bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association and functional studies identify 46 novel loci for alcohol consumption and suggest common genetic mechanisms with neuropsychiatric disorders
Authors: Evangelou Evangelos , Gao He , Chu Congying , Ntritsos Georgios , Blakeley Paul , Butts Andrew R. , Pazoki Raha , Suzuki Hideaki , Koskeridis Fotios , Yiorkas Andrianos M. , Karaman Ibrahim , Elliott Joshua , Aeschbacher Stefanie , Bartz Traci M. , Baumeister Sebastian E. , Braund Peter S. , Brown Michael R. , Brody Jennifer A. , Clarke Toni-Kim , Dimou Niki , Faul Jessica D. , Homuth Georg , Jackson Anne U. , Kentistou Katherine A. , Joshi Peter K. , Lemaitre Rozenn N. , Lind Penelope A. , Lyytikäinen Leo-Pekka , Mangino Massimo , Milaneschi Yuri , Nelson Christopher P. , Nolte Ilja M. , Perälä Mia-Maria , Polasek Ozren , Porteous David , Ratliff Scott M. , Smith Jennifer A. , Stančáková Alena , Teumer Alexander , Tuominen Samuli , Thériault Sébastien , Vangipurapu Jagadish , Whitfield John B. , Wood Alexis , Yao Jie , Yu Bing , Zhao Wei , Arking Dan E. , Auvinen Juha , Liu Chunyu , Männikkö Minna , Risch Lorenz , Rotter Jerome I. , Snieder Harold , Veijola Juha , Blakemore Alexandra I. , Boehnke Michael , Campbell Harry , Conen David , Eriksson Johan G. , Grabe Hans J. , Guo Xiuqing , Harst Pim van der , Hartman Catharina A. , Hayward Caroline , Heath Andrew C. , Jarvelin Marjo-Riitta , Kähönen Mika , Kardia Sharon LR , Kühne Michael , Kuusisto Johanna , Laakso Markku , Lahti Jari , Lehtimäki Terho , McIntosh Andrew M. , Mohlke Karen L. , Morrison Alanna C. , Martin Nicholas G. , Oldehinkel Albertine J. , Penninx Brenda WJH , Psaty Bruce M. , Raitakari Olli T. , Rudan Igor , Samani Nilesh J. , Scott Laura J. , Spector Tim D. , Verweij Niek , Weir David R. , Wilson James F. , Levy Daniel , Tzoulaki Ioanna , Bell Jimmy D. , Matthews Paul , Rothenfluh Adrian , Desrivières Sylvane , Schumann Gunter , Elliott Paul 
Published: October 2018

AbstractExcessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. We conducted a genome-wide association study (GWAS) of alcohol use in ~480,000 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 novel, common loci, and investigated their potential functional significance using magnetic resonance imaging data, gene expression and behavioral studies inDrosophila. Our results identify new genetic pathways associated with alcohol consumption and suggest common genetic mechanisms with several neuropsychiatric disorders including schizophrenia.
GRIPT: A novel case-control analysis method for Mendelian disease gene discovery
Authors: Wang Jun , Zhao Li , Wang Xia , Chen Yong , Xu Mingchu , Soens Zachry T. , Ge Zhongqi , Wang Peter Ronghan , Wang Fei , Chen Rui 
Published: October 2018

AbstractDespite rapid progress of next-generation sequencing (NGS) technologies, the disease-causing genes underpinning about 50% of Mendelian diseases remain elusive. One main challenge is the high genetic heterogeneity of Mendelian diseases in which similar phenotypes are caused by different genes and each gene only accounts for a small proportion of the patients. To overcome this gap, we developed a novel method, the Gene Ranking, Identification and Prediction Tool (GRIPT), for performing case-control analysis of NGS data. Analyses of simulated and real datasets show that GRIPT is well-powered for disease gene discovery, especially for diseases with high locus heterogeneity.
Countering Cross-Individual Variance in Event Related Potentials with Functional Profiling
Authors: Alsufyani Abdulmajeed , Zoumpoulaki Alexia , Filetti Marco , Janssen Dirk P. , Bowman Howard 
Published: October 2018

