bluuebunny/crossref_metadata_2025_split huggingface dataset:
Joint identification of sex and sex-linked scaffolds in non-model organisms using low depth sequencing data
Authors: Nursyifa Casia , Brüniche-Olsen Anna , Erill Genis Garcia , Heller Rasmus , Albrechtsen Anders 
Published: March 2021

AbstractBeing able to assign sex to individuals and identify autosomal and sex-linked scaffolds are essential in most population genomic analyses. Non-model organisms often have genome assemblies at scaffold level and lack characterization of sex-linked scaffolds. Previous methods to identify sex and sex-linked scaffolds have relied on e.g. sequence similarity between the non-model organism and a closely related species or prior knowledge about the sex of the samples to identify sex-linked scaffolds. In the latter case, the difference in depth of coverage between the autosomes and the sex chromosomes are used. Here we present ‘Sex Assignment Through Coverage’ (SATC), a method to identify sample sex and sex-linked scaffolds from NGS data. The method only requires a scaffold level reference assembly and sampling of both sexes with whole genome sequencing (WGS) data. We use the sequencing depth distribution across scaffolds to jointly identify: i) male and female individuals and ii) sex-linked scaffolds. This is achieved through projecting the scaffold depths into a low-dimensional space using principal component analysis (PCA) and subsequent Gaussian mixture clustering. We demonstrate the applicability of our method using data from five mammal species and a bird species complex. The method is open source and freely available athttps://github.com/popgenDK/SATC
COVID Seroprevalence, Symptoms and Mortality During the First Wave of SARS-CoV-2 in Canada
Authors:   Action to beat coronavirus/Action pour battre le coronavirus (Ab-C) Study Investigators, Jha Prabhat 
Published: March 2021

AbstractBackgroundEfforts to stem Canada’s SARS-CoV-2 pandemic can benefit from direct understanding of the prevalence, infection fatality rates (IFRs), and information on asymptomatic infection.MethodsWe surveyed a representative sample of 19,994 adult Canadians about COVID symptoms and analyzed IgG antibodies against SARS-CoV-2 from self-collected dried blood spots (DBS) in 8,967 adults. A sensitive and specific chemiluminescence ELISA detected IgG to the spike trimer. We compared seroprevalence to deaths to establish IFRs and used mortality data to estimate infection levels in nursing home residents.ResultsThe best estimate (high specificity) of adult seroprevalence nationally is 1.7%, but as high as 3.5% (high sensitivity) depending on assay cut-offs. The highest prevalence was in Ontario (2.4-3.9%) and in younger adults aged 18-39 years (2.5-4.4%). Based on mortality, we estimated 13-17% of nursing home residents became infected. The first viral wave infected 0.54-1.08 million adult Canadians, half of whom were <40 years old. The IFR outside nursing homes was 0.20-0.40%, but the COVID mortality rate in nursing home residents was >70 times higher than that in comparably-aged adults living in the community. Seropositivity correlated with COVID symptoms, particularly during March. Asymptomatic adults constituted about a quarter of definite seropositives, with a greater proportion in the elderly.InterpretationCanada had relatively low infection prevalence and low IFRs in the community, but not in nursing homes, during the first viral wave. Self-collected DBS for antibody testing is a practicable strategy to monitor the ongoing second viral wave and, eventually, vaccine-induced immunity among Canadian adults.
A modeling framework for determining modulation of neural-level tuning from non-invasive human fMRI data
Authors: Sadil Patrick , Cowell Rosemary A. , Huber David E. 
Published: March 2021

AbstractMany neuroscience theories assume that tuning modulation of individual neurons underlies changes in human cognition. However, non-invasive fMRI lacks sufficient resolution to visualize this modulation. To address this limitation, we developed an analysis framework called Inferring Neural Tuning Modulation (INTM) for “peering inside” voxels. Precise specification of neural tuning from the BOLD signal is not possible. Instead, INTM compares theoretical alternatives for the form of neural tuning modulation that might underlie changes in BOLD across experimental conditions. The most likely form is identified via formal model comparison, with assumed parametric Normal tuning functions, followed by a non-parametric check of conclusions. We validated the framework by successfully identifying a well-established form of modulation: visual contrast-induced multiplicative gain for orientation tuned neurons. INTM can be applied to any experimental paradigm testing several points along a continuous feature dimension (e.g., direction of motion, isoluminant hue) across two conditions (e.g., with/without attention, before/after learning).
Self-supervised learning of probabilistic prediction through synaptic plasticity in apical dendrites: A normative model
Authors: Rao Arjun , Legenstein Robert , Subramoney Anand , Maass Wolfgang 
Published: March 2021

