bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure of the human TRiC/CCT Subunit 5 associated with hereditary sensory neuropathy
Authors: Pereira Jose H. , McAndrew Ryan P. , Sergeeva Oksana A. , Ralston Corie Y. , King Jonathan A. , Adams Paul D. 
Published: June 2017

AbstractThe human chaperonin TRiC consists of eight non-identical subunits, and its protein-folding activity is critical for cellular health. Misfolded proteins are associated with many human diseases, such as amyloid diseases, cancer, and neuropathies, making TRiC a potential therapeutic target. A detailed structural understanding of its ATP-dependent folding mechanism and substrate recognition is therefore of great importance. Of particular health-related interest is the mutation Histidine 147 to Arginine (H147R) in human TRiC subunit 5 (CCT5), which has been associated with hereditary sensory neuropathy. In this paper, we describe the crystal structures of CCT5 and the CCT5-H147R mutant, which provide important structural information for this vital protein-folding machine in humans. This first X-ray crystallographic study of a single human CCT subunit in the context of a hexadecameric complex can be expanded in the future to the other 7 subunits that form the TRiC complex.
Dosage compensation in the process of inactivation/reactivation during both germ cell development and early embryogenesis in mouse
Authors: Li Xiaoyong , Hu Zhiqiang , Yu Xuelin , Zhang Chen , Ma Binbin , He Lin , Wei Chaochun , Wu Ji 
Published: June 2017

AbstractOhno proposed that dosage compensation in mammals evolved as a two-step mechanism involving X-inactivation and X-upregulation. While X-inactivation is well characterized, it remains to further analysis whether upregulation of the single activated X chromosome in mammals occurs. We obtained RNA-seq data, including single-cell RNA-seq data, from cells undergoing inactivation/reactivation in both germ cell development and early embryogenesis stages in mouse and calculated the X: A ratio from the gene expression. Our results showed that the X: A ratio is always 1, regardless of the number of X chromosomes being transcribed for expressed genes. Furthermore, the single-cell RNA-seq data across individual cells of mouse preimplantation embryos of mixed backgrounds indicated that strain-specific SNPs could be used to distinguish transcription from maternal and paternal chromosomes and further showed that when the paternal was inactivated, the average gene dosage of the active maternal X chromosome was increased to restore the balance between the X chromosome and autosomes. In conclusion, our analysis of RNA-seq data (particularly single-cell RNA-seq) from cells undergoing the process of inactivation/reactivation provides direct evidence that the average gene dosage of the single active X chromosome is upregulated to achieve a similar level to that of two active X chromosomes and autosomes present in two copies.
Sialic acid linkage differentiation of glycopeptides using capillary electrophoresis – electrospray ionization – mass spectrometry
Authors: Kammeijer Guinevere S. M. , Jansen Bas C. , Kohler Isabelle , Heemskerk Anthonius A. M. , Mayboroda Oleg A. , Hensbergen Paul J. , Schappler Julie , Wuhrer Manfred 
Published: June 2017

AbstractSialylation is a glycosylation feature that occurs in different linkages at the non-reducing end of a glycan moiety, the linkage isomers are often differentially associated with various biological processes. Due to very similar physico-chemical properties, the separation of isomeric sialylated glycopeptides remains challenging but of utmost importance in the biomedicine and biotechnology, including biomarker discovery, glyco-engineering and biopharmaceutical characterization. This study presents the implementation of a high-resolution separation platform based on capillary electrophoresis – mass spectrometry (CE–MS) allowing for the selective analysis of α2,3- and α2,6-sialylated glycopeptides. These differentially linked glycopeptides showed an identical fragmentation pattern (collision induced dissociation) but different electrophoretic mobilities, allowing for baseline separation of the different linkages without the need for an extensive sample preparation. The different migration behavior between the two moieties was found to correlate with differences in pKavalues. Using a novel methodology adapted from the so-called internal standard CE approach, a relative difference of 3.4·10−2in pKaunit was determined. This approach was applied for the analysis of tryptic glycopeptides of prostate specific antigen, which shows highly complex and heterogeneous glycosylation. The developed platform therefore appears attractive for the identification of differentially linked sialic acids that may be related to pathological conditions.
Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals
Authors: Miyama Takahiko , Kawase Takakazu , Kitaura Kazutaka , Chishaki Ren , Shibata Masashi , Oshima Kumi , Hamana Hiroshi , Kishi Hiroyuki , Muraguchi Atsushi , Kuzushima Kiyotaka , Saji Hiroh , Shin-I Tadasu , Suzuki Ryuji , Ichinohe Tatsuo 
Published: June 2017

