bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trans-Atlantic exchanges have shaped the population structure of the Lyme disease agent Borrelia burgdorferi sensu stricto
Authors: Castillo-Ramírez S. , Fingerle V. , Jungnick S. , Straubinger R. K. , Krebs S. , Blum H. , Meinel D. M. , Hofmann H. , Guertler P. , Sing A. , Margos G. 
Published: March 2016

AbstractThe origin and population structure of Borrelia burgdorferi sensu stricto (s.s.), the agent of Lyme disease, remain obscure. This tick-transmitted bacterial species occurs in both North America and Europe. We sequenced 17 European isolates (representing the most frequently found sequence types in Europe) and compared these with 17 North American strains. We show that trans-Atlantic exchanges have occurred in the evolutionary history of this species and that a European origin of B. burgdorferi s.s. is marginally more likely than a USA origin. The data further suggest that some European human patients may have acquired their infection in North America. We found three distinct genetically differentiated groups: i) the outgroup species Borrelia bissettii, ii) two divergent strains from Europe, and iii) a group composed of strains from both the USA and Europe. Phylogenetic analysis indicated that different genotypes were likely to have been introduced several times into the same area. Our results demonstrate that irrespective of whether B. burgdorferi s.s. originated in Europe or the USA, later trans-Atlantic exchange(s) have occurred and have shaped the population structure of this genospecies. This study clearly shows the utility of next generation sequencing to obtain a better understanding of the phylogeography of this bacterial species.
Response of Human Osteoblast to n-HA/PEEK—Quantitative Proteomic Study of Bio-effects of Nano-Hydroxyapatite Composite
Authors: Zhao Minzhi , Li Haiyun , Liu Xiaochen , Wei Jie , Ji Jianguo , Yang Shu , Hu Zhiyuan , Wei Shicheng 
Published: March 2016

AbstractNano-sized hydroxyapatite (n-HA) is considered as a bio-active material, which is often mixed into bone implant material, polyetheretherketone (PEEK). To reveal the global protein expression modulations of osteoblast in response to direct contact with the PEEK composite containing high level (40%) nano-sized hydroxyapatite (n-HA/PEEK) and explain its comprehensive bio-effects, quantitative proteomic analysis was conducted on human osteoblast-like cells MG-63 cultured on n-HA/PEEK in comparison with pure PEEK. Results from quantitative proteomic analysis showed that the most enriched categories in the up-regulated proteins were related to calcium ion processes and associated functions while the most enriched categories in the down-regulated proteins were related to RNA process. This enhanced our understanding to the molecular mechanism of the promotion of the cell adhesion and differentiation with the inhibition of the cell proliferation on n-HA/PEEK composite. It also exhibited that although the calcium ion level of incubate environment hadn’t increased, merely the calcium fixed on the surface of material had influence to intracellular calcium related processes, which was also reflect by the higher intracellular Ca2+ concentration of n-HA/PEEK. This study could lead to more comprehensive cognition to the versatile biocompatibility of composite materials. It further proves that proteomics is useful in new bio-effect discovery.
Recovery of Interdependent Networks
Authors: Di Muro M. A. , La Rocca C. E. , Stanley H. E. , Havlin S. , Braunstein L. A. 
Published: March 2016

AbstractRecent network research has focused on the cascading failures in a system of interdependent networks and the necessary preconditions for system collapse. An important question that has not been addressed is how to repair a failing system before it suffers total breakdown. Here we introduce a recovery strategy for nodes and develop an analytic and numerical framework for studying the concurrent failure and recovery of a system of interdependent networks based on an efficient and practically reasonable strategy. Our strategy consists of repairing a fraction of failed nodes, with probability of recovery γ, that are neighbors of the largest connected component of each constituent network. We find that, for a given initial failure of a fraction 1 − p of nodes, there is a critical probability of recovery above which the cascade is halted and the system fully restores to its initial state and below which the system abruptly collapses. As a consequence we find in the plane γ − p of the phase diagram three distinct phases. A phase in which the system never collapses without being restored, another phase in which the recovery strategy avoids the breakdown, and a phase in which even the repairing process cannot prevent system collapse.
Interleukin-31 expression and relation to disease severity in human asthma
Authors: Lai Tianwen , Wu Dong , Li Wen , Chen Min , Yi Zhennan , Huang Dan , Jing Zhiliang , Lü Yingying , Lv Quanchao , Li Dongming , Wu Bin 
Published: March 2016

