bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining experiments and in silico modeling to infer the role of adhesion and proliferation on the collective dynamics of cells
Authors: Melo Hygor P. M. , Maia F. Raquel , Nunes André S. , Reis Rui L. , Oliveira Joaquim M. , Araújo Nuno A. M. 
Published: March 2021

ABSTRACTThe collective dynamics of cells on surfaces and interfaces poses technological and theoretical challenges in the study of morphogenesis, tissue engineering, and cancer. Different mechanisms are at play, including, cell-cell adhesion, cell motility, and proliferation. However, the relative importance of each one is elusive. Here, experiments with a culture of glioblastoma multiforme cells on a substrate are combined with in silico modeling to infer the rate of each mechanism. By parametrizing these rates, the time-dependence of the spatial correlation observed experimentally is reproduced. The obtained results suggest a reduction in cell-cell adhesion with the density of cells. The reason for such reduction and possible implications for the collective dynamics of cancer cells are discussed.
Coupling between cerebrovascular oscillations and CSF flow fluctuation during wakefulness: An fMRI study
Authors: Yang Ho-Ching (Shawn) , Inglis Ben , Talavage Thomas M. , Nair Vidhya Vijayakrishnan , Yao Jinxia (Fiona) , Fitzgerald Bradley , Schwichtenberg Amy J. , Tong Yunjie 
Published: March 2021

AbstractCerebrospinal fluid (CSF) plays an important role in the clearance of metabolic waste products from the brain, yet the driving forces of CSF movement are not fully understood. It is commonly believed that CSF movement is facilitated by blood vessel wall movements (i.e., hemodynamic oscillations) in the brain. A coherent pattern of low frequency hemodynamic oscillations and CSF movement was recently found during non-rapid eye movement (NREM) sleep via functional MRI. However, questions remain regarding 1) the explanation of coupling between hemodynamic oscillations and CSF movement from fMRI signals; 2) the existence of the coupling during wakefulness; 3) the direction of CSF movement. In this resting state fMRI study, we proposed a mechanical model to explain the coupling between hemodynamics and CSF movement through the lens of fMRI. We found that the observed delays between hemodynamics and CSF movement match those predicted by the model. Moreover, by conducting separate fMRI scans of the brain and neck, we confirmed the low frequency CSF movement at the fourth ventricle is bidirectional. Our finding also demonstrates that CSF movement is facilitated by hemodynamic oscillations mainly in the low frequency range, even when the individual is awake.
Oxytocin receptor activation does not mediate associative fear deficits in a Williams Syndrome model
Authors: Nygaard Kayla R. , Swift Raylynn G. , Glick Rebecca M. , Wagner Rachael E. , Maloney Susan E. , Gould Georgianna G. , Dougherty Joseph D. 
Published: March 2021

ABSTRACTWilliams Syndrome is caused by a deletion of 26-28 genes on chromosome 7q11.23. Patients with this disorder have distinct behavioral phenotypes including learning deficits, anxiety, increased phobias, and hypersociability. Some studies also suggest elevated blood oxytocin and altered oxytocin receptor expression, and this oxytocin dysregulation is hypothesized to be involved in the underlying mechanisms driving a subset of these phenotypes. A ‘Complete Deletion’ mouse, modeling the hemizygous critical region deletion in Williams Syndrome, recapitulates many of the phenotypes present in humans. These Complete Deletion mice also exhibited impaired fear responses in the conditioned fear task. Here, we address whether oxytocin dysregulation is responsible for this impaired associative fear memory response. We show direct delivery of an oxytocin receptor antagonist to the central nervous system did not rescue the attenuated contextual or cued fear memory responses in Complete Deletion mice. Thus, increased oxytocin signaling is not acutely responsible for this phenotype. We also evaluated oxytocin receptor and serotonin transporter availability in regions related to fear learning, memory, and sociability using autoradiography in wild type and Complete Deletion mice. While we identified trends in lowered oxytocin receptor expression in the lateral septal nucleus, and trends towards lowered serotonin transporter availability in the striatum and orbitofrontal cortex, we found no significant differences after correction. Together, these data suggest the fear conditioning anomalies in the Williams Syndrome mouse model are independent of any alterations in the oxytocinergic system caused by deletion of the Williams locus.
SpeciesRax: A tool for maximum likelihood species tree inference from gene family trees under duplication, transfer, and loss
Authors: Morel Benoit , Schade Paul , Lutteropp Sarah , Williams Tom A. , Szöllősi Gergely J. , Stamatakis Alexandros 
Published: March 2021