AbstractTo expand our knowledge of the ontogeny of the T-cell receptor (TCR) repertoire of antigen-specific T-cell subsets, we combined next-generation deep sequencing and single-cell multiplex clonotype analysis to evaluate the diversity and frequency of paired TCRs, their functions and whether clonotypic TCRs are shared among different individuals. Using an HLA-A*02-restricted cytomegalovirus (CMV) pp65-derived immunogenic peptide, we found that the more dominant pp65-specific TCR clonotypes in the blood of healthy donors have higher binding affinities for the CMV peptide and arise from clonotypes that are highly shared among individuals. Interestingly, these highly shared HLA-A*02-restricted CMV-specific TCRs were detected in a CMV-seronegative individual as well as in HLA-A*02-negative donors albeit at lower frequency. More intriguingly, these shared TCR clonotypes were abundant in the stem memory T-cell subset, and TCR diversity of the stem memory T-cell repertoire was significantly lower than in the central memory and effector memory T-cell repertoires. These results suggest that the stem memory T-cell subset may serve as a reservoir of highly shared and highly functional memory T-cells.
Adiponectin regulates BMSC osteogenic differentiation and osteogenesis through the Wnt/β-catenin pathway
Authors: Wang Yiyao , Zhang Xiaohui , Shao Jun , Liu Hanghang , Liu Xian , Luo En 
Published: June 2017

AbstractRecent studies have demonstrated the stimulatory effects of adiponectin on bone formation, but the mechanism underlying these effects remains unclear. The Wnt/β-catenin pathway, one of the most important pathways in osteogenesis, has rarely been associated with the osteogenic effects of adiponectin in previous studies. The present study was designed to investigate the effects of adiponectin on bone mesenchymal stem cell (BMSC) osteogenic differentiation and bone formation through the Wnt/β-catenin pathway. We detected adiponectin receptor expression in BMSCs, constructed a recombinant adenovirus containing the human adiponectin gene, and then used the adenovirus to transfect BMSCs in vitro or injected the adenovirus into bone defect areas in animal models. Wnt/β-catenin pathway and osteogenesis were detected by real-time PCR, western blotting, immunofluorescence, HE staining and micro-CT. In both our in vivo and in vitro experiments, we detected higher gene and protein expression levels of the Wnt/β-catenin pathway-related factors β-catenin and cyclinD1 in adiponectin transgenic BMSCs and rats. Similar results were noted regarding the gene and protein expression levels of osteogenesis-related genes. In addition, more new bone formation was observed in the adiponectin-treated groups. Our results indicate that adiponectin could facilitate BMSC osteogenic differentiation and osteogenesis, and the Wnt/β-catenin pathway was involved in the osteogenic effect of adiponectin.
An essential role of PI3K in the control of West Nile virus infection
Authors: Wang Leilei , Yang Long , Fikrig Erol , Wang Penghua 
Published: June 2017

AbstractThe phosphatidyl-inositol-3 kinases (PI3K) pathway regulates a variety of cellular processes, including cell proliferation, RNA processing, protein translation, autophagy, apoptosis and antiviral immunity. Many viruses depend on PI3K signaling for replication. However, its role in flaviviral infection has not been clearly defined. Here we report that PI3K signaling is critical for the control of West Nile virus (WNV) infection by regulating type I IFN (IFN-I) response. Inhibition of PI3K activity by 3-methyl adenine (3-MA), Wortmannin (WM) and LY294002 (LY) increased viral titers by 3–16 folds in primary mouse macrophages, embryonic fibroblasts and human cell lines. Both 3-MA and LY repressed IFN-I mRNA and protein expression significantly. Surprisingly, WM enhanced the mRNA expression of IFN-I and TNF-α, and TNF-α protein production modestly, while dramatically decreased the secreted IFN-I. Further studies showed that the catalytic subunit p110δ of class I PI3K played a role in induction of antiviral immune responses. Lastly translocation of interferon regulatory factor 7(IRF7) from the cytosol to the nuclei was effectively blocked in the presence of PI3K inhibitors. Our results clearly define an antiviral role of PI3K by modulating immune responses and demonstrate differential mode of action of three PI3K inhibitors on IFN-I.
Assessing Spatial and Temporal Patterns of Observed Ground-level Ozone in China
Authors: Wang Wan-Nan , Cheng Tian-Hai , Gu Xing-Fa , Chen Hao , Guo Hong , Wang Ying , Bao Fang-Wen , Shi Shuai-Yi , Xu Bin-Ren , Zuo Xin , Meng Can , Zhang Xiao-Chuan 
Published: June 2017

