bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative molecular profiling of autoreactive CD4 T cells in autoimmune hepatitis
Authors: Renand Amédée , Cervera-Marzal Iñaki , Gil Laurine , Dong Chuang , Kervagoret Erwan , Auble Hélène , Habes Sarah , Cardon Anais , Judor Jean-Paul , Mosnier Jean-François , Brouard Sophie , Gournay Jérôme , Milpied Pierre , Conchon Sophie 
Published: January 2020

AbstractBackground & AimsIn most autoimmune disorders, crosstalk of B cells and CD4 T cells results in the accumulation of autoantibodies. In autoimmune hepatitis (AIH), the presence of anti-Soluble Liver Antigen (SLA or SepSecs) autoantibodies is associated with significantly reduced overall survival, but the associated autoreactive CD4 T cells have not been characterized yet. Here we isolated and deeply characterized SLA-specific CD4 T cells in AIH patients.MethodsWe used briefex vivorestimulation with overlapping SLA-derived peptides to isolate and phenotype circulating SLA-specific CD4 T cells, and integrative single-cell RNA-seq (scRNA-seq) to characterize their transcriptome and TCR repertoire in n=5 AIH patients. SLA-specific CD4 T cells were tracked in peripheral blood through TCR sequencing, to identify their phenotypic niche. We further characterized disease-associated peripheral blood T cells by high content flow cytometry in an additional cohort of n=46 AIH patients and n=18 non-alcoholic steatohepatitis (NASH) controls.ResultsAutoreactive SLA-specific CD4 T cells were only detected in patients with anti-SLA autoantibodies and had a memory PD-1+CXCR5−CCR6−CD27+phenotype. ScRNA-seq revealed their pro-inflammatory/B-Helper profile (IL21, IFNG, TIGIT,CTLA4, NR3C1, CD109, KLRB1andCLEC2D). Autoreactive TCR clonotypes were restricted to the memory PD-1+CXCR5−CD4 T cells. This subset was significantly increased in the blood of AIH patients and supported B cell differentiation through IL-21. Finally, we identified a specific phenotype (PD-1+CD38+CD27+CD127−CXCR5−) of CD4 T cells linked to disease activity and IgG response during AIH.ConclusionsThis work provides for the first time a deep characterization of rare circulating autoreactive CD4 T cells and the identification of their peripheral reservoir in AIH. We also propose a generic phenotype of pathogenic CD4 T cells related to AIH disease activity.
Context-dependent odor learning requires the anterior olfactory nucleus
Authors: Levinson Max , Kolenda Jacob P. , Alexandrou Gabriella J. , Escanilla Olga , Smith David M. , Cleland Thomas A. , Linster Christiane 
Published: January 2020

AbstractLearning to associate the context in which a stimulus occurs is an important aspect of animal learning. We propose that the association of an olfactory stimulus with its multisensory context is mediated by projections from ventral hippocampal networks (vHC) to the anterior olfactory nucleus (AON). Using a contextually-cued olfactory discrimination task, rats were trained to associate two olfactory stimuli with different responses depending on visuo-spatial context. Temporary lesions of the AON or vHC impaired performance on this task. In contrast, such lesions did not impair performance on a non-contextual olfactory discrimination task. Moreover, vHC lesions also impaired performance on an analogous contextually-cued texture discrimination task, whereas AON lesions affected only olfactory contextual associations. We describe a distinct role for the AON in olfactory processing, and conclude that early olfactory networks such as the olfactory bulb and AON function as multimodal integration networks rather than processing olfactory signals exclusively.Significance statementContextual information has long been known to play a key role in cognitive functions such as memory and decision making. We here show the contextual modulation of neural information in early primary sensory networks and its effects on contextually conditional learned behavior. We propose that projections from ventral hippocampus to anterior olfactory nucleus convey contextual information to the early olfactory system, modulating sensory representations and olfactory perception. Using behavioral pharmacology and computational modeling, we show how established network structures can mediate multimodal information and use context to make olfactory decisions.
Transcriptional and Cellular Diversity of the Human Heart
Authors: Tucker Nathan R. , Chaffin Mark , Fleming Stephen J. , Hall Amelia W. , Parsons Victoria A. , Bedi Kenneth , Akkad Amer-Denis , Herndon Caroline N. , Arduini Alessandro , Papangeli Irinna , Roselli Carolina , Aguet François , Choi Seung Hoan , Ardlie Kristin G. , Babadi Mehrtash , Margulies Kenneth B. , Stegmann Christian M. , Ellinor Patrick T. 
Published: January 2020

