic knowledge into consideration. Linguistic knowledge can be represented as either link-based knowledge or preference-based knowledge, and we propose knowledge regularized word representation models (KRWR) to incorporate these prior knowledge for learning distributed word representations. Experiment results demonstrate that our estimated word representation achieves better performance in task of semantic relatedness ranking. This indicates that our methods can efficiently encode both prior knowledge from knowledge bases and statistical knowledge from large-scale text corpora into a unified word representation model, which will benefit many tasks in text mining.", "journal": "PloS one", "sentences": ["Combined with neural language models, distributed word representations achieve significant advantages in computational linguistics and text mining.", "Most existing models estimate distributed word vectors from large-scale data in an unsupervised fashion, which, however, do not take rich linguistic knowledge into consideration.", "Linguistic knowledge can be represented as either link-based knowledge or preference-based knowledge, and we propose knowledge regularized word representation models (KRWR) to incorporate these prior knowledge for learning distributed word representations.", "Experiment results demonstrate that our estimated word representation achieves better performance in task of semantic relatedness ranking.", "This indicates that our methods can efficiently encode both prior knowledge from knowledge bases and statistical knowledge from large-scale text corpora into a unified word representation model, which will benefit many tasks in text mining."], "title": "Incorporating linguistic knowledge for learning distributed word representations."}
{"paper_id": 25605911, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Accumulation of protein- and lipid-containing deposits external to the retinal pigment epithelium (RPE) is common in the aging eye, and has long been viewed as the hallmark of age-related macular degeneration (AMD). The cause for the accumulation and retention of molecules in the sub-RPE space, however, remains an enigma. Here, we present fluorescence microscopy and X-ray diffraction evidence for the formation of small (0.5-20 \u03bcm in diameter), hollow, hydroxyapatite (HAP) spherules in Bruch's membrane in human eyes. These spherules are distinct in form, placement, and staining from the well-known calcification of the elastin layer of the aging Bruch's membrane. Secondary ion mass spectrometry (SIMS) imaging confirmed the presence of calcium phosphate in the spherules and identified cholesterol enrichment in their core. Using HAP-selective fluorescent dyes, we show that all types of sub-RPE deposits in the macula, as well as in the periphery, contain numerous HAP spherules. Immunohistochemical labeling for proteins characteristic of sub-RPE deposits, such as complement factor H, vitronectin, and amyloid beta, revealed that HAP spherules were coated with these proteins. HAP spherules were also found outside the sub-RPE deposits, ready to bind proteins at the RPE/choroid interface. Based on these results, we propose a novel mechanism for the growth, and possibly even the formation, of sub-RPE deposits, namely, that the deposit growth and formation begin with the deposition of insoluble HAP shells around naturally occurring, cholesterol-containing extracellular lipid droplets at the RPE/choroid interface; proteins and lipids then attach to these shells, initiating or supporting the growth of sub-RPE deposits.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Accumulation of protein- and lipid-containing deposits external to the retinal pigment epithelium (RPE) is common in the aging eye, and has long been viewed as the hallmark of age-related macular degeneration (AMD).", "The cause for the accumulation and retention of molecules in the sub-RPE space, however, remains an enigma.", "Here, we present fluorescence microscopy and X-ray diffraction evidence for the formation of small (0.5-20 \u03bcm in diameter), hollow, hydroxyapatite (HAP) spherules in Bruch's membrane in human eyes.", "These spherules are distinct in form, placement, and staining from the well-known calcification of the elastin layer of the aging Bruch's membrane.", "Secondary ion mass spectrometry (SIMS) imaging confirmed the presence of calcium phosphate in the spherules and identified cholesterol enrichment in their core.", "Using HAP-selective fluorescent dyes, we show that all types of sub-RPE deposits in the macula, as well as in the periphery, contain numerous HAP spherules.", "Immunohistochemical labeling for proteins characteristic of sub-RPE deposits, such as complement factor H, vitronectin, and amyloid beta, revealed that HAP spherules were coated with these proteins.", "HAP spherules were also found outside the sub-RPE deposits, ready to bind proteins at the RPE/choroid interface.", "Based on these results, we propose a novel mechanism for the growth, and possibly even the formation, of sub-RPE deposits, namely, that the deposit growth and formation begin with the deposition of insoluble HAP shells around naturally occurring, cholesterol-containing extracellular lipid droplets at the RPE/choroid interface; proteins and lipids then attach to these shells, initiating or supporting the growth of sub-RPE deposits."], "title": "Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye."}
{"paper_id": 23028527, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Recently, we have found that the skin secretions of the Amazonian tree frog Phyllomedusa bicolor contains molecules with antitumor and angiostatic activities and identified one of them as the antimicrobial peptide dermaseptin (Drs) B2. In the present study we further explored the in vitro and in vivo antitumor activity of this molecule and investigated its mechanism of action. We showed that Drs B2 inhibits the proliferation and colony formation of various human tumor cell types, and the proliferation and capillary formation of endothelial cells in vitro. Furthermore, Drs B2 inhibited tumor growth of the human prostate adenocarcinoma cell line PC3 in a xenograft model in vivo. Research on the mechanism of action of Drs B2 on tumor PC3 cells demonstrated a rapid increasing amount of cytosolic lactate dehydrogenase, no activation of caspase-3, and no changes in mitochondrial membrane potential. Confocal microscopy analysis revealed that Drs B2 can interact with the tumor cell surface, aggregate and penetrate the cells. These data together indicate that Drs B2 does not act by apoptosis but possibly by necrosis. In conclusion, Drs B2 could be considered as an interesting and promising pharmacological and therapeutic leader molecule for the treatment of cancer.", "journal": "PloS one", "sentences": ["Recently, we have found that the skin secretions of the Amazonian tree frog Phyllomedusa bicolor contains molecules with antitumor and angiostatic activities and identified one of them as the antimicrobial peptide dermaseptin (Drs) B2.", "In the present study we further explored the in vitro and in vivo antitumor activity of this molecule and investigated its mechanism of action.", "We showed that Drs B2 inhibits the proliferation and colony formation of various human tumor cell types, and the proliferation and capillary formation of endothelial cells in vitro.", "Furthermore, Drs B2 inhibited tumor growth of the human prostate adenocarcinoma cell line PC3 in a xenograft model in vivo.", "Research on the mechanism of action of Drs B2 on tumor PC3 cells demonstrated a rapid increasing amount of cytosolic lactate dehydrogenase, no activation of caspase-3, and no changes in mitochondrial membrane potential.", "Confocal microscopy analysis revealed that Drs B2 can interact with the tumor cell surface, aggregate and penetrate the cells.", "These data together indicate that Drs B2 does not act by apoptosis but possibly by necrosis.", "In conclusion, Drs B2 could be considered as an interesting and promising pharmacological and therapeutic leader molecule for the treatment of cancer."], "title": "Antitumor and angiostatic activities of the antimicrobial peptide dermaseptin B2."}
{"paper_id": 22542185, "labels": ["0", "0", "1", "0", "0", "1"], "abstract": "Neuroepithelial attachments at adherens junctions are essential for the self-renewal of neural stem and progenitor cells and the polarized organization of the developing central nervous system. The balance between stem cell maintenance and differentiation depends on the precise assembly and disassembly of these adhesive contacts, but the gene regulatory mechanisms orchestrating this process are not known. Here, we demonstrate that two Forkhead transcription factors, Foxp2 and Foxp4, are progressively expressed upon neural differentiation in the spinal cord. Elevated expression of either Foxp represses the expression of a key component of adherens junctions, N-cadherin, and promotes the detachment of differentiating neurons from the neuroepithelium. Conversely, inactivation of Foxp2 and Foxp4 function in both chick and mouse results in a spectrum of neural tube defects associated with neuroepithelial disorganization and enhanced progenitor maintenance. Together, these data reveal a Foxp-based transcriptional mechanism that regulates the integrity and cytoarchitecture of neuroepithelial progenitors.", "journal": "Neuron", "sentences": ["Neuroepithelial attachments at adherens junctions are essential for the self-renewal of neural stem and progenitor cells and the polarized organization of the developing central nervous system.", "The balance between stem cell maintenance and differentiation depends on the precise assembly and disassembly of these adhesive contacts, but the gene regulatory mechanisms orchestrating this process are not known.", "Here, we demonstrate that two Forkhead transcription factors, Foxp2 and Foxp4, are progressively expressed upon neural differentiation in the spinal cord.", "Elevated expression of either Foxp represses the expression of a key component of adherens junctions, N-cadherin, and promotes the detachment of differentiating neurons from the neuroepithelium.", "Conversely, inactivation of Foxp2 and Foxp4 function in both chick and mouse results in a spectrum of neural tube defects associated with neuroepithelial disorganization and enhanced progenitor maintenance.", "Together, these data reveal a Foxp-based transcriptional mechanism that regulates the integrity and cytoarchitecture of neuroepithelial progenitors."], "title": "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS."}
{"paper_id": 26690352, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Antibody-mediated rejection (AMR) is a key limiting factor for long-term graft survival in solid organ transplantation. Human leukocyte antigen (HLA) class I (HLA I) antibodies (Abs) play a major role in the pathogenesis of AMR via their interactions with HLA molecules on vascular endothelial cells (ECs). The antioxidant enzyme heme oxygenase (HO)-1 has anti-inflammatory functions in the endothelium. As complement-independent effects of HLA I Abs can activate ECs, it was the goal of the current study to investigate the role of HO-1 on activation of human ECs by HLA I Abs. In cell cultures of various primary human macro- and microvascular ECs treatment with monoclonal pan- and allele-specific HLA I Abs up-regulated the expression of inducible proinflammatory adhesion molecules and chemokines (vascular cell adhesion molecule-1 [VCAM-1], intercellular cell adhesion molecule-1 [ICAM-1], interleukin-8 [IL-8] and monocyte chemotactic protein 1 [MCP-1]). Pharmacological induction of HO-1 with cobalt-protoporphyrin IX reduced, whereas inhibition of HO-1 with either zinc-protoporphyrin IX or siRNA-mediated knockdown increased HLA I Ab-dependent up-regulation of VCAM-1. Treatment with two carbon monoxide (CO)-releasing molecules, which liberate the gaseous HO product CO, blocked HLA I Ab-dependent EC activation. Finally, in an in vitro adhesion assay exposure of ECs to HLA I Abs led to increased monocyte binding, which was counteracted by up-regulation of HO-1. In conclusion, HLA I Ab-dependent EC activation is modulated by endothelial HO-1 and targeted induction of this enzyme may be a novel therapeutic approach for the treatment of AMR in solid organ transplantation.", "journal": "PloS one", "sentences": ["Antibody-mediated rejection (AMR) is a key limiting factor for long-term graft survival in solid organ transplantation.", "Human leukocyte antigen (HLA) class I (HLA I) antibodies (Abs) play a major role in the pathogenesis of AMR via their interactions with HLA molecules on vascular endothelial cells (ECs).", "The antioxidant enzyme heme oxygenase (HO)-1 has anti-inflammatory functions in the endothelium.", "As complement-independent effects of HLA I Abs can activate ECs, it was the goal of the current study to investigate the role of HO-1 on activation of human ECs by HLA I Abs.", "In cell cultures of various primary human macro- and microvascular ECs treatment with monoclonal pan- and allele-specific HLA I Abs up-regulated the expression of inducible proinflammatory adhesion molecules and chemokines (vascular cell adhesion molecule-1 [VCAM-1], intercellular cell adhesion molecule-1 [ICAM-1], interleukin-8 [IL-8] and monocyte chemotactic protein 1 [MCP-1]).", "Pharmacological induction of HO-1 with cobalt-protoporphyrin IX reduced, whereas inhibition of HO-1 with either zinc-protoporphyrin IX or siRNA-mediated knockdown increased HLA I Ab-dependent up-regulation of VCAM-1.", "Treatment with two carbon monoxide (CO)-releasing molecules, which liberate the gaseous HO product CO, blocked HLA I Ab-dependent EC activation.", "Finally, in an in vitro adhesion assay exposure of ECs to HLA I Abs led to increased monocyte binding, which was counteracted by up-regulation of HO-1.", "In conclusion, HLA I Ab-dependent EC activation is modulated by endothelial HO-1 and targeted induction of this enzyme may be a novel therapeutic approach for the treatment of AMR in solid organ transplantation."], "title": "Heme Oxygenase-1 Inhibits HLA Class I Antibody-Dependent Endothelial Cell Activation."}
{"paper_id": 27092944, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The assumption that total abundance of RNAs in a cell is roughly the same in different cells is underlying most studies based on gene expression analyses. But experiments have shown that changes in the expression of some master regulators such as c-MYC can cause global shift in the expression of almost all genes in some cell types like cancers. Such shift will violate this assumption and can cause wrong or biased conclusions for standard data analysis practices, such as detection of differentially expressed (DE) genes and molecular classification of tumors based on gene expression. Most existing gene expression data were generated without considering this possibility, and are therefore at the risk of having produced unreliable results if such global shift effect exists in the data. To evaluate this risk, we conducted a systematic study on the possible influence of the global gene expression shift effect on differential expression analysis and on molecular classification analysis. We collected data with known global shift effect and also generated data to simulate different situations of the effect based on a wide collection of real gene expression data, and conducted comparative studies on representative existing methods. We observed that some DE analysis methods are more tolerant to the global shift while others are very sensitive to it. Classification accuracy is not sensitive to the shift and actually can benefit from it, but genes selected for the classification can be greatly affected.", "journal": "PloS one", "sentences": ["The assumption that total abundance of RNAs in a cell is roughly the same in different cells is underlying most studies based on gene expression analyses.", "But experiments have shown that changes in the expression of some master regulators such as c-MYC can cause global shift in the expression of almost all genes in some cell types like cancers.", "Such shift will violate this assumption and can cause wrong or biased conclusions for standard data analysis practices, such as detection of differentially expressed (DE) genes and molecular classification of tumors based on gene expression.", "Most existing gene expression data were generated without considering this possibility, and are therefore at the risk of having produced unreliable results if such global shift effect exists in the data.", "To evaluate this risk, we conducted a systematic study on the possible influence of the global gene expression shift effect on differential expression analysis and on molecular classification analysis.", "We collected data with known global shift effect and also generated data to simulate different situations of the effect based on a wide collection of real gene expression data, and conducted comparative studies on representative existing methods.", "We observed that some DE analysis methods are more tolerant to the global shift while others are very sensitive to it.", "Classification accuracy is not sensitive to the shift and actually can benefit from it, but genes selected for the classification can be greatly affected."], "title": "The Influence of the Global Gene Expression Shift on Downstream Analyses."}
{"paper_id": 27382962, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "The biosynthesis of iron sulfur (Fe-S) clusters in Bacillus subtilis is mediated by a SUF-type gene cluster, consisting of the cysteine desulfurase SufS, the scaffold protein SufU, and the putative chaperone complex SufB/SufC/SufD. Here, we present the high-resolution crystal structure of the SufS homodimer in its product-bound state (i.e., in complex with pyrodoxal-5'-phosphate, alanine, Cys361-persulfide). By performing hydrogen/deuterium exchange (H/DX) experiments, we characterized the interaction of SufS with SufU and demonstrate that SufU induces an opening of the active site pocket of SufS. Recent data indicate that frataxin could be involved in Fe-S cluster biosynthesis by facilitating iron incorporation. H/DX experiments show that frataxin indeed interacts with the SufS/SufU complex at the active site. Our findings deepen the current understanding of Fe-S cluster biosynthesis, a complex yet essential process, in the model organism B. subtilis.", "journal": "PloS one", "sentences": ["The biosynthesis of iron sulfur (Fe-S) clusters in Bacillus subtilis is mediated by a SUF-type gene cluster, consisting of the cysteine desulfurase SufS, the scaffold protein SufU, and the putative chaperone complex SufB/SufC/SufD.", "Here, we present the high-resolution crystal structure of the SufS homodimer in its product-bound state (i.e., in complex with pyrodoxal-5'-phosphate, alanine, Cys361-persulfide).", "By performing hydrogen/deuterium exchange (H/DX) experiments, we characterized the interaction of SufS with SufU and demonstrate that SufU induces an opening of the active site pocket of SufS.", "Recent data indicate that frataxin could be involved in Fe-S cluster biosynthesis by facilitating iron incorporation.", "H/DX experiments show that frataxin indeed interacts with the SufS/SufU complex at the active site.", "Our findings deepen the current understanding of Fe-S cluster biosynthesis, a complex yet essential process, in the model organism B. subtilis."], "title": "Crystal Structure of Bacillus subtilis Cysteine Desulfurase SufS and Its Dynamic Interaction with Frataxin and Scaffold Protein SufU."}
{"paper_id": 20566894, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Limited number of hematopoietic stem cells in umbilical cord blood (UCB) presents a problem when using UCB for stem cell transplantation. Improving their homing capacity could reduce the need for high initial cell numbers during transplantation procedures. Although it is evident that protein kinase B (PKB/c-Akt) plays an important role in regulation of migration of various cell types, a role for PKB in regulation of migration and homing of human hematopoietic stem and progenitor cells remains to be determined. PKB activity was found to be required for induction of adhesion to bone marrow-derived stromal cells and detrimental for migration of UCB-derived CD34(+) hematopoietic progenitors. In addition, PKB activity was found to positively regulate integrin expression. CD34(+) hematopoietic progenitors, and their capacity to form colonies in vitro, were not affected by transient inhibition of PKB. Finally, transplantation of \u03b22-microglobulin(-/-) nonobese diabetic/severe combined immunodeficient mice with CD34(+) cells ectopically expressing constitutively active PKB resulted in reduced migration to the bone marrow, whereas inhibition of PKB activity resulted in an induction in bone marrow homing and engraftment. These results indicate that transient inhibition of PKB activity may provide a means for ex vivo stem cell manipulation to improve bone marrow transplantation regimes.", "journal": "Blood", "sentences": ["Limited number of hematopoietic stem cells in umbilical cord blood (UCB) presents a problem when using UCB for stem cell transplantation.", "Improving their homing capacity could reduce the need for high initial cell numbers during transplantation procedures.", "Although it is evident that protein kinase B (PKB/c-Akt) plays an important role in regulation of migration of various cell types, a role for PKB in regulation of migration and homing of human hematopoietic stem and progenitor cells remains to be determined.", "PKB activity was found to be required for induction of adhesion to bone marrow-derived stromal cells and detrimental for migration of UCB-derived CD34(+) hematopoietic progenitors.", "In addition, PKB activity was found to positively regulate integrin expression.", "CD34(+) hematopoietic progenitors, and their capacity to form colonies in vitro, were not affected by transient inhibition of PKB.", "Finally, transplantation of \u03b22-microglobulin(-/-) nonobese diabetic/severe combined immunodeficient mice with CD34(+) cells ectopically expressing constitutively active PKB resulted in reduced migration to the bone marrow, whereas inhibition of PKB activity resulted in an induction in bone marrow homing and engraftment.", "These results indicate that transient inhibition of PKB activity may provide a means for ex vivo stem cell manipulation to improve bone marrow transplantation regimes."], "title": "Protein kinase B (PKB/c-akt) regulates homing of hematopoietic progenitors through modulation of their adhesive and migratory properties."}
{"paper_id": 19800408, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "Recent studies suggested that fMRI voxel patterns can convey information represented in columnar-scale neuronal population codes, even when spatial resolution is insufficient to directly image the patterns of columnar selectivity (Kamitani and Tong, 2005; Haynes and Rees, 2005). Sensitivity to subvoxel-scale pattern information, or \"fMRI hyperacuity,\" would greatly enhance the power of fMRI when combined with pattern information analysis techniques (Kriegeskorte and Bandettini, 2007). An individual voxel might weakly reflect columnar-level information if the columns within its boundaries constituted a slightly unbalanced sample of columnar selectivities (Kamitani and Tong, 2005), providing a possible mechanism for fMRI hyperacuity. However, Op de Beeck (2009) suggests that a coarse-scale neuronal organization rather than fMRI hyperacuity may explain the presence of the information in the fMRI patterns. Here we argue (a) that the present evidence does not rule out fMRI hyperacuity, (b) that the mechanism originally suggested for fMRI hyperacuity (biased sampling by averaging within each voxel's boundaries; Kamitani and Tong, 2005) will only produce very weak sensitivity to fine-grained pattern information, and (c) that an alternative mechanism (voxel as complex spatiotemporal filter) is physiologically more accurate and promises stronger sensitivity to fine-grained pattern information: We know that each voxel samples the neuronal activity pattern through a unique fine-grained structure of venous vessels that supply its blood oxygen level-dependent signal. At the simplest level, the drainage domain of a venous vessel may sample the neuronal pattern with a selectivity bias (Gardner, 2009; Shmuel et al., 2009). Beyond biased drainage domains, we illustrate with a simple simulation how temporal properties of the hemodynamics (e.g., the speed of the blood in the capillary bed) can shape spatial properties of a voxel's filter (e.g., how finely structured it is). This suggests that a voxel, together with its signal-supplying vasculature, may best be thought of as a complex spatiotemporal filter. Such a filter may well have greater sensitivity to high spatial frequencies than the Gaussian or averaging-box kernels typically invoked to characterize voxel sampling (compact kernels, both of which would act like anti-aliasing filters that minimize such sensitivity). Importantly, the complex-spatiotemporal-filter hypothesis of fMRI hyperacuity can account for the observed robustness to slight shifts of the voxel grid caused by head motion: Because the fine-grained components of the filter are vascular, they will remain in a constant relationship to the neuronal patterns sampled as the voxel grid is slightly shifted.", "journal": "NeuroImage", "sentences": ["Recent studies suggested that fMRI voxel patterns can convey information represented in columnar-scale neuronal population codes, even when spatial resolution is insufficient to directly image the patterns of columnar selectivity (Kamitani and Tong, 2005; Haynes and Rees, 2005).", "Sensitivity to subvoxel-scale pattern information, or \"fMRI hyperacuity,\" would greatly enhance the power of fMRI when combined with pattern information analysis techniques (Kriegeskorte and Bandettini, 2007).", "An individual voxel might weakly reflect columnar-level information if the columns within its boundaries constituted a slightly unbalanced sample of columnar selectivities (Kamitani and Tong, 2005), providing a possible mechanism for fMRI hyperacuity.", "However, Op de Beeck (2009) suggests that a coarse-scale neuronal organization rather than fMRI hyperacuity may explain the presence of the information in the fMRI patterns.", "Here we argue (a) that the present evidence does not rule out fMRI hyperacuity, (b) that the mechanism originally suggested for fMRI hyperacuity (biased sampling by averaging within each voxel's boundaries; Kamitani and Tong, 2005) will only produce very weak sensitivity to fine-grained pattern information, and (c) that an alternative mechanism (voxel as complex spatiotemporal filter) is physiologically more accurate and promises stronger sensitivity to fine-grained pattern information: We know that each voxel samples the neuronal activity pattern through a unique fine-grained structure of venous vessels that supply its blood oxygen level-dependent signal.", "At the simplest level, the drainage domain of a venous vessel may sample the neuronal pattern with a selectivity bias (Gardner, 2009; Shmuel et al., 2009).", "Beyond biased drainage domains, we illustrate with a simple simulation how temporal properties of the hemodynamics (e.g., the speed of the blood in the capillary bed) can shape spatial properties of a voxel's filter (e.g., how finely structured it is).", "This suggests that a voxel, together with its signal-supplying vasculature, may best be thought of as a complex spatiotemporal filter.", "Such a filter may well have greater sensitivity to high spatial frequencies than the Gaussian or averaging-box kernels typically invoked to characterize voxel sampling (compact kernels, both of which would act like anti-aliasing filters that minimize such sensitivity).", "Importantly, the complex-spatiotemporal-filter hypothesis of fMRI hyperacuity can account for the observed robustness to slight shifts of the voxel grid caused by head motion: Because the fine-grained components of the filter are vascular, they will remain in a constant relationship to the neuronal patterns sampled as the voxel grid is slightly shifted."], "title": "How does an fMRI voxel sample the neuronal activity pattern: compact-kernel or complex spatiotemporal filter?"}
