bluuebunny/crossref_metadata_2025_split huggingface dataset:
An ecological investigation of the capacity to follow simultaneous speech and preferential detection of ones’ own name
Authors: Pinto Danna , Kaufman Maya , Brown Adi , Golumbic Elana Zion 
Published: June 2022

AbstractMany situations require focusing attention on one speaker, while monitoring the environment for potentially important information. Some have proposed that dividing attention among two speakers involves behavioral tradeoffs, due to limited cognitive resources. However the severity of these tradeoffs, particularly under ecologically-valid circumstances, is not well understood. We investigated the capacity to process simultaneous speech using a dual-task paradigm simulating task demands and stimuli encountered in real-life. Participants listened to conversational narratives (Narrative Stream) and monitored a stream of announcements (Barista Stream), to detect when their order was called. We measured participants’ performance, neural activity and skin conductance as they engaged in this dual-task.Participants achieved extremely high dual-task accuracy, with no apparent behavioral tradeoffs. Moreover, robust neural and physiological responses were observed for target-stimuli in the Barista Stream, alongside significant neural speech-tracking of the Narrative Stream. These results suggest that humans have substantial capacity to process simultaneous speech and do not suffer from insufficient processing resources, at least for this highly ecological task-combination and level of perceptual load. Results also confirmed the ecological validity of the advantage for detecting ones’ own name at the behavioral, neural and physiological level, highlighting the contribution of personal relevance when processing simultaneous speech.
Lake Erie fish safe to eat yet afflicted by algal hepatotoxins
Authors: Shahmohamadloo René S. , Bhavsar Satyendra P. , Ortiz Almirall Xavier , Marklevitz Stephen A. C. , Rudman Seth M. , Sibley Paul K. 
Published: June 2022

AbstractMicrocystin toxins from harmful algal blooms (HABs) can accumulate and persist in fish, raising dual concerns about human health risks from consumption and the potential for detrimental impacts on fish populations. However, there are fundamental unknowns about the relationship between HABs and fish populations driven by a lack of field information on toxin accumulation and retention over space and time. We conducted a field study to assess human health risks from consuming fish caught across all life stages of a HAB and to determine the pervasiveness of potentially harmful levels of microcystins on fish populations. We collected 190 fish in 2015 and 2017 from Lake Erie, a large freshwater ecosystem that is highly productive for fisheries and is an epicenter of HABs and microcystin toxicity events. Muscles and livers were analyzed for total microcystins, which was used to conduct a human health risk assessment for comparison against fish consumption advisory benchmarks available for Lake Erie. We find low human health risk from muscle consumption following the World Health Organization’s safety thresholds. However, all fish across capture dates had microcystins in their livers at levels shown to cause adverse effects, suggesting a pervasive and underappreciated toxic stressor. These data demonstrate that microcystins are retained in fish livers well beyond the cessation of HABs and calls for additional research to better understand the effects of sublethal toxic exposures for fish population dynamics, conservation, and related ecosystem services.
Pynoma, PyABraOM and BIOVARS: Towards genetic variant data acquisition and integration
Authors: Carneiro Paola , Colombelli Felipe , Recamonde-Mendoza Mariana , Matte Ursula 
Published: June 2022

