bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a Central Neural Circuit that Regulates Anxiety-induced Bone Loss
Authors: Yang Fan , Liu Yunhui , Chen Shanping , Dai Zhongquan , Yang Dazhi , Gao Dashuang , Shao Jie , Wang Yuyao , Wang Ting , Zhang Zhijian , Zhang Lu , Lu William W , Tu Jie , Li Yinghui , Wang Liping 
Published: October 2019

AbstractThe homeostasis of bone metabolism is finely regulated by the central nervous system and recent studies have suggested that mood disorders, such as anxiety, are closely related to bone metabolic abnormalities; however, our understanding of central neural circuits regulating bone metabolism is still largely limited. In this study, we first demonstrate that confined isolation of human participants under normal gravity resulted in decreased bone density and elevated anxiety levels. We then used an established mouse model to dissect the neural circuitry regulating anxiety-induced bone loss. Combining electrophysiological, optogenetic and chemogenetic approaches, we demonstrate that GABAergic neural circuitry in ventromedial hypothalamus (VMH) modulates anxiety-induced bone loss; importantly, the GABAergic input in VMHdm arose from a specific group of somatostatin neurons in the bed nucleus of the stria terminalis (BNST), which is both indispensable for anxiety-induced bone loss and able to trigger bone loss in the absence of stressors. VGLUT2 neurons in Nucleus tractus solitaries (NTS) and peripheral sympathetic system were employed by this BNST-VMH neural circuit to regulate anxiety-induced bone loss. Overall, we uncovered new GABAergic neural circuitry from the forebrain to hypothalamus, used in the regulation of anxiety-induced bone loss, and revealed a population of somatostatin neurons in BNST not previously implicated in bone mass regulation. These findings thus identify the underlying central neural mechanism of psychiatric disorders, such as anxiety, that influences bone metabolism at the circuit level.One Sentence SummaryIdentification of a new GABAergic neural circuit from forebrain to hypothalamus used for regulation of anxiety-induced bone loss.
Transcriptome reconstruction and functional analysis of eukaryotic marine plankton communities via high-throughput metagenomics and metatranscriptomics
Authors: Vorobev Alexey , Dupouy Marion , Carradec Quentin , Delmont Tom O. , Annamalé Anita , Wincker Patrick , Pelletier Eric 
Published: October 2019

AbstractLarge scale metagenomic and metatranscriptomic data analyses are often restricted by their genecentric approach, limiting the ability to understand organismal and community biology. De novo assembly of large and mosaic eukaryotic genomes from complex meta -omics data remains a challenging task, especially in comparison with more straightforward bacterial and archaeal systems. Here we use a transcriptome reconstruction method based on clustering co-abundant genes across a series of metagenomic samples. We investigated the co-abundance patterns of ~37 million eukaryotic unigenes across 365 metagenomic samples collected during the Tara Oceans expeditions to assess the diversity and functional profiles of marine plankton. We identified ~12 thousand co-abundant gene groups (CAGs), encompassing ~7 million unigenes, including 924 metagenomics based transcriptomes (MGTs, CAGs larger than 500 unigenes). We demonstrated the biological validity of the MGT collection by comparing individual MGTs with available references. We identified several key eukaryotic organisms involved in dimethylsulfoniopropionate (DMSP) biosynthesis and catabolism in different oceanic provinces, thus demonstrating the potential of the MGT collection to provide functional insights on eukaryotic plankton. We established the ability of the MGT approach to capture interspecies associations through the analysis of a nitrogen-fixing haptophyte-cyanobacterial symbiotic association. This MGT collection provides a valuable resource for an exhaustive analysis of eukaryotic plankton in the open ocean by giving access to the genomic content and functional potential of many ecologically relevant eukaryotic species.
Multi-modality neuroimaging brain-age in UK Biobank: relationship to biomedical, lifestyle and cognitive factors
Authors: Cole James H 
Published: October 2019