AbstractIn this study, a simple method called the Weight Template (WT) is proposed for classifying brain responses of individuals into deceiving and non-deceiving. The performance of our method was evaluated on a number of identity deception data sets and on artificial EEG data sets. A comparison was made with a standard method used to measure P3 presence, called Peak-to-Peak. In the real experimental data, the WT showed higher performance in terms of sensitivity and specificity. In the artificial EEG data, in ERPs with low Signal-to-Noise Ratio (SNR), the WT was more resistant to noise and provided more accurate measures.HighlightsWe propose a method for classifying ERPs of the P3 Concealed Information Tests.The new method is based on computing a weighted template (WT) for each individual.The WT is used to characterize the shape of each individual’s P3.The performance of the WT was compared with the standard Peak-to-Peak method.The WT showed higher performance in terms of sensitivity and specificity.
Fusion of DARPin to aldolase enables visualization of small protein by cryoEM
Authors: Yao Qing , Weaver Sara J. , Mock Jee-Young , Jensen Grant J. 
Published: October 2018

AbstractIn recent years, solving protein structures by single particle cryogenic electron microscopy (cryoEM) has become a crucial tool in structural biology. While exciting progress is being made towards the visualization of smaller and smaller macromolecules, the median protein size in both eukaryotes and bacteria is still beyond the reach of single particle cryoEM. To overcome this problem, we implemented a platform strategy in which a small protein target was rigidly attached to a large, symmetric base via a selectable adapter. Seven designs were tested. In the best construct, a designed ankyrin repeat protein (DARPin) was rigidly fused to tetrameric rabbit muscle aldolase through a helical linker. The DARPin retained its ability to bind its target, the 27 kDa green fluorescent protein (GFP). We solved the structure of this complex to 3.0 Å resolution overall, with 5 to 8 Å resolution in the GFP region. As flexibility in the DARPin limited the overall resolution of the target, we describe strategies to rigidify this element.Author summarySingle particle cryogenic electron microscopy (cryoEM) is a technique that uses images of purified proteins to determine their atomic structure. Unfortunately, the majority of proteins in the human and bacterial proteomes are too small to be analyzed by cryoEM. Over the years, several groups have suggested the use of a platform to increase the size of small protein targets. The platform is composed of a large protein base and a selectable adapter that binds the target protein. Here we report a platform based on tetrameric rabbit muscle aldolase that is fused to a Designed Ankyrin Repeat Protein (DARPin). Phage display libraries can be used to generate DARPins against target proteins. The residues mutated in a phage display library to generate a DARPin against a new target do not overlap with the DARPin-base fusion in the platform, thus changing the DARPin identity will not disrupt the platform design. The DARPin adapter used here is capable of binding Green Fluorescent Protein (GFP). We report the structure of GFP to 5 to 8 Å local resolution by single particle cryoEM. Our analysis demonstrates that flexibility in the DARPin-aldolase platform prevents us from achieving higher resolution in the GFP region. We suggest changes to the DARPin design to rigidify the DARPin-aldolase platform. This work expands on current platforms and paves a generally applicable way toward structure determination of small proteins by cryoEM.
Comparative transcriptome analysis reveals higher expression of stress and defense responsive genes in dwarf soybeans obtained from the crossing of G. max and G. soja
Authors: Ban Yong-Wook , Roy Neha Samir , Yang Heejung , Choi Hong-Kyu , Kim Jin-Hyun , babu Prakash , Ha Keon-Soo , Ham Jin-Kwan , Park Kyong Cheul , Choi Ik-Young 
Published: October 2018

AbstractPlant height is an important component of plant architecture and significantly affects crop breeding practices and yield. We obtained a few segregated dwarf soybeans in the populations derived from the crossing of Glycine max var. Peking and Glycine soja var. IT182936 in an F5 RIL population. These dwarf soybeans may be useful genetic resources for plant breeders, geneticists and biologists. We attempted to find differentially expressed genes to classify and understand the regulation of genes related to plant growth in mutant dwarf soybeans, which appeared in the F5 generation. Using the Illumina high-throughput platform, transcriptomes were generated and compared among normal and dwarf soybeans in triplicate. We found complex relationship of the expressed genes to plant growth. There are highly significantly up-/downregulated genes according to the comparison of gene expression in normal and dwarf soybeans. The genes related to disease and stress responses were found to be upregulated in dwarf soybeans. Such over-expression of disease resistance and other immune response genes was targeted to understand how the immune genes regulate the response of plant growth. In addition, photosynthesis-related genes showed very low expression in dwarf lines. The transcriptome expression and genes classified as related to plant growth may be useful resources to researchers studying plant growth.
Umbelliprenin isolated from Ferula sinkiangensis inhibits tumor growth and migration through the disturbance of Wnt signaling pathway in gastric cancer
Authors: Zhang Lijing , Sun Xiaobo , Si Jianyong , Li Guangzhi , Cao Li 
Published: October 2018

