bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-organisation and persistence of antibiotic resistance in evolving plasmid communities
Authors: Zwanzig Martin , Berger Uta 
Published: September 2020

ABSTRACTA key source of genetic variation of microbial populations are plasmids: extrachromosomal genetic elements that replicate autonomously and can be highly mobile between individual cells. Diverse plasmids were found in environmental samples and bacterial populations. Here we explore the mechanisms that help to preserve this gene pool as a fundamental basis for bacterial adaptation. An individual-based model of the plasmidome is presented and used to investigate how intra- and intercellular competition between diverse plasmid types affects the evolution of plasmid communities. It indicates the relative importance of stochastic and deterministic drivers of plasmid persistence both under neutral conditions and when the environment selects for specific plasmid-encoded traits such as antibiotic resistance for a certain period of time. We found that evolving plasmid communities exhibit a cyclical dynamics that contributes to the maintenance of plasmid diversity and the persistence of costly plasmid-mediated antibiotic resistance after stopped abiotic selection.
The piRNA pathway sustains adult neurogenesis by reducing protein synthesis and cellular senescence
Authors: Gasperini C. , Tuntevski K. , Pelizzoli R. , Lo Van A. , Mangoni D. , Cossu R.M. , Pascarella G. , Bianchini P. , Bielefeld P. , Scarpato M. , Pons-Espinal M. , Sanges R. , Diaspro A. , Fitzsimons C.P. , Carninci P. , Gustincich S. , De Pietri Tonelli D 
Published: September 2020

SummaryAdult Neural progenitor cells (aNPCs) ensure lifelong neurogenesis in the mammalian hippocampus. Proper regulation of aNPC fate entails important implications for brain plasticity and healthy aging. Piwi proteins and the small noncoding RNAs interacting with them (piRNAs) are best known in gonads as repressors of transposons. Here, we show that Piwil2 (Mili) and piRNAs are abundant in aNPCs of the postnatal mouse hippocampus and demonstrate that this pathway is essential for proper neurogenesis. Particularly, depleting the piRNA pathway in aNPCs impaired neurogenesis, increased senescence and accordingly the generation of reactive glia. Moreover, this manipulation primarily elevated 5S ribosomal RNA, SINEB1 and mRNAs encoding ribosomal proteins and regulators of translation, resulting in higher polysome density and protein synthesis upon differentiation. Our results provide evidence of an essential role for the piRNA pathway in maintaining homeostasis to sustain neural stem cell fate, underpinning its possible involvement in brain plasticity and successful aging.
Performing Parentage Analysis for Polysomic Inheritances Based on Allelic Phenotypes
Authors: Huang Kang , Huber Gwendolyn , Ritland Kermit , Dunn Derek W. , Li Baoguo 
Published: September 2020

AbstractPolyploidy poses several problems for parentage analysis. We present a new polysomic inheritance model for parentage analysis based on genotypes or allelic phenotypes to solve these problems. The effects of five factors are simultaneously accommodated in this model: (i) double-reduction, (ii) null alleles, (iii) negative amplification, (iv) genotyping errors and (v) self-fertilization. To solve genotyping ambiguity (unknown allele dosage), we developed a new method to establish the likelihood formulas for allelic phenotype data and to simultaneously include the effects of our five chosen factors. We then evaluated and compared the performance of our new method with three established methods by using both simulated data and empirical data from the cultivated blueberry (Vaccinium corymbosum). We also developed and compared the performance of two additional estimators to estimate the geno-typing error rate and the sample rate. We make our new methods freely available in the software packagepolygene, athttp://github.com/huangkang1987/polygene.
Electrical match between initial segment and somatodendritic compartment for action potential backpropagation in retinal ganglion cells
Authors: Goethals Sarah , Sierksma Martijn C. , Nicol Xavier , Réaux-Le Goazigo Annabelle , Brette Romain 
Published: September 2020