AbstractThe brain-age paradigm is proving increasingly useful for exploring ageing-related disease and can predict important future health outcomes. Most brain-age research utilises structural neuroimaging to index brain volume. However, ageing affects multiple aspects of brain structure and function, which can be examined using multi-modality neuroimaging. Using UK Biobank, brain-age was modelled in n=2,205 healthy people with T1-weighted MRI, T2-FLAIR, T2*, diffusion-MRI, task fMRI and resting-state fMRI. In a held-out healthy validation set (n=520), chronological age was accurately predicted (r=0.79, mean absolute error=3.52 years) using LASSO regression, higher than using any modality separately. Thirty-four neuroimaging phenotypes were deemed informative by the regression (after bootstrapping); predominantly grey-matter volume and white-matter microstructure measures. When applied to new individuals from UK Biobank (n=14,701), significant associations with multi-modality brain-predicted age difference (brain-PAD) were found for: stroke history, diabetes diagnosis, smoking, alcohol intake and some, but not all, cognitive measures (corrected p<0.05). Multi-modality neuroimaging can improve brain-age prediction, and derived brain-PAD values are sensitive to biomedical and lifestyle factors that negatively impact brain and cognitive health.
Promoter proximal pausing limits Yki-induced tumorous growth in Drosophila
Authors: Nagarkar Sanket , Wasnik Ruchi , Govada Pravallika , Cohen Stephen , Shashidhara LS 
Published: October 2019

AbstractPromoter proximal pausing (PPP) of RNA Polymerase II has emerged as a crucial rate-limiting-step in the regulation of gene expression. Regulation of PPP is brought about by complexes 7SK snRNP, P-TEFb (Cdk9/cycT) and the Negative Elongation Factor (NELF) which are highly conserved from Drosophila to humans. Here we show that RNAi-mediated depletion of bin3 or Hexim of the 7SK snRNP complex or depletion of individual components of the NELF complex enhance Yki-driven growth leading to neoplastic transformation of Drosophila wing imaginal discs. We also show that increased CDK9 expression cooperates with Yki, in driving neoplastic growth. Interestingly, over-expression of CDK9 on its own or in the background of depletion of one of the components of 7SK snRNP or the NELF complex necessarily and specifically needed Yki over-expression to cause tumorous growth. Genome-wide gene expression analyses suggested that deregulation of protein homeostasis is associated with tumorous growth of wing imaginal discs. As both Fat/Hippo/Yki pathway and PPP are highly conserved, our observations may provide insights into mechanisms of oncogenic function of YAP, the orthologue of Yki in human.
Quantitative properties of a feedback circuit predict frequency-dependent pattern separation
Authors: Braganza Oliver , Müller-Komorowska Daniel , Kelly Tony , Beck Heinz 
Published: October 2019

AbstractFeedback inhibitory motifs are thought to be important for pattern separation across species. How feedback circuits may implement pattern separation of biologically plausible, temporally structured input in mammals is, however, poorly understood. We have quantitatively determined key properties of net feedback inhibition in the mouse dentate gyrus, a region critically involved in pattern separation. Feedback inhibition is recruited steeply with a low dynamic range (0 to 4% of active GCs), and with a non-uniform spatial profile. Additionally, net feedback inhibition shows frequency-dependent facilitation, driven by strongly facilitating mossy fiber inputs. Computational analyses show a significant contribution of the feedback circuit to pattern separation of theta modulated inputs, even within individual theta cycles. Moreover, pattern separation was selectively boosted at gamma frequencies, in particular for highly similar inputs. This effect was highly robust, suggesting that frequency dependent pattern separation is a key feature of the feedback inhibitory microcircuit.
Genome Sequence of Segmented Filamentous Bacteria Present in the Human Intestine
Authors: Jonsson Hans , Hugerth Luisa W. , Sundh John , Andersson Anders F. 
Published: October 2019

SummarySegmented filamentous bacteria (SFB) colonize the small intestine of a variety of animals in a host-specific manner. SFB are physically attached to the host’s intestinal epithelium and affect several functions related to the immune system, among them IgA production and T-cell maturation. Until now, no human-specific SFB genome had been described. Here, we report the metagenomic reconstruction of an SFB genome from a human ileostomy sample. Phylogenomic analysis clusters the genome with the SFB genomes from mouse, rat and turkey, but the genome is genetically distinct, displaying 65-71% average amino acid identity to the other genomes, and is tentatively unique for the human small intestine. By screening human faecal metagenomic datasets, we identified individuals carrying sequences identical to the new SFB-genome. We thus conclude that a unique SFB variant exists in humans and we foresee a renewed interest in the elucidation of SFB functionality in this environment.
Impact of intensive care unit admission during handover on mortality: a propensity matched cohort study
Authors: Midega Thais Dias , Filho Newton Carlos Viana Leite , Nassar Antônio Paulo , Alencar Roger Monteiro , Neto Antônio Capone , Ferraz Leonardo Rolim , Corrêa Thiago Domingos 
Published: October 2019