AbstractIntroductionThe human heart requires a complex ensemble of specialized cell types to perform its essential function. A greater knowledge of the intricate cellular milieu of the heart is critical to increase our understanding of cardiac homeostasis and pathology. As recent advances in low input RNA-sequencing have allowed definitions of cellular transcriptomes at single cell resolution at scale, here we have applied these approaches to assess the cellular and transcriptional diversity of the non-failing human heart.MethodsMicrofluidic encapsulation and barcoding was used to perform single nuclear RNA sequencing with samples from seven human donors, selected for their absence of overt cardiac disease. Individual nuclear transcriptomes were then clustered based upon transcriptional profiles of highly variable genes. These clusters were used as the basis for between-chamber and between-sex differential gene expression analyses and intersection with genetic and pharmacologic dataResultsWe sequenced the transcriptomes of 287,269 single cardiac nuclei, revealing a total of 9 major cell types and 20 subclusters of cell types within the human heart. Cellular subclasses include two distinct groups of resident macrophages, four endothelial subtypes, and two fibroblasts subsets. Comparisons of cellular transcriptomes by cardiac chamber or sex reveal diversity not only in cardiomyocyte transcriptional programs, but also in subtypes involved in extracellular matrix remodeling and vascularization. Using genetic association data, we identified strong enrichment for the role of cell subtypes in cardiac traits and diseases. Finally, intersection of our dataset with genes on cardiac clinical testing panels and the druggable genome reveals striking patterns of cellular specificity.ConclusionsUsing large-scale single nuclei RNA sequencing, we have defined the transcriptional and cellular diversity in the normal human heart. Our identification of discrete cell subtypes and differentially expressed genes within the heart will ultimately facilitate the development of new therapeutics for cardiovascular diseases.
MINREACT: an efficient algorithm for identifying minimal metabolic networks
Authors: Sambamoorthy Gayathri , Raman Karthik 
Published: January 2020

AbstractGenome-scale metabolic models are widely constructed and studied for understanding various design principles underlying metabolism, predominantly redundancy. Metabolic networks are highly redundant and it is possible to minimise the metabolic networks into smaller networks that retain the functionality of the original network. Here, we establish a new method, MinReactthat systematically removes reactions from a given network to identify minimal reactome(s). We show that our method identifies smaller minimal reactomes than existing methods and also scales well to larger metabolic networks. Notably, our method exploits known aspects of network structure and redundancy to identify multiple minimal metabolic networks. We illustrate the utility of MinReactby identifying multiple minimal networks for 74 organisms from the BiGG database. We show that these multiple minimal reactomes arise due to the presence of compensatory reactions/pathways. We further employed MinReactfor a case study to identify the minimal reactomes of different organisms in both glucose and xylose minimal environments. Identification of minimal reactomes of these different organisms elucidate that they exhibit varying levels of redundancy. A comparison of the minimal reactomes on glucose and xylose illustrate that the differences in the reactions required to sustain growth on either medium. Overall, our algorithm provides a rapid and reliable way to identify minimal subsets of reactions that are essential for survival, in a systematic manner.Author summaryAn organism’s metabolism is routinely modelled by a metabolic network, which consists of all the enzyme-catalysed reactions that occur in the organism. These reactions are numerous, majorly due to the presence of redundant reactions that perform compensatory functions. Also, not all the reactions are functional in all environments and are unique to the environmental conditions. So, it is possible to minimise such large metabolic networks into smaller functional networks. Such minimal networks help in easier dissection of the capabilities of the network and also further our understanding of the various redundancies and other design principles occurring in these networks. Here, we have developed a new algorithm for identification of such minimal networks, that is efficient and superior to existing algorithms. We show the utility of our algorithm in identifying such minimal sets of reactions for many known metabolic networks. We have also shown a case study, using our algorithm to identify such minimal networks for different organisms in varied nutrient conditions.
Spinal stretch reflexes support efficient control of reaching
Authors: Weiler Jeffrey , Gribble Paul L , Pruszynski J. Andrew 
Published: January 2020