{"paper_id": 24810364, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Long noncoding RNAs are involved in diseases including cancer. Here, we reported that ANRIL (CDKN2B-AS1), a 3.8-kb long noncoding RNA, recruiting and binding to PRC2, was generally upregulated in human gastric cancer (GC) tissues. In a cohort of 120 GC patients, the higher expression of ANRIL was significantly correlated with a higher TNM stage (P=0.041) and tumor size (P=0.001). Multivariate analyses revealed that ANRIL expression served as an independent predictor for overall survival (P=0.036). Further experiments revealed that ANRIL knockdown significantly repressed the proliferation both in vitro and in vivo. We also showed that E2F1 could induce ANRIL and ANRIL-mediated growth promotion is in part due to epigenetic repression of miR-99a/miR-449a in Trans (controlling the targets--mTOR and CDK6/E2F1 pathway) by binding to PRC2, thus forming a positive feedback loop, continuing to promote GC cell proliferation. To our knowledge, this is the first report showed that the role of ANRIL in the progression of GC and ANRIL could crosstalk with microRNAs in epigenetic level. Our results suggest that ANRIL, as a growth regulator, may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer.", "journal": "Oncotarget", "sentences": ["Long noncoding RNAs are involved in diseases including cancer.", "Here, we reported that ANRIL (CDKN2B-AS1), a 3.8-kb long noncoding RNA, recruiting and binding to PRC2, was generally upregulated in human gastric cancer (GC) tissues.", "In a cohort of 120 GC patients, the higher expression of ANRIL was significantly correlated with a higher TNM stage (P=0.041) and tumor size (P=0.001).", "Multivariate analyses revealed that ANRIL expression served as an independent predictor for overall survival (P=0.036).", "Further experiments revealed that ANRIL knockdown significantly repressed the proliferation both in vitro and in vivo.", "We also showed that E2F1 could induce ANRIL and ANRIL-mediated growth promotion is in part due to epigenetic repression of miR-99a/miR-449a in Trans (controlling the targets--mTOR and CDK6/E2F1 pathway) by binding to PRC2, thus forming a positive feedback loop, continuing to promote GC cell proliferation.", "To our knowledge, this is the first report showed that the role of ANRIL in the progression of GC and ANRIL could crosstalk with microRNAs in epigenetic level.", "Our results suggest that ANRIL, as a growth regulator, may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer."], "title": "Long noncoding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a."}
{"paper_id": 20416265, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The immunoprotective effect of the ligand-binding domain of fibronectin-binding protein (lFnBP) from Staphylococcus aureus (S. aureus) was investigated in a mouse mastitis model. The recombinant lFnBP (rlFnBP) and inactivated S. aureus were emulsified in Freund's adjuvant, mineral oil adjuvant or Seppic adjuvant, respectively. Seven groups of mice (n=12 each) were immunized with these six vaccines or phosphate-buffered saline. The immunoglobulin G (IgG) titers of mice immunized with rlFnBP vaccine were higher than those in the inactivated vaccine group (P<0.01). Antiserum capacities to opsonize adhesion and phagocytosis were significantly greater in the rlFnBP immunization group than in the killed bacteria group (P<0.05). The immunized lactating mice were challenged with S. aureus. At 24h postinfection, the numbers of bacteria recovered in the rlFnBP group were significantly lower than those in the killed bacteria group (P<0.001). Levels of both interleukin-6 (IL-6) and interferon-gamma (IFN-gamma from the mammary glands in the rlFnBP group were higher than those in the inactivated group (P<0.05). Better protection of mammary gland tissue was shown in the rlFnBP group. Thus, the rlFnBP, emulsified in an oil adjuvant, provided strong immune protection against S. aureus mastitis in mice, and could therefore be a promising vaccine candidate against bovine mastitis induced by S. aureus.", "journal": "Vaccine", "sentences": ["The immunoprotective effect of the ligand-binding domain of fibronectin-binding protein (lFnBP) from Staphylococcus aureus (S. aureus) was investigated in a mouse mastitis model.", "The recombinant lFnBP (rlFnBP) and inactivated S. aureus were emulsified in Freund's adjuvant, mineral oil adjuvant or Seppic adjuvant, respectively.", "Seven groups of mice (n=12 each) were immunized with these six vaccines or phosphate-buffered saline.", "The immunoglobulin G (IgG) titers of mice immunized with rlFnBP vaccine were higher than those in the inactivated vaccine group (P<0.01).", "Antiserum capacities to opsonize adhesion and phagocytosis were significantly greater in the rlFnBP immunization group than in the killed bacteria group (P<0.05).", "The immunized lactating mice were challenged with S. aureus.", "At 24h postinfection, the numbers of bacteria recovered in the rlFnBP group were significantly lower than those in the killed bacteria group (P<0.001).", "Levels of both interleukin-6 (IL-6) and interferon-gamma (IFN-gamma from the mammary glands in the rlFnBP group were higher than those in the inactivated group (P<0.05).", "Better protection of mammary gland tissue was shown in the rlFnBP group.", "Thus, the rlFnBP, emulsified in an oil adjuvant, provided strong immune protection against S. aureus mastitis in mice, and could therefore be a promising vaccine candidate against bovine mastitis induced by S. aureus."], "title": "Protective effect of ligand-binding domain of fibronectin-binding protein on mastitis induced by Staphylococcus aureus in mice."}
{"paper_id": 23764646, "labels": ["0", "0", "1", "0", "0", "0"], "abstract": "Previously, reduced single-walled carbon nanotube anions have been used for effective processing and functionalization. Here we report individually separate and distinct (that is, discrete) single-walled carbon nanotube cations, directly generated from a pure anode using a non-aqueous electrochemical technique. Cyclic voltammetry provides evidence for the reversibility of this nanoion electrochemisty, and can be related to the complex electronic density of states of the single-walled carbon nanotubes. Fixed potentiostatic oxidation allows spontaneous dissolution of nanotube cations ('nanotubium'); Raman spectroscopy and transmission electron microscopy show that sequential fractions are purified, separating amorphous carbon and short, defective single-walled carbon nanotubes, initially. The preparation of nanotubium, in principle, enables a new family of nucleophilic grafting reactions for single-walled carbon nanotubes, exploited here, to assemble nanotubes on amine-modified Si surfaces. Other nanoparticle polyelectrolyte cations may be anticipated.", "journal": "Nature communications", "sentences": ["Previously, reduced single-walled carbon nanotube anions have been used for effective processing and functionalization.", "Here we report individually separate and distinct (that is, discrete) single-walled carbon nanotube cations, directly generated from a pure anode using a non-aqueous electrochemical technique.", "Cyclic voltammetry provides evidence for the reversibility of this nanoion electrochemisty, and can be related to the complex electronic density of states of the single-walled carbon nanotubes.", "Fixed potentiostatic oxidation allows spontaneous dissolution of nanotube cations ('nanotubium'); Raman spectroscopy and transmission electron microscopy show that sequential fractions are purified, separating amorphous carbon and short, defective single-walled carbon nanotubes, initially.", "The preparation of nanotubium, in principle, enables a new family of nucleophilic grafting reactions for single-walled carbon nanotubes, exploited here, to assemble nanotubes on amine-modified Si surfaces.", "Other nanoparticle polyelectrolyte cations may be anticipated."], "title": "Giant cationic polyelectrolytes generated via electrochemical oxidation of single-walled carbon nanotubes."}
{"paper_id": 25478460, "labels": ["0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "Hemisection refers to sectioning of a mandibular molar into two halves followed by removal of the diseased root and its coronal portion. Hemisection of a mandibular molar may be a suitable treatment option when the decay is restricted to one root and the other root is healthy. The retained root is endodontically treated and the furcation area is made self-cleansable. Retained tooth structure is restored as premolar which helps to reduce the masticatory load. Hemisection of mandibular molar was often referred to as premolarization. Studies showed that the remaining coronal structure influenced the fracture resistance of endodontically treated maxillary first premolars. Clinical experience showed the viability of tunnel restoration as an alternative to class II conventional cavity preparation in initial proximal lesion. This article discusses a case that presents the novel technique involved in restoration of the remaining hemisected tooth using modified tunnel restoration.", "journal": "Journal of clinical and diagnostic research : JCDR", "sentences": ["Hemisection refers to sectioning of a mandibular molar into two halves followed by removal of the diseased root and its coronal portion.", "Hemisection of a mandibular molar may be a suitable treatment option when the decay is restricted to one root and the other root is healthy.", "The retained root is endodontically treated and the furcation area is made self-cleansable.", "Retained tooth structure is restored as premolar which helps to reduce the masticatory load.", "Hemisection of mandibular molar was often referred to as premolarization.", "Studies showed that the remaining coronal structure influenced the fracture resistance of endodontically treated maxillary first premolars.", "Clinical experience showed the viability of tunnel restoration as an alternative to class II conventional cavity preparation in initial proximal lesion.", "This article discusses a case that presents the novel technique involved in restoration of the remaining hemisected tooth using modified tunnel restoration."], "title": "A novel approach for restoration of hemisectioned mandibular second molar with modified tunnel restoration: a case report."}
{"paper_id": 25674463, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "0"], "abstract": "A 59-year old male had odynophagia and globus sensation for 10\u00a0days prior to his visit. Endoscopically, a fungating mass was observed in the right side of the tongue base (BOT). The peripheral T-cell lymphoma (PTCL) was confirmed by a punch biopsy. The patient was classified as stage IIA according to the Ann Arbor staging classification. Radiation therapy (RT) using volumetric modulated arc therapy (VAMT) began after 8\u00a0cycles of CHOP chemotherapy. Although the patient achieved a complete remission without RT relating morbidity during the follow-up period, recurrence occurred in the right orbit at 3\u00a0months after treatment. The patient received RT with high energy electron on the right orbit. The salvage chemotherapy was followed by RT. The patient died of aggravation of PTCL at 17\u00a0months after VMAT. We report a poor prognostic case of PTCL in BOT with chemotherapy followed by RT.", "journal": "SpringerPlus", "sentences": ["A 59-year old male had odynophagia and globus sensation for 10\u00a0days prior to his visit.", "Endoscopically, a fungating mass was observed in the right side of the tongue base (BOT).", "The peripheral T-cell lymphoma (PTCL) was confirmed by a punch biopsy.", "The patient was classified as stage IIA according to the Ann Arbor staging classification.", "Radiation therapy (RT) using volumetric modulated arc therapy (VAMT) began after 8\u00a0cycles of CHOP chemotherapy.", "Although the patient achieved a complete remission without RT relating morbidity during the follow-up period, recurrence occurred in the right orbit at 3\u00a0months after treatment.", "The patient received RT with high energy electron on the right orbit.", "The salvage chemotherapy was followed by RT.", "The patient died of aggravation of PTCL at 17\u00a0months after VMAT.", "We report a poor prognostic case of PTCL in BOT with chemotherapy followed by RT."], "title": "A poor prognostic case of peripheral T-cell lymphoma in the base of tongue with chemotherapy followed by radiation therapy."}
{"paper_id": 25658586, "labels": ["0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "Macroalgae and filamentous turf algae (FTA) are abundant on degraded coral reefs, and the reproductive responses of corals may indicate sub-lethal stress under these conditions. The percentage of gametogenic stages (PGS) and the maximum diameter of eggs (MDE; or egg size) of Orbicella annularis were used to evaluate the effect of long- (7-10 months) and short-term (2.5 months) FTA removal (treatments T1 and T2, respectively) at both the beginning (May) and the end (August) of gametogenesis. Ramets (individual lobes of a colony) surrounded by FTA (T3) or crustose coralline algae (CCA; T4) were used as controls. The removal of FTA enhanced the development of gametes (i.e., a larger and higher percentage of mature gametes (PMG)) of O. annularis for T1 vs. T3 ramets in May and T1 and T2 vs. T3 ramets in August. Similar values of PGS and MDE between gametes from T3 and T4 in both May and August were unexpected because a previous study had shown that the same ramets of T4 (with higher tissue thickness, chlorophyll a cm-2 and zooxanthellae density and lower mitotic index values) were less stressed than ramets of T3. Evaluating coral stress through reproduction can reveal more sensitive responses than other biological parameters; within reproductive metrics, PGS can be a better stress indicator than egg size. The presence of turf algae strongly impacted the development of gametes and egg size (e.g., PMG in ramets with FTA removal increased almost twofold in comparison with ramets surrounded by FTA in August), most likely exerting negative chronic effects in the long run due to the ubiquity and permanence of turf algae in the Caribbean. These algae can be considered a stressor that affects coral sexual reproduction. Although the effects of turf algae on O. annularis are apparently less severe than those of other stressors, the future of this species is uncertain because of the combined impacts of these effects, the decline of O. annularis populations and the almost complete lack of recruitment.", "journal": "PloS one", "sentences": ["Macroalgae and filamentous turf algae (FTA) are abundant on degraded coral reefs, and the reproductive responses of corals may indicate sub-lethal stress under these conditions.", "The percentage of gametogenic stages (PGS) and the maximum diameter of eggs (MDE; or egg size) of Orbicella annularis were used to evaluate the effect of long- (7-10 months) and short-term (2.5 months) FTA removal (treatments T1 and T2, respectively) at both the beginning (May) and the end (August) of gametogenesis.", "Ramets (individual lobes of a colony) surrounded by FTA (T3) or crustose coralline algae (CCA; T4) were used as controls.", "The removal of FTA enhanced the development of gametes (i.e., a larger and higher percentage of mature gametes (PMG)) of O. annularis for T1 vs. T3 ramets in May and T1 and T2 vs. T3 ramets in August.", "Similar values of PGS and MDE between gametes from T3 and T4 in both May and August were unexpected because a previous study had shown that the same ramets of T4 (with higher tissue thickness, chlorophyll a cm-2 and zooxanthellae density and lower mitotic index values) were less stressed than ramets of T3.", "Evaluating coral stress through reproduction can reveal more sensitive responses than other biological parameters; within reproductive metrics, PGS can be a better stress indicator than egg size.", "The presence of turf algae strongly impacted the development of gametes and egg size (e.g., PMG in ramets with FTA removal increased almost twofold in comparison with ramets surrounded by FTA in August), most likely exerting negative chronic effects in the long run due to the ubiquity and permanence of turf algae in the Caribbean.", "These algae can be considered a stressor that affects coral sexual reproduction.", "Although the effects of turf algae on O. annularis are apparently less severe than those of other stressors, the future of this species is uncertain because of the combined impacts of these effects, the decline of O. annularis populations and the almost complete lack of recruitment."], "title": "The effect of filamentous turf algal removal on the development of gametes of the coral Orbicella annularis."}
{"paper_id": 25201064, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "Accumulation of mutations and single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been identified for their association with cancer risk and disease outcome in a variety of cancers. We have identified cancer risk-associated D-loop SNPs in gastric cancer patients. In this study, we evaluated the predictive value of these SNPs for cancer outcome. Two SNP sites of nucleotides 489C/T and 523-524AC/del were identified for statistically significant prediction of postoperative survival in gastric cancer by univariate analysis with log-rank test. In addition, the mitochondrial DNA haplogroup N (489T) contributed to the good survival of gastric cancer patients compared with the mitochondrial DNA haplogroup M (489C) genotype (relative risk, 1.753; 95\u00a0%CI, 1.005-3.060; p\u2009=\u20090.048) by multivariate analysis with COX hazards model. In conclusion, analysis of genetic polymorphisms in the mitochondrial D-loop can help identify subgroups of patients who are at a high risk of a poor disease outcome.", "journal": "Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine", "sentences": ["Accumulation of mutations and single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been identified for their association with cancer risk and disease outcome in a variety of cancers.", "We have identified cancer risk-associated D-loop SNPs in gastric cancer patients.", "In this study, we evaluated the predictive value of these SNPs for cancer outcome.", "Two SNP sites of nucleotides 489C/T and 523-524AC/del were identified for statistically significant prediction of postoperative survival in gastric cancer by univariate analysis with log-rank test.", "In addition, the mitochondrial DNA haplogroup N (489T) contributed to the good survival of gastric cancer patients compared with the mitochondrial DNA haplogroup M (489C) genotype (relative risk, 1.753; 95\u00a0%CI, 1.005-3.060; p\u2009=\u20090.048) by multivariate analysis with COX hazards model.", "In conclusion, analysis of genetic polymorphisms in the mitochondrial D-loop can help identify subgroups of patients who are at a high risk of a poor disease outcome."], "title": "Mitochondrial DNA haplogroup N is associated good outcome of gastric cancer."}
{"paper_id": 26598153, "labels": ["0", "0", "0", "1", "1"], "abstract": "An adaptive numerical integration scheme for efficient evaluation of the exchange-correlation term using localized basis functions and atom-centered grids is presented. The method treats molecules and systems with periodic boundary conditions on an equal footing. Its computational efficiency and O(N) scaling with the system size is achieved by a hierarchical spatial grouping of basis functions and grid points using an octree. This allows for an efficient screening of negligible contributions and an optimal use of hardware-optimized matrix-matrix multiplication subroutines, such as BLAS. The implementation of the method within the TURBOMOLE program package demonstrates consistent accuracy and efficiency across molecular and periodic systems.", "journal": "Journal of chemical theory and computation", "sentences": ["An adaptive numerical integration scheme for efficient evaluation of the exchange-correlation term using localized basis functions and atom-centered grids is presented.", "The method treats molecules and systems with periodic boundary conditions on an equal footing.", "Its computational efficiency and O(N) scaling with the system size is achieved by a hierarchical spatial grouping of basis functions and grid points using an octree.", "This allows for an efficient screening of negligible contributions and an optimal use of hardware-optimized matrix-matrix multiplication subroutines, such as BLAS.", "The implementation of the method within the TURBOMOLE program package demonstrates consistent accuracy and efficiency across molecular and periodic systems."], "title": "Linear Scaling Hierarchical Integration Scheme for the Exchange-Correlation Term in Molecular and Periodic Systems."}
{"paper_id": 27218454, "labels": ["0", "0", "0", "0", "1"], "abstract": "Transcriptome and genome data from twenty stony coral species and a selection of reference bilaterians were studied to elucidate coral evolutionary history. We identified genes that encode the proteins responsible for the precipitation and aggregation of the aragonite skeleton on which the organisms live, and revealed a network of environmental sensors that coordinate responses of the host animals to temperature, light, and pH. Furthermore, we describe a variety of stress-related pathways, including apoptotic pathways that allow the host animals to detoxify reactive oxygen and nitrogen species that are generated by their intracellular photosynthetic symbionts, and determine the fate of corals under environmental stress. Some of these genes arose through horizontal gene transfer and comprise at least 0.2% of the animal gene inventory. Our analysis elucidates the evolutionary strategies that have allowed symbiotic corals to adapt and thrive for hundreds of millions of years.", "journal": "eLife", "sentences": ["Transcriptome and genome data from twenty stony coral species and a selection of reference bilaterians were studied to elucidate coral evolutionary history.", "We identified genes that encode the proteins responsible for the precipitation and aggregation of the aragonite skeleton on which the organisms live, and revealed a network of environmental sensors that coordinate responses of the host animals to temperature, light, and pH.", "Furthermore, we describe a variety of stress-related pathways, including apoptotic pathways that allow the host animals to detoxify reactive oxygen and nitrogen species that are generated by their intracellular photosynthetic symbionts, and determine the fate of corals under environmental stress.", "Some of these genes arose through horizontal gene transfer and comprise at least 0.2% of the animal gene inventory.", "Our analysis elucidates the evolutionary strategies that have allowed symbiotic corals to adapt and thrive for hundreds of millions of years."], "title": "Comparative genomics explains the evolutionary success of reef-forming corals."}
{"paper_id": 27525439, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Huntington's disease (HD) is a progressive, adult-onset neurodegenerative disease caused by a polyglutamine (polyQ) expansion in the N-terminal region of the protein huntingtin (HTT). There are no cures or disease-modifying therapies for HD. HTT has a highly conserved Akt phosphorylation site at serine 421, and prior work in HD models found that phosphorylation at S421 (S421-P) diminishes the toxicity of mutant HTT (mHTT) fragments in neuronal cultures. However, whether S421-P affects the toxicity of mHTT in vivo remains unknown. In this work, we used murine models to investigate the role of S421-P in HTT-induced neurodegeneration. Specifically, we mutated the human mHTT gene within a BAC to express either an aspartic acid or an alanine at position 421, mimicking tonic phosphorylation (mHTT-S421D mice) or preventing phosphorylation (mHTT-S421A mice), respectively. Mimicking HTT phosphorylation strongly ameliorated mHTT-induced behavioral dysfunction and striatal neurodegeneration, whereas neuronal dysfunction persisted when S421 phosphorylation was blocked. We found that S421 phosphorylation mitigates neurodegeneration by increasing proteasome-dependent turnover of mHTT and reducing the presence of a toxic mHTT conformer. These data indicate that S421 is a potent modifier of mHTT toxicity and offer in vivo validation for S421 as a therapeutic target in HD.", "journal": "The Journal of clinical investigation", "sentences": ["Huntington's disease (HD) is a progressive, adult-onset neurodegenerative disease caused by a polyglutamine (polyQ) expansion in the N-terminal region of the protein huntingtin (HTT).", "There are no cures or disease-modifying therapies for HD.", "HTT has a highly conserved Akt phosphorylation site at serine 421, and prior work in HD models found that phosphorylation at S421 (S421-P) diminishes the toxicity of mutant HTT (mHTT) fragments in neuronal cultures.", "However, whether S421-P affects the toxicity of mHTT in vivo remains unknown.", "In this work, we used murine models to investigate the role of S421-P in HTT-induced neurodegeneration.", "Specifically, we mutated the human mHTT gene within a BAC to express either an aspartic acid or an alanine at position 421, mimicking tonic phosphorylation (mHTT-S421D mice) or preventing phosphorylation (mHTT-S421A mice), respectively.", "Mimicking HTT phosphorylation strongly ameliorated mHTT-induced behavioral dysfunction and striatal neurodegeneration, whereas neuronal dysfunction persisted when S421 phosphorylation was blocked.", "We found that S421 phosphorylation mitigates neurodegeneration by increasing proteasome-dependent turnover of mHTT and reducing the presence of a toxic mHTT conformer.", "These data indicate that S421 is a potent modifier of mHTT toxicity and offer in vivo validation for S421 as a therapeutic target in HD."], "title": "Serine 421 regulates mutant huntingtin toxicity and clearance in mice."}