AbstractInterleukin 31 (IL-31) is a novel T helper type 2 effector cytokine that plays an important role in the pathogenesis of allergic diseases. However, its role in human asthma remains unclear. The aim of this study was to measure IL-31 levels in the serum, bronchoalveolar lavage fluid (BALF) and bronchial tissue of asthmatics and healthy subjects and identify its possible correlation to disease severity. We quantified IL-31 levels in the serum of patients with asthma (n = 44), as well as in controls (n = 22). Of these subjects, 9 asthmatics and five controls underwent bronchoscopy with endobronchial biopsy and BALF collection. Our data showed that serum and BALF IL-31 levels were significantly elevated in patients with asthma compared with controls. Expressions of IL-31 and IL-31 receptor (IL-31RA and OSMR) were more prominent in the bronchial tissue in severe compared to mild asthma and controls. Serum IL-31 levels correlated positively with Th2 related cytokines (IL-5, IL-13 and TSLP), asthma severity or total serum immunoglobulin E (IgE) and inversely with asthma control and the forced expiratory volume in 1 second (FEV1). The current data may provide insight into the underlying pathogenesis of asthma, in which IL-31 has an important pathogenic role.
The RecQ DNA helicase Rqh1 constrains Exonuclease 1-dependent recombination at stalled replication forks
Authors: Osman Fekret , Ahn Jong Sook , Lorenz Alexander , Whitby Matthew C. 
Published: March 2016

AbstractDNA double-strand break (DSB) repair by homologous recombination (HR) involves resection of the break to expose a 3′ single-stranded DNA tail. In budding yeast, resection occurs in two steps: initial short-range resection, performed by Mre11-Rad50-Xrs2 and Sae2; and long-range resection catalysed by either Exo1 or Sgs1-Dna2. Here we use genetic assays to investigate the importance of Exo1 and the Sgs1 homologue Rqh1 for DNA repair and promotion of direct repeat recombination in the fission yeast Schizosaccharomyces pombe. We find that Exo1 and Rqh1 function in alternative redundant pathways for promoting survival following replication fork breakage. Exo1 promotes replication fork barrier-induced direct repeat recombination but intriguingly limits recombination induced by fork breakage. Direct repeat recombination induced by ultraviolet light depends on either Exo1 or Rqh1. Finally, we show that Rqh1 plays a major role in limiting Exo1-dependent direct repeat recombination induced by replication fork stalling but only a minor role in constraining recombination induced by fork breakage. The implications of our findings are discussed in the context of the benefits that long-range resection may bring to processing perturbed replication forks.
Correlation of p-doping in CVD Graphene with Substrate Surface Charges
Authors: Goniszewski S. , Adabi M. , Shaforost O. , Hanham S. M. , Hao L. , Klein N. 
Published: March 2016

AbstractCorrelations between the level of p-doping exhibited in large area chemical vapour deposition (CVD) graphene field effect transistor structures (gFETs) and residual charges created by a variety of surface treatments to the silicon dioxide (SiO2) substrates prior to CVD graphene transfer are measured. Beginning with graphene on untreated thermal oxidised silicon, a minimum conductivity (σmin) occurring at gate voltage Vg = 15 V (Dirac Point) is measured. It was found that more aggressive treatments (O2 plasma and UV Ozone treatments) further increase the gate voltage of the Dirac point up to 65 V, corresponding to a significant increase of the level of p-doping displayed in the graphene. An electrowetting model describing the measured relationship between the contact angle (θ) of a water droplet applied to the treated substrate/graphene surface and an effective gate voltage from a surface charge density is proposed to describe biasing of Vg at σmin and was found to fit the measurements with multiplication of a correction factor, allowing effective non-destructive approximation of substrate added charge carrier density using contact angle measurements.
E-selectin-targeting delivery of microRNAs by microparticles ameliorates endothelial inflammation and atherosclerosis
Authors: Ma Shuangtao , Tian Xiao Yu , Zhang Yunrong , Mu Chaofeng , Shen Haifa , Bismuth Jean , Pownall Henry J. , Huang Yu , Wong Wing Tak 
Published: March 2016