AbstractEfficiently controlling the movement of our hand requires coordinating the motion of multiple joints of the arm. Although it is widely assumed that this type of efficient control is implemented by processing that occurs in the cerebral cortex and brain stem, recent work has shown that spinal circuits can generate efficient motor output that supports keeping the hand in a static location. Here, we show that a spinal pathway can also efficiently control the hand during reaching. In our first experiment we applied multi-joint mechanical perturbations to participant’s elbow and wrist as they began reaching towards a target. We found that spinal stretch reflexes evoked in elbow muscles were not proportional to how much the elbow muscles were stretched but instead were efficiently scaled to the hand’s distance from the target. In our second experiment we applied the same elbow and wrist perturbations but had participants change how they grasped the manipulandum, diametrically altering how the same wrist perturbation moved the hand relative to the reach target. We found that changing the arm’s orientation diametrically altered how spinal reflexes in the elbow muscles were evoked, and in such a way that were again efficiently scaled to the hand’s distance from the target. These findings demonstrate that spinal circuits can help efficiently control the hand during dynamic reaching actions, and show that efficient and flexible motor control is not exclusively dependent on processing that occurs within supraspinal regions of the nervous system.
Risk factors associated with canine overweightness and obesity in an owner-reported survey
Authors: Perry LeeAnn M. , Shmalberg Justin , Tanprasertsuk Jirayu , Massey Dan , Honaker Ryan W. , Jha Aashish R. 
Published: January 2020

AbstractBackgroundOverweightness and obesity in dogs are associated with negative health outcomes. A better understanding of risk factors associated with canine weight is fundamental to identifying preventative interventions and treatments. In this cross-sectional study, we used a direct to consumer approach to collect body condition scores (BCS), as well as demographic, diet, and lifestyle data on 4,446 dogs. BCS was assessed by owners using a 9-point system and categorized as ideal (BCS 4-5), overweight (BCS 6), and obese (BCS 7+). Following univariate analyses, a stepwise procedure was used to select variables which were included in multivariate logistic regression models. One model was created to compare ideal to all overweight and obese dogs, and another was created to compare ideal to obese dogs only. We then used Elastic Net selection and XGBoost variable importance measures to validate these results.ResultsOverall, 1,480 (33%) of dogs were reported to be overweight or obese, of which 356 (8% total) of dogs were reported to be obese. Seven factors were significantly associated with both overweightness/obesity and obesity alone in all three analyses (stepwise, Elastic Net, and XGBoost): diet composition, probiotic supplementation, treat quantity, exercise, age, food motivation level, and pet appetite. Neutering was also associated with overweightness/obesity in all analyses.ConclusionsThis study recapitulated established risk factors associated with BCS (age, exercise, neutering). Moreover, we elucidated associations between previously examined risk factors and BCS (diet composition, treat consumption, and temperament) and identified a novel factor (probiotic supplementation). Specifically, relative to dogs on fresh food diets, BCS was higher in dogs eating dry food both alone and in combination with other foods. Furthermore, dogs receiving probiotics, but not other forms of supplementation, were more likely to have an ideal BCS. Future studies should corroborate these findings with experimental manipulations.
Measuring genetic variation in the multi-ethnic Million Veteran Program (MVP)
Authors: Hunter-Zinck Haley , Shi Yunling , Li Man , Gorman Bryan R. , Ji Sun-Gou , Sun Ning , Webster Teresa , Liem Andrew , Hsieh Paul , Devineni Poornima , Karnam Purushotham , Radhakrishnan Lakshmi , Schmidt Jeanette , Assimes Themistocles L. , Huang Jie , Pan Cuiping , Humphries Donald , Brophy Mary , Moser Jennifer , Muralidhar Sumitra , Huang Grant D. , Przygodzki Ronald , Concato John , Gaziano John M. , Gelernter Joel , O’Donnell Christopher J. , Hauser Elizabeth R. , Zhao Hongyu , O’Leary Timothy J. , Tsao Philip S. , Pyarajan Saiju ,   on behalf of the VA Million Veteran Program
Published: January 2020