AbstractThe action potential of most vertebrate neurons initiates in the axon initial segment (AIS), and is then transmitted to the soma where it is regenerated by somatodendritic sodium channels. For successful transmission, the AIS must produce a strong axial current, so as to depolarize the soma to the threshold for somatic regeneration. Theoretically, this axial current depends on AIS geometry and Na+conductance density. We measured the axial current of mouse RGCs using whole-cell recordings with post-hoc AIS labeling. We found that this current is large, implying high Na+conductance density, and carries a charge that co-varies with capacitance so as to depolarize the soma by ~30 mV. Additionally, we observed that the axial current attenuates strongly with depolarization, consistent with sodium channel inactivation, but temporally broadens so as to preserve the transmitted charge. Thus, the AIS appears to be organized so as to reliably backpropagate the axonal action potential.
Evolutionary dynamics of transposable elements in bdelloid rotifers
Authors: Nowell Reuben W. , Wilson Christopher G. , Almeida Pedro , Schiffer Philipp H. , Fontaneto Diego , Becks Lutz , Rodriguez Fernando , Arkhipova Irina R. , Barraclough Timothy G. 
Published: September 2020

AbstractTransposable elements (TEs) are selfish genomic parasites whose ability to spread autonomously is facilitated by sexual reproduction in their hosts. If hosts become obligately asexual, TE frequencies and dynamics are predicted to change dramatically, but the long-term outcome is unclear. Here, we test current theory using whole-genome sequence data from eight species of bdelloid rotifers, a class of invertebrates where males are thus far unknown. Contrary to expectations, we find a diverse range of active TEs in bdelloid genomes, at an overall frequency within the range seen in sexual species. We find no evidence that TEs are spread by cryptic recombination or restrained by unusual DNA repair mechanisms, but we report that bdelloids share a large and unusual expansion of genes involved in RNAi-mediated TE suppression. This suggests that enhanced cellular defence mechanisms might mitigate the deleterious effects of active TEs and compensate for the consequences of long-term asexuality.
DMA-tudor interaction modules control the specificity ofin vivocondensates
Authors: Courchaine Edward M. , Barentine Andrew E.S. , Straube Korinna , Bewersdorf Joerg , Neugebauer Karla M. 
Published: September 2020

SummaryBiomolecular condensation is a widespread mechanism of cellular compartmentalization. Because the ‘survival of motor neuron protein’ (SMN) is required for the formation of three different membraneless organelles (MLOs), we hypothesized that at least one region of SMN employs a unifying mechanism of condensation. Unexpectedly, we show here that SMN’s globular tudor domain was sufficient for dimerization-induced condensationin vivo, while its two intrinsically disordered regions (IDRs) were not. The condensate-forming property of the SMN tudor domain required binding to its ligand, dimethylarginine (DMA), and was shared by at least seven additional tudor domains in six different proteins. Remarkably, asymmetric versus symmetric DMA determined whether two distinct nuclear MLOs – gems and Cajal bodies – were separate or overlapping. These findings show that the combination of a tudor domain bound to its DMA ligand – DMA-tudor – represents a versatile yet specific interaction module that regulates MLO assembly and defines their composition.
Mouse fertilization triggers a conserved transcription program in one-cell embryos
Authors: Asami Maki , Lam Brian Y. H. , Hoffmann Martin , Suzuki Toru , Lu Xin , VerMilyea Matthew D. , Yoshida Naoko , Ma Marcella K. , Rainbow Kara , Braun Stefanie , Patwary Nina , Yeo Giles S. H. , Klein Christoph A. , Perry Anthony C. F. 
Published: September 2020

Following fertilization, the new embryo reprograms parental genomes to begin transcription (embryonic genome activation, EGA). EGA is indispensable for development, but its dynamics, profile or when it initiates in vertebrates are unknown. We here characterize the onset of transcription in mouse one-cell embryos. Precise embryo staging eliminated noise to reveal a cascading program ofde novotranscription initiating within six hours of fertilization. This immediate EGA (iEGA) utilized canonical promoters, produced spliced transcripts, was distinctive and predominantly driven by the maternal genome. Expression represented pathways not only associated with embryo development but with cancer. In human one-cell embryos, hundreds of genes were up-regulated days earlier than thought, with conservation to mouse iEGA. These findings provide a functional basis for epigenetic analysis in early-stage embryos and illuminate networks governing totipotency and other cell-fate transitions.One Sentence SummaryFertilization instates transcription in mouse and human one-cell embryos far sooner than thought and is programmed.
Whole-genome sequencing of 1,171 elderly admixed individuals from the largest Latin American metropolis (São Paulo, Brazil)
Authors: Naslavsky Michel S. , Scliar Marilia O. , Yamamoto Guilherme L. , Wang Jaqueline Yu Ting , Zverinova Stepanka , Karp Tatiana , Nunes Kelly , Ceroni José Ricardo Magliocco , de Carvalho Diego Lima , da Silva Simões Carlos Eduardo , Bozoklian Daniel , Nonaka Ricardo , Silva Nayane dos Santos Brito , da Silva Souza Andreia , de Souza Andrade Heloísa , Passos Marília Rodrigues Silva , Castro Camila Ferreira Bannwart , Mendes-Junior Celso T. , Mercuri Rafael L. V. , Miller Thiago L. A. , Buzzo Jose Leonel , Rego Fernanda O. , Araújo Nathalia M , Magalhães Wagner CS , Célia Mingroni-Netto Regina , Borda Victor , Guio Heinner , Barreto Mauricio L , Lima-Costa Maria Fernanda , Horta Bernardo L , Tarazona-Santos Eduardo , Meyer Diogo , Galante Pedro A. F. , Guryev Victor , Castelli Erick C. , Duarte Yeda A. O. , Passos-Bueno Maria Rita , Zatz Mayana 
Published: September 2020