AbstractE-selectin is a surface marker of endothelial cell (EC) inflammation, one of the hallmarks of atherogenesis. Thus, we tested the hypothesis that delivery of microRNA (miR)-146a and miR-181b with an E-selectin-targeting multistage vector (ESTA-MSV) to inflamed endothelium covering atherosclerotic plaques inhibits atherosclerosis. Cy5-conjugated miR-146a and miR-181b were packaged in polyethylene glycol-polyethyleneimine (PEG/PEI) nanoparticles and loaded into ESTA-MSV microparticles. Both miRs were downregulated in tumor necrosis factor (TNF)-α-treated ECs. Transfection of TNF-α-treated mouse aortas and cultured ECs with miRs was more efficient with ESTA-MSV than with the PEG/PEI. Likewise, miR-146a/-181b packaged in ESTA-MSV efficiently suppressed the chemokines, CCL2, CCL5, CCL8 and CXCL9 and monocyte adhesion to ECs. Complementaryin vivotests were conducted in male apolipoprotein E-deficient mice fed a Western diet and injected intravenously with the particles prepared as above biweekly for 12 weeks. Treatment with miRs packaged in ESTA-MSV but not in PEG/PEI reduced atherosclerotic plaque size. Concurrently, vascular inflammation markers, including macrophages in aortic root lesions and chemokine expression in aortic tissues were reduced while the vascular smooth muscle cells and collagen increased in plaques from ESTA-MSV/miRs-treatedvs.vehicle-treated mice. Our data supported our hypothesis that ESTA-MSV microparticle-mediated delivery of miR-146a/-181b ameliorates endothelial inflammation and atherosclerosis.
Necessity of capillary modes in a minimal model of nanoscale hydrophobic solvation
Authors: Vaikuntanathan Suriyanarayanan , Rotskoff Grant , Hudson Alexander , Geissler Phillip L. 
Published: March 2016

Significance
Hydrophobic effects, which play a crucial role in many chemical and biological processes, originate in the statistics of microscopic density fluctuations in liquid water. Chandler has established the foundation for a simple and unified understanding of these effects, by identifying essential aspects of water’s intermolecular structure while accounting for its proximity to phase coexistence. Here, we show that coarse-grained models based on this perspective, when constructed to include the statistics of capillary waves at interfaces, can achieve remarkable agreement with results of atomistically detailed simulations. Highly efficient and lacking adjustable parameters, such models hold promise as powerful tools for studying multiscale problems in hydrophobic solvation.
Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing
Authors: Falaleeva Marina , Pages Amadis , Matuszek Zaneta , Hidmi Sana , Agranat-Tamir Lily , Korotkov Konstantin , Nevo Yuval , Eyras Eduardo , Sperling Ruth , Stamm Stefan 
Published: March 2016

SignificanceC/D box small nucleolar RNAs (SNORDs) are abundant, short, nucleoli-residing, noncoding RNAs that guide the methyltransferase fibrillarin to perform 2′-O-methylation of target RNAs. We identified 29 SNORDs present in a fibrillarin-containing fraction as well as a fibrillarin-free fraction enriched in spliceosomes. One of these SNORDs,SNORD27, directsrRNAmethylation and regulates alternative pre-mRNA splicing (AS) ofE2F7pre-mRNA, a transcriptional repressor of cell cycle-regulated genes.SNORD27likely regulatesE2F7pre-mRNA AS by masking splice sites through base pairing. This previously unidentified function of SNORDs increases the number of factors regulating AS, a critical step in the expression of the vast majority of human genes, and highlights a potential coupling between AS, cell cycle, proliferation, and ribosome biogenesis.
Autoantibody-boosted T-cell reactivation in the target organ triggers manifestation of autoimmune CNS disease
Authors: Flach Anne-Christine , Litke Tanja , Strauss Judith , Haberl Michael , Gómez César Cordero , Reindl Markus , Saiz Albert , Fehling Hans-Jörg , Wienands Jürgen , Odoardi Francesca , Lühder Fred , Flügel Alexander 
Published: March 2016

