bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current challenges in microbiome metadata collection
Authors: Rosenfeld Gabriel , Angelova Angelina , Shin Chris , Quinones Mariam , Hurt Darrell 
Published: May 2021

AbstractWhile the biomedical community has embraced data sharing (e.g. results, raw data) and supported establishment of large research consortia (e.g. the Human Microbiome Project) aimed to standardize the quality of important sets of microbiome sequencing data, the reusability of most microbiome data is still limited by the quality of its associated metadata. To ensure that microbiome data is indeed FAIR (Findable, Accessible, Interoperable, and Reusable), it is necessary to consider tools and approaches that make it easier to provide high-quality metadata that is fit for purpose moving forward. Such tools and approaches could be informed by current efforts to harmonize and improve the quality of extant microbiome metadata.
Seasonal song variation in male Carolina Wrens (Thryothorus ludovicianus)
Authors: Keating Holly R. , Reichard Dustin G. 
Published: May 2021

ABSTRACTBirdsong’s primary function is attracting and stimulating mates and repelling rivals during the breeding season. However, many species also sing during the nonbreeding season, which raises questions about the function of nonbreeding song and the proximate mechanisms underlying its production. In this study, we compared spectral and temporal measurements from a large sample of breeding (N= 267) and nonbreeding songs (N= 283) of Carolina Wrens (Thryothorus ludovicianus), a nonmigratory, temperate species that sings year-round. We found that breeding songs were longer than nonbreeding songs and had more syllables within each song. Trill rate, the number of notes per syllable, minimum and maximum frequency and frequency bandwidth did not differ detectably between the two seasons. This study is the first to examine seasonal song differences in Carolina Wrens and provides a basis for future investigations into the drivers behind this seasonal variation.
Metamorphosis imposes variable constraints on genome expansion through effects on development
Authors: Mueller Rachel L , Cressler Clayton E , Schwarz Rachel S , Chong Rebecca A , Butler Marguerite A 
Published: May 2021

AbstractGenome size varies ~ 100,000-fold across eukaryotes and has long been hypothesized to be influenced by metamorphosis in animals. Transposable element accumulation has been identified as a major driver of increase, but the nature of constraints limiting the size of genomes has remained unclear, even as traits such as cell size and rate of development co-vary strongly with genome size. Salamanders, which possess diverse metamorphic and non-metamorphic life histories, have the largest vertebrate genomes — 3 to 40 times that of humans — as well as the largest range of variation in genome size. We tested 13 biologically-inspired hypotheses exploring how the form of metamorphosis imposes varying constraints on genome expansion in a broadly representative phylogeny containing 118 species of salamanders. We show that metamorphosis during which animals undergo the most extensive and synchronous remodeling imposes the most severe constraint against genome expansion, with the severity of constraint decreasing with reduced extent and synchronicity of remodeling. More generally, our work demonstrates the potential for broader interpretation of phylogenetic comparative analysis in exploring the balance of multiple evolutionary pressures shaping phenotypic evolution.
Differential Regulation of Rice Transcriptome toRhizoctonia solaniinfection
Authors: Das Akash , Mazahar Moin , Sahu Ankur , Kshattry Mrinmoy , Kirti P.B. , Barah Pankaj 
Published: May 2021

ABSTRACTSheath Blight (SB) disease in rice crop caused by the infection of the fungal pathogenRhizoctonia solani(R. solani) is one of the severe rice diseases that can cause up to 50% yield losses. Naturally occurring rice varieties resistant to SB have not been reported yet. We have performed a Time-Series RNA-Seq analysis on a widely cultivated rice variety BPT-5204 for identifying its transcriptomic response signatures toR. solaniinfection at 1st, 2ndand 5thday post inoculation (dpi). In total, 428, 3225 and 1225 genes were differentially expressed in the treated rice plants post 1, 2 and 5 dpi, respectively. GO and KEGG enrichment analysis identified significant processes and pathways differentially altered in the rice plant after the fungal infection. Machine learning and network based integrative approach was used to construct Transcriptional Regulatory Networks (TRNs) of the rice plant at the three Time Points. Regulatory network analysis identified SUB1B, MYB30 and CCA1 as important regulatory hub Transcription Factors in rice duringR. solaniinfection. Jasmonic acid signaling pathway was activated and in contrast, photosynthesis and carbon fixation processes were significantly compromised. Involvement of MAPK, CYPs, Peroxidases and PAL genes was observed in response to the fungal infection. Circadian clock was also strongly influenced byR. solaniinfection. Our integrative analysis identified 7 putative SB resistant genes altered in rice afterR. solaniinfection and provided a better understanding of rice plant response toR. solaniinfection.One sentence summaryTime series expression analysis of rice variety BPT-5204 identifies key molecular signatures involved in rice plant response toR. solaniinfection.
A Phylogenomic Framework for Charting the Diversity and Evolution of Giant Viruses
Authors: Aylward Frank O. , Moniruzzaman Mohammad , Ha Anh D. , Koonin Eugene V. 
Published: May 2021