AbstractSensory information is processed by the brain not in a simple feedforward fashion. Rather, bottom-up inputs are combined in pyramidal cells of sensory cortices with top-down information from higher brain areas that arrives through synapses in apical dendrites. The exact functional role of these top-down inputs has remained unknown. A promising abstract model posits that they provide probabilistic priors for bottom-up sensory inputs. We show that this hypothesis is consistent with a large number of experimental about synaptic plasticity in apical dendrites, in particular with the prominent role of NMDA-spikes. We identify conditions under which this synaptic plasticity could approximate the gold standard for self-supervised learning of probabilistic priors: logistic regression. Furthermore, this perspective suggests an additional functional role for the complex structure of the dendritic arborization plays: It enables the neuron to learn substantially more complex landscapes of probabilistic priors.
Discovery and validation of novel human genomic safe harbor sites for gene and cell therapies
Authors: Aznauryan Erik , Yermanos Alexander , Kinzina Elvira , Kapetanovic Edo , Milanova Denitsa , Church George M. , Reddy Sai T. 
Published: March 2021

SummaryExisting approaches for the integration and expression of genes of interest in a desired human cellular context are marred by the safety concerns related to either the random nature of viral-mediated integration or unpredictable pattern of gene expression in currently employed targeted genomic integration sites. Disadvantages of these methods lead to their limited use in clinical practice, thus encouraging future research in identifying novel human genomic sites that allow for predictable and safe expression of genes of interest. We conducted a bioinformatic search followed by experimental validation of novel genomic sites and identified two that demonstrated stable expression of integrated reporter and therapeutic genes without detrimental changes to cellular transcriptome. The cell-type agnostic criteria used in our bioinformatic search suggest wide-scale applicability of our sites for engineering of a diverse range of tissues for therapeutic as well as enhancement purposes, including modified T-cells for cancer therapy and engineered skin to ameliorate inherited diseases and aging. Additionally, the stable and robust levels of gene expression from identified sites allow for their use in industry-scale biomanufacturing of desired proteins in human cells.
Bovine milk somatic cell transcriptomic response toStaphylococcus aureusis dependent on strain genotype
Authors: Niedziela Dagmara A. , Cormican Paul , Foucras Gilles , Leonard Finola C. , Keane Orla M. 
Published: March 2021

AbstractBackgroundMastitis is an economically important disease of dairy cows with Staphylococcus aureus a major cause worldwide. Challenge of Holstein-Friesian cows demonstrated that S. aureus strain MOK124, which belongs to Clonal Complex (CC)151, caused clinical mastitis, while strain MOK023, belonging to CC97, caused mild or subclinical mastitis. The aim of this study was to elucidate the molecular mechanisms of the host immune response utilising a transcriptomic approach. Milk somatic cells were collected from cows infected with either S. aureus MOK023 or MOK124 at 0, 24, 48, 72 and 168 hours post-infection (hpi) and analysed for differentially expressed (DE) genes in response to each strain.ResultsIn response to MOK023, 1278, 2278, 1986 and 1750 DE genes were found at 24, 48, 72 and 168 hpi, respectively, while 2293, 1979, 1428 and 1544 DE genes were found in response to MOK124 at those time points. Genes involved in milk production (CSN1, CSN10, CSN1S2, CSN2, a-LACTA and PRLR) were downregulated in response to both strains, with a more pronounced decrease in the MOK124 group. Immune response pathways such as NF-κB and TNF signalling were overrepresented in response to both strains at 24 hpi. These immune pathways continued to be overrepresented in the MOK023 group at 48 and 72 hpi, while the Hippo signalling, extracellular matrix interaction (ECM) and tight junction pathways were overrepresented in the MOK124 group between 48 and 168 hpi. Cellular composition analysis demonstrated that a neutrophil response was predominant in response to MOK124, while M1 macrophages were the main milk cell type post-infection in the MOK023 group.ConclusionsA switch from immune response pathways to pathways involved in maintaining the integrity of the epithelial cell layer was observed in the MOK124 group from 48 hpi, which coincided with the occurrence of clinical signs in the infected animals. The higher proportion of M1 macrophages in the MOK023 group and lack of substantial neutrophil recruitment in response to MOK023 may indicate immune evasion by this strain. The results of this study highlight that the somatic cell transcriptomic response to S. aureus is dependent on the genotype of the infecting strain.
Smartphone deprivation alters cortical sensorimotor processing of the hand
Authors: Ghosh Arko 
Published: March 2021