AbstractSpecies tree inference from gene family trees is becoming increasingly popular because it can account for discordance between the species tree and the corresponding gene family trees. In particular, methods that can account for multiple-copy gene families exhibit potential to leverage paralogy as informative signal. At present, there does not exist any widely adopted inference method for this purpose. Here, we present SpeciesRax, the first maximum likelihood method that can infer a rooted species tree from a set of gene family trees and can account for gene duplication, loss, and transfer events. By explicitly modelling events by which gene trees can depart from the species tree, SpeciesRax leverages the phylogenetic rooting signal in gene trees. SpeciesRax infers species tree branch lengths in units of expected substitutions per site and branch support values via paralogy-aware quartets extracted from the gene family trees. Using both empirical and simulated datasets we show that SpeciesRax is at least as accurate as the best competing methods while being one order of magnitude faster on large datasets at the same time. We used SpeciesRax to infer a biologically plausible rooted phylogeny of the vertebrates comprising 188 species from 31612 gene families in one hour using 40 cores. SpeciesRax is available under GNU GPL athttps://github.com/BenoitMorel/GeneRaxand on BioConda.
An 18S V4 rDNA metabarcoding dataset of protist diversity in the Atlantic inflow to the Arctic Ocean, through the year and down to 1000 m depth
Authors: Egge Elianne , Elferink Stephanie , Vaulot Daniel , John Uwe , Bratbak Gunnar , Larsen Aud , Edvardsen Bente 
Published: March 2021

AbstractArctic marine protist communities have been understudied due to challenging sampling conditions, in particular during winter and in deep waters. The aim of this study was to improve our knowledge on Arctic protist diversity through the year, both in the epipelagic (< 200 m depth) and mesopelagic zones (200-1000 m depth). Sampling campaigns were performed in 2014, during five different months, to capture the various phases of the Arctic primary production: January (winter), March (pre-bloom), May (spring bloom), August (post-bloom) and November (early winter). The cruises were undertaken west and north of the Svalbard archipelago, where warmer Atlantic waters from the West Spitsbergen Current meets cold Arctic waters from the Arctic Ocean. From each cruise, station, and depth, 50 L of sea water were collected and the plankton was size-fractionated by serial filtration into four size fractions between 0.45-200 µm, representing the picoplankton, nanoplankton and microplankton. In addition vertical net hauls were taken from 50 m depth to the surface at selected stations. From the plankton samples DNA was extracted, the V4 region of the 18S rRNA-gene was amplified by PCR with universal eukaryote primers and the amplicons were sequenced by Illumina high-throughput sequencing. Sequences were clustered into Amplicon Sequence Variants (ASVs), representing protist genotypes, with the dada2 pipeline. Taxonomic classification was made against the curated Protist Ribosomal Reference database (PR2). Altogether 6,536 protist ASVs were obtained (including 54 fungal ASVs). Both ASV richness and taxonomic composition were strongly dependent on size-fraction, season, and depth. ASV richness was generally higher in the smaller fractions, and higher in winter and the mesopelagic samples than in samples from the well-lit epipelagic zone during summer. During spring and summer, the phytoplankton groups diatoms, chlorophytes and haptophytes dominated in the epipelagic zone. Parasitic and heterotrophic groups such as Syndiniales and certain dinoflagel-lates dominated in the mesopelagic zone all year, as well as in the epipelagic zone during the winter. The dataset is available at https://doi.org/10.17882/79823, (Egge et al., 2014).
Identifying and correcting for misspecifications in GWAS summary statistics and polygenic scores
Authors: Privé Florian , Arbel Julyan , Aschard Hugues , Vilhjálmsson Bjarni J. 
Published: March 2021