SignificanceAlthough T cells are the main players in autoimmune CNS inflammation, the role of B cells is being increasingly appreciated. We here investigated possible scenarios of how B cells could participate in the initiation of autoimmune CNS disease. We show that myelin-reactive autoantibodies accumulate in CNS-resident phagocytes, thereby concentrating myelin antigens in these cells and increasing the cells’ capacity to present the autoantigen to invading myelin-reactive T cells. Consequently, these T cells are stimulated and more easily reach the threshold for clinically relevant reactivation within the CNS tissue. This previously unidentified mechanism is of potential clinical relevance because it provides a scientific explanation for immune processes leading to disease initiation and induction of relapses in multiple sclerosis and other autoimmune CNS disorders.
UniProt-DAAC: domain architecture alignment and classification, a new method for automatic functional annotation in UniProtKB
Authors: Doğan Tunca , MacDougall Alistair , Saidi Rabie , Poggioli Diego , Bateman Alex , O’Donovan Claire , Martin Maria J. 
Published: March 2016

Abstract
Motivation: Similarity-based methods have been widely used in order to infer the properties of genes and gene products containing little or no experimental annotation. New approaches that overcome the limitations of methods that rely solely upon sequence similarity are attracting increased attention. One of these novel approaches is to use the organization of the structural domains in proteins.
Results: We propose a method for the automatic annotation of protein sequences in the UniProt Knowledgebase (UniProtKB) by comparing their domain architectures, classifying proteins based on the similarities and propagating functional annotation. The performance of this method was measured through a cross-validation analysis using the Gene Ontology (GO) annotation of a sub-set of UniProtKB/Swiss-Prot. The results demonstrate the effectiveness of this approach in detecting functional similarity with an average F-score: 0.85. We applied the method on nearly 55.3 million uncharacterized proteins in UniProtKB/TrEMBL resulted in 44 818 178 GO term predictions for 12 172 114 proteins. 22% of these predictions were for 2 812 016 previously non-annotated protein entries indicating the significance of the value added by this approach.
Availability and implementation: The results of the method are available at: ftp://ftp.ebi.ac.uk/pub/contrib/martin/DAAC/.
Contact: tdogan@ebi.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
Tally: a scoring tool for boundary determination between repetitive and non-repetitive protein sequences
Authors: Richard François D. , Alves Ronnie , Kajava Andrey V. 
Published: March 2016

Abstract
Motivation: Tandem Repeats (TRs) are abundant in proteins, having a variety of fundamental functions. In many cases, evolution has blurred their repetitive patterns. This leads to the problem of distinguishing between sequences that contain highly imperfect TRs, and the sequences without TRs. The 3D structure of proteins can be used as a benchmarking criterion for TR detection in sequences, because the vast majority of proteins having TRs in sequences are built of repetitive 3D structural blocks. According to our benchmark, none of the existing scoring methods are able to clearly distinguish, based on the sequence analysis, between structures with and without 3D TRs.
Results: We developed a scoring tool called Tally, which is based on a machine learning approach. Tally is able to achieve a better separation between sequences with structural TRs and sequences of aperiodic structures, than existing scoring procedures. It performs at a level of 81% sensitivity, while achieving a high specificity of 74% and an Area Under the Receiver Operating Characteristic Curve of 86%. Tally can be used to select a set of structurally and functionally meaningful TRs from all TRs detected in proteomes. The generated dataset is available for benchmarking purposes. Availability and implementation: Source code is available upon request. Tool and dataset can be accessed through our website: http://bioinfo.montp.cnrs.fr/?r=Tally.
Contact: andrey.kajava@crbm.cnrs.fr
Supplementary information: Supplementary data are available at Bioinformatics online.
The spatiotemporal order of signaling events unveils the logic of development signaling
Authors: Zhu Hao , Owen Markus R. , Mao Yanlan 
Published: March 2016