AbstractIntroductionHandover is a process of transferring information, responsibility and authority for providing care of critically ill patients from a departing intensivist to an oncoming intensivist. The effect of i admission during a medical handover on clinical outcomes is unknown.ObjectivesOur purpose was to evaluate the impact of ICU admission during a medical handover on clinical outcomes.MethodsPost hoc analysis of a cohort study addressing the effect of ICU admissions during the handover on outcomes. This retrospective, single center, propensity matched cohort study was conducted in a 41-bed open general ICU located in a private tertiary care hospital in São Paulo, Brazil. Based on time of ICU admission, patients were categorized into two cohorts: handover group (ICU admission between 6:30 am to 7:30 or 6:30 pm to 7:30 pm) or control group (admission between 7:31 am to 6:29 pm or 7:31 pm to 6:29 am). Patients in the handover group were propensity matched to patients in the control group at 1:2 ratio. Our primary outcome was hospital mortality.ResultsBetween June 1, 2013 and May 31, 2015, 6,650 adult patients were admitted to the ICU. Following exclusion of ineligible participants, 5,779 patients [389 (6.7%) in handover group and 5390 (93.3%) in control group] were eligible for propensity score matching, of whom 1,166 were successfully matched [389 (33.4%) handover group and 777 (66.6%) in control group]. Before matching, hospital mortality was 14.1% (55/389 patients) in handover group compared to 11.7% (628/5,390) in control group (p=0.142). After propensity-score matching, ICU admission during handover was not associated with increased risk of ICU (OR, 1.40; 95% CI, 0.92 to 2.11; p=0.11) and hospital (OR, 1.23; 95%CI, 0.85 to 1.75; p=0.26) mortality. ICU and hospital length of stay did not differ between the groups.ConclusionIn this propensity-matched single center cohort study, ICU admission during medical handover did not affect clinical outcomes.
Heritability and relationship of oxytocin receptor gene variants with social behavior and central oxytocin in colony-reared adult female rhesus macaques
Authors: De Leon Desirée , Walum Hasse , McCormack Kai M. , LaPrairie Jamie L. , Lindell Stephen G. , Firesryche Ashley , Johnson Zach , Wilson Mark E. , Barr Christina S. , Sanchez Mar M. , Young Larry J. 
Published: October 2019

AbstractThe genetic contributions to sociality are an important research focus for understanding individual variation in social function and risk of social deficits in neurodevelopmental disorders (e.g. autism). The neuropeptide oxytocin (OXT) and its receptor, OXTR, influence social behavior across species. In humans and animals, common variants within the OXTR gene (OXTR) have been associated with varying socio-behavioral traits. However, the reported magnitude of influence of individual variants on complex behavior has been inconsistent. Compared to human studies, non-human primate (NHP) studies in controlled environments have the potential to result in robust effects detectable in relatively small samples. Here we estimate heritability of social behavior and central OXT concentrations in 214 socially-housed adult female rhesus macaques, a species sharing high similarity with humans in genetics, physiology, brain and social complexity. We present a bioinformatically-informed approach for identifying single nucleotide polymorphisms (SNPs) with likely biological relevance. We tested 13 common SNPs in regulatory and coding regions ofOXTRfor associations with behavior (pro-social, anxiety-like, and aggressive) and OXT concentration in cerebrospinal fluid (CSF). We found moderate rates of heritability for both social behavior and CSF OXT concentrations. No tested SNPs showed significant associations with behaviors or CSF in this sample. Associations between OXT CSF and social behavior were not significant either. SNP effect sizes were generally comparable to those reported in human studies of complex traits. While environmental control and a socio-biological similarity with humans is an advantage of rhesus models for detecting smaller genetic effects, it is insufficient to obviate large sample sizes necessary for appropriate statistical power.
Effects of initial microbial biomass abundance on respiration during pine litter decomposition
Authors: Albright Michaeline B.N. , Runde Andreas , Lopez Deanna , Gans Jason , Sevanto Sanna , Woolf Dominic , Dunbar John 
Published: October 2019