{"paper_id": 26492260, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Mosquitoes are a public health concern because they are vectors of pathogen, which cause human-related diseases. It is well known that the occurrence of mosquitoes is highly influenced by meteorological conditions (e.g., temperature and precipitation) and land use, but there are insufficient studies quantifying their impacts. Therefore, three analytical methods were applied to determine the relationships between urban mosquito occurrence, land use type, and meteorological factors: cluster analysis based on land use types; principal component analysis (PCA) based on mosquito occurrence; and three prediction models, support vector machine (SVM), classification and regression tree (CART), and random forest (RF). We used mosquito data collected at 12 sites from 2011 to 2012. Mosquito abundance was highest from August to September in both years. The monitoring sites were differentiated into three clusters based on differences in land use type such as culture and sport areas, inland water, artificial grasslands, and traffic areas. These clusters were well reflected in PCA ordinations, indicating that mosquito occurrence was highly influenced by land use types. Lastly, the RF represented the highest predictive power for mosquito occurrence and temperature-related factors were the most influential. Our study will contribute to effective control and management of mosquito occurrences.", "journal": "International journal of environmental research and public health", "sentences": ["Mosquitoes are a public health concern because they are vectors of pathogen, which cause human-related diseases.", "It is well known that the occurrence of mosquitoes is highly influenced by meteorological conditions (e.g., temperature and precipitation) and land use, but there are insufficient studies quantifying their impacts.", "Therefore, three analytical methods were applied to determine the relationships between urban mosquito occurrence, land use type, and meteorological factors: cluster analysis based on land use types; principal component analysis (PCA) based on mosquito occurrence; and three prediction models, support vector machine (SVM), classification and regression tree (CART), and random forest (RF).", "We used mosquito data collected at 12 sites from 2011 to 2012.", "Mosquito abundance was highest from August to September in both years.", "The monitoring sites were differentiated into three clusters based on differences in land use type such as culture and sport areas, inland water, artificial grasslands, and traffic areas.", "These clusters were well reflected in PCA ordinations, indicating that mosquito occurrence was highly influenced by land use types.", "Lastly, the RF represented the highest predictive power for mosquito occurrence and temperature-related factors were the most influential.", "Our study will contribute to effective control and management of mosquito occurrences."], "title": "Modeling Occurrence of Urban Mosquitos Based on Land Use Types and Meteorological Factors in Korea."}
{"paper_id": 24743184, "labels": ["0", "0", "0", "0", "0", "1", "0", "0"], "abstract": "Intra-tumour genetic heterogeneity is the result of ongoing evolutionary change within each cancer. The expansion of genetically distinct sub-clonal populations may explain the emergence of drug resistance, and if so, would have prognostic and predictive utility. However, methods for objectively quantifying tumour heterogeneity have been missing and are particularly difficult to establish in cancers where predominant copy number variation prevents accurate phylogenetic reconstruction owing to horizontal dependencies caused by long and cascading genomic rearrangements. To address these challenges, we present MEDICC, a method for phylogenetic reconstruction and heterogeneity quantification based on a Minimum Event Distance for Intra-tumour Copy-number Comparisons. Using a transducer-based pairwise comparison function, we determine optimal phasing of major and minor alleles, as well as evolutionary distances between samples, and are able to reconstruct ancestral genomes. Rigorous simulations and an extensive clinical study show the power of our method, which outperforms state-of-the-art competitors in reconstruction accuracy, and additionally allows unbiased numerical quantification of tumour heterogeneity. Accurate quantification and evolutionary inference are essential to understand the functional consequences of tumour heterogeneity. The MEDICC algorithms are independent of the experimental techniques used and are applicable to both next-generation sequencing and array CGH data.", "journal": "PLoS computational biology", "sentences": ["Intra-tumour genetic heterogeneity is the result of ongoing evolutionary change within each cancer.", "The expansion of genetically distinct sub-clonal populations may explain the emergence of drug resistance, and if so, would have prognostic and predictive utility.", "However, methods for objectively quantifying tumour heterogeneity have been missing and are particularly difficult to establish in cancers where predominant copy number variation prevents accurate phylogenetic reconstruction owing to horizontal dependencies caused by long and cascading genomic rearrangements.", "To address these challenges, we present MEDICC, a method for phylogenetic reconstruction and heterogeneity quantification based on a Minimum Event Distance for Intra-tumour Copy-number Comparisons.", "Using a transducer-based pairwise comparison function, we determine optimal phasing of major and minor alleles, as well as evolutionary distances between samples, and are able to reconstruct ancestral genomes.", "Rigorous simulations and an extensive clinical study show the power of our method, which outperforms state-of-the-art competitors in reconstruction accuracy, and additionally allows unbiased numerical quantification of tumour heterogeneity.", "Accurate quantification and evolutionary inference are essential to understand the functional consequences of tumour heterogeneity.", "The MEDICC algorithms are independent of the experimental techniques used and are applicable to both next-generation sequencing and array CGH data."], "title": "Phylogenetic quantification of intra-tumour heterogeneity."}
{"paper_id": 20079546, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "It has been previously shown that cardiac troponin (cTn) is released in response to prolonged endurance exercise. The influence of short-duration high-intensity exercise upon the release of cTn is not known. We examined cardiac troponin I (cTnI) release pre-, during and post-30 min of high-intensity running exercise in eight recreationally active males (age 29\u00b13 years; VO2peak 53\u00b111 ml kg min(-1)). Following exercise, cTnI increased in six of the eight participants. Four participants showed a minimal response (<0.05 \u00b5g/l) post-exercise. In contrast, two participants showed a progressive increase in cTnI (>0.1 \u00b5g/l) following exercise which peaked 3-4 h post-exercise. cTnI returned below the detection limit of the assay in all bar one of the participants 24 h post-exercise. These data are the first to show that cTnI can be released following short-duration high-intensity exercise. Clinicians should be aware that exercise-induced release of cTnI is not limited to prolonged endurance activity.", "journal": "International journal of cardiology", "sentences": ["It has been previously shown that cardiac troponin (cTn) is released in response to prolonged endurance exercise.", "The influence of short-duration high-intensity exercise upon the release of cTn is not known.", "We examined cardiac troponin I (cTnI) release pre-, during and post-30 min of high-intensity running exercise in eight recreationally active males (age 29\u00b13 years; VO2peak 53\u00b111 ml kg min(-1)).", "Following exercise, cTnI increased in six of the eight participants.", "Four participants showed a minimal response (<0.05 \u00b5g/l) post-exercise.", "In contrast, two participants showed a progressive increase in cTnI (>0.1 \u00b5g/l) following exercise which peaked 3-4 h post-exercise.", "cTnI returned below the detection limit of the assay in all bar one of the participants 24 h post-exercise.", "These data are the first to show that cTnI can be released following short-duration high-intensity exercise.", "Clinicians should be aware that exercise-induced release of cTnI is not limited to prolonged endurance activity."], "title": "Cardiac troponin I is released following high-intensity short-duration exercise in healthy humans."}
{"paper_id": 27210069, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "Circadian rhythms in behaviour and physiology are important for animal health and survival. Studies with individually isolated animals in the laboratory have consistently emphasized the dominant role of light for the entrainment of circadian rhythms to relevant environmental cycles. Although in nature interactions with conspecifics are functionally significant, social signals are typically not considered important time-givers for the animal circadian clock. Our results challenge this view. By studying honeybees in an ecologically relevant context and using a massive data set, we demonstrate that social entrainment can be potent, may act without direct contact with other individuals and does not rely on gating the exposure to light. We show for the first time that social time cues stably entrain the clock, even in animals experiencing conflicting photic and social environmental cycles. These findings add to the growing appreciation for the importance of studying circadian rhythms in ecologically relevant contexts.", "journal": "Nature communications", "sentences": ["Circadian rhythms in behaviour and physiology are important for animal health and survival.", "Studies with individually isolated animals in the laboratory have consistently emphasized the dominant role of light for the entrainment of circadian rhythms to relevant environmental cycles.", "Although in nature interactions with conspecifics are functionally significant, social signals are typically not considered important time-givers for the animal circadian clock.", "Our results challenge this view.", "By studying honeybees in an ecologically relevant context and using a massive data set, we demonstrate that social entrainment can be potent, may act without direct contact with other individuals and does not rely on gating the exposure to light.", "We show for the first time that social time cues stably entrain the clock, even in animals experiencing conflicting photic and social environmental cycles.", "These findings add to the growing appreciation for the importance of studying circadian rhythms in ecologically relevant contexts."], "title": "Potent social synchronization can override photic entrainment of circadian rhythms."}
{"paper_id": 26773037, "labels": ["0", "0", "0", "0", "0", "1", "0", "1"], "abstract": "The third-generation tyrosine kinase inhibitor (TKI) ponatinib shows activity against all common BCR-ABL1 single mutants, including the highly resistant BCR-ABL1-T315I mutant, improving outcome for patients with refractory chronic myeloid leukemia (CML). However, responses are variable, and causal baseline factors have not been well-studied. The type and number of low-level BCR-ABL1 mutations present after imatinib resistance has prognostic significance for subsequent treatment with nilotinib or dasatinib as second-line therapy. We therefore investigated the impact of low-level mutations detected by sensitive mass-spectrometry before ponatinib initiation (baseline) on treatment response in 363 TKI-resistant patients enrolled in the PONATINIB for Chronic Myeloid Leukemia Evaluation and Ph(+)Acute Lymphoblastic Leukemia trial, including 231 patients in chronic phase (CP-CML). Low-level mutations were detected in 53 patients (15%, including low-level T315I in 14 patients); most, however, did not undergo clonal expansion during ponatinib treatment and, moreover, no specific individual mutations were associated with inferior outcome. We demonstrate however, that the number of mutations detectable by mass spectrometry after TKI resistance is associated with response to ponatinib treatment and could be used to refine the therapeutic approach. Although CP-CML patients with T315I (63/231, 27%) had superior responses overall, those with multiple mutations detectable by mass spectrometry (20, 32%) had substantially inferior responses compared with those with T315I as the sole mutation detected (43, 68%). In contrast, for CP-CML patients without T315I, the inferior responses previously observed with nilotinib/dasatinib therapy for imatinib-resistant patients with multiple mutations were not seen with ponatinib treatment, suggesting that ponatinib may prove to be particularly advantageous for patients with multiple mutations detectable by mass spectrometry after TKI resistance.", "journal": "Blood", "sentences": ["The third-generation tyrosine kinase inhibitor (TKI) ponatinib shows activity against all common BCR-ABL1 single mutants, including the highly resistant BCR-ABL1-T315I mutant, improving outcome for patients with refractory chronic myeloid leukemia (CML).", "However, responses are variable, and causal baseline factors have not been well-studied.", "The type and number of low-level BCR-ABL1 mutations present after imatinib resistance has prognostic significance for subsequent treatment with nilotinib or dasatinib as second-line therapy.", "We therefore investigated the impact of low-level mutations detected by sensitive mass-spectrometry before ponatinib initiation (baseline) on treatment response in 363 TKI-resistant patients enrolled in the PONATINIB for Chronic Myeloid Leukemia Evaluation and Ph(+)Acute Lymphoblastic Leukemia trial, including 231 patients in chronic phase (CP-CML).", "Low-level mutations were detected in 53 patients (15%, including low-level T315I in 14 patients); most, however, did not undergo clonal expansion during ponatinib treatment and, moreover, no specific individual mutations were associated with inferior outcome.", "We demonstrate however, that the number of mutations detectable by mass spectrometry after TKI resistance is associated with response to ponatinib treatment and could be used to refine the therapeutic approach.", "Although CP-CML patients with T315I (63/231, 27%) had superior responses overall, those with multiple mutations detectable by mass spectrometry (20, 32%) had substantially inferior responses compared with those with T315I as the sole mutation detected (43, 68%).", "In contrast, for CP-CML patients without T315I, the inferior responses previously observed with nilotinib/dasatinib therapy for imatinib-resistant patients with multiple mutations were not seen with ponatinib treatment, suggesting that ponatinib may prove to be particularly advantageous for patients with multiple mutations detectable by mass spectrometry after TKI resistance."], "title": "The impact of multiple low-level BCR-ABL1 mutations on response to ponatinib."}
{"paper_id": 26496337, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Patients with carcinoma of the ampulla of Vater (CAV) have better outcomes among periampullary malignancies. However, little is known about the metastatic lymph node ratio (LNR) as a prognostic factor for resectable CAV. We retrospectively reviewed our CAV patients undergoing curative surgery and analyzed their prognostic factors.A total of 212 CAV patients who received radical surgery at Chang Gung Memorial Hospital, Linkou, between 2000 and 2010 were admitted in this study. The lymph node ratio was defined as the number of metastatic lymph nodes (LNs) divided by the total number of LNs removed. The patients' demographic data, comorbidities, operation type, and tumor features were analyzed retrospectively for survival prediction of patients.The median age of the patients was 62 years, and 57% of the patients were men. The surgical procedure was standard pancreaticoduodenectomy and pylorus-preserving pancreaticoduodenectomy in 53% and 47% of the patients, respectively. The median follow-up duration was 32.6 months, and 50% of the patients had died by the end of the study. The median overall survival time (OS) and disease-free survival time (DFS) were 65.8 and 33.7 months, respectively. In multivariate analysis, patients with a metastatic LNR >0.056 had a significantly poor prognosis in both OS and DFS.A metastatic LNR >0.056 predicted a poor DFS and OS in CAV patients after radical surgery. Greater awareness on the impact of metastatic LNR may help clinicians provide appropriate adjuvant treatment for high-risk CAV patients.", "journal": "Medicine", "sentences": ["Patients with carcinoma of the ampulla of Vater (CAV) have better outcomes among periampullary malignancies.", "However, little is known about the metastatic lymph node ratio (LNR) as a prognostic factor for resectable CAV.", "We retrospectively reviewed our CAV patients undergoing curative surgery and analyzed their prognostic factors.A total of 212 CAV patients who received radical surgery at Chang Gung Memorial Hospital, Linkou, between 2000 and 2010 were admitted in this study.", "The lymph node ratio was defined as the number of metastatic lymph nodes (LNs) divided by the total number of LNs removed.", "The patients' demographic data, comorbidities, operation type, and tumor features were analyzed retrospectively for survival prediction of patients.The median age of the patients was 62 years, and 57% of the patients were men.", "The surgical procedure was standard pancreaticoduodenectomy and pylorus-preserving pancreaticoduodenectomy in 53% and 47% of the patients, respectively.", "The median follow-up duration was 32.6 months, and 50% of the patients had died by the end of the study.", "The median overall survival time (OS) and disease-free survival time (DFS) were 65.8 and 33.7 months, respectively.", "In multivariate analysis, patients with a metastatic LNR >0.056 had a significantly poor prognosis in both OS and DFS.A metastatic LNR >0.056 predicted a poor DFS and OS in CAV patients after radical surgery.", "Greater awareness on the impact of metastatic LNR may help clinicians provide appropriate adjuvant treatment for high-risk CAV patients."], "title": "Prognostic Value of the Metastatic Lymph Node Ratio in Patients With Resectable Carcinoma of Ampulla of Vater."}
{"paper_id": 27525858, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Although the Val34Leu polymorphism in blood coagulation factor XIII-A (FXIII-A) has been implicated in the pathogenesis of intracerebral hemorrhage (ICH), the results of research conducted thus far have been inconclusive. In this meta-analysis, we have assessed the association between the FXIII-A Val34Leu polymorphism and ICH risk. Published reports pertaining to this association were retrieved from the PubMed database, and the data from these studies were pooled and statistically analyzed with Stata 12.0. Summary odds ratios (OR) and 95% confidence intervals (95%CI) were calculated according to a fixed-effect or a random-effect model (as appropriate). The initial search identified 520 articles, only seven of which (retrospective studies) met the inclusion criteria and were included in this meta-analysis. These studies comprised 727 ICH patients and 1968 controls. The results of a combined analysis showed no significant association between the FXIII-A Val34Leu polymorphism and ICH risk in the overall population (Leu/Leu vs Val/Val: OR = 1.41, 95%CI = 0.82-2.43; Val/Leu vs Val/Val: OR = 1.08, 95%CI = 0.89-1.30; dominant model: OR = 1.14, 95%CI = 0.95-1.36; recessive model: OR = 0.72, 95%CI = 0.43-1.22). The results of this meta-analysis suggest that the FXIII-A Val34Leu polymorphism is not associated with ICH risk in a Caucasian population. Further large and well-designed studies must be conducted to confirm this preliminary conclusion.", "journal": "Genetics and molecular research : GMR", "sentences": ["Although the Val34Leu polymorphism in blood coagulation factor XIII-A (FXIII-A) has been implicated in the pathogenesis of intracerebral hemorrhage (ICH), the results of research conducted thus far have been inconclusive.", "In this meta-analysis, we have assessed the association between the FXIII-A Val34Leu polymorphism and ICH risk.", "Published reports pertaining to this association were retrieved from the PubMed database, and the data from these studies were pooled and statistically analyzed with Stata 12.0.", "Summary odds ratios (OR) and 95% confidence intervals (95%CI) were calculated according to a fixed-effect or a random-effect model (as appropriate).", "The initial search identified 520 articles, only seven of which (retrospective studies) met the inclusion criteria and were included in this meta-analysis.", "These studies comprised 727 ICH patients and 1968 controls.", "The results of a combined analysis showed no significant association between the FXIII-A Val34Leu polymorphism and ICH risk in the overall population (Leu/Leu vs Val/Val: OR = 1.41, 95%CI = 0.82-2.43; Val/Leu vs Val/Val: OR = 1.08, 95%CI = 0.89-1.30; dominant model: OR = 1.14, 95%CI = 0.95-1.36; recessive model: OR = 0.72, 95%CI = 0.43-1.22).", "The results of this meta-analysis suggest that the FXIII-A Val34Leu polymorphism is not associated with ICH risk in a Caucasian population.", "Further large and well-designed studies must be conducted to confirm this preliminary conclusion."], "title": "Association between the Val34Leu polymorphism in blood coagulation factor XIII-A and intracerebral hemorrhage: a meta-analysis."}
{"paper_id": 25473052, "labels": ["0", "0", "0", "0", "1"], "abstract": "The particle structure of human T-cell leukemia virus type 1 (HTLV-1) is poorly characterized. Here, we have used cryo-electron tomography to analyze HTLV-1 particle morphology. Particles produced from MT-2 cells were polymorphic, roughly spherical, and varied in size. Capsid cores, when present, were typically poorly defined polyhedral structures with at least one curved region contacting the inner face of the viral membrane. Most of the particles observed lacked a defined capsid core, which likely impacts HTLV-1 particle infectivity.", "journal": "Journal of virology", "sentences": ["The particle structure of human T-cell leukemia virus type 1 (HTLV-1) is poorly characterized.", "Here, we have used cryo-electron tomography to analyze HTLV-1 particle morphology.", "Particles produced from MT-2 cells were polymorphic, roughly spherical, and varied in size.", "Capsid cores, when present, were typically poorly defined polyhedral structures with at least one curved region contacting the inner face of the viral membrane.", "Most of the particles observed lacked a defined capsid core, which likely impacts HTLV-1 particle infectivity."], "title": "Analysis of human T-cell leukemia virus type 1 particles by using cryo-electron tomography."}
{"paper_id": 24616628, "labels": ["0", "0", "0", "0", "0"], "abstract": "Rhythmic sandstone-mudstone-coal succession of the Barakar Formation (early Permian) manifests a transition from lower braided-fluvial to upper tide-wave influenced, estuarine setting. Monospecific assemblage of marine trace fossil Chondrites isp. in contemporaneous claystone beds in the upper Barakar succession from two Gondwana basins (namely, the Raniganj Basin and the Talchir Basin) in eastern peninsular India signifies predominant marine incursion during end early Permian. Monospecific Chondrites ichnoassemblage in different sedimentary horizons in geographically wide apart (~400 km) areas demarcates multiple short-spanned phases of anoxia in eastern India. Such anoxia is interpreted as intermittent falls in oxygen level in an overall decreasing atmospheric oxygenation within the late Paleozoic global oxygen-carbon dioxide fluctuations.", "journal": "TheScientificWorldJournal", "sentences": ["Rhythmic sandstone-mudstone-coal succession of the Barakar Formation (early Permian) manifests a transition from lower braided-fluvial to upper tide-wave influenced, estuarine setting.", "Monospecific assemblage of marine trace fossil Chondrites isp.", "in contemporaneous claystone beds in the upper Barakar succession from two Gondwana basins (namely, the Raniganj Basin and the Talchir Basin) in eastern peninsular India signifies predominant marine incursion during end early Permian.", "Monospecific Chondrites ichnoassemblage in different sedimentary horizons in geographically wide apart (~400 km) areas demarcates multiple short-spanned phases of anoxia in eastern India.", "Such anoxia is interpreted as intermittent falls in oxygen level in an overall decreasing atmospheric oxygenation within the late Paleozoic global oxygen-carbon dioxide fluctuations."], "title": "Chondrites isp. indicating late paleozoic atmospheric anoxia in Eastern Peninsular India."}