AbstractMotivationAdvances in genomic sequencing of human populations have generated a large amount of genomics data deposited in multiple sources. Programmatic batch searches executed at once are of great scientific interest to ease genomic investigations by retrieving and integrating this massive and decentralized data with little manual intervention.ResultsPynoma and PyABraOM APIs were developed to offer multiple queries in gnomAD and ABraOM databases, respectively. A centralized search in these databases with data integration is offered by a third API, BIOVARS, which combines the resulting information with statistical and graphical visualizations. The implemented features are demonstrated in a case study using ACE2, ADAM17 and TMPRSS2 genes, which presents a generalizable workflow that shows how our APIs facilitate the access and integration of valuable biological data.AvailabilityAll the APIs are written in Python 3. Graphical visualizations for the retrieved data are provided by using the R language version 4.1. The source codes are publicly available and hosted on GitHub (github.com/bioinfo-hcpa).Contactumatte@hcpa.edu.brSupplementary informationSupplementary data is available at github@nbioinfo-hcpa.
Efficacy of Parainfluenza Virus 5 (PIV5)-vectored Intranasal COVID-19 Vaccine as a Single Dose Vaccine and as a Booster against SARS-CoV-2 Variants
Authors: Beavis Ashley C. , Li Zhuo , Briggs Kelsey , Huertas-Díaz María Cristina , Wrobel Elizabeth R. , Najera Maria , An Dong , Orr-Burks Nichole , Murray Jackelyn , Patil Preetish , Huang Jiachen , Mousa Jarrod , Hao Linhui , Hsiang Tien-Ying , Gale Michael , Harvey Stephen B. , Tompkins S. Mark , Hogan Robert Jeffrey , Lafontaine Eric R. , Jin Hong , He Biao 
Published: June 2022

AbstractImmunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has greatly reduced coronavirus disease 2019 (COVID-19)-related deaths and hospitalizations, but waning immunity and the emergence of variants capable of immune escape indicate the need for novel SARS-CoV-2 vaccines. An intranasal parainfluenza virus 5 (PIV5)-vectored COVID-19 vaccine CVXGA1 has been proven efficacious in animal models and blocks contact transmission of SARS-CoV-2 in ferrets. CVXGA1 vaccine is currently in human clinical trials in the United States. This work investigates the immunogenicity and efficacy of CVXGA1 and other PIV5-vectored vaccines expressing additional antigen SARS-CoV-2 nucleoprotein (N) or SARS-CoV-2 variant spike (S) proteins of beta, delta, gamma, and omicron variants against homologous and heterologous challenges in hamsters. A single intranasal dose of CVXGA1 induces neutralizing antibodies against SARS-CoV-2 WA1 (ancestral), delta variant, and omicron variant and protects against both homologous and heterologous virus challenges. Compared to mRNA COVID-19 vaccine, neutralizing antibody titers induced by CVXGA1 were well-maintained over time. When administered as a boost following two doses of a mRNA COVID-19 vaccine, PIV5-vectored vaccines expressing the S protein from WA1 (CVXGA1), delta, or omicron variants generate higher levels of cross-reactive neutralizing antibodies compared to three doses of a mRNA vaccine. In addition to the S protein, the N protein provides added protection as assessed by the highest body weight gain post-challenge infection. Our data indicates that PIV5-vectored COVID-19 vaccines, such as CVXGA1, can serve as booster vaccines against emerging variants.ImportanceWith emerging new variants of concern (VOC), SARS-CoV 2 continues to be a major threat to human health. Approved COVID-19 vaccines have been less effective against these emerging VOCs. This work demonstrates the protective efficacy, and strong boosting effect, of a new intranasal viral-vectored vaccine against SARS-CoV-2 variants in hamsters.
Genomics of cold adaptations in the Antarctic notothenioid fish radiation
Authors: Bista Iliana , Wood Jonathan M. D. , Desvignes Thomas , McCarthy Shane A. , Matschiner Michael , Ning Zemin , Tracey Alan , Torrance James , Sims Ying , Chow William , Smith Michelle , Oliver Karen , Haggerty Leanne , Salzburger Walter , Postlethwait John H. , Howe Kerstin , Clark Melody S. , Detrich William H. , Cheng C.-H. Christina , Miska Eric A. , Durbin Richard 
Published: June 2022