AbstractMicrobial biomass is increasingly used to predict respiration in soil organic carbon (SOC) models. Its increased use combined with the difficulty of accurately measuring this variable points a need to directly assess the importance of microbial biomass abundance for carbon (C) cycling. To test the hypothesis that the initial microbial biomass abundance (i.e. biomass abundance on new plant litter) is a strong driver of plant litter C cycling, we manipulated biomass abundance by 10 and 100-fold dilution and composition using 12 source communities on sterile pine litter and measured respiration in microcosms for 30 days. In the first two days of microbial growth on fresh litter, a 100-fold difference in initial biomass abundance caused an average difference in respiration of nearly 300%, but the effect rapidly declined to less than 30% in 10 days and to 14% in 30 days. Parallel simulations with a soil carbon model, SOMIC 1.0, also predicted a 14% difference over 30 days, consistent with the experimental results. Model simulations predicted convergence of cumulative CO2 to within 10% in three months and within 4% in three years. Rapid microbial growth likely attenuates the effects of large initial differences in biomass abundance. In contrast, the persistence of source community as an explanatory factor in driving differences in respiration across microcosms supports the importance of microbial composition in C cycling. Overall, the results suggest that the initial abundance of microbial biomass on litter is a weak driver of C flux from litter decomposition over long timescales (months to years) when litter communities have equal nutrient availability. By extension, slight variation in the timing of microbial dispersal to fresh litter is likely to be a minor factor in long-term C flux.ImportanceMicrobial biomass is one of the most common microbial parameters used in land carbon (C) cycle models, however, it is notoriously difficult to measure accurately. To understand the consequences of mismeasurement, as well as the broader importance of microbial biomass abundance as a direct driver of ecological phenomena, greater quantitative understanding of the role of microbial biomass abundance in environmental processes is needed. Using microcosms, we manipulated the initial biomass of numerous microbial communities across a 100-fold range and measured effects on CO2 production during plant litter decomposition. We found that the effects of initial biomass abundance on CO2 production was largely attenuated within a week, while the effects of community type remained significant over the course of the experiment. Overall, our results suggest that initial microbial biomass abundance in litter decomposition within an ecosystem is a weak driver of long-term C cycling dynamics.
Transcriptomic profiling of PBDE-exposed HepaRG cells unveils critical lncRNA-PCG pairs involved in intermediary metabolism
Authors: Zhang Angela , Li Cindy Yanfei , Kelly Edward J. , Sheppard Lianne , Cui Julia Yue 
Published: October 2019

ABSTRACTPolybrominated diphenyl ethers (PBDEs) were formally used as flame-retardants and are chemically stable, lipophlic persistent organic pollutants which are known to bioaccumulate in humans. Although its toxicities are well characterized, little is known about the changes in transcriptional regulation caused by PBDE exposure. Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of transcriptional and translational processes. It is hypothesized that lncRNAs can regulate nearby protein-coding genes (PCGs) and changes in the transcription of lncRNAs may act incisto perturb gene expression of its neighboring PCGs. The goals of this study were to 1) characterize PCGs and lncRNAs that are differentially regulated from exposure to PBDEs; 2) identify PCG-lncRNA pairs through genome annotation and predictive binding tools; and 3) determine enriched canonical pathways caused by differentially expressed lncRNA-PCGs pairs. HepaRG cells, which are human-derived hepatic cells that accurately represent gene expression profiles of human liver tissue, were exposed to BDE-47 and BDE-99 at a dose of 25 μM for 24 hours. Differentially expressed lncRNA-PCG pairs were identified through DESeq2 and HOMER; significant canonical pathways were determined through Ingenuity Pathway Analysis (IPA). LncTar was used to predict the binding of 19 lncRNA-PCG pairs with known roles in drug-processing pathways. Genome annotation revealed that the majority of the differentially expressed lncRNAs map to PCG introns. PBDEs regulated overlapping pathways with PXR and CAR such as protein ubiqutination pathway and PPARα-RXRα activation but also regulate distinctive pathways involved in intermediary metabolism. BDE-47 uniquely regulated signaling by Rho Family GTPases and PBDE-99 uniquely regulates JAK/Stat signaling, bile acid biosynthesis, sirtuin signaling pathway, and autophagy. In conclusion, lncRNAs play essential roles in modifying important pathways involved in intermediary metabolism such as carbohydrate and lipid metabolism.
THAP11F80Lcobalamin disorder-associated mutation reveals normal and pathogenic THAP11 functions in gene expression and cell proliferation
Authors: Dehaene Harmonie , Praz Viviane , Lhôte Philippe , Lopes Maykel , Herr Winship 
Published: October 2019