{"paper_id": 26076455, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available to treat Chagas disease; however, they have limitations, including long treatment courses and toxicity. Strategies to overcome these limitations include the identification of new drugs with specific target profiles, re-dosing regimens for the current drugs, drug repositioning and combination therapy. In this work, we evaluated combination therapy as an approach for optimization of the current therapeutic regimen for Chagas disease. The curative action of benznidazole/itraconazole combinations was explored in an established infection of the mice model with the T. cruzi Y strain. The activities of the benznidazole/itraconazole combinations were compared with the results from those receiving the same dosage of each individual drug. The administration of benznidazole/itraconazole in combination eliminated parasites from the blood more efficiently than each drug alone. Here, there was a significant reduction of the number of treatment days (number of doses) necessary to induce parasitemia suppression with the benznidazole/itraconazole combination, as compared to each compound administered alone. These results clearly indicate the enhanced effects of these drugs in combination, particularly at the dose of 75 mg/kg, as the effects observed with the drug combinations were four times more effective than those of each drug used alone. Moreover, benznidazole/itraconazole treatment was shown to prevent or decrease the typical lesions associated with chronic experimental Chagas disease, as illustrated by similar levels of inflammatory cells and fibrosis in the cardiac muscle tissue of healthy and treated mice. These results emphasize the importance of exploring the potential of combination treatments with currently available compounds to specifically treat Chagas disease.", "journal": "PloS one", "sentences": ["The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available to treat Chagas disease; however, they have limitations, including long treatment courses and toxicity.", "Strategies to overcome these limitations include the identification of new drugs with specific target profiles, re-dosing regimens for the current drugs, drug repositioning and combination therapy.", "In this work, we evaluated combination therapy as an approach for optimization of the current therapeutic regimen for Chagas disease.", "The curative action of benznidazole/itraconazole combinations was explored in an established infection of the mice model with the T. cruzi Y strain.", "The activities of the benznidazole/itraconazole combinations were compared with the results from those receiving the same dosage of each individual drug.", "The administration of benznidazole/itraconazole in combination eliminated parasites from the blood more efficiently than each drug alone.", "Here, there was a significant reduction of the number of treatment days (number of doses) necessary to induce parasitemia suppression with the benznidazole/itraconazole combination, as compared to each compound administered alone.", "These results clearly indicate the enhanced effects of these drugs in combination, particularly at the dose of 75 mg/kg, as the effects observed with the drug combinations were four times more effective than those of each drug used alone.", "Moreover, benznidazole/itraconazole treatment was shown to prevent or decrease the typical lesions associated with chronic experimental Chagas disease, as illustrated by similar levels of inflammatory cells and fibrosis in the cardiac muscle tissue of healthy and treated mice.", "These results emphasize the importance of exploring the potential of combination treatments with currently available compounds to specifically treat Chagas disease."], "title": "Benznidazole/Itraconazole Combination Treatment Enhances Anti-Trypanosoma cruzi Activity in Experimental Chagas Disease."}
{"paper_id": 23395961, "labels": ["0", "0", "0", "0", "0", "1", "0", "1", "0", "1"], "abstract": "Ribosomes, the protein factories of living cells, translate genetic information carried by messenger RNAs into proteins, and are thus involved in virtually all aspects of cellular development and maintenance. The few available structures of the eukaryotic ribosome reveal that it is more complex than its prokaryotic counterpart, owing mainly to the presence of eukaryote-specific ribosomal proteins and additional ribosomal RNA insertions, called expansion segments. The structures also differ among species, partly in the size and arrangement of these expansion segments. Such differences are extreme in kinetoplastids, unicellular eukaryotic parasites often infectious to humans. Here we present a high-resolution cryo-electron microscopy structure of the ribosome of Trypanosoma brucei, the parasite that is transmitted by the tsetse fly and that causes African sleeping sickness. The atomic model reveals the unique features of this ribosome, characterized mainly by the presence of unusually large expansion segments and ribosomal-protein extensions leading to the formation of four additional inter-subunit bridges. We also find additional rRNA insertions, including one large rRNA domain that is not found in other eukaryotes. Furthermore, the structure reveals the five cleavage sites of the kinetoplastid large ribosomal subunit (LSU) rRNA chain, which is known to be cleaved uniquely into six pieces, and suggests that the cleavage is important for the maintenance of the T. brucei ribosome in the observed structure. We discuss several possible implications of the large rRNA expansion segments for the translation-regulation process. The structure could serve as a basis for future experiments aimed at understanding the functional importance of these kinetoplastid-specific ribosomal features in protein-translation regulation, an essential step towards finding effective and safe kinetoplastid-specific drugs.", "journal": "Nature", "sentences": ["Ribosomes, the protein factories of living cells, translate genetic information carried by messenger RNAs into proteins, and are thus involved in virtually all aspects of cellular development and maintenance.", "The few available structures of the eukaryotic ribosome reveal that it is more complex than its prokaryotic counterpart, owing mainly to the presence of eukaryote-specific ribosomal proteins and additional ribosomal RNA insertions, called expansion segments.", "The structures also differ among species, partly in the size and arrangement of these expansion segments.", "Such differences are extreme in kinetoplastids, unicellular eukaryotic parasites often infectious to humans.", "Here we present a high-resolution cryo-electron microscopy structure of the ribosome of Trypanosoma brucei, the parasite that is transmitted by the tsetse fly and that causes African sleeping sickness.", "The atomic model reveals the unique features of this ribosome, characterized mainly by the presence of unusually large expansion segments and ribosomal-protein extensions leading to the formation of four additional inter-subunit bridges.", "We also find additional rRNA insertions, including one large rRNA domain that is not found in other eukaryotes.", "Furthermore, the structure reveals the five cleavage sites of the kinetoplastid large ribosomal subunit (LSU) rRNA chain, which is known to be cleaved uniquely into six pieces, and suggests that the cleavage is important for the maintenance of the T. brucei ribosome in the observed structure.", "We discuss several possible implications of the large rRNA expansion segments for the translation-regulation process.", "The structure could serve as a basis for future experiments aimed at understanding the functional importance of these kinetoplastid-specific ribosomal features in protein-translation regulation, an essential step towards finding effective and safe kinetoplastid-specific drugs."], "title": "High-resolution cryo-electron microscopy structure of the Trypanosoma brucei ribosome."}
{"paper_id": 27493216, "labels": ["0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "The dystrophin glycoprotein complex, which connects the cell membrane to the basement membrane, is essential for a variety of biological events, including maintenance of muscle integrity. An O-mannose-type GalNAc-\u03b21,3-GlcNAc-\u03b21,4-(phosphate-6)-Man structure of \u03b1-dystroglycan (\u03b1-DG), a subunit of the complex that is anchored to the cell membrane, interacts directly with laminin in the basement membrane. Reduced glycosylation of \u03b1-DG is linked to some types of inherited muscular dystrophy; consistent with this relationship, many disease-related mutations have been detected in genes involved in O-mannosyl glycan synthesis. Defects in protein O-linked mannose \u03b21,2-N-acetylglucosaminyltransferase 1 (POMGnT1), a glycosyltransferase that participates in the formation of GlcNAc-\u03b21,2-Man glycan, are causally related to muscle-eye-brain disease (MEB), a congenital muscular dystrophy, although the role of POMGnT1 in postphosphoryl modification of GalNAc-\u03b21,3-GlcNAc-\u03b21,4-(phosphate-6)-Man glycan remains elusive. Our crystal structures of POMGnT1 agreed with our previous results showing that the catalytic domain recognizes substrate O-mannosylated proteins via hydrophobic interactions with little sequence specificity. Unexpectedly, we found that the stem domain recognizes the \u03b2-linked GlcNAc of O-mannosyl glycan, an enzymatic product of POMGnT1. This interaction may recruit POMGnT1 to a specific site of \u03b1-DG to promote GlcNAc-\u03b21,2-Man clustering and also may recruit other enzymes that interact with POMGnT1, e.g., fukutin, which is required for further modification of the GalNAc-\u03b21,3-GlcNAc-\u03b21,4-(phosphate-6)-Man glycan. On the basis of our findings, we propose a mechanism for the deficiency in postphosphoryl modification of the glycan observed in POMGnT1-KO mice and MEB patients.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["The dystrophin glycoprotein complex, which connects the cell membrane to the basement membrane, is essential for a variety of biological events, including maintenance of muscle integrity.", "An O-mannose-type GalNAc-\u03b21,3-GlcNAc-\u03b21,4-(phosphate-6)-Man structure of \u03b1-dystroglycan (\u03b1-DG), a subunit of the complex that is anchored to the cell membrane, interacts directly with laminin in the basement membrane.", "Reduced glycosylation of \u03b1-DG is linked to some types of inherited muscular dystrophy; consistent with this relationship, many disease-related mutations have been detected in genes involved in O-mannosyl glycan synthesis.", "Defects in protein O-linked mannose \u03b21,2-N-acetylglucosaminyltransferase 1 (POMGnT1), a glycosyltransferase that participates in the formation of GlcNAc-\u03b21,2-Man glycan, are causally related to muscle-eye-brain disease (MEB), a congenital muscular dystrophy, although the role of POMGnT1 in postphosphoryl modification of GalNAc-\u03b21,3-GlcNAc-\u03b21,4-(phosphate-6)-Man glycan remains elusive.", "Our crystal structures of POMGnT1 agreed with our previous results showing that the catalytic domain recognizes substrate O-mannosylated proteins via hydrophobic interactions with little sequence specificity.", "Unexpectedly, we found that the stem domain recognizes the \u03b2-linked GlcNAc of O-mannosyl glycan, an enzymatic product of POMGnT1.", "This interaction may recruit POMGnT1 to a specific site of \u03b1-DG to promote GlcNAc-\u03b21,2-Man clustering and also may recruit other enzymes that interact with POMGnT1, e.g., fukutin, which is required for further modification of the GalNAc-\u03b21,3-GlcNAc-\u03b21,4-(phosphate-6)-Man glycan.", "On the basis of our findings, we propose a mechanism for the deficiency in postphosphoryl modification of the glycan observed in POMGnT1-KO mice and MEB patients."], "title": "Carbohydrate-binding domain of the POMGnT1 stem region modulates O-mannosylation sites of \u03b1-dystroglycan."}
{"paper_id": 20823254, "labels": ["0", "0", "0", "0", "1", "1"], "abstract": "Aerosols could be injected into the upper atmosphere to engineer the climate by scattering incident sunlight so as to produce a cooling tendency that may mitigate the risks posed by the accumulation of greenhouse gases. Analysis of climate engineering has focused on sulfate aerosols. Here I examine the possibility that engineered nanoparticles could exploit photophoretic forces, enabling more control over particle distribution and lifetime than is possible with sulfates, perhaps allowing climate engineering to be accomplished with fewer side effects. The use of electrostatic or magnetic materials enables a class of photophoretic forces not found in nature. Photophoretic levitation could loft particles above the stratosphere, reducing their capacity to interfere with ozone chemistry; and, by increasing particle lifetimes, it would reduce the need for continual replenishment of the aerosol. Moreover, particles might be engineered to drift poleward enabling albedo modification to be tailored to counter polar warming while minimizing the impact on equatorial climates.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Aerosols could be injected into the upper atmosphere to engineer the climate by scattering incident sunlight so as to produce a cooling tendency that may mitigate the risks posed by the accumulation of greenhouse gases.", "Analysis of climate engineering has focused on sulfate aerosols.", "Here I examine the possibility that engineered nanoparticles could exploit photophoretic forces, enabling more control over particle distribution and lifetime than is possible with sulfates, perhaps allowing climate engineering to be accomplished with fewer side effects.", "The use of electrostatic or magnetic materials enables a class of photophoretic forces not found in nature.", "Photophoretic levitation could loft particles above the stratosphere, reducing their capacity to interfere with ozone chemistry; and, by increasing particle lifetimes, it would reduce the need for continual replenishment of the aerosol.", "Moreover, particles might be engineered to drift poleward enabling albedo modification to be tailored to counter polar warming while minimizing the impact on equatorial climates."], "title": "Photophoretic levitation of engineered aerosols for geoengineering."}
{"paper_id": 22511926, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Diffuse large B cell lymphoma (DLBCL) is a clinically and genetically heterogeneous disease. A small subset of DLBCLs has translocations involving the MYC locus and an additional group has a molecular signature resembling Burkitt lymphoma (mBL). Presently, identification of such cases by morphology is unreliable and relies on cytogenetic or complex molecular methods such as gene transcriptional profiling. Herein, we describe an immunohistochemical (IHC) method for identifying DLBCLs with increased MYC protein expression. We tested 77 cases of DLBCL and identified 15 cases with high MYC protein expression (nuclear staining in >50% of tumor cells). All MYC translocation positive cases had increased MYC protein expression by this IHC assay. In addition, gene set enrichment analysis (GSEA) of the DLBCL transcriptional profiles revealed that tumors with increased MYC protein expression (regardless of underlying MYC translocation status) had coordinate upregulation of MYC target genes, providing molecular confirmation of the IHC results. We then generated a molecular classifier derived from the MYC IHC results in our cases and employed it to successfully classify mBLs from two previously reported independent case series, providing additional confirmation that the MYC IHC results identify clinically important subsets of DLBCLs. Lastly, we found that DLBCLs with high MYC protein expression had inferior overall survival when treated with R-CHOP. In conclusion, the IHC method described herein can be used to readily identify the biologically and clinically distinct cases of MYC-driven DLBCL, which represent a clinically significant subset of DLBCL cases due to their inferior overall survival.", "journal": "PloS one", "sentences": ["Diffuse large B cell lymphoma (DLBCL) is a clinically and genetically heterogeneous disease.", "A small subset of DLBCLs has translocations involving the MYC locus and an additional group has a molecular signature resembling Burkitt lymphoma (mBL).", "Presently, identification of such cases by morphology is unreliable and relies on cytogenetic or complex molecular methods such as gene transcriptional profiling.", "Herein, we describe an immunohistochemical (IHC) method for identifying DLBCLs with increased MYC protein expression.", "We tested 77 cases of DLBCL and identified 15 cases with high MYC protein expression (nuclear staining in >50% of tumor cells).", "All MYC translocation positive cases had increased MYC protein expression by this IHC assay.", "In addition, gene set enrichment analysis (GSEA) of the DLBCL transcriptional profiles revealed that tumors with increased MYC protein expression (regardless of underlying MYC translocation status) had coordinate upregulation of MYC target genes, providing molecular confirmation of the IHC results.", "We then generated a molecular classifier derived from the MYC IHC results in our cases and employed it to successfully classify mBLs from two previously reported independent case series, providing additional confirmation that the MYC IHC results identify clinically important subsets of DLBCLs.", "Lastly, we found that DLBCLs with high MYC protein expression had inferior overall survival when treated with R-CHOP.", "In conclusion, the IHC method described herein can be used to readily identify the biologically and clinically distinct cases of MYC-driven DLBCL, which represent a clinically significant subset of DLBCL cases due to their inferior overall survival."], "title": "Immunohistochemical detection of MYC-driven diffuse large B-cell lymphomas."}
{"paper_id": 25770424, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "The TGF-\u03b2/BMP family plays an important role in multiple stages of tooth development. TGF-\u03b2/BMP signaling is required for odontoblast differentiation and dentin formation; however, the precise molecular mechanisms underlying dentin formation remain unclear. To address the role of TGF-\u03b2/BMP signaling in dentin formation, we analyzed mice in which Smad4, a key intracellular mediator of TGF-\u03b2/BMP signaling, was subjected to tissue-specific ablation under the control of Dspp, OC, or Col1a1 promoters. Three independent Smad4 conditional knockout mice exhibited various dentin defects in the crowns and roots of their molars depending on the transactivator. In all mutant molars, crown dentin thickness was thinner than that of the control. In addition, impaired dentin was found in the cervical region and root furcation area. Although the initial differentiation of odontoblasts was normal, odontoblast polarity abruptly decreased and the expression of Col1a1, OC, and Dspp was reduced in the odontoblasts of mutant molars. In Dspp-Cre-mediated Smad4 disruption mice, primary dentin formation was slightly delayed, while secondary dentin formation was severely affected in the cervical region of the molars. These results indicate that TGF-\u03b2/BMP signaling is required for odontoblast maturation and dentin formation in a stage- and site-dependent manner.", "journal": "Biochemical and biophysical research communications", "sentences": ["The TGF-\u03b2/BMP family plays an important role in multiple stages of tooth development.", "TGF-\u03b2/BMP signaling is required for odontoblast differentiation and dentin formation; however, the precise molecular mechanisms underlying dentin formation remain unclear.", "To address the role of TGF-\u03b2/BMP signaling in dentin formation, we analyzed mice in which Smad4, a key intracellular mediator of TGF-\u03b2/BMP signaling, was subjected to tissue-specific ablation under the control of Dspp, OC, or Col1a1 promoters.", "Three independent Smad4 conditional knockout mice exhibited various dentin defects in the crowns and roots of their molars depending on the transactivator.", "In all mutant molars, crown dentin thickness was thinner than that of the control.", "In addition, impaired dentin was found in the cervical region and root furcation area.", "Although the initial differentiation of odontoblasts was normal, odontoblast polarity abruptly decreased and the expression of Col1a1, OC, and Dspp was reduced in the odontoblasts of mutant molars.", "In Dspp-Cre-mediated Smad4 disruption mice, primary dentin formation was slightly delayed, while secondary dentin formation was severely affected in the cervical region of the molars.", "These results indicate that TGF-\u03b2/BMP signaling is required for odontoblast maturation and dentin formation in a stage- and site-dependent manner."], "title": "Temporo-spatial requirement of Smad4 in dentin formation."}
{"paper_id": 24210919, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "The regulation of protein-coding and noncoding RNAs is linked to nuclear processes, including chromatin modifications and gene silencing. However, the mechanisms that distinguish RNAs and mediate their functions are poorly understood. We describe a nuclear RNA-processing network in fission yeast with a core module comprising the Mtr4-like protein, Mtl1, and the zinc-finger protein, Red1. The Mtl1-Red1 core promotes degradation of mRNAs and noncoding RNAs and associates with different proteins to assemble heterochromatin via distinct mechanisms. Mtl1 also forms Red1-independent interactions with evolutionarily conserved proteins named Nrl1 and Ctr1, which associate with splicing factors. Whereas Nrl1 targets transcripts with cryptic introns to form heterochromatin at developmental genes and retrotransposons, Ctr1 functions in processing intron-containing telomerase RNA. Together with our discovery of widespread cryptic introns, including in noncoding RNAs, these findings reveal unique cellular strategies for recognizing regulatory RNAs and coordinating their functions in response to developmental and environmental cues.", "journal": "Cell", "sentences": ["The regulation of protein-coding and noncoding RNAs is linked to nuclear processes, including chromatin modifications and gene silencing.", "However, the mechanisms that distinguish RNAs and mediate their functions are poorly understood.", "We describe a nuclear RNA-processing network in fission yeast with a core module comprising the Mtr4-like protein, Mtl1, and the zinc-finger protein, Red1.", "The Mtl1-Red1 core promotes degradation of mRNAs and noncoding RNAs and associates with different proteins to assemble heterochromatin via distinct mechanisms.", "Mtl1 also forms Red1-independent interactions with evolutionarily conserved proteins named Nrl1 and Ctr1, which associate with splicing factors.", "Whereas Nrl1 targets transcripts with cryptic introns to form heterochromatin at developmental genes and retrotransposons, Ctr1 functions in processing intron-containing telomerase RNA.", "Together with our discovery of widespread cryptic introns, including in noncoding RNAs, these findings reveal unique cellular strategies for recognizing regulatory RNAs and coordinating their functions in response to developmental and environmental cues."], "title": "Mtr4-like protein coordinates nuclear RNA processing for heterochromatin assembly and for telomere maintenance."}
{"paper_id": 26976599, "labels": ["0", "0", "0", "0", "0", "1", "1"], "abstract": "In eukaryotes, DNA polymerase \u03b4 (pol \u03b4) is responsible for replicating the lagging strand template and anchors to the proliferating cell nuclear antigen (PCNA) sliding clamp to form a holoenzyme. The stability of this complex is integral to every aspect of lagging strand replication. Most of our understanding comes from Saccharomyces cerevisae where the extreme stability of the pol \u03b4 holoenzyme ensures that every nucleobase within an Okazaki fragment is faithfully duplicated before dissociation but also necessitates an active displacement mechanism for polymerase recycling and exchange. However, the stability of the human pol \u03b4 holoenzyme is unknown. We designed unique kinetic assays to analyze the processivity and stability of the pol \u03b4 holoenzyme. Surprisingly, the results indicate that human pol \u03b4 maintains a loose association with PCNA while replicating DNA. Such behavior has profound implications on Okazaki fragment synthesis in humans as it limits the processivity of pol \u03b4 on undamaged DNA and promotes the rapid dissociation of pol \u03b4 from PCNA on stalling at a DNA lesion.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["In eukaryotes, DNA polymerase \u03b4 (pol \u03b4) is responsible for replicating the lagging strand template and anchors to the proliferating cell nuclear antigen (PCNA) sliding clamp to form a holoenzyme.", "The stability of this complex is integral to every aspect of lagging strand replication.", "Most of our understanding comes from Saccharomyces cerevisae where the extreme stability of the pol \u03b4 holoenzyme ensures that every nucleobase within an Okazaki fragment is faithfully duplicated before dissociation but also necessitates an active displacement mechanism for polymerase recycling and exchange.", "However, the stability of the human pol \u03b4 holoenzyme is unknown.", "We designed unique kinetic assays to analyze the processivity and stability of the pol \u03b4 holoenzyme.", "Surprisingly, the results indicate that human pol \u03b4 maintains a loose association with PCNA while replicating DNA.", "Such behavior has profound implications on Okazaki fragment synthesis in humans as it limits the processivity of pol \u03b4 on undamaged DNA and promotes the rapid dissociation of pol \u03b4 from PCNA on stalling at a DNA lesion."], "title": "Stability of the human polymerase \u03b4 holoenzyme and its implications in lagging strand DNA synthesis."}
{"paper_id": 24859227, "labels": ["0", "0", "0", "0", "0", "0", "1", "0", "0", "1"], "abstract": "Mutations in the only known mammalian iron exporter ferroportin cause a rare iron overload disorder termed ferroportin disease. Two distinct clinical phenotypes are caused by different disease mechanisms: mutations in ferroportin either cause loss of iron export function or gain of function due to resistance to hepcidin, the peptide hormone that normally downregulates ferroportin. The aim of the present study was to examine the disease mechanisms of the thus far unclassified A69T and D181V ferroportin mutations. We overexpressed wild-type and mutant ferroportin fused to green fluorescent protein in human embryonic kidney cells and used a (59)Fe-assay, intracellular ferritin concentrations, confocal microscopy and flow cytometry to study iron export function, subcellular localization and the responsiveness to hepcidin. While the A69T ferroportin mutation seems not to affect the iron export function it causes dose-dependent hepcidin resistance. We further found that D181V mutated ferroportin is iron export defective and hepcidin resistant, similar to the loss of function mutations A77D and C367X. This indicates that intact iron export might be necessary for hepcidin-induced downregulation of ferroportin. This hypothesis was investigated by studying the hepcidin response under modulation of iron availability. Incubation of wild-type ferroportin overexpressing cells with holo-transferrin increases the hepcidin effect whereas chelating extracellular ferrous iron causes hepcidin resistance. In this study we present data that postulates to classify the D181V ferroportin mutation as loss of function and the A69T mutation as dose-dependent hepcidin resistant and outline a possible causal link between iron export function and the hepcidin effect.", "journal": "Biochimica et biophysica acta", "sentences": ["Mutations in the only known mammalian iron exporter ferroportin cause a rare iron overload disorder termed ferroportin disease.", "Two distinct clinical phenotypes are caused by different disease mechanisms: mutations in ferroportin either cause loss of iron export function or gain of function due to resistance to hepcidin, the peptide hormone that normally downregulates ferroportin.", "The aim of the present study was to examine the disease mechanisms of the thus far unclassified A69T and D181V ferroportin mutations.", "We overexpressed wild-type and mutant ferroportin fused to green fluorescent protein in human embryonic kidney cells and used a (59)Fe-assay, intracellular ferritin concentrations, confocal microscopy and flow cytometry to study iron export function, subcellular localization and the responsiveness to hepcidin.", "While the A69T ferroportin mutation seems not to affect the iron export function it causes dose-dependent hepcidin resistance.", "We further found that D181V mutated ferroportin is iron export defective and hepcidin resistant, similar to the loss of function mutations A77D and C367X.", "This indicates that intact iron export might be necessary for hepcidin-induced downregulation of ferroportin.", "This hypothesis was investigated by studying the hepcidin response under modulation of iron availability.", "Incubation of wild-type ferroportin overexpressing cells with holo-transferrin increases the hepcidin effect whereas chelating extracellular ferrous iron causes hepcidin resistance.", "In this study we present data that postulates to classify the D181V ferroportin mutation as loss of function and the A69T mutation as dose-dependent hepcidin resistant and outline a possible causal link between iron export function and the hepcidin effect."], "title": "Impact of D181V and A69T on the function of ferroportin as an iron export pump and hepcidin receptor."}