AbstractThe Million Veteran Program (MVP), initiated by the Department of Veterans Affairs (VA), aims to collect consented biosamples from at least one million Veterans. Presently, blood samples have been collected from over 800,000 enrolled participants. The size and diversity of the MVP cohort, as well as the availability of extensive VA electronic health records make it a promising resource for precision medicine. MVP is conducting array-based genotyping to provide genome-wide scan of the entire cohort, in parallel with whole genome sequencing, methylation, and other omics assays. Here, we present the design and performance of MVP 1.0 custom Axiom®array, which was designed and developed as a single assay to be used across the multi-ethnic MVP cohort. A unified genetic quality control analysis was developed and conducted on an initial tranche of 485,856 individuals leading to a high-quality dataset of 459,777 unique individuals. 668,418 genetic markers passed quality control and showed high quality genotypes not only on common variants but also on rare variants. We confirmed the substantial ancestral diversity of MVP with nearly 30% non-European individuals, surpassing other large biobanks. We also demonstrated the quality of the MVP dataset by replicating established genetic associations with height in European Americans and African Americans ancestries. This current data set has been made available to approved MVP researchers for genome-wide association studies and other downstream analyses. Further data releases will be available for analysis as recruitment at the VA continues and the cohort expands both in size and diversity.
QTL mapping reveals genomic regions for yield based on incremental tolerance index to drought stress and related agronomic traits in canola
Authors: Raman Harsh , Raman Rosy , Mathews Ky , Diffey Simon , Salisbury Phil 
Published: January 2020

AbstractDrought stress especially at the reproductive stage is a major limiting factor that compromises the productivity and profitability of canola in many regions of the world. Improved genetics for drought tolerance would enable the identification and development of resilient varieties, resulting in increased canola production. The main objective of this study was to dissect the genetic basis of seed yield under water-limited conditions in canola. A doubled haploid population derived from a cross between two Australian parental lines, RP04 and Ag-Outback, was evaluated to identify the genetic variation in fractional normalised deviation vegetative index (NDVI), above ground shoot biomass accumulation, flowering time, and plasticity in seed yield under irrigated and rainfed field conditions in two consecutive years. An irrigation treatment was applied at the 50% flowering stage and an incremental drought tolerance index (DTI) was estimated for seed yield. By utilising a genetic linkage map based on 18,851 genome-wide DArTseq markers, we identified 25 genomic regions significantly associated with different traits (LOD ≥ 3), accounting for 5.5 to 22.3% of the genotypic variance. Three significant genomic regions on chromosome A06, A10 and C04 were associated with DTI for seed yield. Some of the QTL were localised in the close proximity of candidates genes involved in traits contributing to drought escape and drought avoidance mechanisms, includingFLOWERING LOCUS T(FT) andFLOWERING LOCUS C(FLC). Trait-marker associations identified herein can be validated across diverse environments, and the sequence based markers may be used in a marker assisted selection breeding strategy to enhance drought tolerance in canola breeding germplasm.
Subliminal perception can be predicted from prestimulus activity
Authors: Railo Henry , Piccin Roberto , Lukasik Karolina M. 
Published: January 2020