AbstractBrain areas representing the body can change in response to behavioral alterations. This idea is firmly established for the adult cortex in response to extraordinary alterations such as traumatic amputation or casting of the limb. Here we address how adult cortical sensorimotor processing alters in response to a subtle perturbation in the form of smartphone deprivation lasting for ~7 days. We quantified the sensorimotor processes associated with the fingertips before and after the deprivation in right-handed smartphone users. The measurements were contrasted with those of a control group with unperturbed smartphone behavior. First, smartphone tapping speed in daily life became slower after the deprivation. Second, according to reaction time tests conducted in the laboratory the asymmetrically superior performance of the right vs. left thumb was eroded by the deprivation. Third, according to EEG measurements at physical rest, tactile stimulation at the right thumb tip resulted in smaller signal amplitudes after the deprivation. Moreover, the EEG measurements during smartphone use revealed larger signal amplitudes for tactile stimulation at the right little fingertip after the deprivation. We show that cortical plasticity can occur by merely disengaging from a common day-to-day behavior. We suggest that in daily life the adult brain continuously and selectively updates its sensorimotor processing according to recent experience.
NPAS4 in the medial prefrontal cortex mediates chronic social defeat stress-induced anhedonia and dendritic spine loss
Authors: Hughes Brandon W , Siemsen Benjamin M , Berto Stefano , Kumar Jaswinder , Cornbrooks Rebecca G , Akiki Rose Marie , Carter Jordan S , Scofield Michael D , Cowan Christopher W , Taniguchi Makoto 
Published: March 2021

AbstractChronic stress can produce reward system deficits (i.e. anhedonia) and other common symptoms associated with depressive disorders, as well as neural circuit hypofunction in the medial prefrontal cortex (mPFC). However, the molecular mechanisms by which chronic stress promotes depressive-like behavior and hypofrontality remain unclear. We show here that the neuronal activity-regulated transcription factor, NPAS4, in the mPFC is regulated by chronic social defeat stress (CSDS), and it’s required in this brain region for CSDS-induced changes in sucrose preference and natural reward motivation. Interestingly, NPAS4 is not required for CSDS-induced social avoidance or anxiety-like behavior. We also find that mPFC NPAS4 is required for CSDS-induced reduction of pyramidal cell dendritic spine density, revealing a relationship between mPFC dendritic spine changes and anhedonia-like behavior, but not social avoidance behavior. Finally, transcriptomic analysis from the mPFC revealed that NPAS4 influences expression of numerous genes linked to glutamatergic synapses and ribosomal function, as well as many dysregulated genes observed in common neuropsychiatric disorders, including depression. Together our findings reveal an essential role for the activity-regulated transcription factor, NPAS4, in chronic stress-induced mPFC hypofunction and anhedonia.
Glucagon-like peptide 1 receptor-mediated stimulation of a GABAergic projection from the bed nucleus of the stria terminalis to the hypothalamic paraventricular nucleus
Authors: Povysheva Nadya , Zheng Huiyuan , Rinaman Linda 
Published: March 2021