AbstractNumerous novel adaptations characterise the radiation of notothenioids, the dominant fish group in the freezing seas of the Southern Ocean. To improve understanding of the evolution of this iconic fish group, we generated and analysed new genome assemblies for 24 species covering all major subgroups of the radiation. We present a new estimate for the onset of the radiation at 10.7 million years ago, based on a time-calibrated phylogeny derived from genome-wide sequence data. We identify a two-fold variation in genome size, driven by expansion of multiple transposable element families, and use long-read sequencing data to reconstruct two evolutionarily important, highly repetitive gene family loci. First, we present the most complete reconstruction to date of the antifreeze glycoprotein gene family, whose emergence enabled survival in sub-zero temperatures, showing the expansion of the antifreeze gene locus from the ancestral to the derived state. Second, we trace the loss of haemoglobin genes in icefishes, the only vertebrates lacking functional haemoglobins, through complete reconstruction of the two haemoglobin gene clusters across notothenioid families. Finally, we show that both the haemoglobin and antifreeze genomic loci are characterised by multiple transposon expansions that may have driven the evolutionary history of these genes.
Role of TM3 in claudin-15 strand flexibility: a molecular dynamics study
Authors: Fuladi Shadi , McGuinness Sarah , Khalili-Araghi Fatemeh 
Published: June 2022

AbstractClaudins are cell-cell adhesion proteins within tight junctions that connect epithelial cells together. Claudins polymerize into a network of strand-like structures within the membrane of adjoining cells and create ion channels that control paracellular permeability to water and small molecules. Tight junction morphology and barrier function is tissue specific and regulated by claudin subtypes. Here, we present a molecular dynamics study of claudin-15 strands within lipid membranes and the role of a single-point mutation (A134P) on the third transmembrane helix (TM3) of claudin-15 in determining the morphology of the strand. Our results indicate that the A134P mutation significantly affects the lateral flexibility of the strands, increasing the persistence length of claudin-15 strands by a factor of three. Analyses of claudin-claudin contact in our µsecond-long trajectories show that the mutation does not alter the intermolecular contacts (interfaces) between claudins. However, the dynamics and frequency of interfacial contacts are significantly affected. The A134P mutation introduces a kink in TM3 of claudin-15 similar to the one observed in claudin-3 crystal structure. The kink on TM3 skews the rotational flexibility of the claudins in the strands and limits their fluctuation in one direction. This asymmetric movement in the context of the double rows reduces the lateral flexibility of the strand and leads to higher persistence lengths of the mutant.
Phenotypic trait variation in a long-term, multisite common garden of Scots pine in Scotland
Authors: Beaton Joan , Perry Annika , Cottrell Joan , Iason Glenn , Stockan Jenni , Cavers Stephen 
Published: June 2022

AbstractMultisite common garden experiments, exposing common pools of genetic diversity to a range of environments, allow quantification of plastic and genetic components of trait variation. For tree species, such studies must be long term as they typically only express mature traits after many years. As well as evaluating standing genetic diversity, these experiments provide an ongoing test of genetic variation against changing environmental conditions and form a vital resource for understanding how species respond to abiotic and biotic variation. Finally, quantitative assessments of phenotypic variation are essential to pair with rapidly accumulating genomic data to advance understanding of the genetic basis of trait variation, and its interaction with climatic change.We describe a multisite, population-progeny, common garden experiment of the economically and ecologically important tree species, Scots pine, collected from across its native range in Scotland and grown in three contrasting environments. Phenotypic traits, including height, stem diameter and budburst were measured over 14 growing seasons from nursery to field site. The datasets presented have a wide range of applications.
Modeling the Diverse Effects of Divisive Normalization on Noise Correlations
Authors: Weiss Oren , Bounds Hayley A. , Adesnik Hillel , Coen-Cagli Ruben 
Published: June 2022