AbstractTwelve human THAP proteins share the THAP domain, an evolutionary conserved zinc-finger DNA-binding domain. Studies of different THAP proteins have indicated roles in gene transcription, cell proliferation and development. We have analyzed this protein family, focusing on THAP7 and THAP11. We show that human THAP proteins possess differing homo- and heterodimer formation properties and interaction abilities with the transcriptional co-regulator HCF-1. HEK-293 cells lacking THAP7 were viable but proliferated more slowly. In contrast, HEK-293 cells were very sensitive to THAP11 alteration. Nevertheless, HEK-293 cells bearing a THAP11 mutation identified in a patient suffering from cobalamin disorder (THAP11F80L) were viable although proliferated more slowly. Cobalamin disorder is an inborn vitamin deficiency characterized by neurodevelopmental abnormalities, most often owing to biallelic mutations in theMMACHCgene, whose gene product MMACHC is a key enzyme in the cobalamin (vitamin B12) metabolic pathway. We show that THAP11F80Lselectively affected promoter binding by THAP11, having more deleterious effects on a subset of THAP11 targets, and resulting in altered patterns of gene expression. In particular, THAP11F80Lexhibited a strong effect on association with theMMACHCpromoter and led to a decrease inMMACHCgene transcription, suggesting that the THAP11F80Lmutation is directly responsible for the observed cobalamin disorder.
Dementia is Associated with a Syndrome of Global Neuropsychiatric Disturbance
Authors: Royall Donald R. , Palmer Raymond F. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2019

AbstractObjectiveGlobal factors have been identified in measures of cognitive performance (i.e., Spearman’s g) and psychopathology (i.e., “General Psychopathology”, “p”). Dementia is also strongly determined by the latent phenotype “δ”, derived from g. We wondered if the Behavior and Psychological Symptoms of Dementia (BPSD) might arise from an association between δ and p.Methodsδ and p were constructed by confirmatory factor analyses in data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). δ and orthogonal factors representing “domain-specific” variance in memory (MEM) and executive function (EF) were regressed onto p and orthogonal factors representing “domain-specific” variance in positive (+) and negative (-) symptoms rated by the Neuropsychiatric Inventory Nursing Home Questionnaire (NPI-Q) by multiple regression in a structural equation model (SAM) framework.ResultsModel fit was excellent (CFI = 0.98, RMSEA = 0.03). δ was strongly associated with p, (+) and (-) and strongly associated with p (r = −0.57, p<0.001). All three associations were inverse (adverse). Independently of δ, MEM was uniquely associated with (+), while ECF was associated with (-). Both associations were moderately strong. ECF was also weakly associated with p.ConclusionsDementia severity (δ) derived from general intelligence (g) is specifically associated with general psychopathology (p). This is p’s first demonstration in an elderly sample and the first to distinguish the global behavioral and psychological symptoms specific to dementia (BPSSD) from behavioral disturbances arising by way of non-dementing, albeit likely disease-specific, processes affecting domain-specific cognitive and behavioral constructs. Our findings call into question the utility of proposed regional interventions in BPSSD, and point to the need to explore global interventions against dementia-specific behavioral features.
Pangenomic read mapping
Authors: Anari Siavash Sheikhizadeh , de Ridder Dick , Schranz M. Eric , Smit Sandra 
Published: October 2019

AbstractIn modern genomics, mapping reads to a single reference genome is common practice. However, a reference genome does not necessarily accurately represent a population or species and as a result a substantial percentage of reads often cannot be mapped. A number of graph-based variation-aware mapping methods have recently been proposed to remedy this. Here, we propose an alternative multi-reference approach, which aligns reads to large collections of genomes simultaneously. Our approach, an extension to our pangenomics suite PanTools (https://git.wur.nl/bioinformatics/pantools), is as accurate as state-of the-art tools but more efficient on large numbers of genomes. We successfully applied PanTools to map genomic and metagenomic reads to large collections of viral, archaeal, bacterial, fungal and plant genomes.