{"paper_id": 20717541, "labels": ["0", "0", "0", "1", "1"], "abstract": "The relationship between the incidence of norovirus-associated gastroenteritis outbreaks (NAGOs) in Victoria, Australia for the period 2002-2007 and rainfall was examined. Statistical analysis involving the correlation between time series indicated that there was a statistically significant (p < 0.05) correlation between monthly NAGO incidence and average monthly rainfall. There was a lag of an average of about three months between peak average rainfall and a NAGO epidemic. The findings thus indicate rainfall can influence NAGO incidence. In an era where there is concern about the potential effects of global warming on weather patterns, it should be borne in mind that future changes in NAGO incidence may reflect altered world weather patterns.", "journal": "International journal of environmental research and public health", "sentences": ["The relationship between the incidence of norovirus-associated gastroenteritis outbreaks (NAGOs) in Victoria, Australia for the period 2002-2007 and rainfall was examined.", "Statistical analysis involving the correlation between time series indicated that there was a statistically significant (p < 0.05) correlation between monthly NAGO incidence and average monthly rainfall.", "There was a lag of an average of about three months between peak average rainfall and a NAGO epidemic.", "The findings thus indicate rainfall can influence NAGO incidence.", "In an era where there is concern about the potential effects of global warming on weather patterns, it should be borne in mind that future changes in NAGO incidence may reflect altered world weather patterns."], "title": "The incidence of norovirus-associated gastroenteritis outbreaks in Victoria, Australia (2002-2007) and their relationship with rainfall."}
{"paper_id": 24982969, "labels": ["0", "0", "0", "0", "1", "1"], "abstract": "The characterization of the dynamics of traffic states remains fundamental to seeking for the solutions of diverse traffic problems. To gain more insights into traffic dynamics in the temporal domain, this paper explored temporal characteristics and distinct regularity in the traffic evolution process of urban traffic network. We defined traffic state pattern through clustering multidimensional traffic time series using self-organizing maps and construct a pattern transition network model that is appropriate for representing and analyzing the evolution progress. The methodology is illustrated by an application to data flow rate of multiple road sections from Network of Shenzhen's Nanshan District, China. Analysis and numerical results demonstrated that the methodology permits extracting many useful traffic transition characteristics including stability, preference, activity, and attractiveness. In addition, more information about the relationships between these characteristics was extracted, which should be helpful in understanding the complex behavior of the temporal evolution features of traffic patterns.", "journal": "TheScientificWorldJournal", "sentences": ["The characterization of the dynamics of traffic states remains fundamental to seeking for the solutions of diverse traffic problems.", "To gain more insights into traffic dynamics in the temporal domain, this paper explored temporal characteristics and distinct regularity in the traffic evolution process of urban traffic network.", "We defined traffic state pattern through clustering multidimensional traffic time series using self-organizing maps and construct a pattern transition network model that is appropriate for representing and analyzing the evolution progress.", "The methodology is illustrated by an application to data flow rate of multiple road sections from Network of Shenzhen's Nanshan District, China.", "Analysis and numerical results demonstrated that the methodology permits extracting many useful traffic transition characteristics including stability, preference, activity, and attractiveness.", "In addition, more information about the relationships between these characteristics was extracted, which should be helpful in understanding the complex behavior of the temporal evolution features of traffic patterns."], "title": "Transition characteristic analysis of traffic evolution process for urban traffic network."}
{"paper_id": 27035957, "labels": ["0", "0", "0", "0", "1", "0", "0", "1"], "abstract": "We investigated the propagation patterns of cutaneous vibration in the hand during interactions with touched objects. Prior research has highlighted the importance of vibrotactile signals during haptic interactions, but little is known of how vibrations propagate throughout the hand. Furthermore, the extent to which the patterns of vibrations reflect the nature of the objects that are touched, and how they are touched, is unknown. Using an apparatus comprised of an array of accelerometers, we mapped and analyzed spatial distributions of vibrations propagating in the skin of the dorsal region of the hand during active touch, grasping, and manipulation tasks. We found these spatial patterns of vibration to vary systematically with touch interactions and determined that it is possible to use these data to decode the modes of interaction with touched objects. The observed vibration patterns evolved rapidly in time, peaking in intensity within a few milliseconds, fading within 20-30 ms, and yielding interaction-dependent distributions of energy in frequency bands that span the range of vibrotactile sensitivity. These results are consistent with findings in perception research that indicate that vibrotactile information distributed throughout the hand can transmit information regarding explored and manipulated objects. The results may further clarify the role of distributed sensory resources in the perceptual recovery of object attributes during active touch, may guide the development of approaches to robotic sensing, and could have implications for the rehabilitation of the upper extremity.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["We investigated the propagation patterns of cutaneous vibration in the hand during interactions with touched objects.", "Prior research has highlighted the importance of vibrotactile signals during haptic interactions, but little is known of how vibrations propagate throughout the hand.", "Furthermore, the extent to which the patterns of vibrations reflect the nature of the objects that are touched, and how they are touched, is unknown.", "Using an apparatus comprised of an array of accelerometers, we mapped and analyzed spatial distributions of vibrations propagating in the skin of the dorsal region of the hand during active touch, grasping, and manipulation tasks.", "We found these spatial patterns of vibration to vary systematically with touch interactions and determined that it is possible to use these data to decode the modes of interaction with touched objects.", "The observed vibration patterns evolved rapidly in time, peaking in intensity within a few milliseconds, fading within 20-30 ms, and yielding interaction-dependent distributions of energy in frequency bands that span the range of vibrotactile sensitivity.", "These results are consistent with findings in perception research that indicate that vibrotactile information distributed throughout the hand can transmit information regarding explored and manipulated objects.", "The results may further clarify the role of distributed sensory resources in the perceptual recovery of object attributes during active touch, may guide the development of approaches to robotic sensing, and could have implications for the rehabilitation of the upper extremity."], "title": "Spatial patterns of cutaneous vibration during whole-hand haptic interactions."}
{"paper_id": 24866846, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Using micro-level longitudinal data from Southern Sweden for 1813 to 1968, this work evaluates the effect of exposure to disease in early life on mortality over the entire life course and separately by sex. The local rates of post-early neonatal mortality are considered indicators of early life disease exposure, and these rates are calculated specifically for each person based on birth date. The loss in median remaining life among exposed individuals who survived to age 1 is 1.1 years for females and 2.1 years for males. Exposed individuals show a cross-over from lower to higher relative mortality as they age. This change occurs in adulthood for males and in old age for females. During adulthood, exposed males present higher rates of death than exposed females. These results are new to the literature and shed light on the importance of adopting a full life course approach and capturing sex differences when evaluating the long-term impacts of early life exposures.", "journal": "Social science & medicine (1982)", "sentences": ["Using micro-level longitudinal data from Southern Sweden for 1813 to 1968, this work evaluates the effect of exposure to disease in early life on mortality over the entire life course and separately by sex.", "The local rates of post-early neonatal mortality are considered indicators of early life disease exposure, and these rates are calculated specifically for each person based on birth date.", "The loss in median remaining life among exposed individuals who survived to age 1 is 1.1 years for females and 2.1 years for males.", "Exposed individuals show a cross-over from lower to higher relative mortality as they age.", "This change occurs in adulthood for males and in old age for females.", "During adulthood, exposed males present higher rates of death than exposed females.", "These results are new to the literature and shed light on the importance of adopting a full life course approach and capturing sex differences when evaluating the long-term impacts of early life exposures."], "title": "Early life effects across the life course: the impact of individually defined exogenous measures of disease exposure on mortality by sex in 19th- and 20th-century Southern Sweden."}
{"paper_id": 27153067, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Metal ions play a functional role in numerous biochemical processes and cellular pathways. Indeed, about 40% of all enzymes of known 3D structure require a metal ion to be able to perform catalysis. The interactions of the metals with the macromolecular framework determine their chemical properties and reactivity. The relevant interactions involve both the coordination sphere of the metal ion and the more distant interactions of the so-called second sphere, i.e., the non-bonded interactions between the macromolecule and the residues coordinating the metal (metal ligands). The metal ligands and the residues in their close spatial proximity define what we call a minimal functional site (MFS). MFSs can be automatically extracted from the 3D structures of metal-binding biological macromolecules deposited in the Protein Data Bank (PDB). They are 3D templates that describe the local environment around a metal ion or metal cofactor and do not depend on the overall macromolecular structure. MFSs provide a different view on metal-binding proteins and nucleic acids, completely focused on the metal. Here we present different protocols and tools based upon the concept of MFS to obtain deeper insight into the structural and functional properties of metal-binding macromolecules. We also show that structure conservation of MFSs in metalloproteins relates to local sequence similarity more strongly than to overall protein similarity.", "journal": "International journal of molecular sciences", "sentences": ["Metal ions play a functional role in numerous biochemical processes and cellular pathways.", "Indeed, about 40% of all enzymes of known 3D structure require a metal ion to be able to perform catalysis.", "The interactions of the metals with the macromolecular framework determine their chemical properties and reactivity.", "The relevant interactions involve both the coordination sphere of the metal ion and the more distant interactions of the so-called second sphere, i.e., the non-bonded interactions between the macromolecule and the residues coordinating the metal (metal ligands).", "The metal ligands and the residues in their close spatial proximity define what we call a minimal functional site (MFS).", "MFSs can be automatically extracted from the 3D structures of metal-binding biological macromolecules deposited in the Protein Data Bank (PDB).", "They are 3D templates that describe the local environment around a metal ion or metal cofactor and do not depend on the overall macromolecular structure.", "MFSs provide a different view on metal-binding proteins and nucleic acids, completely focused on the metal.", "Here we present different protocols and tools based upon the concept of MFS to obtain deeper insight into the structural and functional properties of metal-binding macromolecules.", "We also show that structure conservation of MFSs in metalloproteins relates to local sequence similarity more strongly than to overall protein similarity."], "title": "Minimal Functional Sites in Metalloproteins and Their Usage in Structural Bioinformatics."}
{"paper_id": 23407828, "labels": ["0", "0", "0", "0", "1", "0", "1", "1", "1"], "abstract": "Biosilicification is widespread across the eukaryotes and requires concentration of silicon in intracellular vesicles. Knowledge of the molecular mechanisms underlying this process remains limited, with unrelated silicon-transporting proteins found in the eukaryotic clades previously studied. Here, we report the identification of silicon transporter (SIT)-type genes from the siliceous loricate choanoflagellates Stephanoeca diplocostata and Diaphanoeca grandis. Until now, the SIT gene family has been identified only in diatoms and other siliceous stramenopiles, which are distantly related to choanoflagellates among the eukaryotes. This is the first evidence of similarity between SITs from different eukaryotic supergroups. Phylogenetic analysis indicates that choanoflagellate and stramenopile SITs form distinct monophyletic groups. The absence of putative SIT genes in any other eukaryotic groups, including non-siliceous choanoflagellates, leads us to propose that SIT genes underwent a lateral gene transfer event between stramenopiles and loricate choanoflagellates. We suggest that the incorporation of a foreign SIT gene into the stramenopile or choanoflagellate genome resulted in a major metabolic change: the acquisition of biomineralized silica structures. This hypothesis implies that biosilicification has evolved multiple times independently in the eukaryotes, and paves the way for a better understanding of the biochemical basis of silicon transport through identification of conserved sequence motifs.", "journal": "Proceedings. Biological sciences / The Royal Society", "sentences": ["Biosilicification is widespread across the eukaryotes and requires concentration of silicon in intracellular vesicles.", "Knowledge of the molecular mechanisms underlying this process remains limited, with unrelated silicon-transporting proteins found in the eukaryotic clades previously studied.", "Here, we report the identification of silicon transporter (SIT)-type genes from the siliceous loricate choanoflagellates Stephanoeca diplocostata and Diaphanoeca grandis.", "Until now, the SIT gene family has been identified only in diatoms and other siliceous stramenopiles, which are distantly related to choanoflagellates among the eukaryotes.", "This is the first evidence of similarity between SITs from different eukaryotic supergroups.", "Phylogenetic analysis indicates that choanoflagellate and stramenopile SITs form distinct monophyletic groups.", "The absence of putative SIT genes in any other eukaryotic groups, including non-siliceous choanoflagellates, leads us to propose that SIT genes underwent a lateral gene transfer event between stramenopiles and loricate choanoflagellates.", "We suggest that the incorporation of a foreign SIT gene into the stramenopile or choanoflagellate genome resulted in a major metabolic change: the acquisition of biomineralized silica structures.", "This hypothesis implies that biosilicification has evolved multiple times independently in the eukaryotes, and paves the way for a better understanding of the biochemical basis of silicon transport through identification of conserved sequence motifs."], "title": "A family of diatom-like silicon transporters in the siliceous loricate choanoflagellates."}
{"paper_id": 25446811, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "There is considerable individual variation in the propensity of animals to attribute incentive salience to discrete reward cues, but to date most of this research has been conducted in male rats. The purpose of this study was to determine whether sex influences the propensity to attribute incentive salience to a food cue, using rats from two different outbred strains (Sprague-Dawley [SD] and Heterogeneous Stock [HS]). The motivational value of a food cue was assessed in two ways: (i) by the ability of the cue to elicit approach toward it and (ii) by its ability to act as a conditioned reinforcer. We found that female SD rats acquired Pavlovian conditioned approach behavior slightly faster than males, but no sex difference was detected in HS rats, and neither strain showed a sex difference in asymptotic performance of approach behavior. Moreover, female approach behavior did not differ across estrous cycle. Compared to males, females made more active responses during the test for conditioned reinforcement, although they made more inactive responses as well. We conclude that although there are small sex differences in performance on these tasks, these are probably not due to a notable sex difference in the propensity to attribute incentive salience to a food cue.", "journal": "Behavioural brain research", "sentences": ["There is considerable individual variation in the propensity of animals to attribute incentive salience to discrete reward cues, but to date most of this research has been conducted in male rats.", "The purpose of this study was to determine whether sex influences the propensity to attribute incentive salience to a food cue, using rats from two different outbred strains (Sprague-Dawley [SD] and Heterogeneous Stock [HS]).", "The motivational value of a food cue was assessed in two ways: (i) by the ability of the cue to elicit approach toward it and (ii) by its ability to act as a conditioned reinforcer.", "We found that female SD rats acquired Pavlovian conditioned approach behavior slightly faster than males, but no sex difference was detected in HS rats, and neither strain showed a sex difference in asymptotic performance of approach behavior.", "Moreover, female approach behavior did not differ across estrous cycle.", "Compared to males, females made more active responses during the test for conditioned reinforcement, although they made more inactive responses as well.", "We conclude that although there are small sex differences in performance on these tasks, these are probably not due to a notable sex difference in the propensity to attribute incentive salience to a food cue."], "title": "Individual variation in the propensity to attribute incentive salience to a food cue: influence of sex."}
{"paper_id": 20044029, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Here, we investigated the modulation of cytosolic phospholipase A(2) (cPLA(2))-mediated arachidonic acid (AA) release by the polyprenylated acylphloroglucinol hyperforin. Hyperforin increased AA release from human platelets up to 2.6 fold (maximal effect at 10microM) versus unstimulated cells, which was blocked by cPLA(2)alpha-inhibition, and induced translocation of cPLA(2) to a membrane compartment. Interestingly, these stimulatory effects of hyperforin were even more pronounced after depletion of intracellular Ca(2+) by EDTA plus BAPTA/AM. Hyperforin induced phosphorylation of cPLA(2) at Ser505 and activated p38 mitogen-activated protein kinase (MAPK), and inhibition of p38 MAPK by SB203580 prevented cPLA(2) phosphorylation. However, neither AA release nor translocation of cPLA(2) was abrogated by SB203580. In cell-free assays using liposomes prepared from different lipids, hyperforin failed to stimulate phospholipid hydrolysis by isolated cPLA(2) in the presence of Ca(2+). However, when Ca(2+) was omitted, hyperforin caused a prominent increase in cPLA(2) activity using liposomes composed of 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphoethanolamine but not of 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine (PAPC) unless the PAPC liposomes were enriched in cholesterol (20 to 50%). Finally, two-dimensional (1)H-MAS-NMR analysis visualized the directed insertion of hyperforin into POPC liposomes. Together, hyperforin, through insertion into phospholipids, may facilitate cPLA(2) activation by enabling its access towards select lipid membranes independent of Ca(2+) ions. Such Ca(2+)- and phosphorylation-independent mechanism of cPLA(2) activation may apply also to other membrane-interfering molecules.", "journal": "Biochimica et biophysica acta", "sentences": ["Here, we investigated the modulation of cytosolic phospholipase A(2) (cPLA(2))-mediated arachidonic acid (AA) release by the polyprenylated acylphloroglucinol hyperforin.", "Hyperforin increased AA release from human platelets up to 2.6 fold (maximal effect at 10microM) versus unstimulated cells, which was blocked by cPLA(2)alpha-inhibition, and induced translocation of cPLA(2) to a membrane compartment.", "Interestingly, these stimulatory effects of hyperforin were even more pronounced after depletion of intracellular Ca(2+) by EDTA plus BAPTA/AM.", "Hyperforin induced phosphorylation of cPLA(2) at Ser505 and activated p38 mitogen-activated protein kinase (MAPK), and inhibition of p38 MAPK by SB203580 prevented cPLA(2) phosphorylation.", "However, neither AA release nor translocation of cPLA(2) was abrogated by SB203580.", "In cell-free assays using liposomes prepared from different lipids, hyperforin failed to stimulate phospholipid hydrolysis by isolated cPLA(2) in the presence of Ca(2+).", "However, when Ca(2+) was omitted, hyperforin caused a prominent increase in cPLA(2) activity using liposomes composed of 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphoethanolamine but not of 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine (PAPC) unless the PAPC liposomes were enriched in cholesterol (20 to 50%).", "Finally, two-dimensional (1)H-MAS-NMR analysis visualized the directed insertion of hyperforin into POPC liposomes.", "Together, hyperforin, through insertion into phospholipids, may facilitate cPLA(2) activation by enabling its access towards select lipid membranes independent of Ca(2+) ions.", "Such Ca(2+)- and phosphorylation-independent mechanism of cPLA(2) activation may apply also to other membrane-interfering molecules."], "title": "Hyperforin induces Ca(2+)-independent arachidonic acid release in human platelets by facilitating cytosolic phospholipase A(2) activation through select phospholipid interactions."}
{"paper_id": 20617047, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Linear regression models are often used to represent the cost and effectiveness of medical treatment. The covariates used may include sociodemographic variables, such as age, gender or race; clinical variables, such as initial health status, years of treatment or the existence of concomitant illnesses; and a binary variable indicating the treatment received. However, most studies estimate only one model, which usually includes all the covariates. This procedure ignores the question of uncertainty in model selection. In this paper, we examine four alternative Bayesian variable selection methods that have been proposed. In this analysis, we estimate the inclusion probability of each covariate in the real model conditional on the data. Variable selection can be useful for estimating incremental effectiveness and incremental cost, through Bayesian model averaging, as well as for subgroup analysis.", "journal": "International journal of environmental research and public health", "sentences": ["Linear regression models are often used to represent the cost and effectiveness of medical treatment.", "The covariates used may include sociodemographic variables, such as age, gender or race; clinical variables, such as initial health status, years of treatment or the existence of concomitant illnesses; and a binary variable indicating the treatment received.", "However, most studies estimate only one model, which usually includes all the covariates.", "This procedure ignores the question of uncertainty in model selection.", "In this paper, we examine four alternative Bayesian variable selection methods that have been proposed.", "In this analysis, we estimate the inclusion probability of each covariate in the real model conditional on the data.", "Variable selection can be useful for estimating incremental effectiveness and incremental cost, through Bayesian model averaging, as well as for subgroup analysis."], "title": "Bayesian variable selection in cost-effectiveness analysis."}