AbstractPublicly available genome-wide association studies (GWAS) summary statistics exhibit uneven quality, which can impact the validity of follow-up analyses. First, we present an overview of possible misspecifications that come with GWAS summary statistics. Then, in both simulations and real data analyses, we show that additional information such as imputation INFO scores, allele frequencies, and per-variant sample sizes in GWAS summary statistics can be used to detect possible issues and correct for misspecifications in the GWAS summary statistics. One important motivation for us is to improve the predictive performance of polygenic scores built from these summary statistics. Unfortunately, due to the lack of reporting standards for GWAS summary statistics, this additional information is not systematically reported. We also show that using well-matched LD references can improve model fit and translate into more accurate prediction. Finally, we discuss how to make polygenic score methods such as lassosum and LDpred2 more robust to these misspecifications to improve their predictive power.
Enrichment of SARS-CoV-2 entry factors and interacting intracellular genes in peripheral immune cells
Authors: Devaprasad Abhinandan , Pandit Aridaman 
Published: March 2021

AbstractSARS-CoV-2 uses ACE2 and TMPRSS2 to gain entry into the cell. However, recent studies have shown that SARS-CoV-2 may use additional host factors that are required for the viral lifecycle. Here we used publicly available datasets, CoV associated genes and machine learning algorithms to explore the SARS-CoV-2 interaction landscape in different tissues. We find that in general a small fraction of cells expresses ACE2 in the different tissues including nasal, bronchi and lungs. We show that a small fraction of immune cells (including T-cells, macrophages, dendritic cells) found in tissues also express ACE2. We show that healthy circulating immune cells do not express ACE2 and TMPRSS2. However, a small fraction of circulating immune cells (including dendritic cells, monocytes, T-cells) in the PBMC of COVID-19 patients express ACE2 and TMPRSS2. Additionally, we found that a large spectrum of cells (in circulation and periphery) in both healthy and COVID-19 positive patients were significantly enriched for SARS-CoV-2 factors. Thus, we propose that further research is needed to explore if SARS-CoV-2 can directly infect peripheral immune cells to better understand the virus’ mechanism of action.
Detection of pathogenic splicing events from RNA-sequencing data using dasper
Authors: Zhang David , Reynolds Regina H. , Garcia-Ruiz Sonia , Gustavsson Emil K , Sethi Sid , Aguti Sara , Barbosa Ines A. , Collier Jack J. , Houlden Henry , McFarland Robert , Muntoni Francesco , Oláhová Monika , Poulton Joanna , Simpson Michael , Pitceathly Robert D.S. , Taylor Robert W. , Zhou Haiyan , Deshpande Charu , Botia Juan A. , Collado-Torres Leonardo , Ryten Mina 
Published: March 2021

AbstractAlthough next-generation sequencing technologies have accelerated the discovery of novel gene-to-disease associations, many patients with suspected Mendelian diseases still leave the clinic without a genetic diagnosis. An estimated one third of these patients will have disorders caused by mutations impacting splicing. RNA-sequencing has been shown to be a promising diagnostic tool, however few methods have been developed to integrate RNA-sequencing data into the diagnostic pipeline. Here, we introducedasper, an R/Bioconductor package that improves upon existing tools for detecting aberrant splicing by using machine learning to incorporate disruptions in exon-exon junction counts as well as coverage.dasperis designed for diagnostics, providing a rank-based report of how aberrant each splicing event looks, as well as including visualization functionality to facilitate interpretation. We validatedasperusing 16 patient-derived fibroblast cell lines harbouring pathogenic variants known to impact splicing. We find thatdasperis able to detect pathogenic splicing events with greater accuracy than existingLeafCutterMDor z-score approaches. Furthermore, by only applying a broad OMIM gene filter (without any variant-level filters),dasperis able to detect pathogenic splicing events within the top 10 most aberrant identified for each patient. Since using publicly available control data minimises costs associated with incorporating RNA-sequencing into diagnostic pipelines, we also investigate the use of 504 GTEx fibroblast samples as controls. We find thatdasperleverages publicly available data effectively, ranking pathogenic splicing events in the top 25. Thus, we believedaspercan increase diagnostic yield for a pathogenic splicing variants and enable the efficient implementation of RNA-sequencing for diagnostics in clinical laboratories.
A variable-gain stochastic pooling motif mediates information transfer from receptor assemblies into NF-κB
Authors: Cruz J. Agustin , Mokashi Chaitanya S. , Kowalczyk Gabriel J. , Guo Yue , Zhang Qiuhong , Gupta Sanjana , Schipper David L. , Lee Robin E. C. 
Published: March 2021