AbstractWe previously reported that GABAergic neurons within the ventral anterior lateral bed nucleus of the stria terminalis (alBST) express glucagon-like peptide 1 receptor (GLP1R) in rats, and that virally-mediated “knock-down” of GLP1R expression in the alBST prolongs the hypothalamic-pituitary-adrenal axis response to acute stress. Given other evidence that a GABAergic projection pathway from ventral alBST serves to limit stress-induced activation of the HPA axis, we hypothesized that GLP1 signaling promotes activation of GABAergic ventral alBST neurons that project directly to the paraventricular nucleus of the hypothalamus (PVN). After PVN microinjection of fluorescent retrograde tracer followed by preparation ofex vivorat brain slices, whole-cell patch clamp recordings were made in identified PVN-projecting neurons within the ventral alBST. Bath application of Exendin-4 (a specific GLP1R agonist) indirectly depolarized PVN-projecting neurons in the ventral alBST and adjacent hypothalamic parastrial nucleus (PS) via circuit-mediated effects that increased excitatory synaptic inputs and decreased inhibitory synaptic inputs to the PVN-projecting neurons; these effects were occluded by prior bath application of a GLP1R antagonist. Additional retrograde tracing experiments combined within situhybridization confirmed that PVN-projecting neurons within the ventral alBST/PS are GABAergic, and do not express GLP1R mRNA. Conversely, GLP1 mRNA is expressed by a subset of GABAergic neurons within the oval subnucleus of the dorsal alBST that project into the ventral alBST. Our novel findings reveal a potential GLP1R-mediated mechanism through which the alBST exerts inhibitory control over the endocrine HPA axis.
Paucimyces polynucleatusgen. nov, sp. nov., a novel polycentric genus of anaerobic gut fungi from the feces of a wild blackbuck antelope
Authors: Hanafy Radwa A. , Youssef Noha H. , Elshahed Mostafa 
Published: March 2021

AbstractThe anaerobic gut fungi (AGF, phylum Neocallimastigomycota) reside in the alimentary tracts of herbivores. Multiple novel, yet-uncultured AGF taxa have recently been identified in culture-independent diversity surveys. Here, we report on the isolation and characterization of the first representative of the RH5 lineage from fecal samples of a wild blackbuck (Indian Antelope) from Sutton County, Texas, USA. The isolates displayed medium sized (2-4 mm) compact circular colonies on agar roll tubes and thin loose biofilm-like growth in liquid medium. Microscopic examination revealed monoflagellated zoospores and polycentric thalli with highly branched nucleated filamentous rhizomycelium, a growth pattern encountered in a minority of described AGF genera so far. The obtained isolates are characterized by formation of spherical vesicles at the hyphal tips from which multiple sporangia formed either directly on the spherical vesicles or at the end of sporangiophores. Phylogenetic analysis using the D1/D2 regions of the large ribosomal subunit (D/D2 LSU) and the ribosomal internal transcribed spacer 1 (ITS1) revealed sequence similarities of 93.5%, and 81.3%, respectively, to the closest cultured relatives (Orpinomyces joyoniistrain D3A (D1/D2 LSU), andJoblinomyces apicalisstrain GFH681 (ITS1). Substrate utilization experiments using the type strain (BB-3) demonstrated growth capabilities on a wide range of mono-, oligo-, and polysaccharides, including glucose, xylose, mannose, fructose, cellobiose, sucrose, maltose, trehalose, lactose, cellulose, xylan, starch, and raffinose. We propose accommodating these novel isolates in a new genus and species, for which the namePaucimyces polynucleatusis proposed. The type species is strain BB-3.
Direct molecular evidence for an ancient, conserved developmental toolkit controlling post-transcriptional gene regulation in land plants
Authors: Jia Haiyan , Aadland Kelsey , Kolaczkowski Oralia , Kolaczkowski Bryan 
Published: March 2021