Abstract
Motivation: Animals from worms and insects to birds and mammals show distinct body plans; however, the embryonic development of diverse body plans with tissues and organs within is controlled by a surprisingly few signaling pathways. It is well recognized that combinatorial use of and dynamic interactions among signaling pathways follow specific logic to control complex and accurate developmental signaling and patterning, but it remains elusive what such logic is, or even, what it looks like.
Results: We have developed a computational model for Drosophila eye development with innovated methods to reveal how interactions among multiple pathways control the dynamically generated hexagonal array of R8 cells. We obtained two novel findings. First, the coupling between the long-range inductive signals produced by the proneural Hh signaling and the short-range restrictive signals produced by the antineural Notch and EGFR signaling is essential for generating accurately spaced R8s. Second, the spatiotemporal orders of key signaling events reveal a robust pattern of lateral inhibition conducted by Ato-coordinated Notch and EGFR signaling to collectively determine R8 patterning. This pattern, stipulating the orders of signaling and comparable to the protocols of communication, may help decipher the well-appreciated but poorly defined logic of developmental signaling.
Availability and implementation: The model is available upon request.
Contact: hao.zhu@ymail.com
Supplementary information: Supplementary data are available at Bioinformatics online.
Assessing statistical significance in multivariable genome wide association analysis
Authors: Buzdugan Laura , Kalisch Markus , Navarro Arcadi , Schunk Daniel , Fehr Ernst , Bühlmann Peter 
Published: March 2016

AbstractMotivation: Although Genome Wide Association Studies (GWAS) genotype a very large number of single nucleotide polymorphisms (SNPs), the data are often analyzed one SNP at a time. The low predictive power of single SNPs, coupled with the high significance threshold needed to correct for multiple testing, greatly decreases the power of GWAS.Results: We propose a procedure in which all the SNPs are analyzed in a multiple generalized linear model, and we show its use for extremely high-dimensional datasets. Our method yields P-values for assessing significance of single SNPs or groups of SNPs while controlling for all other SNPs and the family wise error rate (FWER). Thus, our method tests whether or not a SNP carries any additional information about the phenotype beyond that available by all the other SNPs. This rules out spurious correlations between phenotypes and SNPs that can arise from marginal methods because the ‘spuriously correlated’ SNP merely happens to be correlated with the ‘truly causal’ SNP. In addition, the method offers a data driven approach to identifying and refining groups of SNPs that jointly contain informative signals about the phenotype. We demonstrate the value of our method by applying it to the seven diseases analyzed by the Wellcome Trust Case Control Consortium (WTCCC). We show, in particular, that our method is also capable of finding significant SNPs that were not identified in the original WTCCC study, but were replicated in other independent studies.Availability and implementation: Reproducibility of our research is supported by the open-source Bioconductor package hierGWAS.Contact: peter.buehlmann@stat.math.ethz.chSupplementary information: Supplementary data are available at Bioinformatics online.
Dynamic software design for clinical exome and genome analyses: insights from bioinformaticians, clinical geneticists, and genetic counselors
Authors: Shyr Casper , Kushniruk Andre , van Karnebeek Clara D.M. , Wasserman Wyeth W. 
Published: March 2016

Abstract
Background The transition of whole-exome and whole-genome sequencing (WES/WGS) from the research setting to routine clinical practice remains challenging.
Objectives With almost no previous research specifically assessing interface designs and functionalities of WES and WGS software tools, the authors set out to ascertain perspectives from healthcare professionals in distinct domains on optimal clinical genomics user interfaces.
Methods A series of semi-scripted focus groups, structured around professional challenges encountered in clinical WES and WGS, were conducted with bioinformaticians (n = 8), clinical geneticists (n = 9), genetic counselors (n = 5), and general physicians (n = 4).
Results Contrary to popular existing system designs, bioinformaticians preferred command line over graphical user interfaces for better software compatibility and customization flexibility. Clinical geneticists and genetic counselors desired an overarching interactive graphical layout to prioritize candidate variants—a “tiered” system where only functionalities relevant to the user domain are made accessible. They favored a system capable of retrieving consistent representations of external genetic information from third-party sources. To streamline collaboration and patient exchanges, the authors identified user requirements toward an automated reporting system capable of summarizing key evidence-based clinical findings among the vast array of technical details.
Conclusions Successful adoption of a clinical WES/WGS system is heavily dependent on its ability to address the diverse necessities and predilections among specialists in distinct healthcare domains. Tailored software interfaces suitable for each group is likely more appropriate than the current popular “one size fits all” generic framework. This study provides interfaces for future intervention studies and software engineering opportunities.