AbstractAs whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enabled identifying ~2,000 novel mobile element insertions, nearly 5Mb of genomic segments absent from human genome reference, and over 140 novel alleles from HLA genes. We reclassified and curated nearly four hundred variant's pathogenicity assertions in genes associated with dominantly inherited Mendelian disorders and calculated the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observed that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS.
Antibody potency, effector function and combinations in protection from SARS-CoV-2 infectionin vivo
Authors: Schäfer Alexandra , Muecksch Frauke , Lorenzi Julio C. C. , Leist Sarah R. , Cipolla Melissa , Bournazos Stylianos , Schmidt Fabian , Gazumyan Anna , Baric Ralph S. , Robbiani Davide F. , Hatziioannou Theodora , Ravetch Jeffrey V. , Bieniasz Paul D. , Nussenzweig Michel C. , Sheahan Timothy P. 
Published: September 2020

AbstractSARS-CoV-2, the causative agent of COVID-19, is responsible for over 24 million infections and 800,000 deaths since its emergence in December 2019. There are few therapeutic options and no approved vaccines. Here we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a mouse adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA).In vitroantibody neutralization potency did not uniformly correlate within vivoactivity, and some hu-mAbs were more potent in combinationin vivo. Analysis of antibody Fc regions revealed that binding to activating Fc receptors is essential for optimal protection against SARS-CoV-2 MA. The data indicate that hu-mAb protective activity is dependent on intact effector function and thatin vivotesting is required to establish optimal hu-mAb combinations for COVID-19 prevention.
Zika virus alters centrosome organization to suppress the innate immune response
Authors: Kodani Andrew , Knopp Kristeene A. , Di Lullo Elizabeth , Retallack Hanna , Kriegstein Arnold R. , DeRisi Joseph L. , Reiter Jeremy F. 
Published: September 2020

AbstractZika virus (ZIKV) is a flavivirus transmitted via mosquitoes and sex to cause congenital neurodevelopmental defects, including microcephaly. Inherited forms of microcephaly (MCPH) are associated with disrupted centrosome organization. Similarly, we found that ZIKV infection disrupted centrosome organization. ZIKV infection disrupted the organization of centrosomal proteins including CEP63, a MCPH-associated protein. The ZIKV nonstructural protein NS3 bound CEP63, and expression of NS3 was sufficient to alter centrosome architecture and CEP63 localization. Loss of CEP63 suppressed ZIKV-induced centrosome disorganization, indicating that ZIKV requires CEP63 to disrupt centrosome organization. ZIKV infection or loss of CEP63 decreased the centrosomal localization and stability of TANK-binding kinase 1 (TBK1), a regulator of the innate immune response. ZIKV infection or loss of CEP63 also increased the centrosomal accumulation of the CEP63 interactors, Mindbomb1 (MIB1) and DTX4, ubiquitin ligases that respectively activate and degrade TBK1. Therefore, we propose that ZIKV NS3 binds CEP63 to increase centrosomal DTX4 localization and destabilization of TBK1, thereby tempering the innate immune response. In addition to identifying a mechanism by which CEP63 controls the innate immune responses in ZIKV infection, we propose that the altered centrosomal organization caused by altered CEP63 function may contribute to ZIKV-associated microcephaly.
Identifying HIV-1 RNA splice variant protein interactomes using HyPR-MSSV
Authors: Knoener Rachel A. , Evans Edward L. , Becker Jordan T. , Scalf Mark , Benner Bayleigh E. , Sherer Nathan M. , Smith Lloyd M. 
Published: September 2020