AbstractThe traditional herb medicine Ferula sinkiangensis K. M. Shen (F. sinkiangensis) has been used to treat stomach disorders in Xinjiang District for centuries. Umbelliprenin is the effective component isolated from F. sinkiangensis which is particularly found in plants of the family Ferula. We previously reported the promising effects of Umbelliprenin against gastric cancer cells, but its anti-migration effect remained unknown. Here we investigated the anti-migration effect and mechanism of Umbelliprenin in human gastric cancer cells. In SRB assay, Umbelliprenin showed cytotoxic activities in the gastric cancer cell lines AGS and BGC-823 in a dose-and-time-dependent manner, while it showed lower cytotoxic activity in the normal gastric epithelium cell line GES-1. During transwell, scratch and colony assays, the migration of tumor cells was inhibited by Umbelliprenin treatment. The expression levels of the Wnt-associated signaling pathway proteins were analyzed with western blots, and the results showed that Umbelliprenin decreased the expression levels of proteins of the Wnt signalling pathway, such as Wnt-2, β-catenin, GSK-3β, p-GSK-3β, Survivin and c-myc. The translocation of β-catenin to the nucleus was also inhibited by Umbelliprenin treatment. In TCF reporter assay, the transcriptional activity of T-cell factor/lymphoid enhancer factor (TCF/LEF) was decreased after Umbelliprenin treatment. Thein vivo results suggested that Umbelliprenin induced little to no harm in the lung, heart and kidney. Overall, these data provided evidence that Umbelliprenin may inhibit the growth, invasion and migration of gastric cancer cells by disturbing the Wnt signaling pathway.
One of the gang: social group dynamics in a juvenile passerine bird
Authors: Franks Victoria R. , Ewen John G. , McCready Mhairi , Marcus Rowcliffe J. , Smith Donal , Thorogood Rose 
Published: October 2018

AbstractLiving in groups comes with many potential benefits, especially for juveniles. Naïve individuals may learn how to forage, or avoid predators through group vigilance. Understanding these benefits, however, requires an appreciation of the opportunities juveniles have to associate with (and learn from) others. Here we describe social groups in terms of residency, movement, relatedness, and social associations from the perspective of juvenile hihi, a threatened New Zealand passerine bird. Over three years, we identified individuals in groups, their relatedness, and behavioural interactions. Using multistate analysis, we compared movement and residency of adults and juveniles and found that groups were composed predominately of juveniles which remained at group sites for longer than more transient adults. Movement of juveniles between groups did occur but was generally low. There was no evidence that siblings and parents were likely to be seen in groups together. With an initial understanding of group structure, we next asked what characteristics predicted assortment in social network associations. By identifying groups of co-occurring juveniles from time-stamped observations of individual hihi and building a social network, we found that juveniles were most likely to associate with other juveniles. Associations were also predominantly based on locations where hihi spent the most time, reflecting limited movement among separate groups. We suggest groups are best described as “gangs” where young hihi have little interaction with adults. These spatially-separated groups of juveniles may have consequences for social information use during the first few months of independence in young birds.
Accumulating computational resource usage of genomic data analysis workflow to optimize cloud computing instance selection
Authors: Ohta Tazro , Tanjo Tomoya , Ogasawara Osamu 
Published: October 2018