AbstractElevated ground-level ozone (O3), which is an important aspect of air quality related to public health, has been causing increasing concern. This study investigated the spatiotemporal distribution of ground-level O3 concentrations in China using a dataset from the Chinese national air quality monitoring network during 2013–2015. This research analyzed the diurnal, monthly and yearly variation of O3 concentrations in both sparsely and densely populated regions. In particular, 6 major Chinese cities were selected to allow a discussion of variations in O3 levels in detail, Beijing, Chengdu, Guangzhou, Lanzhou, Shanghai, and Urumchi, located on both sides of the Heihe-Tengchong line. Data showed that the nationwide 3-year MDA8 of ground-level O3 was 80.26 μg/m3. Ground-level O3 concentrations exhibited monthly variability peaking in summer and reaching the lowest levels in winter. The diurnal cycle reached a minimum in morning and peaked in the afternoon. Yearly average O3 MDA8 concentrations in Beijing, Chengdu, Lanzhou, and Shanghai in 2015 increased 12%, 25%, 34%, 22%, respectively, when compared with those in 2013. Compared with World Health Organization O3 guidelines, Beijing, Chengdu, Guangzhou, and Shanghai suffered O3 pollution in excess of the 8-hour O3 standard for more than 30% of the days in 2013 to 2015.
Integrated optical waveguide-based fluorescent immunosensor for fast and sensitive detection of microcystin-LR in lakes: Optimization and Analysis
Authors: Liu Lanhua , Zhou Xiaohong , Wilkinson James S. , Hua Ping , Song Baodong , Shi Hanchang 
Published: June 2017

AbstractNowadays, biosensor technologies which can detect various contaminants in water quickly and cost-effectively are in great demand. Herein, we report an integrated channel waveguide-based fluorescent immunosensor with the ability to detect a maximum of 32 contaminants rapidly and simultaneously. In particular, we use waveguide tapers to improve the efficiency of excitation and collection of fluorescent signals in the presence of fluorophore photobleaching in a solid surface bioassay. Under the optimized waveguide geometry, this is the first demonstration of using such a type of waveguide immunosensor for the detection of microcystin-LR (MC-LR) in lake water. The waveguide chip was activated by (3-Mercaptopropyl) trimethoxysilane/N-(4-maleimidobutyryloxy) succinimide (MTS/GMBS) for immobilization of BSA-MC-LR conjugate, which was confirmed to have uniform monolayer distribution by atomic force microscopy. All real lake samples, even those containing MC-LR in the sub-microgram per liter range (e.g. 0.5 μg/L), could be determined by the immunosensor with recovery rates between 84% and 108%, confirming its application potential in the measurement of MC-LR in real water samples.
No-scanning 3D measurement method using ultrafast dimensional conversion with a chirped optical frequency comb
Authors: Kato Takashi , Uchida Megumi , Minoshima Kaoru 
Published: June 2017

AbstractA simultaneously high-precision, wide-range, and ultrafast time-resolution one-shot 3D shape measurement method is presented. Simultaneous times of flight from multiple positions to a target encoded in a chirped optical frequency comb can be obtained from spectral interferometry. We experimentally demonstrate a one-shot imaging profile measurement of a known step height of 480 µm with µm-level accuracy. We further demonstrate the extension of the dynamic range by measuring in one shot a large step height of 3 m while maintaining high accuracy using the accurate pulse-to-pulse separation of the optical frequency comb. The proposed method with its large dynamic range and measurement versatility can be applied to a broad range of applications, including microscopic structures, objects with large size or aspect ratio, and ultrafast time-resolved imaging. This study provides a powerful and versatile tool for 3D measurement, where various ranges of measurement performances can be tailored to demand.
Heritability and responses to high fat diet of plasma lipidomics in a twin study
Authors: Frahnow Turid , Osterhoff Martin A. , Hornemann Silke , Kruse Michael , Surma Michal A. , Klose Christian , Simons Kai , Pfeiffer Andreas F. H. 
Published: June 2017