ABSTRACTHIV-1 generates unspliced (US), partially spliced (PS), and completely spliced (CS) classes of RNAs; each playing distinct roles in viral replication. Elucidating their host protein “interactomes” is crucial to understanding virus-host interplay. Here, we present HyPR-MSSVfor isolation of US, PS, and CS transcripts from a single population of infected CD4+ T-cells and mass spectrometric identification of theirin vivoprotein interactomes. Analysis revealed 212 proteins differentially associated with the unique RNA classes; including, preferential association of regulators of RNA stability with US- and PS-transcripts and, unexpectedly, mitochondria-linked proteins with US-transcripts. Remarkably, >80 of these factors screened by siRNA knock-down impacted HIV-1 gene expression. Fluorescence microscopy confirmed several to co-localize with HIV-1 US RNA and exhibit changes in abundance and/or localization over the course of infection. This study validates HyPR-MSSVfor discovery of viral splice variant protein interactomes and provides an unprecedented resource of factors and pathways likely important to HIV-1 replication.
Wetland birds in the northern prairie pothole region may show sensitivity to agriculture
Authors: Daniel Jody , Polan Heather , Rooney Rebecca C 
Published: September 2020

AbstractWetland losses in the Northern Prairie Pothole Region (NPPR) are largely attributed to agriculture. Since land-use is known to influence bird habitat selection, bird community composition is likely sensitive to the extent of neighboring agricultural activity. We determined which local and landscape habitat variables are most predictive of wetland bird assemblage occurrence in southern Alberta. We:1) identified distinct bird assemblages with a cluster analysis, 2) identified which species were indicative of these assemblages using an indicator species analysis and 3) predicted which bird assemblage would occur in a wetland with a classification and regression tree. Avian assemblages were more loosely defined and had few indicator species. Importantly, assemblages were specific to the natural region in which the wetland occurred. Also, landscapes with higher agricultural activity generally supported waterfowl and shorebirds, likely because agricultural activities excluded wetland-dependent birds that nest in upland habitat. Though waterfowl and shorebirds show poor sensitivity to surrounding landscape composition, edge-nesting wetland avifauna may make good indicators of ecological integrity.
Neural interactions in developing rhythmogenic spinal networks: Insights from computational modeling
Authors: Shevtsova Natalia A. , Ha Ngoc T. , Rybak Ilya A. , Dougherty Kimberly J. 
Published: September 2020

AbstractThe mechanisms involved in generation of rhythmic locomotor activity in the mammalian spinal cord remain poorly understood. These mechanisms supposedly rely on both intrinsic properties of constituting neurons and interactions between them. A subset of Shox2 neurons was found to contribute to generation of spinal locomotor activity, but the possible cellular basis for rhythmic bursting in these neurons remains unknown. Ha and Dougherty (2018) recently revealed the presence of bidirectional electrical coupling between Shox2 neurons in neonatal spinal cords, which can be critically involved in neuronal synchronization and generation of populational bursting. Gap junctional connections found between functionally-related Shox2 interneurons decrease with age, possibly being replaced by increasing interactions through chemical synapses. Here, we developed a computational model of a heterogeneous population of neurons sparsely connected by electrical or/and chemical synapses and investigated the dependence of frequency of populational bursting on the type and strength of neuronal interconnections. The model proposes a mechanistic explanation for emergence of a synchronized rhythmic activity in the neuronal population and provides insights into the mechanisms of the locomotor rhythm generation.
A contiguous de novo genome assembly of sugar beet EL10 (Beta vulgaris L.)
Authors: McGrath J. Mitchell (Mitch) , Funk Andrew , Galewski Paul , Ou Shujun , Townsend Belinda , Davenport Karen , Daligault Hajnalka , Johnson Shannon , Lee Joyce , Hastie Alex , Darracq Aude , Willems Glenda , Barnes Steve , Liachko Ivan , Sullivan Shawn , Koren Sergey , Phillippy Adam , Wang Jie , Liu Tiffany , Pulman Jane , Childs Kevin , Yocum Anastasia , Fermin Damian , Mutasa-Göttgens Effie , Stevanato Piergiorgio , Taguchi Kazunori , Dorn Kevin 
Published: September 2020