{"paper_id": 26464626, "labels": ["0", "0", "0", "0", "0", "0", "1", "0", "1"], "abstract": "Alpha B crystallin was characterized as a negative prognostic factor in breast cancer. BCL2 has an antiapoptotic role and sustains cell survival in vitro, ironically BCL2 expression has been associated with a good prognosis of breast cancer patients. To investigate the significance of alpha B crystallin and BCL2 expression in breast cancer and the relationship between these proteins, we performed immunohistochemical staining for both proteins in human breast cancer tissues. In the present study, overexpression of alpha B crystallin was observed more frequently in triple negative cancer (9/20, 45%) than in luminal type cancer (8/53, 15.1%, P=0.02161). BCL2 tended to be more highly expressed in luminal type cancer than in HER2 and triple negative cancer types (luminal: 36/53, 68%, HER2: 2/9, 22%, triple negative: 7/20 35%, P=0.008652). In multivariate analysis using ANCOVA, alpha B crystallin was related to short overall survival (P=0.017173). These findings suggest that alpha B crystallin is an independent prognostic factor of infiltrating ductal carcinoma. BCL2 was not associated with survival in multivariate analysis using ANCOVA. Thus, in our study BCL2 was not an independent prognostic indicator.", "journal": "International journal of clinical and experimental pathology", "sentences": ["Alpha B crystallin was characterized as a negative prognostic factor in breast cancer.", "BCL2 has an antiapoptotic role and sustains cell survival in vitro, ironically BCL2 expression has been associated with a good prognosis of breast cancer patients.", "To investigate the significance of alpha B crystallin and BCL2 expression in breast cancer and the relationship between these proteins, we performed immunohistochemical staining for both proteins in human breast cancer tissues.", "In the present study, overexpression of alpha B crystallin was observed more frequently in triple negative cancer (9/20, 45%) than in luminal type cancer (8/53, 15.1%, P=0.02161).", "BCL2 tended to be more highly expressed in luminal type cancer than in HER2 and triple negative cancer types (luminal: 36/53, 68%, HER2: 2/9, 22%, triple negative: 7/20 35%, P=0.008652).", "In multivariate analysis using ANCOVA, alpha B crystallin was related to short overall survival (P=0.017173).", "These findings suggest that alpha B crystallin is an independent prognostic factor of infiltrating ductal carcinoma.", "BCL2 was not associated with survival in multivariate analysis using ANCOVA.", "Thus, in our study BCL2 was not an independent prognostic indicator."], "title": "Expression of alpha B crystallin and BCL2 in patients with infiltrating ductal carcinoma."}
{"paper_id": 26257691, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Increasing evidence suggests that the prefrontal cortex (PFC) is influenced by sex steroids and that some cognitive functions dependent on the PFC may be sexually differentiated in humans. Past work has identified a male advantage on certain complex reinforcement learning tasks, but it is unclear which latent task components are important to elicit the sex difference. The objective of the current study was to investigate whether there are sex differences on measures of response inhibition and valenced feedback processing, elements that are shared by previously studied reinforcement learning tasks. Healthy young adults (90 males, 86 females) matched in general intelligence completed the Probabilistic Selection Task (PST), a Simon task, and the Stop-Signal task. On the PST, females were more accurate than males in learning from positive (but not negative) feedback. On the Simon task, males were faster than females, especially in the face of incongruent stimuli. No sex difference was observed in Stop-Signal reaction time. The current findings provide preliminary support for a sex difference in the processing of valenced feedback and in interference inhibition.", "journal": "Frontiers in psychology", "sentences": ["Increasing evidence suggests that the prefrontal cortex (PFC) is influenced by sex steroids and that some cognitive functions dependent on the PFC may be sexually differentiated in humans.", "Past work has identified a male advantage on certain complex reinforcement learning tasks, but it is unclear which latent task components are important to elicit the sex difference.", "The objective of the current study was to investigate whether there are sex differences on measures of response inhibition and valenced feedback processing, elements that are shared by previously studied reinforcement learning tasks.", "Healthy young adults (90 males, 86 females) matched in general intelligence completed the Probabilistic Selection Task (PST), a Simon task, and the Stop-Signal task.", "On the PST, females were more accurate than males in learning from positive (but not negative) feedback.", "On the Simon task, males were faster than females, especially in the face of incongruent stimuli.", "No sex difference was observed in Stop-Signal reaction time.", "The current findings provide preliminary support for a sex difference in the processing of valenced feedback and in interference inhibition."], "title": "Sex-dependent effects on tasks assessing reinforcement learning and interference inhibition."}
{"paper_id": 26731476, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Histone demethylase upregulation has been observed in human cancers, yet it is unknown whether this is a bystander event or a driver of tumorigenesis. We found that overexpression of lysine-specific demethylase 4A (KDM4A, also known as JMJD2A) was positively correlated with Gleason score and metastasis in human prostate tumors. Overexpression of JMJD2A resulted in the development of prostatic intraepithelial neoplasia in mice, demonstrating that JMJD2A can initiate prostate cancer development. Moreover, combined overexpression of JMJD2A and the ETS transcription factor ETV1, a JMJD2A-binding protein, resulted in prostate carcinoma formation in mice haplodeficient for the phosphatase and tensin homolog (Pten) tumor-suppressor gene. Additionally, JMJD2A cooperated with ETV1 to increase expression of yes associated protein 1 (YAP1), a Hippo pathway component that itself was associated with prostate tumor aggressiveness. ETV1 facilitated the recruitment of JMJD2A to the YAP1 promoter, leading to changes in histone lysine methylation in a human prostate cancer cell line. Further, YAP1 expression largely rescued the growth inhibitory effects of JMJD2A depletion in prostate cancer cells, indicating that YAP1 is a downstream effector of JMJD2A. Taken together, these data reveal a JMJD2A/ETV1/YAP1 axis that promotes prostate cancer initiation and that may be a suitable target for therapeutic inhibition.", "journal": "The Journal of clinical investigation", "sentences": ["Histone demethylase upregulation has been observed in human cancers, yet it is unknown whether this is a bystander event or a driver of tumorigenesis.", "We found that overexpression of lysine-specific demethylase 4A (KDM4A, also known as JMJD2A) was positively correlated with Gleason score and metastasis in human prostate tumors.", "Overexpression of JMJD2A resulted in the development of prostatic intraepithelial neoplasia in mice, demonstrating that JMJD2A can initiate prostate cancer development.", "Moreover, combined overexpression of JMJD2A and the ETS transcription factor ETV1, a JMJD2A-binding protein, resulted in prostate carcinoma formation in mice haplodeficient for the phosphatase and tensin homolog (Pten) tumor-suppressor gene.", "Additionally, JMJD2A cooperated with ETV1 to increase expression of yes associated protein 1 (YAP1), a Hippo pathway component that itself was associated with prostate tumor aggressiveness.", "ETV1 facilitated the recruitment of JMJD2A to the YAP1 promoter, leading to changes in histone lysine methylation in a human prostate cancer cell line.", "Further, YAP1 expression largely rescued the growth inhibitory effects of JMJD2A depletion in prostate cancer cells, indicating that YAP1 is a downstream effector of JMJD2A.", "Taken together, these data reveal a JMJD2A/ETV1/YAP1 axis that promotes prostate cancer initiation and that may be a suitable target for therapeutic inhibition."], "title": "Histone demethylase JMJD2A drives prostate tumorigenesis through transcription factor ETV1."}
{"paper_id": 24417579, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Biological assays formatted as microarrays have become a critical tool for the generation of the comprehensive data sets required for systems-level understanding of biological processes. Manual annotation of data extracted from images of microarrays, however, remains a significant bottleneck, particularly for protein microarrays due to the sensitivity of this technology to weak artifact signal. In order to automate the extraction and curation of data from protein microarrays, we describe an algorithm called Crossword that logically combines information from multiple approaches to fully automate microarray segmentation. Automated artifact removal is also accomplished by segregating structured pixels from the background noise using iterative clustering and pixel connectivity. Correlation of the location of structured pixels across image channels is used to identify and remove artifact pixels from the image prior to data extraction. This component improves the accuracy of data sets while reducing the requirement for time-consuming visual inspection of the data. Crossword enables a fully automated protocol that is robust to significant spatial and intensity aberrations. Overall, the average amount of user intervention is reduced by an order of magnitude and the data quality is increased through artifact removal and reduced user variability. The increase in throughput should aid the further implementation of microarray technologies in clinical studies.", "journal": "Journal of proteome research", "sentences": ["Biological assays formatted as microarrays have become a critical tool for the generation of the comprehensive data sets required for systems-level understanding of biological processes.", "Manual annotation of data extracted from images of microarrays, however, remains a significant bottleneck, particularly for protein microarrays due to the sensitivity of this technology to weak artifact signal.", "In order to automate the extraction and curation of data from protein microarrays, we describe an algorithm called Crossword that logically combines information from multiple approaches to fully automate microarray segmentation.", "Automated artifact removal is also accomplished by segregating structured pixels from the background noise using iterative clustering and pixel connectivity.", "Correlation of the location of structured pixels across image channels is used to identify and remove artifact pixels from the image prior to data extraction.", "This component improves the accuracy of data sets while reducing the requirement for time-consuming visual inspection of the data.", "Crossword enables a fully automated protocol that is robust to significant spatial and intensity aberrations.", "Overall, the average amount of user intervention is reduced by an order of magnitude and the data quality is increased through artifact removal and reduced user variability.", "The increase in throughput should aid the further implementation of microarray technologies in clinical studies."], "title": "Crossword: a fully automated algorithm for the segmentation and quality control of protein microarray images."}
{"paper_id": 26579042, "labels": ["0", "0", "0", "0", "0", "1"], "abstract": "The tendency to perceive an artificial effector as part of one's own body is known to depend on temporal criteria, like the synchrony between stimulus events informing about the effector. The role of spatial factors is less well understood. Rather than physical distance, which has been manipulated in previous studies, we investigated the role of relative, context-induced distance between the participant's real hand and an artificial hand stimulated synchronously or asynchronously with the real hand. We replicated previously reported distance effects in a virtual reality setup: the perception of ownership increased with decreased distance, and the impact of synchrony was stronger for short distances. More importantly, we found that ownership perception and impact of synchrony were affected by previous distance: the same, medium distance between real and artificial hand induced more pronounced ownership after having experienced a far-distance condition than after a near-distance condition. This suggests that subjective, context-induced spatial reference frames contribute to ownership perception, which does not seem to fit with the idea of fixed spatial criteria and/or permanent body representations as the sole determinants of perceived body ownership.", "journal": "Frontiers in psychology", "sentences": ["The tendency to perceive an artificial effector as part of one's own body is known to depend on temporal criteria, like the synchrony between stimulus events informing about the effector.", "The role of spatial factors is less well understood.", "Rather than physical distance, which has been manipulated in previous studies, we investigated the role of relative, context-induced distance between the participant's real hand and an artificial hand stimulated synchronously or asynchronously with the real hand.", "We replicated previously reported distance effects in a virtual reality setup: the perception of ownership increased with decreased distance, and the impact of synchrony was stronger for short distances.", "More importantly, we found that ownership perception and impact of synchrony were affected by previous distance: the same, medium distance between real and artificial hand induced more pronounced ownership after having experienced a far-distance condition than after a near-distance condition.", "This suggests that subjective, context-induced spatial reference frames contribute to ownership perception, which does not seem to fit with the idea of fixed spatial criteria and/or permanent body representations as the sole determinants of perceived body ownership."], "title": "The virtual hand illusion is moderated by context-induced spatial reference frames."}
{"paper_id": 27089157, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Nonsuicidal self-injury (NSSI) and suicidal behaviors, both important issues in adolescent health care, are frequently associated and possibly clinically related. Our objective was to explore the views of relations between nonsuicidal self-injury and suicidal behaviors during adolescence and young adulthood (11-25 years) expressed in the scientific (medical and psychological) literature. We adopted a textual approach to the process of synthesis to tell the story of the findings from the included studies. Our narrative systematic review of 64 articles found that they share the same risk factors. Integrated models envision nonsuicidal self-injury as a gateway enabling teens to acquire the capability for suicide. Because suicidal behavior short-circuits thought, it is difficult to conceive an intention to die during adolescents' acts of self-injury. Intention is constructed by the narrative of the act, influenced by numerous elements from the psychopathologic, cultural, religious, and philosophic context. Techniques of mentalizing-based treatments and work on the meaning that adolescents attribute to their behaviors might improve care.", "journal": "PloS one", "sentences": ["Nonsuicidal self-injury (NSSI) and suicidal behaviors, both important issues in adolescent health care, are frequently associated and possibly clinically related.", "Our objective was to explore the views of relations between nonsuicidal self-injury and suicidal behaviors during adolescence and young adulthood (11-25 years) expressed in the scientific (medical and psychological) literature.", "We adopted a textual approach to the process of synthesis to tell the story of the findings from the included studies.", "Our narrative systematic review of 64 articles found that they share the same risk factors.", "Integrated models envision nonsuicidal self-injury as a gateway enabling teens to acquire the capability for suicide.", "Because suicidal behavior short-circuits thought, it is difficult to conceive an intention to die during adolescents' acts of self-injury.", "Intention is constructed by the narrative of the act, influenced by numerous elements from the psychopathologic, cultural, religious, and philosophic context.", "Techniques of mentalizing-based treatments and work on the meaning that adolescents attribute to their behaviors might improve care."], "title": "Relations between Nonsuicidal Self-Injury and Suicidal Behavior in Adolescence: A Systematic Review."}
{"paper_id": 27044072, "labels": ["0", "0", "0", "0", "0", "0", "0"], "abstract": "We report superresolution optical sectioning using a multiangle total internal reflection fluorescence (TIRF) microscope. TIRF images were constructed from several layers within a normal TIRF excitation zone by sequentially imaging and photobleaching the fluorescent molecules. The depth of the evanescent wave at different layers was altered by tuning the excitation light incident angle. The angle was tuned from the highest (the smallest TIRF depth) toward the critical angle (the largest TIRF depth) to preferentially photobleach fluorescence from the lower layers and allow straightforward observation of deeper structures without masking by the brighter signals closer to the coverglass. Reconstruction of the TIRF images enabled 3D imaging of biological samples with 20-nm axial resolution. Two-color imaging of epidermal growth factor (EGF) ligand and clathrin revealed the dynamics of EGF-activated clathrin-mediated endocytosis during internalization. Furthermore, Bayesian analysis of images collected during the photobleaching step of each plane enabled lateral superresolution (<100 nm) within each of the sections.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["We report superresolution optical sectioning using a multiangle total internal reflection fluorescence (TIRF) microscope.", "TIRF images were constructed from several layers within a normal TIRF excitation zone by sequentially imaging and photobleaching the fluorescent molecules.", "The depth of the evanescent wave at different layers was altered by tuning the excitation light incident angle.", "The angle was tuned from the highest (the smallest TIRF depth) toward the critical angle (the largest TIRF depth) to preferentially photobleach fluorescence from the lower layers and allow straightforward observation of deeper structures without masking by the brighter signals closer to the coverglass.", "Reconstruction of the TIRF images enabled 3D imaging of biological samples with 20-nm axial resolution.", "Two-color imaging of epidermal growth factor (EGF) ligand and clathrin revealed the dynamics of EGF-activated clathrin-mediated endocytosis during internalization.", "Furthermore, Bayesian analysis of images collected during the photobleaching step of each plane enabled lateral superresolution (<100 nm) within each of the sections."], "title": "Axial superresolution via multiangle TIRF microscopy with sequential imaging and photobleaching."}
{"paper_id": 20488168, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "It was demonstrated in our recent study that Zn(2+) had dual effects on Ca(2+)-permeable AMPA receptors on carp retinal horizontal cells. However, the possible mechanism(s) underlying the Zn(2+) effects is still unclear. In the present study, we examined the Zn(2+) effects in the presence of cyclothiazide (CTZ), an allosteric potentiator of AMPA receptors, which could attenuate the receptor desensitization. It was shown that the potentiation effect that low concentration Zn(2+) (10 microM) exerted on the amplitude of the current mediated by Ca(2+)-permeable AMPA receptors was more remarkable in the presence of moderate concentration of CTZ (20 microM). Meanwhile, the inhibitory effect induced by high concentration Zn(2+) (1 mM) was not affected by CTZ. Furthermore, the involvement of extracellular Ca(2+) in the Zn(2+) effects was also examined. It was shown that the inhibitory effect induced by high concentration Zn(2+) (1 mM) was abolished or significantly attenuated in Ca(2+)-free (0 mM) Ringer's, but significantly enhanced in high-Ca(2+) (20 mM) Ringer's. However, the Zn(2+) (10 microM) potentiation effect was not changed either in Ca(2+)-free (0 mM) or high-Ca(2+) (20 mM) Ringer's. These results suggest that the Zn(2+) potentiation effect involves the interaction with CTZ-binding site on the AMPA receptors, while the Zn(2+) inhibitory effect is related to the extracellular Ca(2+) concentration. Overall, the dual effects that Zn(2+) exerts on Ca(2+)-permeable AMPA receptors on retinal horizontal cells are mediated by separate mechanisms.", "journal": "Brain research", "sentences": ["It was demonstrated in our recent study that Zn(2+) had dual effects on Ca(2+)-permeable AMPA receptors on carp retinal horizontal cells.", "However, the possible mechanism(s) underlying the Zn(2+) effects is still unclear.", "In the present study, we examined the Zn(2+) effects in the presence of cyclothiazide (CTZ), an allosteric potentiator of AMPA receptors, which could attenuate the receptor desensitization.", "It was shown that the potentiation effect that low concentration Zn(2+) (10 microM) exerted on the amplitude of the current mediated by Ca(2+)-permeable AMPA receptors was more remarkable in the presence of moderate concentration of CTZ (20 microM).", "Meanwhile, the inhibitory effect induced by high concentration Zn(2+) (1 mM) was not affected by CTZ.", "Furthermore, the involvement of extracellular Ca(2+) in the Zn(2+) effects was also examined.", "It was shown that the inhibitory effect induced by high concentration Zn(2+) (1 mM) was abolished or significantly attenuated in Ca(2+)-free (0 mM) Ringer's, but significantly enhanced in high-Ca(2+) (20 mM) Ringer's.", "However, the Zn(2+) (10 microM) potentiation effect was not changed either in Ca(2+)-free (0 mM) or high-Ca(2+) (20 mM) Ringer's.", "These results suggest that the Zn(2+) potentiation effect involves the interaction with CTZ-binding site on the AMPA receptors, while the Zn(2+) inhibitory effect is related to the extracellular Ca(2+) concentration.", "Overall, the dual effects that Zn(2+) exerts on Ca(2+)-permeable AMPA receptors on retinal horizontal cells are mediated by separate mechanisms."], "title": "The mechanisms of Zn2+ effects on Ca2+-permeable AMPA receptors on carp retinal horizontal cells."}
{"paper_id": 23330019, "labels": ["0", "0", "0", "0", "0", "0", "1"], "abstract": "Cholangiocarcinomas (CCs) show intraluminal spread to bile ducts and periductal infiltration associated with vascular, lymphatic and perineural invasion in addition to direct penetration. Recently, the peribiliary gland networks located around the hilar and extrahepatic bile ducts have been reportedly to be involved in a variety of biliary diseases. However, the pathological features and roles of these networks in the carcinogenesis and progression of CCs remain to be explored. Recently, we experienced two cases of hilar CC showing a nodular sclerosing growth grossly and histologically well-differentiated adenocarcinomas, with an extensive involvement of the peribiliary gland networks. In situ like spread of carcinoma cells in the bile duct lumen was focal in one case and not identifiable in the other. In contrast, other 4 cases of ordinary hilar CC which were also well-differentiated adenocarcinomas, showed variable intraductal luminal spread and also extensive periductal infiltration irrespective of the peribiliary gland network. In conclusion, the present study showed a unique form of periductal spread of CCs with preferential and extensive involvement of the peribiliary gland networks.", "journal": "International journal of clinical and experimental pathology", "sentences": ["Cholangiocarcinomas (CCs) show intraluminal spread to bile ducts and periductal infiltration associated with vascular, lymphatic and perineural invasion in addition to direct penetration.", "Recently, the peribiliary gland networks located around the hilar and extrahepatic bile ducts have been reportedly to be involved in a variety of biliary diseases.", "However, the pathological features and roles of these networks in the carcinogenesis and progression of CCs remain to be explored.", "Recently, we experienced two cases of hilar CC showing a nodular sclerosing growth grossly and histologically well-differentiated adenocarcinomas, with an extensive involvement of the peribiliary gland networks.", "In situ like spread of carcinoma cells in the bile duct lumen was focal in one case and not identifiable in the other.", "In contrast, other 4 cases of ordinary hilar CC which were also well-differentiated adenocarcinomas, showed variable intraductal luminal spread and also extensive periductal infiltration irrespective of the peribiliary gland network.", "In conclusion, the present study showed a unique form of periductal spread of CCs with preferential and extensive involvement of the peribiliary gland networks."], "title": "Spread of hilar cholangiocarcinomas via peribiliary gland network: a hither-to-unrecognized route of periductal infiltration."}