AbstractIndividuals are able to discriminate visual stimuli they report not consciously seeing. This phenomenon is known as “subliminal perception.” Such capacity is often assumed to be relatively automatic in nature, and rely on stimulus-driven activity in low-level cortical areas. Instead, here we asked to what extent neural activity before stimulus presentation influences subliminal perception. We asked participants to discriminate the location of a briefly presented low-contrast visual stimulus, and then rate how well they saw the stimulus. Consistent with previous studies, participants correctly discriminated with slightly above chance-level accuracy the location of a stimulus they reported not seeing. Signal detection analyses indicated that while subjects categorized their percepts as “unconscious”, their capacity to discriminate these stimuli lay on the same continuum as conscious vision. We show that the accuracy of discriminating the location of a subliminal stimulus could be predicted with relatively high accuracy (AUC = .70) based on lateralized electroencephalographic (EEG) activity before the stimulus, the hemifield where the stimulus was presented, and accuracy of previous trial’s discrimination response. Altogether, our results suggest that rather than being a separate unconscious capacity, subliminal perception is based on similar processes as conscious vison.
Determination of the full deformation tensor by multi-Bragg fast scanning nano X-ray diffraction
Authors: Johannes Andreas , Rensberg Jura , Grünewald Tilman A. , Schöppe Philipp , Ritzer Maurizio , Rosenthal Martin , Ronning Carsten , Burghammer Manfred 
Published: January 2020

This work showcases a method to map the full deformation tensor in a single micro-sized crystal. It is shown that measuring the position of two Bragg reflections in reciprocal space is sufficient to obtain the full deformation tensor, if the condition of incompressibility of the material is imposed. This method is used to reveal the surface tension induced deformation at the edges of an as-grown single-crystal VO2 microwire. All components of the deformation tensor of the microwire were measured down to an absolute value of 10−4 in an 8 × 14 µm projected area of the wire. With a beam-defined spatial resolution of 150 × 150 nm, the measurement time was merely 2.5 h.
Alternative regulatory policies, compliance and corporate governance quality
Authors: Bajra Ujkan , Čadež Simon 
Published: January 2020

PurposeThe purpose of this paper is to examine empirically the evolution of corporate compliance with the eighth Company Law Directive (CLD) over time, the relationship between the degree of compliance with the eighth CLD and corporate governance quality (CGQ), and the relative effect of compliance with the eighth CLD and Sarbanes–Oxley Act (SOX) on CGQ.Design/methodology/approachThe hypotheses are tested on a sample of EU firms that are cross listed in the EU and the USA and, thus, subject to both EU and US legislation, using fixed effects panel regression analysis.FindingsThe authors find that compliance levels with the eighth CLD are increasing over time, yet they vary considerably across constituent provisions. The authors also find that higher compliance is positively related to CGQ, although the effect size is higher for compliance with the eighth CLD than for compliance with SOX.Originality/valueThis study is original from many perspectives. Unlike most prior studies, which rely on binary variables to represent the constructs appraised in this study, novel and advanced measures of compliance and CGQ are constructed. Next, this study examines EU firms that have received very little research interest compared to US firms. Third, in an innovative approach, the authors appraise the relationship between the degree of compliance and CGQ longitudinally at both the aggregate and the constituent provision levels.
Big data and HR analytics in the digital era
Authors: Dahlbom Pauli , Siikanen Noora , Sajasalo Pasi , Jarvenpää Marko 
Published: January 2020

PurposeThe purpose of this paper is to focus on how the HR function takes advantage of human resource analytics (HRA), including big data (BD), and discuss factors hindering HRA and data utilization. Moreover, the authors discuss the implications of the HRA-induced role transformation of the human resource (HR) function.Design/methodology/approachThis is an explorative case study based on qualitative interviews in nine leading Finnish companies.FindingsThe results indicate that both technical and human obstacles, operating with very basic HR processes and traditional information systems and poor data quality, hinder adoption of advanced HRA. This, combined with lacking skills in analytics and business understanding, inability to go beyond reporting, misconceptions related to BD and traditional compliance-oriented HR culture pose further challenges for the data analytics capacity and business partner role of the HR function. Senior executives expect no significant advancements of HRA, while HR professionals saw potential value in BD, although skepticism was not uncommon. The results point toward a need for increased cooperation with data analysts and HR professionals in provision and understanding the HR-related data for business-related decision making. Furthermore, cultural change and organizational redesign may be called for, in addition to overcoming technological obstacles related to BD, for it to have an impact on HR practices. HRA utilization and role transition of the HR function seem closely related and this transformation can be mutually reinforcing.Originality/valueThis study provides and theorizes explorative data on HRA within a group of some of the largest Finnish companies, pointing toward an immature state of the art in BD and HRA utilization and there being a relationship between HRA and the role transition of the HR function in organizations.