AbstractBackgroundContainer virtualization technologies such as Docker became popular in the bioinformatics domain as they improve portability and reproducibility of software deployment. Along with software packaged in containers, the workflow description standards Common Workflow Language also enabled to perform data analysis on multiple different computing environments with ease. These technologies accelerate the use of on-demand cloud computing platform which can scale out according to the amount of data. However, to optimize the time and the budget on a use of cloud, users need to select a suitable instance type corresponding to the resource requirements of their workflows.ResultsWe developed CWL-metrics, a system to collect runtime metrics of Docker containers and workflow metadata to analyze resource requirement of workflows. We demonstrated the analysis by using seven transcriptome quantification workflows on six instance types. The result showed instance type options of lower financial cost and faster execution time with required amount of computational resources.ConclusionsThe summary of resource requirements of workflow executions provided by CWL-metrics can help users to optimize the selection of cloud computing instance. The runtime metrics data also accelerate to share workflows among different workflow management frameworks.
A diagnostic multiplex PCR scheme for identification of plant-associated bacteria of the genusPantoea
Authors: Kini Kossi , Agnimonhan Raoul , Dossa Rachelle , Silué Drissa , Koebnik Ralf 
Published: October 2018

AbstractBackgroundThe genusPantoeaforms a complex of more than 25 species, among which several cause diseases of several crop plants, including rice. Notably, strains ofPantoea ananatisandPantoea stewartiihave been found to cause bacterial leaf blight of rice in Togo and Benin, while other authors have observed thatPantoea agglomeranscan also cause bacterial leaf blight of rice. The contribution of these and perhaps other species ofPantoeato plant diseases and yield losses of crop plants is currently not well documented, partly due to the lack of efficient diagnostic tools.ResultUsing 34 whole genome sequences of the three-major plant-pathogenicPantoeaspecies, a set of PCR primers that specifically detect each of the three species,P. agglomerans,P. ananatis, andP. stewartii, was designed. A multiplex PCR protocol which can distinguish these three species and also detects members of otherPantoeaspecies was further developed. Upon validation on a set of reference strains, 609 suspectedPantoeastrains that were isolated from rice leaves or seeds originating from 11 African countries were screened. In total, 41P. agglomeransstrains from eight countries, 79P. ananatisstrains from nine countries, 269P. stewartiistrains from nine countries and 220 unsolvedPantoeastrains from ten countries were identified. The PCR protocol allowed detectingPantoeabacteria grown in vitro, in planta and in rice seeds. The detection threshold was estimated at 5 ng/mL of total genomic DNA and 1 × 105CFU/mL of heated cells.ConclusionThis new molecular diagnostic tool will help accurately diagnose major plant-pathogenic species ofPantoea. Due to its robustness, specificity, sensitivity, and cost efficiency it will be very useful for plant protection services and for the epidemiological surveillance of these important crop-threatening bacteria.
Transcriptional profiling of isogenic Friedreich ataxia induced pluripotent stem cell-derived neurons
Authors: Lai Jiun-I , Nachun Daniel , Petrosyan Lina , Throesch Benjamin , Campau Erica , Gao Fuying , Baldwin Kristin K. , Coppola Giovanni , Gottesfeld Joel M. , Soragni Elisabetta 
Published: October 2018

AbstractFriedreich ataxia (FRDA) is a rare childhood neurodegenerative disorder with no effective treatment. FRDA is caused by transcriptional silencing of the FXN gene and consequent loss of the essential mitochondrial protein frataxin. Based on the knowledge that a GAA•TTC repeat expansion in the first intron of FXN leads to heterochromatin formation and gene silencing, we have shown that members of the 2-aminobenzamide family of histone deacetylase inhibitors (HDACi) reproducibly increase FXN mRNA levels in induced pluripotent stem cell (iPSC)-derived FRDA neuronal cells and in peripheral blood mononuclear cells from patients treated with the drug in a phase I clinical trial. How the reduced expression of frataxin leads to neurological and other systemic symptoms in FRDA patients remains unclear. Similarly to other triplet repeat disorders, it is not known why only specific cells types are affected in the disease, primarily the large sensory neurons of the dorsal root ganglia and cardiomyocytes. The combination of iPSC technology and genome editing techniques offers the unique possibility of addressing these questions in a relevant cell model of the disease, without the confounding effect of different genetic backgrounds. We derived a set of isogenic iPSC lines that differ only in the length of the GAA•TTC repeats, using “scarless” gene-editing methods (helper-dependent adenovirus-mediated homologous recombination). To uncover the gene expression signature due to GAA•TTC repeat expansion in FRDA neuronal cells and the effect of HDACi on these changes, we performed transcriptomic analysis of iPSC-derived central nervous system (CNS) and isogenic sensory neurons by RNA sequencing. We find that multiple cellular pathways are commonly affected by the loss of frataxin in CNS and peripheral nervous system neurons and these changes are partially restored by HDACi treatment.
Attenuation of chronic antiviral T cell responses through constitutive COX2-dependent prostanoid synthesis by lymph node fibroblasts
Authors: Schaeuble Karin , Cannelle Hélène , Favre Stéphanie , Huang Hsin-Ying , Oberle Susanne G. , Zehn Dietmar , Luther Sanjiv A. 
Published: October 2018