AbstractA myriad of inflammatory cytokines regulate signaling pathways to maintain cellular homeostasis. The IKK complex is an integration hub for cytokines that govern NF-κB signaling. In response to inflammation, IKK is activated through recruitment to receptor-associated protein assemblies. How and what information IKK complexes transmit about the milieu are open questions. Here we track dynamics of IKK complexes and nuclear NF-κB to identify upstream signaling features that determine same-cell responses. Experiments and modeling of single complexes reveals their size, number, and timing relays cytokine-specific information with feedback control that is independent of transcription. Our results provide evidence for variable-gain stochastic pooling, a noise-reducing motif that enables parsimonious and cytokine-specific information transfer. We propose that emergent properties of stochastic pooling are general principles of receptor signaling.One Sentence SummaryA variable-gain stochastic pooling motif mediates robust and tunable information transmission from the extracellular milieu into the cell.
Fasciola hepaticafatty acid binding protein (Fh12) induces apoptosis and tolerogenic properties in murine bone marrow derived dendritic cells
Authors: Ruiz-Jiménez Caleb , Celias Daiana P. , Valdés Bianca , Ramos-Pérez Willy D. , Cervi Laura , Espino Ana M. 
Published: March 2021

ABSTRACTIn a previous study we demonstrated thatFasciola hepaticafatty acid binding protein (Fh12) significantly suppress macrophage function by inhibiting IL-6, IL-1B, tumor necrosis factor (TNF) and IL-12 production in TLR4-stimulated murine macrophages, an effect mediated through the signaling of CD14 co-receptor without affecting the viability of these cells. Given that dendritic cells (DCs) are immune cells that play a central role in the initiation of primary immune responses and that are the only antigen-presenting cells capable of stimulating naive T-cells, in the present study we investigated the effect of Fh12 on DCs. We found that Fh12 exerts a strong suppressive effect on activation and function of DCs. However, in contrast to the effect observed on macrophages, Fh12 induces early and late apoptosis of DCs being this phenomenon dose-dependent and CD14-coreceptor independent. At low concentration Fh12 modulates the LPS-induced DCs maturation status by suppressing the MHC-II, and co-stimulatory molecules CD40 and CD80 surface expression together with the pro-inflammatory cytokines IL-12p70 and IL-6 production whereas increase the IL-10 levels. Besides, Fh12 decreased the ability of LPS-activated DCs to induce IFNg production against allogeneic splenocytes, while increasing IL-4 production. We have described for the first time the ability of Fh12 to modify selectively the viability of DCs by apoptosis induction. The selective diminution in DCs survival could be aF. hepaticastrategy in order to prevent a host immune response during the earliest phases of infection.
The trade-off between color and size in lizards’ conspicuous tails
Authors: Guidi Raiane dos Santos , São-Pedro Vinicius de Avelar , da Silva Holda Ramos , Costa Gabriel Correa , Pessoa Daniel Marques Almeida 
Published: March 2021

AbstractA tail of conspicuous coloration is hypothesized to be an advantageous trait for many species of lizards. Predator attacks would be directed to a non-vital, and autotomizable, body part, increasing the chance of survival. However, as body size increases it also increases the signaling area that could attract predators from greater distances, increasing the overall chance of predation. Here, we test the hypothesis that there is a trade-off between tail color and size, affecting predation probabilities. We used plasticine replicas of lizards to study the predation patterns of small and large lizards with red and blue tails. In a natural environment, we exposed six hundred replicas subjected to the attack of free-ranging predators. Large red-tailed models were attacked more quickly, and more intensely, by birds. Mammals and unidentified predators showed no preference for any size or colors. The attacks were not primarily directed to conspicuous tails when compared to the body or the head of our replicas. Our study suggests that red color signals in large lizards could enhance their detection by visually oriented predators (i.e., birds). The efficacy of conspicuous tails as a decoy may rely on associated behavioral displays, which are hard to test with static replicas.HighlightsThe roles of blue and red tails as decoys were not corroborated.Tail color and size interact while influencing predation rates.Larger red-tailed lizards are more prone to be attacked by birds.The benefit of having conspicuous tails appears to decrease as body size increases.
Cis-regulatory elements of the cholinergic gene locus in the silkwormBombyx mori
Authors: Banzai Kota , Izumi Susumu 
Published: March 2021