AbstractLipidomics have a great potential as clinical tool for monitoring metabolic changes in health and disease. Nevertheless hardly anything is known about the heritability of lipids. Therefore, it is necessary to clarify how and how much we can affect these progresses in individuals. In our interventional twin study (46 healthy, non-obese twin pairs) we investigated the lipid profile in plasma samples after switching from a low fat diet to an isocaloric high fat diet (HFD) to characterize the metabolic adaptation. Additionally we used the ACE model for Additive genetics, Common and unique Environment as well as linear mixed modelling to analyse the heritability of lipids. The heritability of lipids varied between 0–62% and applied to lipid species rather than to lipid classes. Phospholipids showed the highest inheritance. In addition, sex, body mass index (BMI) and age were important modifiers. The lipid profile changed already after one week of HFD and diverged further after 5 weeks of additional HFD. Basal concentrations of specific lipids within phospholipids are strongly inherited and are likely to be associated with heritable disease risks. BMI, sex and age were major modifiers. Nutrition strongly alters specific lipid classes, and has to be controlled in clinical association studies.
Machine Learning and Network Analysis of Molecular Dynamics Trajectories Reveal Two Chains of Red/Ox-specific Residue Interactions in Human Protein Disulfide Isomerase
Authors: Karamzadeh Razieh , Karimi-Jafari Mohammad Hossein , Sharifi-Zarchi Ali , Chitsaz Hamidreza , Salekdeh Ghasem Hosseini , Moosavi-Movahedi Ali Akbar 
Published: June 2017

AbstractThe human protein disulfide isomerase (hPDI), is an essential four-domain multifunctional enzyme. As a result of disulfide shuffling in its terminal domains, hPDI exists in two oxidation states with different conformational preferences which are important for substrate binding and functional activities. Here, we address the redox-dependent conformational dynamics of hPDI through molecular dynamics (MD) simulations. Collective domain motions are identified by the principal component analysis of MD trajectories and redox-dependent opening-closing structure variations are highlighted on projected free energy landscapes. Then, important structural features that exhibit considerable differences in dynamics of redox states are extracted by statistical machine learning methods. Mapping the structural variations to time series of residue interaction networks also provides a holistic representation of the dynamical redox differences. With emphasizing on persistent long-lasting interactions, an approach is proposed that compiled these time series networks to a single dynamic residue interaction network (DRIN). Differential comparison of DRIN in oxidized and reduced states reveals chains of residue interactions that represent potential allosteric paths between catalytic and ligand binding sites of hPDI.
Burden of sleep disturbances and associated risk factors: A cross-sectional survey among HIV-infected persons on antiretroviral therapy across China
Authors: Huang Xiaojie , Li Huiqin , Meyers Kathrine , Xia Wei , Meng Zhihao , Li Chongxi , Bai Jinsong , He Shenghua , Cai Weiping , Huang Chengyu , Liu Shuiqing , Wang Hui , Ling Xuemei , Ma Ping , Tan Daling , Wang Fuxiang , Ruan Lianguo , Zhao Hongxin , Wei Hongxia , Liu Yanfen , Yu Jianhua , Lu Hongzhou , Wang Min , Zhang Tong , Chen Hui , Wu Hao 
Published: June 2017

AbstractThis study evaluated the prevalence and factors associated with sleep disturbance in a large cohort of HIV-infected patients across China. A cross-sectional study was conducted among HIV-infected patients on antiretroviral therapy at 20 AIDS clinics. The Pittsburgh Sleep Quality Index was self-administered by subjects. Socio-demographic characteristics, medical history and HIV-related clinical data were collected. 4103 patients had complete data for analysis. Sleep disturbances were observed in 43.1% of patients. Associated factors in multivariable analysis included psychological factors: anxiety (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.44–4.00; P < 0.001), depression (OR, 2.09; 95% CI, 1.70–2.57; P < 0.001), and both anxiety and depression (OR, 5.90; 95% CI, 4.86–7.16; P < 0.001); sociodemographic factors: MSM (OR, 1.26; 95% CI, 1.04–1.52; P﻿ = 0.018), being single (OR, 1.45; 95%CI 1.21–1.74; P < 0.001), higher education (OR, ﻿1.25; 95% CI, 1.03–1.53; P = 0.025)﻿; and clinical factors: suboptimal adherence (OR,1.51; 95% CI,1.23–1.85; P < 0.001), regimen-switching (OR, 1.94; 95% CI, 1.12–3.35; P = 0.018), and antidepressant use (OR, 1.98; 95% CI, 1.47–2.67; P = 0.044). Prevalence of sleep disturbance is high in this large Chinese cohort. Associated factors appear related to psychological and social-demographic factors. Health workers may consider routinely assessing sleep disturbances among HIV-infected patients, especially in the first three months after HIV diagnosis, and referring for mental health services, which may positively impact adherence to treatment.
Comparative transcriptomic and proteomic analyses provide insights into the key genes involved in high-altitude adaptation in the Tibetan pig
Authors: Zhang Bo , Chamba Yangzom , Shang Peng , Wang Zhixiu , Ma Jun , Wang Liyuang , Zhang Hao 
Published: June 2017