{"paper_id": 22046448, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Guillain-Barr\u00e9 syndrome (GBS) is a monophasic immune neuropathic disorder in which a significant proportion of patients have incomplete recovery. The patients with incomplete recovery almost always have some degree of failure of axon regeneration and target reinnervation. Anti-ganglioside antibodies (Abs) are the most commonly recognized autoimmune markers in all forms of GBS and specific Abs are associated with the slow/poor recovery. We recently demonstrated that specific anti-ganglioside Abs inhibit axonal regeneration and nerve repair in preclinical models by activation of small GTPase RhoA and its downstream effectors. The objective of this study was to determine whether erythropoietin (EPO), a pleiotropic cytokine with neuroprotective and neurotrophic properties, enhances nerve regeneration in preclinical cell culture and animal models of autoimmune neuropathy/nerve repair generated with monoclonal and patient derived Abs. Primary neuronal cultures and a standardized sciatic crush nerve model were used to assess the efficacy of EPO in reversing inhibitory effects of anti-ganglioside Abs on nerve repair. We found that EPO completely reversed the inhibitory effects of anti-ganglioside Abs on axon regeneration in cell culture models and significantly improved nerve regeneration/repair in an animal model. Moreover, EPO-induced proregenerative effects in nerve cells are through EPO receptors and Janus kinase 2/Signal transducer and activator of transcription 5 pathway and not via early direct modulation of small GTPase RhoA. These preclinical studies indicate that EPO is a viable candidate drug to develop further for neuroprotection and enhancing nerve repair in patients with GBS.", "journal": "PloS one", "sentences": ["Guillain-Barr\u00e9 syndrome (GBS) is a monophasic immune neuropathic disorder in which a significant proportion of patients have incomplete recovery.", "The patients with incomplete recovery almost always have some degree of failure of axon regeneration and target reinnervation.", "Anti-ganglioside antibodies (Abs) are the most commonly recognized autoimmune markers in all forms of GBS and specific Abs are associated with the slow/poor recovery.", "We recently demonstrated that specific anti-ganglioside Abs inhibit axonal regeneration and nerve repair in preclinical models by activation of small GTPase RhoA and its downstream effectors.", "The objective of this study was to determine whether erythropoietin (EPO), a pleiotropic cytokine with neuroprotective and neurotrophic properties, enhances nerve regeneration in preclinical cell culture and animal models of autoimmune neuropathy/nerve repair generated with monoclonal and patient derived Abs.", "Primary neuronal cultures and a standardized sciatic crush nerve model were used to assess the efficacy of EPO in reversing inhibitory effects of anti-ganglioside Abs on nerve repair.", "We found that EPO completely reversed the inhibitory effects of anti-ganglioside Abs on axon regeneration in cell culture models and significantly improved nerve regeneration/repair in an animal model.", "Moreover, EPO-induced proregenerative effects in nerve cells are through EPO receptors and Janus kinase 2/Signal transducer and activator of transcription 5 pathway and not via early direct modulation of small GTPase RhoA.", "These preclinical studies indicate that EPO is a viable candidate drug to develop further for neuroprotection and enhancing nerve repair in patients with GBS."], "title": "Erythropoietin enhances nerve repair in anti-ganglioside antibody-mediated models of immune neuropathy."}
{"paper_id": 22995296, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Natural killer cells are lymphocytes of the innate immune system that play a key role in the direct elimination of transformed or virus-infected cells. Recently, it has been reported that NK cells can attack cancer cells with stem cell-like properties. In this study, we isolated ovarian cancer cell lines CAOV3 and TOV21G with and without CD24, which has been reported as an ovarian cancer stem cell marker, and compared their drug resistance and susceptibility to NK cell lysis. The isolated CD24(+) CAOV3 and TOV21G cells were more resistant to cisplatin and doxorubicin anti-cancer drugs. Also, CD24(+) CAOV3 and TOV21G cells were more susceptible to NK cell lysis compared with CD24(-) cells. In order to identify reasons for the differing NK cell susceptibility, we examined NK cell-killing mechanisms against CD24(+) cancer cell lines by analyzing NKG2D ligands, MHC class I molecules, and natural cytotoxic receptor ligands expression on target cells. Consistently, CD24(+) CAOV3 and TOV21G cells showed up-regulated NKG2D ligands and down-regulated MHC class I molecule expression. These findings show that CD24(+) ovarian cancer cell lines are more resistant to antitumor drugs but are more susceptible to NK cell lysis; thus, NK cell immunotherapy might be useful in eliminating ovarian cancer stem cells and preventing tumor recurrence and metastasis.", "journal": "Biochemical and biophysical research communications", "sentences": ["Natural killer cells are lymphocytes of the innate immune system that play a key role in the direct elimination of transformed or virus-infected cells.", "Recently, it has been reported that NK cells can attack cancer cells with stem cell-like properties.", "In this study, we isolated ovarian cancer cell lines CAOV3 and TOV21G with and without CD24, which has been reported as an ovarian cancer stem cell marker, and compared their drug resistance and susceptibility to NK cell lysis.", "The isolated CD24(+) CAOV3 and TOV21G cells were more resistant to cisplatin and doxorubicin anti-cancer drugs.", "Also, CD24(+) CAOV3 and TOV21G cells were more susceptible to NK cell lysis compared with CD24(-) cells.", "In order to identify reasons for the differing NK cell susceptibility, we examined NK cell-killing mechanisms against CD24(+) cancer cell lines by analyzing NKG2D ligands, MHC class I molecules, and natural cytotoxic receptor ligands expression on target cells.", "Consistently, CD24(+) CAOV3 and TOV21G cells showed up-regulated NKG2D ligands and down-regulated MHC class I molecule expression.", "These findings show that CD24(+) ovarian cancer cell lines are more resistant to antitumor drugs but are more susceptible to NK cell lysis; thus, NK cell immunotherapy might be useful in eliminating ovarian cancer stem cells and preventing tumor recurrence and metastasis."], "title": "Susceptibility of CD24(+) ovarian cancer cells to anti-cancer drugs and natural killer cells."}
{"paper_id": 23119049, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Astrocytes participate in brain functions through Ca(2+) signals, including Ca(2+) waves and Ca(2+) oscillations. Currently the mechanisms of Ca(2+) signals in astrocytes are not fully clear. Here, we present a computational model to specify the relative contributions of different Ca(2+) flows between the extracellular space, the cytoplasm and the endoplasmic reticulum of astrocytes to the generation of spontaneous Ca(2+) oscillations (CASs) and cortical spreading depression (CSD)-triggered Ca(2+) waves (CSDCWs) in a one-dimensional astrocyte network. This model shows that CASs depend primarily on Ca(2+) released from internal stores of astrocytes, and CSDCWs depend mainly on voltage-gated Ca(2+) influx. It predicts that voltage-gated Ca(2+) influx is able to generate Ca(2+) waves during the process of CSD even after depleting internal Ca(2+) stores. Furthermore, the model investigates the interactions between CASs and CSDCWs and shows that the pass of CSDCWs suppresses CASs, whereas CASs do not prevent the generation of CSDCWs. This work quantitatively analyzes the generation of astrocytic Ca(2+) signals and indicates different mechanisms underlying CSDCWs and non-CSDCWs. Research on the different types of Ca(2+) signals might help to understand the ways by which astrocytes participate in information processing in brain functions.", "journal": "PloS one", "sentences": ["Astrocytes participate in brain functions through Ca(2+) signals, including Ca(2+) waves and Ca(2+) oscillations.", "Currently the mechanisms of Ca(2+) signals in astrocytes are not fully clear.", "Here, we present a computational model to specify the relative contributions of different Ca(2+) flows between the extracellular space, the cytoplasm and the endoplasmic reticulum of astrocytes to the generation of spontaneous Ca(2+) oscillations (CASs) and cortical spreading depression (CSD)-triggered Ca(2+) waves (CSDCWs) in a one-dimensional astrocyte network.", "This model shows that CASs depend primarily on Ca(2+) released from internal stores of astrocytes, and CSDCWs depend mainly on voltage-gated Ca(2+) influx.", "It predicts that voltage-gated Ca(2+) influx is able to generate Ca(2+) waves during the process of CSD even after depleting internal Ca(2+) stores.", "Furthermore, the model investigates the interactions between CASs and CSDCWs and shows that the pass of CSDCWs suppresses CASs, whereas CASs do not prevent the generation of CSDCWs.", "This work quantitatively analyzes the generation of astrocytic Ca(2+) signals and indicates different mechanisms underlying CSDCWs and non-CSDCWs.", "Research on the different types of Ca(2+) signals might help to understand the ways by which astrocytes participate in information processing in brain functions."], "title": "Modeling the contributions of Ca2+ flows to spontaneous Ca2+ oscillations and cortical spreading depression-triggered Ca2+ waves in astrocyte networks."}
{"paper_id": 27380260, "labels": ["0", "0", "0", "0", "0", "0", "1", "0", "1"], "abstract": "The use of Bacillus subtilis in synthetic biology and metabolic engineering is highly desirable to take advantage of the unique metabolic pathways present in this organism. To do this, an evaluation of B. subtilis' intrinsic biological parts is required to determine the best strategies to accurately regulate metabolic circuits and expression of target proteins. The strengths of promoter candidates were evaluated by measuring relative fluorescence units of a green fluorescent protein reporter, integrated into B. subtilis' chromosome. A total of 84 predicted promoter sequences located upstream of different classes of proteins including heat shock proteins, cell-envelope proteins, and proteins resistant against toxic metals (based on similarity) and other kinds of genes were tested. The expression levels measured ranged from 0.0023 to 4.53-fold of the activity of the well-characterized strong promoter P43. No significant shifts were observed when strains, carrying different promoter candidates, were cultured at high temperature or in media with ethanol, but some strains showed increased activity when cultured under high osmotic pressure. Randomly selected promoter candidates were tested and found to activate transcription of thermostable \u03b2-galactosidase (bgaB) at a similar level, implying the ability of these sequences to function as promoter elements in multiple genetic contexts. In addition, selected promoters elevated the final production of both cytoplasmic bgaB and secreted protein \u03b1-amylase to about fourfold and twofold, respectively. The generated data allows a deeper understanding of B. subtilis' metabolism and will facilitate future work to develop this organism for synthetic biology.", "journal": "PloS one", "sentences": ["The use of Bacillus subtilis in synthetic biology and metabolic engineering is highly desirable to take advantage of the unique metabolic pathways present in this organism.", "To do this, an evaluation of B. subtilis' intrinsic biological parts is required to determine the best strategies to accurately regulate metabolic circuits and expression of target proteins.", "The strengths of promoter candidates were evaluated by measuring relative fluorescence units of a green fluorescent protein reporter, integrated into B. subtilis' chromosome.", "A total of 84 predicted promoter sequences located upstream of different classes of proteins including heat shock proteins, cell-envelope proteins, and proteins resistant against toxic metals (based on similarity) and other kinds of genes were tested.", "The expression levels measured ranged from 0.0023 to 4.53-fold of the activity of the well-characterized strong promoter P43.", "No significant shifts were observed when strains, carrying different promoter candidates, were cultured at high temperature or in media with ethanol, but some strains showed increased activity when cultured under high osmotic pressure.", "Randomly selected promoter candidates were tested and found to activate transcription of thermostable \u03b2-galactosidase (bgaB) at a similar level, implying the ability of these sequences to function as promoter elements in multiple genetic contexts.", "In addition, selected promoters elevated the final production of both cytoplasmic bgaB and secreted protein \u03b1-amylase to about fourfold and twofold, respectively.", "The generated data allows a deeper understanding of B. subtilis' metabolism and will facilitate future work to develop this organism for synthetic biology."], "title": "Promoter Screening from Bacillus subtilis in Various Conditions Hunting for Synthetic Biology and Industrial Applications."}
{"paper_id": 23926341, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Human cytomegalovirus (HCMV), a betaherpesvirus, can cause severe disease in immunosuppressed patients and following congenital infection. A vaccine that induces both humoral and cellular immunity may be required to prevent congenital infection. Dense bodies (DBs) are complex, noninfectious particles produced by HCMV-infected cells and may represent a vaccine option. As knowledge of the antigenicity and immunogenicity of DB is incomplete, we explored characterization methods and defined DB production methods, followed by systematic evaluation of neutralization and cell-mediated immune responses to the DB material in BALB/c mice. DBs purified from Towne-infected cultures treated with the viral terminase inhibitor 2-bromo-5,6-dichloro-1-beta-d-ribofuranosyl benzimidazole riboside (BDCRB) were characterized by nanoparticle tracking analysis (NTA), two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), immunoblotting, quantitative enzyme-linked immunosorbent assay, and other methods. The humoral and cellular immune responses to DBs were compared to the immunogenicity of glycoprotein B (gB) administered with the adjuvant AddaVax (gB/AddaVax). DBs induced neutralizing antibodies that prevented viral infection of cultured fibroblasts and epithelial cells and robust cell-mediated immune responses to multiple viral proteins, including pp65, gB, and UL48. In contrast, gB/AddaVax failed to induce neutralizing antibodies that prevented infection of epithelial cells, highlighting a critical difference in the humoral responses induced by these vaccine candidates. Our data advance the potential for the DB vaccine approach, demonstrate important immunogenicity properties, and strongly support the further evaluation of DBs as a CMV vaccine candidate.", "journal": "Journal of virology", "sentences": ["Human cytomegalovirus (HCMV), a betaherpesvirus, can cause severe disease in immunosuppressed patients and following congenital infection.", "A vaccine that induces both humoral and cellular immunity may be required to prevent congenital infection.", "Dense bodies (DBs) are complex, noninfectious particles produced by HCMV-infected cells and may represent a vaccine option.", "As knowledge of the antigenicity and immunogenicity of DB is incomplete, we explored characterization methods and defined DB production methods, followed by systematic evaluation of neutralization and cell-mediated immune responses to the DB material in BALB/c mice.", "DBs purified from Towne-infected cultures treated with the viral terminase inhibitor 2-bromo-5,6-dichloro-1-beta-d-ribofuranosyl benzimidazole riboside (BDCRB) were characterized by nanoparticle tracking analysis (NTA), two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), immunoblotting, quantitative enzyme-linked immunosorbent assay, and other methods.", "The humoral and cellular immune responses to DBs were compared to the immunogenicity of glycoprotein B (gB) administered with the adjuvant AddaVax (gB/AddaVax).", "DBs induced neutralizing antibodies that prevented viral infection of cultured fibroblasts and epithelial cells and robust cell-mediated immune responses to multiple viral proteins, including pp65, gB, and UL48.", "In contrast, gB/AddaVax failed to induce neutralizing antibodies that prevented infection of epithelial cells, highlighting a critical difference in the humoral responses induced by these vaccine candidates.", "Our data advance the potential for the DB vaccine approach, demonstrate important immunogenicity properties, and strongly support the further evaluation of DBs as a CMV vaccine candidate."], "title": "Cytomegalovirus vaccine strain towne-derived dense bodies induce broad cellular immune responses and neutralizing antibodies that prevent infection of fibroblasts and epithelial cells."}
{"paper_id": 20352822, "labels": ["0", "0", "1", "0", "0"], "abstract": "Well-crystallized cerium dioxide with cubic phase were formed and self-assembly grown to nanofibers or nanosheets via a solvothermal precipitation from near-supercritical fluids without any help of metal catalysts or capping agents. The self-assembly attachment process without any preferred or selective orientation dominated the growth of the polycrystalline nanofibers or nanosheets consisting of grains of approximately 3 nm to which are formed by the coalescence of the single crystalline cerium oxide seeds. The growth is attributed to be driven by phase separation due to partial compatibility between ethyl alcohol and supercritical carbon dioxide fluid during the precipitation reaction, not by different surface energies or defects. With increasing temperature, the nanofibers with a weblike network structure were formed and then fused to large spherical particles. As a result, the polycrystalline fibers or sheets consisting of pure cerium dioxide phase were produced by the solvothermal reaction with an aid of the supercritical carbon dioxide from the alcoholic metal salt solution.", "journal": "Journal of nanoscience and nanotechnology", "sentences": ["Well-crystallized cerium dioxide with cubic phase were formed and self-assembly grown to nanofibers or nanosheets via a solvothermal precipitation from near-supercritical fluids without any help of metal catalysts or capping agents.", "The self-assembly attachment process without any preferred or selective orientation dominated the growth of the polycrystalline nanofibers or nanosheets consisting of grains of approximately 3 nm to which are formed by the coalescence of the single crystalline cerium oxide seeds.", "The growth is attributed to be driven by phase separation due to partial compatibility between ethyl alcohol and supercritical carbon dioxide fluid during the precipitation reaction, not by different surface energies or defects.", "With increasing temperature, the nanofibers with a weblike network structure were formed and then fused to large spherical particles.", "As a result, the polycrystalline fibers or sheets consisting of pure cerium dioxide phase were produced by the solvothermal reaction with an aid of the supercritical carbon dioxide from the alcoholic metal salt solution."], "title": "Growth of nanostructured polycrystalline cerium oxide through a solvothermal precipitation using near-supercritical fluids."}
{"paper_id": 23865702, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "We summarized the data related to foods high in saturated fat and risk of mortality. We searched Cochrane Library, MEDLINE, EMBASE, and ProQuest for studies from January 1952 to May 2012. We identified 26 publications with individual dietary data and all-cause, total cancer, or cardiovascular mortality as endpoints. Pooled relative risk estimates demonstrated that high intakes of milk, cheese, yogurt, and butter were not associated with a significantly increased risk of mortality compared with low intakes. High intakes of meat and processed meat were significantly associated with an increased risk of mortality but were associated with a decreased risk in a subanalysis of Asian studies. The overall quality of studies was variable. Associations varied by food group and population. This may be because of factors outside saturated fat content of individual foods. There is an ongoing need for improvement in assessment tools and methods that investigate food sources of saturated fat and mortality to inform dietary guidelines.", "journal": "American journal of public health", "sentences": ["We summarized the data related to foods high in saturated fat and risk of mortality.", "We searched Cochrane Library, MEDLINE, EMBASE, and ProQuest for studies from January 1952 to May 2012.", "We identified 26 publications with individual dietary data and all-cause, total cancer, or cardiovascular mortality as endpoints.", "Pooled relative risk estimates demonstrated that high intakes of milk, cheese, yogurt, and butter were not associated with a significantly increased risk of mortality compared with low intakes.", "High intakes of meat and processed meat were significantly associated with an increased risk of mortality but were associated with a decreased risk in a subanalysis of Asian studies.", "The overall quality of studies was variable.", "Associations varied by food group and population.", "This may be because of factors outside saturated fat content of individual foods.", "There is an ongoing need for improvement in assessment tools and methods that investigate food sources of saturated fat and mortality to inform dietary guidelines."], "title": "Food sources of saturated fat and the association with mortality: a meta-analysis."}
{"paper_id": 22232287, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "We previously showed that equilibrative nucleoside transporter 1 (ENT1) is a primary ribavirin transporter in human hepatocytes. However, because the role of this transporter in the antiviral mechanism of the drug remains unclear, the present study aimed to elucidate the role of ENT1 in ribavirin antiviral action. OR6 cells, a hepatitis C virus (HCV) replication system, were used to evaluate both ribavirin uptake and efficacy. The ribavirin transporter in OR6 cells was identified by mRNA expression analyses and transport assays. Nitrobenzylmercaptopurine riboside (NBMPR) and micro-RNA targeted to ENT1 mRNA (miR-ENT1) were used to reduce the ribavirin uptake level in OR6 cells. Our results showed that ribavirin antiviral activity was associated with its accumulation in OR6 cells, which was also closely associated with the uptake of the drug. It was found that the primary ribavirin transporter in OR6 cells was ENT1 and that inhibition of ENT1-mediated ribavirin uptake by NBMPR significantly attenuated the antiviral activity of the drug as well as its accumulation in OR6 cells. The results also showed that even a small reduction in the ENT1-mediated ribavirin uptake, achieved in this case using miR-ENT1, caused a significant decrease in its antiviral activity, thus indicating that the ENT1-mediated ribavirin uptake level determined its antiviral activity level in OR6 cells. In conclusion, our results show that by facilitating its uptake and accumulation in OR6 cells, ENT1 plays a pivotal role in the antiviral effectiveness of ribavirin and therefore provides an important insight into the efficacy of the drug in anti-HCV therapy.", "journal": "Antimicrobial agents and chemotherapy", "sentences": ["We previously showed that equilibrative nucleoside transporter 1 (ENT1) is a primary ribavirin transporter in human hepatocytes.", "However, because the role of this transporter in the antiviral mechanism of the drug remains unclear, the present study aimed to elucidate the role of ENT1 in ribavirin antiviral action.", "OR6 cells, a hepatitis C virus (HCV) replication system, were used to evaluate both ribavirin uptake and efficacy.", "The ribavirin transporter in OR6 cells was identified by mRNA expression analyses and transport assays.", "Nitrobenzylmercaptopurine riboside (NBMPR) and micro-RNA targeted to ENT1 mRNA (miR-ENT1) were used to reduce the ribavirin uptake level in OR6 cells.", "Our results showed that ribavirin antiviral activity was associated with its accumulation in OR6 cells, which was also closely associated with the uptake of the drug.", "It was found that the primary ribavirin transporter in OR6 cells was ENT1 and that inhibition of ENT1-mediated ribavirin uptake by NBMPR significantly attenuated the antiviral activity of the drug as well as its accumulation in OR6 cells.", "The results also showed that even a small reduction in the ENT1-mediated ribavirin uptake, achieved in this case using miR-ENT1, caused a significant decrease in its antiviral activity, thus indicating that the ENT1-mediated ribavirin uptake level determined its antiviral activity level in OR6 cells.", "In conclusion, our results show that by facilitating its uptake and accumulation in OR6 cells, ENT1 plays a pivotal role in the antiviral effectiveness of ribavirin and therefore provides an important insight into the efficacy of the drug in anti-HCV therapy."], "title": "ENT1, a ribavirin transporter, plays a pivotal role in antiviral efficacy of ribavirin in a hepatitis C virus replication cell system."}
{"paper_id": 26496295, "labels": ["0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Triple-negative breast cancer (TNBC) is aggressive, with high risk of visceral metastasis and death. A substantial proportion of patients with TNBC is associated with BRCA mutations, implying that these tumors are sensitive to DNA-damaging agents. We report successful treatment of a metastatic TNBC in a woman with a BRCA2 germline mutation using combined bevacizumab/paclitaxel/carboplatin (BPC) therapy. The patient was pregnant and had liver metastases, and a complete clinical response was sustained for approximately 5 years. Mastectomy was performed during the 29th week of pregnancy, and the baby was later delivered by caesarean section. Subsequently, multiple metastases in both liver lobes were detected using computed tomography and magnetic resonance imaging and the patient was treated with a BPC regimen, which led to complete disappearance of metastatic lesions in the liver. No additional treatment was provided, and after 5 years the patient consented to direct sequencing of BRCA2 and a 6781delG mutation was identified. At the most recent (5-year) follow-up, the patient was alive with good quality of life and no evidence of metastases.This finding suggests that BPC therapy might be considered a good therapeutic option for the treatment of metastatic TNBC in a woman with a BRCA2 germline mutation.", "journal": "Medicine", "sentences": ["Triple-negative breast cancer (TNBC) is aggressive, with high risk of visceral metastasis and death.", "A substantial proportion of patients with TNBC is associated with BRCA mutations, implying that these tumors are sensitive to DNA-damaging agents.", "We report successful treatment of a metastatic TNBC in a woman with a BRCA2 germline mutation using combined bevacizumab/paclitaxel/carboplatin (BPC) therapy.", "The patient was pregnant and had liver metastases, and a complete clinical response was sustained for approximately 5 years.", "Mastectomy was performed during the 29th week of pregnancy, and the baby was later delivered by caesarean section.", "Subsequently, multiple metastases in both liver lobes were detected using computed tomography and magnetic resonance imaging and the patient was treated with a BPC regimen, which led to complete disappearance of metastatic lesions in the liver.", "No additional treatment was provided, and after 5 years the patient consented to direct sequencing of BRCA2 and a 6781delG mutation was identified.", "At the most recent (5-year) follow-up, the patient was alive with good quality of life and no evidence of metastases.This finding suggests that BPC therapy might be considered a good therapeutic option for the treatment of metastatic TNBC in a woman with a BRCA2 germline mutation."], "title": "Liver Metastasis of a Triple-Negative Breast Cancer and Complete Remission for 5 Years After Treatment With Combined Bevacizumab/Paclitaxel/Carboplatin: Case Report and Review of the Literature."}