AbstractDivisive normalization, a prominent descriptive model of neural activity, is employed by theories of neural coding across many different brain areas. Yet, the relationship between normalization and the statistics of neural responses beyond single neurons remains largely unexplored. Here we focus on noise correlations, a widely studied pairwise statistic, because its stimulus and state dependence plays a central role in neural coding. Existing models of covariability typically ignore normalization despite empirical evidence suggesting it affects correlation structure in neural populations. We therefore propose a pairwise stochastic divisive normalization model that accounts for the effects of normalization and other factors on covariability. We first show that normalization modulates noise correlations in qualitatively different ways depending on whether normalization is shared between neurons, and we discuss how to infer when normalization signals are shared. We then apply our model to calcium imaging data from mouse primary visual cortex (V1), and find that it accurately fits the data, often outperforming a popular alternative model of correlations. Our analysis indicates that normalization signals are often shared between V1 neurons in this dataset. Our model will enable quantifying the relation between normalization and covariability in a broad range of neural systems, which could provide new constraints on circuit mechanisms of normalization and their role in information transmission and representation.Author SummaryCortical responses are often variable across identical experimental conditions, and this variability is shared between neurons (noise correlations). These noise correlations have been studied extensively to understand how they impact neural coding and what mechanisms determine their properties. Here we show how correlations relate to divisive normalization, a mathematical operation widely adopted to describe how the activity of a neuron is modulated by other neurons via divisive gain control. We introduce the first statistical model of this relation. We extensively validate the model and investigate parameter inference in synthetic data. We find that our model, when applied to data from mouse visual cortex, outperforms a popular model of noise correlations that does not include normalization, and it reveals diverse influences of normalization on correlations. Our work demonstrates a framework to measure the relation between noise correlations and the parameters of the normalization model, which could become an indispensable tool for quantitative investigations of noise correlations in the wide range of neural systems that exhibit normalization.
Prioritized docking of synaptic vesicles provided by a rapid recycling pathway
Authors: Tran Van , Marty Alain 
Published: June 2022

AbstractIt is known that endocytosis of synaptic vesicles, and docking of these vesicles to their release sites, are regulated in a similar manner, but it has remained unclear whether the two processes are linked together mechanistically. To address this issue, we studied vesicular release during repeated trains of presynaptic action potentials. Synaptic responses decreased whenthe inter-train interval was shortened, indicating a gradual exhaustion of the recycling pool of vesicles, with a resting capacity of about 180 vesicles per active zone. This effect was partially counteracted by activation of a rapid recycling pathway that depended on the activation of myosin light chain kinase and that had a capacity of 200 vesicles per active zone. Vesicles arising from the rapid recycling route were preferentially docked in comparison with vesicles coming from an upstream pool, demonstrating a differential sorting of vesicles inside the readily releasable pool depending on their origin.
Identification of biomarkers and pathways for focal segmental glomerulosclerosis using next generation sequencing data and bioinformatics analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya 
Published: June 2022

AbstractFocal segmental glomerulosclerosis (FSGS) is a renal disease leading threat to human health around the world. Here we aimed to explore novel molecular and potential therapeutic targets in FSGS through adopting integrated bioinformatics tools. Next generation sequencing (NGS) data of GSE197307 was available from Gene Expression Omnibus (GEO) database. Furthermore, differentially expressed genes (DEGs) were screened using the DESeq2 package in R software. Gene ontology (GO) and REACTOME pathway enrichment analyses of DEGs were performed via g:Profiler. Then, the protein-protein interaction (PPI) network, miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed using the HIPPIE, miRNet and NetworkAnalyst databases. Hub genes were validated using the receiver operating characteristic curve (ROC) analysis. By performing DEGs analysis, 488 up regulated genes and 488 down regulated genes were successfully identified from GSE197307, respectively. And they were mainly enriched in the terms of multicellular organismal process, cell periphery, protein binding, metabolism, immune system process, signaling receptor binding and immune system. Based on the data of protein–protein interaction (PPI), miRNA-hub gene regulatory network and TF-hub gene regulatory network, the top hub genes were ranked, including ILK, DDX5, MATR3, ALB, FOS, MKI67, PLK1, TNF, LCK and GTSE1. Bioinformatics analysis of NGS data identified signaling pathways and hub genes, potentially representing molecular mechanisms for the occurrence, progression, and risk prediction in FSGS.
G307S DNAM-1 mutation exacerbates autoimmune encephalomyelitis via enhancing CD4+ T cell activation
Authors: Murata Rikito , Kinoshita Shota , Matsuda Kenshiro , Kawaguchi Atsushi , Shibuya Akira , Shibuya Kazuko 
Published: June 2022