AbstractLarge DNA viruses of the phylumNucleocytoviricotahave recently emerged as important members of ecosystems around the globe that challenge traditional views of viral complexity. Numerous members of this phylum that cannot be classified within established families have recently been reported, and there is presently a strong need for a robust phylogenomic and taxonomic framework for these viruses. Here we report a comprehensive phylogenomic analysis of theNucleocytoviricota, present a set of giant virus orthologous groups (GVOGs) together with a benchmarked reference phylogeny, and delineate a hierarchical taxonomy within this phylum. We show that the majority ofNucleocytoviricotadiversity can be partitioned into 6 orders, 32 families, and 344 genera, substantially expanding the number of currently recognized taxonomic ranks for these viruses. We integrate our results within a megataxonomy that has been adopted for all viruses to establish a unifying framework for the study ofNucleocytoviricotadiversity, evolution, and environmental distribution.
The CTPase activity of ParB acts as a timing mechanism to control the dynamics and function of prokaryotic DNA partition complexes
Authors: Osorio-Valeriano Manuel , Altegoer Florian , Das Chandan K. , Steinchen Wieland , Panis Gaël , Connolley Lara , Giacomelli Giacomo , Feddersen Helge , Corrales-Guerrero Laura , Giammarinaro Pietro , Hanßmann Juri , Bramkamp Marc , Viollier Patrick H. , Murray Seán , Schäfer Lars V. , Bange Gert , Thanbichler Martin 
Published: May 2021

SUMMARYDNA partitioning CTPases of the ParB family mediate the segregation of bacterial chromosomes and low-copy number plasmids. They act as DNA-sliding clamps that are loaded atparSmotifs in the centromeric region of target DNA molecules and then spread laterally to form large nucleoprotein complexes that serve as docking points for the DNA segregation machinery. Here, we identify conformational changes that underlie the CTP- andparS-dependent closure of ParB clamps. Moreover, we solve crystal structures of ParB in the pre- and post-hydrolysis state and provide insights into the catalytic mechanism underlying nucleotide hydrolysis. The characterization of CTPase-deficient ParB variants reveals that CTP hydrolysis serves as a timing mechanism to control the sliding time of ParB. Hyperstable clamps are trapped on the DNA, leading to excessing spreading and severe chromosome segregation defectsin vivo. These findings clarify the role of the ParB CTPase cycle in partition complex dynamics and function and thus complete our understanding of this prototypic CTP-dependent molecular switch.
Identification of Splice Regulators of Fibronectin-EIIIA and EIIIB by Direct Measurement of Exon Usage in a Flow-Cytometry Based CRISPR Screen
Authors: Hensel Jessica , Heineman Brent , Kimble Amy , Jellison Evan , Reese Bo , Murphy Patrick 
Published: May 2021