{"paper_id": 26385350, "labels": ["0", "0", "0", "1", "1", "0", "1", "1"], "abstract": "Somatic hypermutation and class-switch recombination of the immunoglobulin (Ig) genes occur in germinal center (GC) B cells and are initiated through deamination of cytidine to uracil by activation-induced cytidine deaminase (AID). Resulting uracil-guanine mismatches are processed by uracil DNA glycosylase (UNG)-mediated base-excision repair and MSH2-mediated mismatch repair (MMR) to yield mutations and DNA strand lesions. Although off-target AID activity also contributes to oncogenic point mutations and chromosome translocations associated with GC and post-GC B-cell lymphomas, the role of downstream AID-associated DNA repair pathways in the pathogenesis of lymphoma is unknown. Here, we show that simultaneous deficiency of UNG and MSH2 or MSH2 alone causes genomic instability and a shorter latency to the development of BCL6-driven diffuse large B-cell lymphoma (DLBCL) in a murine model. The additional development of several BCL6-independent malignancies in these mice underscores the critical role of MMR in maintaining general genomic stability. In contrast, absence of UNG alone is highly protective and prevents the development of BCL6-driven DLBCL. We further demonstrate that clonal and nonclonal mutations arise within non-Ig AID target genes in the combined absence of UNG and MSH2 and that DNA strand lesions arise in an UNG-dependent manner but are offset by MSH2. These findings lend insight into a complex interplay whereby potentially deleterious UNG activity and general genomic instability are opposed by the protective influence of MSH2, producing a net protective effect that promotes immune diversification while simultaneously attenuating malignant transformation of GC B cells.", "journal": "Blood", "sentences": ["Somatic hypermutation and class-switch recombination of the immunoglobulin (Ig) genes occur in germinal center (GC) B cells and are initiated through deamination of cytidine to uracil by activation-induced cytidine deaminase (AID).", "Resulting uracil-guanine mismatches are processed by uracil DNA glycosylase (UNG)-mediated base-excision repair and MSH2-mediated mismatch repair (MMR) to yield mutations and DNA strand lesions.", "Although off-target AID activity also contributes to oncogenic point mutations and chromosome translocations associated with GC and post-GC B-cell lymphomas, the role of downstream AID-associated DNA repair pathways in the pathogenesis of lymphoma is unknown.", "Here, we show that simultaneous deficiency of UNG and MSH2 or MSH2 alone causes genomic instability and a shorter latency to the development of BCL6-driven diffuse large B-cell lymphoma (DLBCL) in a murine model.", "The additional development of several BCL6-independent malignancies in these mice underscores the critical role of MMR in maintaining general genomic stability.", "In contrast, absence of UNG alone is highly protective and prevents the development of BCL6-driven DLBCL.", "We further demonstrate that clonal and nonclonal mutations arise within non-Ig AID target genes in the combined absence of UNG and MSH2 and that DNA strand lesions arise in an UNG-dependent manner but are offset by MSH2.", "These findings lend insight into a complex interplay whereby potentially deleterious UNG activity and general genomic instability are opposed by the protective influence of MSH2, producing a net protective effect that promotes immune diversification while simultaneously attenuating malignant transformation of GC B cells."], "title": "AID-associated DNA repair pathways regulate malignant transformation in a murine model of BCL6-driven diffuse large B-cell lymphoma."}
{"paper_id": 25311807, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1", "1"], "abstract": "Infection with influenza A virus can lead to increased susceptibility to subsequent bacterial infection, often with Streptococcus pneumoniae. Given the substantial modification of the lung environment that occurs following pathogen infection, there is significant potential for modulation of immune responses. In this study, we show that infection of mice with influenza virus, followed by the noninvasive EF3030 strain of Streptococcus pneumoniae, leads to a significant decrease in the virus-specific CD8(+) T cell response in the lung. Adoptive-transfer studies suggest that this reduction contributes to disease in coinfected animals. The reduced number of lung effector cells in coinfected animals was associated with increased death, as well as a reduction in cytokine production in surviving cells. Further, cells that retained the ability to produce IFN-\u03b3 exhibited a decreased potential for coproduction of TNF-\u03b1. Reduced cytokine production was directly correlated with a decrease in the level of mRNA. Negative regulation of cells in the mediastinal lymph node was minimal compared with that present in the lung, supporting a model of selective regulation in the tissue harboring high pathogen burden. These results show that entry of a coinfecting pathogen can have profound immunoregulatory effects on an ongoing immune response. Together, these findings reveal a novel dynamic interplay between concurrently infecting pathogens and the adaptive immune system.", "journal": "Journal of immunology (Baltimore, Md. : 1950)", "sentences": ["Infection with influenza A virus can lead to increased susceptibility to subsequent bacterial infection, often with Streptococcus pneumoniae.", "Given the substantial modification of the lung environment that occurs following pathogen infection, there is significant potential for modulation of immune responses.", "In this study, we show that infection of mice with influenza virus, followed by the noninvasive EF3030 strain of Streptococcus pneumoniae, leads to a significant decrease in the virus-specific CD8(+) T cell response in the lung.", "Adoptive-transfer studies suggest that this reduction contributes to disease in coinfected animals.", "The reduced number of lung effector cells in coinfected animals was associated with increased death, as well as a reduction in cytokine production in surviving cells.", "Further, cells that retained the ability to produce IFN-\u03b3 exhibited a decreased potential for coproduction of TNF-\u03b1.", "Reduced cytokine production was directly correlated with a decrease in the level of mRNA.", "Negative regulation of cells in the mediastinal lymph node was minimal compared with that present in the lung, supporting a model of selective regulation in the tissue harboring high pathogen burden.", "These results show that entry of a coinfecting pathogen can have profound immunoregulatory effects on an ongoing immune response.", "Together, these findings reveal a novel dynamic interplay between concurrently infecting pathogens and the adaptive immune system."], "title": "Coinfection with Streptococcus pneumoniae negatively modulates the size and composition of the ongoing influenza-specific CD8\u207a T cell response."}
{"paper_id": 26627255, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Switched antibody classes are important for efficient immune responses. Aberrant antibody production to otherwise harmless antigens may result in autoimmunity. The protein kinase fms-like tyrosine kinase 3 receptor (Flt3) has an important role during early B-cell development, but the role of Flt3 in peripheral B cells has not been assessed before. Herein we describe a previously unappreciated role for Flt3 in IgG1 class-switch recombination (CSR) and production. We show that Flt3 is reexpressed on B-cell lymphoma 6(+) germinal center B cells in vivo and following LPS activation of peripheral B cells in vitro. Absence of Flt3 signaling in Flt3 ligand-deficient mice results in impaired IgG1 CSR and accumulation of IgM-secreting plasma cells. On activated B cells, Flt3 is coexpressed and functions in synergy with the common-gamma chain receptor family. B cells from Flt3 ligand-deficient mice have impaired IL-4R signaling, with reduced phosphorylation of signal transducer and activator of transcription (Stat) 6, and demonstrate a failure to initiate CSR to IgG1 with low expression of \u03b31 germ-line transcripts, resulting in impaired IgG1 production. Thus, functional synergy between Flt3 and IL-4R signaling is critical for Stat-mediated regulation of sterile \u03b31 germ-line transcripts and CSR to IgG1.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["Switched antibody classes are important for efficient immune responses.", "Aberrant antibody production to otherwise harmless antigens may result in autoimmunity.", "The protein kinase fms-like tyrosine kinase 3 receptor (Flt3) has an important role during early B-cell development, but the role of Flt3 in peripheral B cells has not been assessed before.", "Herein we describe a previously unappreciated role for Flt3 in IgG1 class-switch recombination (CSR) and production.", "We show that Flt3 is reexpressed on B-cell lymphoma 6(+) germinal center B cells in vivo and following LPS activation of peripheral B cells in vitro.", "Absence of Flt3 signaling in Flt3 ligand-deficient mice results in impaired IgG1 CSR and accumulation of IgM-secreting plasma cells.", "On activated B cells, Flt3 is coexpressed and functions in synergy with the common-gamma chain receptor family.", "B cells from Flt3 ligand-deficient mice have impaired IL-4R signaling, with reduced phosphorylation of signal transducer and activator of transcription (Stat) 6, and demonstrate a failure to initiate CSR to IgG1 with low expression of \u03b31 germ-line transcripts, resulting in impaired IgG1 production.", "Thus, functional synergy between Flt3 and IL-4R signaling is critical for Stat-mediated regulation of sterile \u03b31 germ-line transcripts and CSR to IgG1."], "title": "Murine germinal center B cells require functional Fms-like tyrosine kinase 3 signaling for IgG1 class-switch recombination."}
{"paper_id": 26579916, "labels": ["0", "0", "0", "0", "1"], "abstract": "The effects of edge chemistry on the relative stability and electronic properties of zigzag boron nitride nanoribbons (ZBNNRs) are investigated. Among all functional groups considered, fully hydroxylated ZBNNRs are found to be the most energetically stable. When an in-plane external electric field is applied perpendicular to the axis of both hydrogenated and hydroxylated ZBNNRs, a spin-polarized half-metallic state is induced, whose character is different than that predicted for zigzag graphene nanoribbons. The onset field for achieving the half-metallic state is found to mainly depend on the width of the ribbon. Our results indicate that edge functionalization of ZBNNRs may open the way for the design of new nanoelectronic and nanospintronic devices.", "journal": "Journal of chemical theory and computation", "sentences": ["The effects of edge chemistry on the relative stability and electronic properties of zigzag boron nitride nanoribbons (ZBNNRs) are investigated.", "Among all functional groups considered, fully hydroxylated ZBNNRs are found to be the most energetically stable.", "When an in-plane external electric field is applied perpendicular to the axis of both hydrogenated and hydroxylated ZBNNRs, a spin-polarized half-metallic state is induced, whose character is different than that predicted for zigzag graphene nanoribbons.", "The onset field for achieving the half-metallic state is found to mainly depend on the width of the ribbon.", "Our results indicate that edge functionalization of ZBNNRs may open the way for the design of new nanoelectronic and nanospintronic devices."], "title": "Effects of Edge Oxidation on the Structural, Electronic, and Magnetic Properties of Zigzag Boron Nitride Nanoribbons."}
{"paper_id": 27100290, "labels": ["0", "0", "0", "0", "1"], "abstract": "The large majority of human immunodeficiency virus type 1 (HIV-1) markers of disease progression/severity previously identified have been associated with alterations in host genetic and immune responses, with few studies focused on viral genetic markers correlate with changes in disease severity. This study presents a cross-sectional/longitudinal study of HIV-1 single nucleotide polymorphisms (SNPs) contained within the viral promoter or long terminal repeat (LTR) in patients within the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort. HIV-1 LTR SNPs were found to associate with the classical clinical disease parameters CD4+ T-cell count and log viral load. They were found in both defined and undefined transcription factor binding sites of the LTR. A novel SNP identified at position 108 in a known COUP (chicken ovalbumin upstream promoter)/AP1 transcription factor binding site was significantly correlated with binding phenotypes that are potentially the underlying cause of the associated clinical outcome (increase in viral load and decrease in CD4+ T-cell count).", "journal": "PloS one", "sentences": ["The large majority of human immunodeficiency virus type 1 (HIV-1) markers of disease progression/severity previously identified have been associated with alterations in host genetic and immune responses, with few studies focused on viral genetic markers correlate with changes in disease severity.", "This study presents a cross-sectional/longitudinal study of HIV-1 single nucleotide polymorphisms (SNPs) contained within the viral promoter or long terminal repeat (LTR) in patients within the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort.", "HIV-1 LTR SNPs were found to associate with the classical clinical disease parameters CD4+ T-cell count and log viral load.", "They were found in both defined and undefined transcription factor binding sites of the LTR.", "A novel SNP identified at position 108 in a known COUP (chicken ovalbumin upstream promoter)/AP1 transcription factor binding site was significantly correlated with binding phenotypes that are potentially the underlying cause of the associated clinical outcome (increase in viral load and decrease in CD4+ T-cell count)."], "title": "HIV-1 Promoter Single Nucleotide Polymorphisms Are Associated with Clinical Disease Severity."}
{"paper_id": 26976587, "labels": ["0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "An extensive region of the Eastern Tropical South Pacific (ETSP) Ocean has surface waters that are nitrate-poor yet phosphate-rich. It has been proposed that this distribution of surface nutrients provides a geochemical niche favorable for N2fixation, the primary source of nitrogen to the ocean. Here, we present results from two cruises to the ETSP where rates of N2fixation and its contribution to export production were determined with a suite of geochemical and biological measurements. N2fixation was only detectable using nitrogen isotopic mass balances at two of six stations, and rates ranged from 0 to 23 \u00b5mol N m(-2)d(-1)based on sediment trap fluxes. Whereas the fractional importance of N2fixation did not change, the N2-fixation rates at these two stations were several-fold higher when scaled to other productivity metrics. Regardless of the choice of productivity metric these N2-fixation rates are low compared with other oligotrophic locations, and the nitrogen isotope budgets indicate that N2fixation supports no more than 20% of export production regionally. Although euphotic zone-integrated short-term N2-fixation rates were higher, up to 100 \u00b5mol N m(-2)d(-1), and detected N2fixation at all six stations, studies of nitrogenase gene abundance and expression from the same cruises align with the geochemical data and together indicate that N2fixation is a minor source of new nitrogen to surface waters of the ETSP. This finding is consistent with the hypothesis that, despite a relative abundance of phosphate, iron may limit N2fixation in the ETSP.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "sentences": ["An extensive region of the Eastern Tropical South Pacific (ETSP) Ocean has surface waters that are nitrate-poor yet phosphate-rich.", "It has been proposed that this distribution of surface nutrients provides a geochemical niche favorable for N2fixation, the primary source of nitrogen to the ocean.", "Here, we present results from two cruises to the ETSP where rates of N2fixation and its contribution to export production were determined with a suite of geochemical and biological measurements.", "N2fixation was only detectable using nitrogen isotopic mass balances at two of six stations, and rates ranged from 0 to 23 \u00b5mol N m(-2)d(-1)based on sediment trap fluxes.", "Whereas the fractional importance of N2fixation did not change, the N2-fixation rates at these two stations were several-fold higher when scaled to other productivity metrics.", "Regardless of the choice of productivity metric these N2-fixation rates are low compared with other oligotrophic locations, and the nitrogen isotope budgets indicate that N2fixation supports no more than 20% of export production regionally.", "Although euphotic zone-integrated short-term N2-fixation rates were higher, up to 100 \u00b5mol N m(-2)d(-1), and detected N2fixation at all six stations, studies of nitrogenase gene abundance and expression from the same cruises align with the geochemical data and together indicate that N2fixation is a minor source of new nitrogen to surface waters of the ETSP.", "This finding is consistent with the hypothesis that, despite a relative abundance of phosphate, iron may limit N2fixation in the ETSP."], "title": "Low rates of nitrogen fixation in eastern tropical South Pacific surface waters."}
{"paper_id": 24082068, "labels": ["0", "0", "0", "0", "0", "0", "0", "0", "0", "1"], "abstract": "Streptococcus pneumoniae (pneumococcus) frequently colonizes the human nasopharynx and is an important cause of pneumonia, meningitis, sinusitis, and otitis media. The outer cell surface of pneumococcus may assume various degrees of negative charge depending on the polysaccharide capsule, of which more than 90 serotypes have been identified. The negative charge of capsular polysaccharides has been proposed to electrostatically repel pneumococci from phagocytic cells, and avoidance of phagocytosis correlates with higher carriage prevalence. We hypothesized that the surface charge of pneumococcus contributes to its success in nasopharyngeal carriage by modulating resistance to phagocyte-mediated killing. Here, we measured the surface charge (zeta potential) of laboratory-constructed strains that share a genetic background but differ in serotype and of clinical strains that differ in serotype and genetic background. A more negative surface charge correlated with higher resistance to nonopsonic killing by human neutrophils in vitro. In addition, a more negative zeta potential was associated with higher carriage prevalence in human populations before and after the widespread use of the pneumococcal conjugate vaccine PCV7. We also confirmed that capsule is the major determinant of net surface charge in clinical isolates with diverse backgrounds. We noted that exceptions exist to the idea that a higher magnitude of negative charge predicts higher prevalence. The results indicated that zeta potential is strongly influenced by pneumococcal capsule type but is unlikely to be the only important mechanism by which capsule interacts with host.", "journal": "Infection and immunity", "sentences": ["Streptococcus pneumoniae (pneumococcus) frequently colonizes the human nasopharynx and is an important cause of pneumonia, meningitis, sinusitis, and otitis media.", "The outer cell surface of pneumococcus may assume various degrees of negative charge depending on the polysaccharide capsule, of which more than 90 serotypes have been identified.", "The negative charge of capsular polysaccharides has been proposed to electrostatically repel pneumococci from phagocytic cells, and avoidance of phagocytosis correlates with higher carriage prevalence.", "We hypothesized that the surface charge of pneumococcus contributes to its success in nasopharyngeal carriage by modulating resistance to phagocyte-mediated killing.", "Here, we measured the surface charge (zeta potential) of laboratory-constructed strains that share a genetic background but differ in serotype and of clinical strains that differ in serotype and genetic background.", "A more negative surface charge correlated with higher resistance to nonopsonic killing by human neutrophils in vitro.", "In addition, a more negative zeta potential was associated with higher carriage prevalence in human populations before and after the widespread use of the pneumococcal conjugate vaccine PCV7.", "We also confirmed that capsule is the major determinant of net surface charge in clinical isolates with diverse backgrounds.", "We noted that exceptions exist to the idea that a higher magnitude of negative charge predicts higher prevalence.", "The results indicated that zeta potential is strongly influenced by pneumococcal capsule type but is unlikely to be the only important mechanism by which capsule interacts with host."], "title": "Surface charge of Streptococcus pneumoniae predicts serotype distribution."}
{"paper_id": 26582836, "labels": ["0", "0", "0", "0", "0", "0", "0", "1", "1"], "abstract": "Hospitals strive to reduce methicillin-resistant Staphylococcus aureus (MRSA) prevalence via active surveillance of inpatient populations. Rapid and inexpensive screening methods are utilized when molecular methods are not operationally feasible. In this multisite clinical trial, the utility of Bio-Rad's MRSASelect II was evaluated for MRSA identification from remnant nares and wound swabs. The prevalence of MRSA was 11.1% (n = 1,384) from nares samples and 18.1% (n = 842) from wound samples. MRSASelect II had an overall concordance of 95.4% (confidence interval [CI] = 94.5% to 96.2%) compared to a broth-enriched reference standard. Comparisons between results, stratified by examination times, exhibited a nonsignificant trend toward increased positivity at prolonged incubation times. Cefoxitin screening of colonies directly from MRSASelect II was 96.7% (95.8% to 97.3%) concordant compared to testing of colonies following broth enrichment. A comparison of MRSASelect and MRSASelect II revealed no statistical differences; however, the latter exhibited earlier positivity, greater selectivity, and more intense indicator staining, which resulted in facilitated differentiation of positive results. MRSASelect II agar is a simple, rapid, and robust method to routinely screen patients for MRSA colonization without the need for additional testing.", "journal": "Journal of clinical microbiology", "sentences": ["Hospitals strive to reduce methicillin-resistant Staphylococcus aureus (MRSA) prevalence via active surveillance of inpatient populations.", "Rapid and inexpensive screening methods are utilized when molecular methods are not operationally feasible.", "In this multisite clinical trial, the utility of Bio-Rad's MRSASelect II was evaluated for MRSA identification from remnant nares and wound swabs.", "The prevalence of MRSA was 11.1% (n = 1,384) from nares samples and 18.1% (n = 842) from wound samples.", "MRSASelect II had an overall concordance of 95.4% (confidence interval [CI] = 94.5% to 96.2%) compared to a broth-enriched reference standard.", "Comparisons between results, stratified by examination times, exhibited a nonsignificant trend toward increased positivity at prolonged incubation times.", "Cefoxitin screening of colonies directly from MRSASelect II was 96.7% (95.8% to 97.3%) concordant compared to testing of colonies following broth enrichment.", "A comparison of MRSASelect and MRSASelect II revealed no statistical differences; however, the latter exhibited earlier positivity, greater selectivity, and more intense indicator staining, which resulted in facilitated differentiation of positive results.", "MRSASelect II agar is a simple, rapid, and robust method to routinely screen patients for MRSA colonization without the need for additional testing."], "title": "Multicenter Evaluation of MRSASelect II Chromogenic Agar for Identification of Methicillin-Resistant Staphylococcus aureus from Wound and Nasal Specimens."}
{"paper_id": 26866362, "labels": ["0", "0", "1", "1", "0", "1", "1"], "abstract": "A repertoire of transcription initiation factors engage the core promoter of mRNA genes to recruit RNA polymerase (Pol) II to initiate transcription, yet their precise spatial organization remains unclear. Using ChIP-exo, here we detail the interactions and genomic organization of initiation factors TBP, TFIIB, and Pol II at mRNA genes and within CpG islands. We find that when Pol II moves into a transcriptionally paused state, TBP/TFIIB remain at the promoter. We show that TBP and TFIIB bound to the core promoter at two separate, resolvable locations that coincided with sites of divergent transcription initiation. We also examine the precise binding of TBP at Pol III transcribed tRNA genes. We find that TBP crosslinked to tRNA genes in a similar manner as at Pol II transcribed genes. This comprehensive and high resolution genome-wide detection of the initiation machinery produces a consolidated view of transcription initiation events humans at Pol II coding and Pol III transcribed tRNA genes.", "journal": "PloS one", "sentences": ["A repertoire of transcription initiation factors engage the core promoter of mRNA genes to recruit RNA polymerase (Pol) II to initiate transcription, yet their precise spatial organization remains unclear.", "Using ChIP-exo, here we detail the interactions and genomic organization of initiation factors TBP, TFIIB, and Pol II at mRNA genes and within CpG islands.", "We find that when Pol II moves into a transcriptionally paused state, TBP/TFIIB remain at the promoter.", "We show that TBP and TFIIB bound to the core promoter at two separate, resolvable locations that coincided with sites of divergent transcription initiation.", "We also examine the precise binding of TBP at Pol III transcribed tRNA genes.", "We find that TBP crosslinked to tRNA genes in a similar manner as at Pol II transcribed genes.", "This comprehensive and high resolution genome-wide detection of the initiation machinery produces a consolidated view of transcription initiation events humans at Pol II coding and Pol III transcribed tRNA genes."], "title": "Genomic Organization of Human Transcription Initiation Complexes."}