AbstractFibroblastic reticular cells (FRC) of lymphoid T zones actively promote T cell trafficking, homeostasis and expansion, but can also attenuate excessive T cell responses via inducible nitric oxide and constitutive prostanoid release. It has remained unclear under which conditions these FRC-derived mediators can dampen T cell responses and whether this occurs in vivo. Here we confirm that murine lymph node FRC produce prostaglandin E2 (PGE2) in a cyclooxygenase-2 (COX2)-dependent and inflammation-independent fashion. We show that this COX2/PGE2 pathway is active during both strong and weak T cell responses, in contrast to nitric oxide which only comes into play during strong T cell responses. In chronic infections in vivo, PGE2-receptor signaling in virus-specific CD8 T cells was shown by others to suppress T cell survival and function. Using CCL19cre x COX2flox/flox mice we now identify CCL19cre+ FRC as the critical source of this COX2-dependent suppressive factor, suggesting PGE2-expressing FRC within lymphoid tissues are an interesting therapeutic target to improve T cell mediated pathogen control during chronic infection.
Spatial signature of white matter hyperintensities in stroke patients
Authors: Schirmer Markus D. , Giese Anne-Katrin , Fotiadis Panagiotis , Etherton Mark R. , Cloonan Lisa , Viswanathan Anand , Greenberg Steven M. , Wu Ona , Rost Natalia S. 
Published: October 2018

AbstractPurposeWhite matter hyperintensity (WMH) is a common phenotype across a variety of neurological diseases, particularly prevalent in stroke patients; however, vascular territory dependent variation in WMH burden has not yet been identified. Here, we sought to investigate the spatial specificity of WMH burden in patients with acute ischemic stroke (AIS).Materials and MethodsWe created a novel age-appropriate high-resolution brain template and anatomically delineated the cerebral vascular territories. We used WMH masks derived from the clinical T2 FLAIR MRI scans and spatial normalization of the template to discriminate between WMH volume within each subject’s anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) territories. Linear regression modeling including age, sex, common vascular risk factors, and TOAST stroke subtypes was used to assess for spatial specificity of WMH volume (WMHv) in a cohort of 882 AIS patients.ResultsMean age of this cohort was 65.23±14.79 years, 61.7% were male, 63.6% were hypertensive, 35.8% never smoked. Mean WMHv was 11.58c +/-13.49 cc. There were significant differences in territory-specific, relative to global, WMH burden. In contrast to PCA territory, age (0.018±0.002, p<0.001) and small-vessel stroke subtype (0.212±0.098, p<0.001) were associated with relative increase of WMH burden within the anterior (ACA and MCA) territories, whereas male sex (−0.275±0.067, p<0.001) was associated with a relative decrease in WMHv.ConclusionsOur data establish the spatial specificity of WMH distribution in relation to vascular territory and risk factor exposure in AIS patients and offer new insights into the underlying pathology.
An approach for the protection of users’ book browsing preference privacy in a digital library
Authors: Wu Zongda , Zheng Chengren , Xiejian Jian , Zhou Zhifeng , Xu Guandong , Chen Enhong 
Published: October 2018

Purpose
The problem of privacy protection in digital libraries is causing people to have increasingly extensive concerns. This study aims to design an approach to protect the preference privacy behind users’ book browsing behaviors in a digital library.

Design/methodology/approach
This paper proposes a client-based approach, whose basic idea is to construct a group of plausible book browsing dummy behaviors, and submit them together with users’ true behaviors to the untrusted server, to cover up users’ sensitive preferences.

Findings
Both security analysis and evaluation experiment demonstrate the effectiveness of the approach, which can ensure the privacy security of users’ book browsing preferences on the untrusted digital library server, without compromising the usability, accuracy and efficiency of book services.

Originality/value
To the best of the authors’ knowledge, this paper provides the first attempt to the protection of users’ behavior privacy in digital libraries, which will have a positive influence on the development of privacy-preserving libraries in the new network era.