AbstractA contiguous assembly of the inbred ‘EL10’ sugar beet (Beta vulgaris ssp. vulgaris) genome was constructed using PacBio long read sequencing, BioNano optical mapping, Hi-C scaffolding, and Illumina short read error correction. The EL10.1 assembly was 540 Mb, of which 96.7% was contained in nine chromosome-sized pseudomolecules with lengths from 52 to 65 Mb, and 31 contigs with a median size of 282 kb that remained unassembled. Gene annotation incorporating RNAseq data and curated sequences via the MAKER annotation pipeline generated 24,255 gene models. Results indicated that the EL10.1 genome assembly is a contiguous genome assembly highly congruent with the published sugar beet reference genome. Gross duplicate gene analyses of EL10.1 revealed little large-scale intra-genome duplication. Reduced gene copy number for well-annotated gene families relative to other core eudicots was observed, especially for transcription factors. Variation in genome size in B. vulgaris was investigated by flow cytometry among 50 individuals drawn from EL10 progeny and three unrelated germplasm accessions, producing estimates from 633 to 875 Mb/1C. Read depth mapping with short-read whole genome sequences from other sugar beet germplasm suggested that relatively few regions of the sugar beet genome appeared associated with high-copy number variation.
Network Modeling and Inference of Peroxisome Proliferator-Activated Receptor Pathway in High fat diet-linked Obesity
Authors: Vundavilli Haswanth , Tripathi Lokesh P. , Datta Aniruddha , Mizuguchi Kenji 
Published: September 2020

AbstractSystems biology aims to understand how holistic systems theory can be used to explain the observable living system characteristics, and mathematical modeling tools have been successful in understanding the intricate relationships underlying cellular functions. Lately, researchers have been interested in understanding molecular mechanisms underlying obesity, which is a major health concern worldwide and has been linked to several diseases. Various mechanisms such as peroxisome proliferator-activated receptors (PPARs) are known to modulate obesity-induced inflammation and its consequences. In this study, we have modeled the PPAR pathway using a Bayesian model and inferred the sub-pathways that are potentially responsible for the activation of the output processes that are associated with high fat diet (HFD)-induced obesity. We examined a previously published dataset from a study that compared gene expression profiles of 40 mice maintained on HFD against 40 mice fed with chow diet (CD). Our simulations have highlighted that GPCR and FATCD36 sub-pathways were aberrantly active in HFD mice and are therefore favorable targets for anti-obesity strategies. We further cross-validated our observations with experimental results from the literature. We believe that mathematical models such as those presented in the present study can help in inferring other pathways and deducing significant biological relationships.
Antibody interference by a non-neutralizing antibody abrogates humoral protection againstPlasmodiumliver stage
Authors: Vijayan Kamalakannan , Chandrasekaran Ramyavardhanee , Trakhimets Olesya , Brown Samantha L. , Dambrauskas Nicholas , Zuck Meghan , Visweswaran Ganesh Ram R. , Watson Alexander , Raappana Andrew , Carbonetti Sara , Kelnhofer-Millevolte Laurel , Glennon Elizabeth K.K. , Postiglione Rachel , Sather D. Noah , Kaushansky Alexis 
Published: September 2020

AbstractBoth subunit and attenuated whole sporozoite vaccination strategies againstPlasmodiuminfection have shown promising initial results in malaria-naïve westerners but exhibited less efficacy in malaria-exposed individuals in endemic areas. It has been hypothesized that preexisting immunity to malaria represents a significant roadblock to the development of a protective vaccine. Here, we demonstrate proof-of-concept that non-neutralizing antibodies (nNAb) can directly interfere with protective anti-PyCSP humoral responses. We developed and characterized a novel monoclonal antibody, RAM1, against theP. yoeliisporozoite major surface antigen, circumsporozoite protein (CSP). Unlike the canonicalPyCSP repeat domain binding and neutralizing antibody (NAb) 2F6, RAM1 does not inhibit sporozoite traversal or entry of hepatocytesin vitro. Though 2F6 and RAM1 bind non-overlapping regions of the CSP-repeat domain, pretreatment with RAM1 abrogated 2F6’s capacity to block sporozoite traversal and invasionin vitro. Importantly, RAM1 reduced the efficacy of the polyclonal humoral response against CSPin vivo,paralleling the observed reduced efficacy of RTS,S in malaria-exposed populations. Taken together, our data demonstrate the interference of non-neutralizing antibodies with the efficacy of NAbs and may impact the efficacy of anti-CSP vaccines in malaria-exposed individuals.