ABSTRACTGenes ofcholine acetyltransferase(ChAT) andvesicular acetylcholine transporter(VAChT) are encoded in the same gene locus, called the cholinergic gene locus. They are essential in cholinergic neurons to maintain their functional phenotype. The genomic structure of the cholinergic gene locus is conserved among invertebrates to mammals. However, it is still inconclusive how cholinergic genes express only in cholinergic neurons in insects. In this study, we analyzed the upstream sequence of cholinergic gene locus in the silkwormBombyx morito identify specificcis-regulatory regions. We found multiple enhancer regions that are localized within 1 kb upstream of the cholinergic gene locus. The combination of promoter assays using small deletions and bioinformatic analysis among insect species illuminates two conserved sequences in thecis-regulatory region: TGACGTA and CCAAT, which are known as the cAMP response element and CAAT box, respectively. We found that dibutyryl-cAMP, an analog of cAMP, influences the expression ofChAT. Tissue-specific expression analysis of transcriptional factors showed potential candidates that control the cholinergic gene locus expression. Our investigation provides new insight into the regulation mechanism of cholinergic neuron-specific gene machinery in this lepidopteran insect.
DISTEMA: distance map-based estimation of single protein model accuracy with attentive 2D convolutional neural network
Authors: Chen Xiao , Cheng Jianling 
Published: March 2021

AbstractBackgroundEstimation of the accuracy (quality) of protein structural models is important for both prediction and use of protein structural models. Deep learning methods have been used to integrate protein structure features to predict the quality of protein models. Inter-residue distances are key information for predicting protein’s tertiary structures and therefore have good potentials to predict the quality of protein structural models. However, few methods have been developed to fully take advantage of predicted inter-residue distance maps to estimate the accuracy of a single protein structural model.ResultWe developed an attentive 2D convolutional neural network (CNN) with channel-wise attention to take only a raw difference map between the inter-residue distance map calculated from a single protein model and the distance map predicted from the protein sequence as input to predict the quality of the model. The network comprises multiple convolutional layers, batch normalization layers, dense layers, and Squeeze-and-Excitation blocks with attention to automatically extract features relevant to protein model quality from the raw input without using any expert-curated features. We evaluated DISTEMA’s capability of selecting the best models for CASP13 targets in terms of ranking loss of GDT-TS score. The ranking loss of DISTEMA is 0.079, lower than several state-of-the-art single-model quality assessment methods. The work demonstrates that using raw inter-residue distance information alone with deep learning can predict the quality of protein structural models reasonably well.
Tbx1, a 22q11.2-encoded gene, is a link between alterations in fimbria myelination and cognitive speed in mice
Authors: Hiramoto Takeshi , Sumiyoshi Akira , Yamauchi Takahira , Tanigaki Kenji , Shi Qian , Kang Gina , Ryoke Rie , Nonaka Hiroi , Enomoto Shingo , Izumi Takeshi , Bhat Manzoor A. , Kawashima Ryuta , Hiroi Noboru 
Published: March 2021

AbstractCopy number variants (CNVs) have provided a reliable entry point to identify structural correlates of atypical cognitive development. Hemizygous deletion of human chromosome 22q11.2 is associated with impaired cognitive function; however, the mechanisms by which numerous genes encoded in this CNV contribute to cognitive deficits via diverse structural alterations in the brain remain unclear. This study aimed to determine the cellular basis of the link between alterations in brain structure and cognitive functions in a mouse model. The heterozygosity ofTbx1, a22q11.2 gene, altered the composition of myelinated axons in the fimbria, reduced oligodendrocyte production capacity, and slowed the acquisition of spatial memory and cognitive flexibility. Our findings provide a cellular basis for specific cognitive dysfunctions that occur in patients with loss-of-functionTBX1variants and 22q11.2 hemizygous deletion.TeaserA risk gene for autism alters myelin composition in the hippocampal connection and slows cognitive speed.