AbstractAlthough rs763361, which causes a non-synonymous glycine-to-serine mutation at residue 307 (G307S mutation) of the DNAM-1 immunoreceptor, is a single-nucleotide polymorphism (SNP) associated with autoimmune disease susceptibility, little is known about how the SNP is involved in pathogenesis. Here, we established CD4+ T cells expressing wild-type or G307S DNAM-1 and showed that the costimulatory signal from G307S DNAM-1 induced greater pro-inflammatory cytokine production and cell proliferation than that from wild-type DNAM-1. The G307S mutation also enhanced the recruitment of the tyrosine kinase Lck and augmented tyrosine phosphorylation at residue 322 (Tyr322) of DNAM-1. However, conversion of Tyr322 of DNAM-1 to phenylalanine (Y322F mutation) canceled the enhanced activation of CD4+ T cell transfectants expressing G307S DNAM-1. Adoptive transfer of myelin-antigen-specific CD4+ T cells expressing G307S DNAM-1 into mice exacerbated experimental autoimmune encephalomyelitis compared with the transfer of cells expressing wild-type DNAM-1. These findings suggest that rs763361 is a gain-of-function mutation that enhances DNAM-1-mediated costimulatory signaling for proinflammatory responses.
Single-cell multi-omics defines the cell-type specific impact of splicing aberrations in human hematopoietic clonal outgrowths
Authors: Gaiti Federico , Chamely Paulina , Hawkins Allegra G. , Cortés-López Mariela , Swett Ariel D. , Ganesan Saravanan , Mouhieddine Tarek H. , Dai Xiaoguang , Kluegel Lloyd , Chen Celine , Batta Kiran , Beaulaurier John , Drong Alexander W. , Hickey Scott , Dusaj Neville , Mullokandov Gavriel , Su Jiayu , Chaligné Ronan , Juul Sissel , Harrington Eoghan , Knowles David A. , Wiseman Daniel H. , Ghobrial Irene M. , Taylor Justin , Abdel-Wahab Omar , Landau Dan A. 
Published: June 2022

ABSTRACTRNA splicing factors are recurrently affected by alteration-of-function mutations in clonal blood disorders, highlighting the importance of splicing regulation in hematopoiesis. However, our understanding of the impact of dysregulated RNA splicing has been hampered by the inability to distinguish mutant and wildtype cells in primary patient samples, the cell-type complexity of the hematopoietic system, and the sparse and biased coverage of splice junctions by short-read sequencing typically used in single-cell RNA sequencing. To overcome these limitations, we developed GoT-Splice by integrating Genotyping of Transcriptomes (GoT) with enhanced efficiency long-read single-cell transcriptome profiling, as well as proteogenomics (with CITE-seq). This allowed for the simultaneous single-cell profiling of gene expression, cell surface protein markers, somatic mutation status, and RNA splicing. We applied GoT-Splice to bone marrow progenitors from patients with myelodysplastic syndrome (MDS) affected by mutations in the most prevalent mutated RNA splicing factor – the core RNA splicing factor SF3B1. High-resolution mapping of SF3B1mut vs. SF3B1wt hematopoietic progenitors revealed a fitness advantage of SF3B1mut cells in the megakaryocytic-erythroid lineage, resulting in an expansion of SF3B1mut erythroid progenitor (EP) cells. SF3B1mut EP cells exhibited upregulation of genes involved in regulation of cell cycle and mRNA translation. Long-read single-cell transcriptomes revealed the previously reported increase of aberrant 3’ splicing site usage in SF3B1mut cells. However, the ability to profile splicing within individual cell populations uncovered distinct cryptic 3’ splice site usage across different progenitor populations, as well as stage-specific aberrant splicing during erythroid maturation. Lastly, as splice factor mutations occur in clonal hematopoiesis (CH) with increased risk of neoplastic transformation, we applied GoT-Splice to CH samples. These data revealed that the erythroid lineage bias, as well as cell-type specific cryptic 3’ splice site usage in SF3B1mut cells, precede overt MDS. Collectively, we present an expanded multi-omics single-cell toolkit to define the cell-type specific impact of somatic mutations on RNA splicing, from the earliest phases of clonal outgrowths to overt neoplasia, directly in human samples.