AbstractThe extracellular matrix protein fibronectin (FN) is alternatively spliced in a variety of inflammatory conditions, resulting in increased inclusion of alternative exons EIIIA and EIIIB. Inclusion of these exons affects fibril formation, fibrosis, and inflammation. To define upstream regulators of alternative splicing in FN, we have developed anin vitroflow-cytometry based assay, using RNA-binding probes to determine alternative exon inclusion level in aortic endothelial cells. This approach allows us to detect exon inclusion in the primary transcripts themselves, rather than in surrogate splicing reporters. We validated this assay in cells with and without FN-EIIIA and –EIIIB expression. In a small-scale CRISPR KO screen of candidate regulatory splice factors, we successfully detected known regulators of EIIIA and EIIIB splicing, and detected several novel regulators. Finally, we show the potential in this approach to broadly interrogate upstream signaling pathways in aortic endothelial cells with a genome-wide CRISPR-KO screen, implicating the TNFalpha and RIG-I-like signaling pathways and genes involved in the regulation of fibrotic responses. Thus, we provide a novel means to screen the regulation of splicing of endogenous transcripts, and predict novel pathways in the regulation of FN-EIIIA inclusion.
Amino acid sensor conserved from bacteria to humans
Authors: Gumerov Vadim M. , Andrianova Ekaterina P. , Matilla Miguel A. , Dolphin Annette C. , Krell Tino , Zhulin Igor B. 
Published: May 2021

ABSTRACTAmino acids are recognized as signals by various receptors in bacteria, archaea, and eukaryotes. However, no common mechanism for amino acid recognition is currently known. Here we show that a subclass of a ubiquitous extracellular domain dCache_1 contains a simple amino acid recognition motif, and it is found throughout the Tree of Life. In bacteria, this motif exclusively binds amino acids, including GABA, and it is present in all major receptor types. In humans, this motif is found in α2δ subunits of voltage-gated calcium channels that are implicated in neuropathic pain and neurodevelopmental disorders. Our findings suggest that GABA-derived drugs bind to the same motif in human α2δ subunits that binds natural GABA ligands in bacterial chemoreceptors.
Simultaneous Brain, Brainstem and Spinal Cord pharmacological-fMRI reveals endogenous opioid network interactions mediating attentional analgesia
Authors: Oliva Valeria , Hartley-Davies Ron , Moran Rosalyn , Pickering Anthony E. , Brooks Jonathan C.W. 
Published: May 2021

SummaryPain perception is decreased by shifting attentional focus away from a threatening event. This attentional analgesia engages parallel descending control pathways from anterior cingulate (ACC) to locus coeruleus, and ACC to periaqueductal grey (PAG) – rostral ventromedial medulla (RVM), indicating possible roles for noradrenergic or opioidergic neuromodulators. To determine which pathway modulates nociceptive activity in humans we used simultaneous whole brain-spinal cord pharmacological-fMRI (N=39) across three sessions. Noxious thermal forearm stimulation generated somatotopic-activation of dorsal horn (DH, C6 segment) whose activity mirrored attentional pain modulation. Activity in an adjacent cluster reported the interaction between task and noxious stimulus. Effective connectivity analysis revealed that ACC recruits PAG and RVM to modulate spinal cord activity. Blocking endogenous opioids with Naltrexone impairs attentional analgesia and disrupts RVM-DH and ACC-PAG connectivity. Noradrenergic augmentation with Reboxetine did not alter attentional analgesia. Cognitive pain modulation is mediated by opioidergic ACC-PAG-RVM descending control which supresses spinal nociceptive activity.
Inherited Human Sex Reversal due to Loss of a Water-Mediated Hydrogen Bond at a Conserved Protein-DNA Interface
Authors: Chen Yen-Shan , Racca Joseph , Amir Dan , Haas Elisha , Weiss Michael A. 
Published: May 2021

ABSTRACTMale sex determination in mammals is initiated by SRY, a Y-encoded architectural transcription factor. The protein contains a high-mobility-group (HMG) box that mediates sequence-specific DNA bending. Mutations in SRY causing XY gonadal dysgenesis (Swyer syndrome) cluster in the box. Although such mutations usually arisede novoin spermatogenesis, some are inherited: male development occurs in one genetic background (the father) but not another (the sterile XY daughter). Here, we comparede novoand inherited mutations at an invariant Tyr adjoining the motif’s basic tail (consensus position 72; Y127C and Y127F in intact SRY). Crystal structures of homologous SOX-DNA complexes suggest that the wild-type side chain’spara-OH group anchors a water-mediated hydrogen bond to the DNA backbone. In an embryonic gonadal cell line, Y127C (de novo) led to accelerated proteasomal proteolysis and blocked transcriptional activity; activity remained low on rescue of expression by chemical proteasome inhibition. Y127F (inherited) preserved substantial transcriptional activity: 91(±11)% on SRY overexpression and 65(±17)% at physiological expression. Control studies indicated no change in protein lifetime or nuclear localization. Only subtle biophysical perturbations were observedin vitro. Although though inherited variant’s specific DNA affinity was only twofold lower than wild type, stopped-flow kinetic analysis revealed a sevenfold decrease in lifetime of the complex. Time-resolved fluorescence energy transfer (using a 15-base pair DNA site) demonstrated native mean DNA bending but with a slightly widened distribution of end-to-end DNA distances. Our findings highlight the contribution of a single water-mediated hydrogen bond to robustness of a genetic switch in human development.
YAP/TAZ Maintain the Proliferative Capacity and Structural Organization of Radial Glial Cells During Brain Development
Authors: Lavado Alfonso , Gangwar Ruchika , Paré Joshua , Wan Shibiao , Fan Yiping , Cao Xinwei 
Published: May 2021