ABSTRACTRNA interference (RNAi) plays important roles in organism development through post-transcriptional regulation of specific target mRNAs. Target specificity is largely controlled by base-pair complementarity between micro-RNA (miRNA) regulatory elements and short regions of the target mRNA. The pattern of miRNA production in a cell interacts with the cell’s mRNA transcriptome to generate a specific network of post-transcriptional regulation that can play critical roles in cellular metabolism, differentiation, tissue/organ development and developmental timing. In plants, miRNA production is orchestrated in the nucleus by a suite of proteins that control transcription of the pri-miRNA gene, post-transcriptional processing and nuclear export of the mature miRNA. In the model plant, Arabidopsis thaliana, post-transcriptional processing of miRNAs is controlled by a pair of physically-interacting proteins, HYL1 and DCL1. However, the evolutionary history of the HYL1-DCL1 interaction is unknown, as is its structural basis. Here we use ancestral sequence reconstruction and functional characterization of ancestral HYL1 in vitro and in vivo to better understand the origin and evolution of the HYL1-DCL1 interaction and its impact on miRNA production and plant development. We found the ancestral plant HYL1 evolved high affinity for both double-stranded RNA (dsRNA) and its DCL1 partner very early in plant evolutionary history, before the divergence of mosses from seed plants (~500 Ma), and these high-affinity interactions remained largely conserved throughout plant evolutionary history. Structural modeling and molecular binding experiments suggest that the second of two double-stranded RNA-binding motifs (DSRMs) in HYL1 may interact tightly with the first of two C-terminal DCL1 DSRMs to mediate the HYL1-DCL1 physical interaction necessary for efficient miRNA production. Transgenic expression of the nearly 200 Ma-old ancestral flowering-plant HYL1 in A. thaliana was sufficient to rescue many key aspects of plant development disrupted by HYL1− knockout and restored near-native miRNA production, suggesting that the functional partnership of HYL1-DCL1 originated very early in and was strongly conserved throughout the evolutionary history of terrestrial plants. Overall, our results are consistent with a model in which miRNA-based gene regulation evolved as part of a conserved plant ‘developmental toolkit’; its role in generating developmental novelty is probably related to the relatively rapid evolution of miRNA genes.
Estimation of in-scanner head pose changes during structural MRI using a convolutional neural network trained on eye tracker video
Authors: Pardoe Heath R , Martin Samantha P , Zhao Yijun , George Allan , Yuan Hui , Zhou Jingjie , Liu Wei , Devinsky Orrin 
Published: March 2021

AbstractIntroductionIn-scanner head motion is a common cause of reduced image quality in neuroimaging, and causes systematic brain-wide changes in cortical thickness and volumetric estimates derived from structural MRI scans. There are few widely available methods for measuring head motion during structural MRI. Here, we train a deep learning predictive model to estimate changes in head pose using video obtained from an in-scanner eye tracker during an EPI-BOLD acquisition with participants undertaking deliberate in-scanner head movements. The predictive model was used to estimate head pose changes during structural MRI scans, and correlated with cortical thickness and subcortical volume estimates.Methods21 healthy controls (age 32 ± 13 years, 11 female) were studied. Participants carried out a series of stereotyped prompted in-scanner head motions during acquisition of an EPI-BOLD sequence with simultaneous recording of eye tracker video. Motion-affected and motion-free whole brain T1-weighted MRI were also obtained. Image coregistration was used to estimate changes in head pose over the duration of the EPI-BOLD scan, and used to train a predictive model to estimate head pose changes from the video data. Model performance was quantified by assessing the coefficient of determination (R2). We evaluated the utility of our technique by assessing the relationship between video-based head pose changes during structural MRI and (i) vertex-wise cortical thickness and (ii) subcortical volume estimates.ResultsVideo-based head pose estimates were significantly correlated with ground truth head pose changes estimated from EPI-BOLD imaging in a hold-out dataset. We observed a general brain-wide overall reduction in cortical thickness with increased head motion, with some isolated regions showing increased cortical thickness estimates with increased motion. Subcortical volumes were generally reduced in motion affected scans.ConclusionsWe trained a predictive model to estimate changes in head pose during structural MRI scans using in-scanner eye tracker video. The method is independent of individual image acquisition parameters and does not require markers to be to be fixed to the patient, suggesting it may be well suited to clinical imaging and research environments. Head pose changes estimated using our approach can be used as covariates for morphometric image analyses to improve the neurobiological validity of structural imaging studies of brain development and disease.