AbstractTibetan pigs that inhabit the Tibetan Plateau exhibit striking phenotypic and physiological differences from lowland pigs, and have adapted well to extreme conditions. However, the mechanisms involved in regulating gene expression at high altitude in these animals are not fully understood. In this study, we obtained transcriptomic and proteomic data from the heart tissues of Tibetan and Yorkshire pigs raised in the highlands (TH and YH) and lowlands (TL and YL) via RNA-seq and iTRAQ (isobaric tags for relative and absolute quantitation) analyses, respectively. Comparative analyses of TH vs. YH, TH vs.TL, TL vs. YL, and YH vs. YL yielded 299, 169, 242, and 368 differentially expressed genes (DEGs), and 473, 297, 394, and 297 differentially expressed proteins (DEPs), respectively. By functional annotation of these DEGs and DEPs, genes that were enriched in the HIF-1 signaling pathway (NPPA, ERK2, ENO3, and EGLN3), VEGF signaling pathway (ERK2, A2M, FGF1, CTGF, and DPP4), and hypoxia-related processes (CRYAB, EGLN3, TGFB2, DPP4, and ACE) were identified as important candidate genes for high-altitude adaptation in the Tibetan pig. This study enhances our understanding of the molecular mechanisms involved in hypoxic adaptation in pigs, and furthers our understanding of human hypoxic diseases.
Prediction of lncRNA-protein interactions using HeteSim scores based on heterogeneous networks
Authors: Xiao Yun , Zhang Jingpu , Deng Lei 
Published: June 2017

AbstractMassive studies have indicated that long non-coding RNAs (lncRNAs) are critical for the regulation of cellular biological processes by binding with RNA-related proteins. However, only a few experimentally supported lncRNA-protein associations have been reported. Existing network-based methods are typically focused on intrinsic features of lncRNA and protein but ignore the information implicit in the topologies of biological networks associated with lncRNAs. Considering the limitations in previous methods, we propose PLPIHS, an effective computational method for Predicting lncRNA-Protein Interactions using HeteSim Scores. PLPIHS uses the HeteSim measure to calculate the relatedness score for each lncRNA-protein pair in the heterogeneous network, which consists of lncRNA-lncRNA similarity network, lncRNA-protein association network and protein-protein interaction network. An SVM classifier to predict lncRNA-protein interactions is built with the HeteSim scores. The results show that PLPIHS performs significantly better than the existing state-of-the-art approaches and achieves an AUC score of 0.97 in the leave-one-out validation test. We also compare the performances of networks with different connectivity density and find that PLPIHS performs well across all the networks. Furthermore, we use the proposed method to identify the related proteins for lncRNA MALAT1. Highly-ranked proteins are verified by the biological studies and demonstrate the effectiveness of our method.
Revealing protein networks and gene-drug connectivity in cancer from direct information
Authors: Jiang Xian-Li , Martinez-Ledesma Emmanuel , Morcos Faruck 
Published: June 2017

AbstractThe connection between genetic variation and drug response has long been explored to facilitate the optimization and personalization of cancer therapy. Crucial to the identification of drug response related genetic features is the ability to separate indirect correlations from direct correlations across abundant datasets with large number of variables. Here we analyzed proteomic and pharmacogenomic data in cancer tissues and cell lines using a global statistical model connecting protein pairs, genes and anti-cancer drugs. We estimated this model using direct coupling analysis (DCA), a powerful statistical inference method that has been successfully applied to protein sequence data to extract evolutionary signals that provide insights on protein structure, folding and interactions. We used Direct Information (DI) as a metric of connectivity between proteins as well as gene-drug pairs. We were able to infer important interactions observed in cancer-related pathways from proteomic data and predict potential connectivities in cancer networks. We also identified known and potential connections for anti-cancer drugs and gene mutations using DI in pharmacogenomic data. Our findings suggest that gene-drug connections predicted with direct couplings can be used as a reliable guide to cancer therapy and expand our understanding of the effects of gene alterations on drug efficacies.