AbstractThe Hippo pathway regulates the development and homeostasis of many tissues and in many species. It controls the activity of two paralogous transcriptional coactivators, YAP and TAZ (YAP/TAZ). Although previous studies have established that aberrant YAP/TAZ activation is detrimental to mammalian brain development, whether and how endogenous levels of YAP/TAZ activity regulate brain development remain unclear. Here, we show that during mammalian cortical development, YAP/TAZ are specifically expressed in apical neural progenitor cells known as radial glial cells (RGCs). The subcellular localization of YAP/TAZ undergoes dynamic changes as corticogenesis proceeds. YAP/TAZ are required for maintaining the proliferative potential and structural organization of RGCs, and their ablation during cortical development reduces the numbers of cortical projection neurons and causes the loss of ependymal cells, resulting in hydrocephaly. Transcriptomic analysis using sorted RGCs reveals gene expression changes in YAP/TAZ-depleted cells that correlate with mutant phenotypes. Thus, our study has uncovered essential functions of YAP/TAZ during mammalian brain development and revealed the transcriptional mechanism of their action.
Reinforcement learning modeling reveals a reward-history-dependent strategy underlying reversal learning in squirrel monkeys
Authors: Bari Bilal A. , Moerke Megan J. , Jedema Hank P. , Effinger Devin P. , Cohen Jeremiah Y. , Bradberry Charles W. 
Published: May 2021

AbstractInsight into psychiatric disease and development of therapeutics relies on behavioral tasks that study similar cognitive constructs in multiple species. The reversal learning task is one popular paradigm that probes flexible behavior, aberrations of which are thought to be important in a number of disease states. Despite widespread use, there is a need for a high-throughput primate model that can bridge the genetic, anatomic, and behavioral gap between rodents and humans. Here, we trained squirrel monkeys, a promising preclinical model, on an image-guided deterministic reversal learning task. We found that squirrel monkeys exhibited two key hallmarks of behavior found in other species: integration of reward history over many trials and a side-specific bias. We adapted a reinforcement learning model and demonstrated that it could simulate monkey-like behavior, capture training-related trajectories, and provide insight into the strategies animals employed. These results validate squirrel monkeys as a model in which to study behavioral flexibility.
Predicting T Cell Quality During Manufacturing Through an Artificial Intelligence-based Integrative Multi-Omics Analytical Platform
Authors: Odeh-Couvertier Valerie Y. , Dwarshuis Nathan J. , Colonna Maxwell B. , Levine Bruce L. , Edison Arthur S. , Kotanchek Theresa , Roy Krishnendu , Torres-Garcia Wandaliz 
Published: May 2021

AbstractLarge-scale, reproducible manufacturing of therapeutic cells with consistently high quality is vital for translation to clinically effective and widely accessible cell therapies. However, the biological and logistical complexity of manufacturing a living product, including challenges associated with their inherent variability and uncertainties of process parameters, currently make it difficult to achieve predictable cell-product quality. Using a degradable microscaffold-based T cell process as an example, we developed an Artificial Intelligence (AI)-driven experimental-computational platform to identify a set of critical process parameters (CPP) and critical quality attributes (CQA) from heterogeneous, high dimensional, time-dependent multi-omics data, measurable during early stages of manufacturing and predictive of end-of-manufacturing product quality. Sequential, Design-of-Experiment (DOE)-based studies, coupled with an agnostic machine-learning framework, were used to extract feature combinations from media assessment that were highly predictive of total live CD4+and CD8+naïve and central memory (CD63L+CCR7+) T cells and their ratio in the end-product. This computational workflow could be broadly applied to any cell therapy and provide a roadmap for discovering CQAs and CPPs in cell manufacturing.
Meta-analytic maps of brain activity evoked by cognitive function diverge from resting state networks
Authors: Palmucci Matías , Tagliazucchi Enzo 
Published: May 2021

AbstractSpontaneous human brain activity is organized into resting state networks (RSN), complex patterns of synchronized activity that account for the majority of brain metabolism. The correspondence between these patterns and those elicited by task performance suggests that spontaneous brain activity originates from the stream of ongoing cognitive processing. Here we investigate a large number of meta-analytic activation maps obtained from Neurosynth (www.neurosynth.org) to establish that task-rest similarity can be inflated by two potential sources of bias. Applying a hierarchical module detection algorithm to a network representation of activation map similarity, we showed that the correspondence between RSN and task-evoked activity tends to hold only for the largest spatial scales. Second, we established that this correspondence is biased by the inclusion of maps related to neuroanatomical terms (e.g. “parietal”, “occipital”, “cingulate”, etc.). Our results challenge the cognitive origin of spontaneous brain activity, suggesting that anatomically-constrained homeostatic processes could also play an important role in the inception and shaping of human resting state activity fluctuations.
Quantitative assessment of multiple fish species around artificial reefs using environmental DNA metabarcoding
Authors: Sato Masaaki , Inoue Nariaki , Nambu Ryogen , Furuich Naoki , Imaizumi Tomohito , Ushio Masayuki 
Published: May 2021

AbstractSince the early 1970s, many artificial reefs (ARs) have been deployed in Japanese coastal waters to create fisheries grounds. Recently, researchers began to use environmental DNA (eDNA) methods for biodiversity monitoring of aquatic species. A metabarcoding approach using internal standard DNAs (i.e., quantitative MiSeq sequencing) makes it possible to monitor eDNA concentrations of multiple species simultaneously. This method can improve the efficiency of monitoring AR effects on fishes. Our study investigated distributions of marine fishes at ARs and surrounding stations in the open oceanographic environment of Tateyama Bay, central Japan, using quantitative MiSeq sequencing and echo sounder survey. Using the quantitative metabarcoding method, we found higher quantities of fish eDNAs at the ARs than at surrounding stations and different fish species compositions between them. Comparisons with eco sounder survey also showed positive correlations between fish eDNA concentration and echo intensity, which indicates a highly localized signal of eDNA at each sampling station. These results suggest that quantitative MiSeq sequencing is a promising technique to complement conventional methods to monitor distributions of multiple fish species.
Intracellular and intercellular gene regulatory networks inference from time-course individual RNA-Seq
Authors: Kashima Makoto , Shida Yuki , Yamashiro Takashi , Hirata Hiromi , Kurosaka Hiroshi 
Published: May 2021

AbstractGene regulatory network (GRN) inference is an effective approach to understand the molecular mechanisms underlying biological events. Generally, GRN inference mainly targets intracellular regulatory relationships such as transcription factors and their associated targets. In multicellular organisms, there are both intracellular and intercellular regulatory mechanisms. Thus, we hypothesize that GRNs inferred from time-course individual (whole embryo) RNA-Seq during development can reveal intercellular regulatory relationships (signaling pathways) underlying the development. Here, we conducted time-course bulk RNA-Seq of individual mouse embryos during early development, followed by pseudo-time analysis and GRN inference. The results demonstrated that GRN inference from RNA-Seq with pseudo-time can be applied for individual bulk RNA-Seq similar to scRNA-Seq. Validation using an experimental-source-based database showed that our approach could significantly infer GRN for all transcription factors in the database. Furthermore, the inferred ligand-related and receptor-related downstream genes were significantly overlapped. Thus, the inferred GRN based on whole organism could include intercellular regulatory relationships, which cannot be inferred from scRNA-Seq based only on gene expression data. Overall, inferring GRN from time-course bulk RNA-Seq is an effective approach for understanding the regulatory relationships underlying biological events in multicellular organisms.