bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic profiling of fibropapillomatosis in green sea turtles (Chelonia mydas) from South Texas
Authors: Blackburn Nicholas B. , Leandro Ana Cristina , Nahvi Nina , Devlin Mariana A. , Leandro Marcelo , Escobedo Ignacio Martinez , Peralta Juan M. , George Jeff , Stacy Brian A. , deMaar Thomas W. , Blangero John , Keniry Megan , Curran Joanne E 
Published: October 2020

ABSTRACTSea turtle fibropapillomatosis (FP) is a tumor promoting disease that is one of several threats globally to endangered sea turtle populations. The prevalence of FP is highest in green sea turtle (Chelonia mydas) populations, and historically has shown considerable temporal growth. FP tumors can significantly affect the ability of turtles to forage for food and avoid predation and can grow to debilitating sizes. In the current study, based in South Texas, we have applied transcriptome sequencing to FP tumors and healthy control tissue to study the gene expression profiles of FP. By identifying differentially expressed turtle genes in FP, and matching these genes to their closest human ortholog we draw on the wealth of human based knowledge, specifically human cancer, to identify new insights into the biology of sea turtle FP. We show that several genes aberrantly expressed in FP tumors have known tumor promoting biology in humans, includingCTHRC1andNLRC5, and provide support that disruption of the Wnt signaling pathway is a feature of FP. Further, we profiled the expression of current targets of immune checkpoint inhibitors from human oncology in FP tumors and identified potential candidates for future studies.
KCC2 is required for the survival of mature neurons but not for their development
Authors: Kontou Georgina , Ng Josephine , Cardarelli Ross Andrew , Howden Jack , Choi Catherine , Ren Qiu , Kittler Josef , Brandon Nicholas , Moss Stephen J. , Smalley Joshua L. 
Published: October 2020

ABSTRACTThe K+/Cl– co-transporter KCC2 (SLC12A5) allows mature neurons in the CNS to maintain low intracellular Cl−levels that are critical in mediating fast hyperpolarizing synaptic inhibition via type A γ-aminobutyric acid receptors GABAARs. In accordance with this, compromised KCC2 activity results in seizures but whether such deficits directly contribute to the subsequent changes in neuronal viability that lead to epileptogenesis, remains to be assessed. Canonical hyperpolarizing GABAAR currents develop postnatally which reflect a progressive increase in KCC2 expression levels and activity. To investigate the role that KCC2 plays in regulating neuronal viability and architecture we have conditionally ablated KCC2 expression in developing and mature neurons. Decreasing KCC2 expression resulted in the rapid activation of the extrinsic apoptotic pathway, in mature hippocampal neurons. Intriguingly, direct pharmacological inhibition of KCC2 in mature neurons resulted in the rapid activation of the extrinsic apoptotic pathway. In contrast, ablating KCC2 expression in immature neurons had no discernable effects on their subsequent development, arborization or dendritic structure. However ablating KCC2 expression in immature neurons was sufficient to prevent the subsequent postnatal development of hyperpolarizing GABAAR currents. Collectively, our results demonstrate that KCC2 plays a critical role in neuronal survival by limiting apoptosis, and mature neurons are highly sensitive to loss of KCC2 function. In contrast KCC2 appears to play a minimal role in mediating neuronal development or architecture.
Multiple Mechanisms Underlie State-Independent Inhibitory Effects of Norfluoxetine on TREK-2 K2P Channels
Authors: Proks Peter , Schewe Marcus , Conrad Linus J. , Rao Shanlin , Rathje Kristin , Rödström Karin E. J. , Carpenter Elisabeth P. , Baukrowitz Thomas , Tucker Stephen J 
Published: October 2020

ABSTRACTThe TREK subfamily of Two-Pore Domain (K2P) K+channels are inhibited by fluoxetine and its metabolite, norfluoxetine (NFx). Although not the principal targets of this antidepressant, TREK channel inhibition by NFx has provided important insights into the conformational changes associated with channel gating and highlighted the role of the selectivity filter in this process. But despite the availability of TREK-2 crystal structures with NFx bound, the precise mechanisms underlying NFx inhibition remain elusive. NFx has previously been proposed to be a state-dependent inhibitor, but its binding site suggests many possible ways in which this positively charged drug might inhibit channel activity. Here we show that NFx exerts multiple effects on single channel behavior that influence both the open and closed states of the channel, and that the channel can become highly activated by 2-APB whilst remaining in the down conformation. We also show that that the inhibitory effects of NFx are unrelated to its positive charge, but can be influenced by agonists such as ML335 which alter filter stability, as well as by an intrinsic voltage-dependent gating process within the filter. NFx therefore not only inhibits channel activity by altering the equilibrium between up and down conformations, but can also directly influence filter gating. These results provide further insight into the complex allosteric mechanisms that modulate filter-gating in TREK K2P channels and highlight the different ways that filter gating can be regulated to permit polymodal regulation.
LncRNAPAINTis Associated with Aggressive Prostate Cancer and Dysregulation of Slug and Related Genes
Authors: Hasan Md Faqrul , Ganapathy Kavya , Sun Jiao , Ayman Khatib , Andl Thomas , Saulakova Julia N. , Coppola Domenico , Zhang Wei , Chakrabarti Ratna 
Published: October 2020

AbstractLong non-coding RNAs (lncRNAs) play regulatory roles in cellular processes and their aberrant expression may drive cancer progression. Here we report the function of a lncRNAPAINT(Prostate Cancer Associated Intergenic Non-Coding Transcript) in promoting prostate cancer (PCa) progression. Upregulation ofPAINTwas noted in advanced stage and metastatic PCa. Inhibition ofPAINTdecreased cell proliferation, S-phase progression, increased expression of apoptotic markers, and improved sensitivity to docetaxel and Aurora kinase inhibitor VX-680. Inhibition ofPAINTdecreased cell migration and reduced expression of Slug and Vimentin. Ectopic expression ofPAINTsuppressed E-cadherin, increased S-phase progression and cell migration.PAINTexpression in PCa cells induced larger colony formation and higher expression of mesenchymal markers. Transcriptome analysis followed by qRT-PCR validation showed differentially expressed genes involved in epithelial mesenchymal transition (EMT), apoptosis and drug resistance inPAINT-expressing cells. Our study establishes an oncogenic function ofPAINTin PCa.
Modeling the Opening SARS-CoV-2 Spike: an Investigation of its Dynamic Electro-Geometric Properties
Authors: Kucherova Anna , Strango Selma , Sukenik Shahar , Theillard Maxime 
Published: October 2020

AbstractThe recent COVID-19 pandemic has brought about a surge of crowd-sourced initiatives aimed at simulating the proteins of the SARS-CoV-2 virus. A bottleneck currently exists in translating these simulations into tangible predictions that can be leveraged for pharmacological studies. Here we report on extensive electrostatic calculations done on an exascale simulation of the opening of the SARS-CoV-2 spike protein, performed by the Folding@home initiative. We compute the electric potential as the solution of the non-linear Poisson-Boltzmann equation using a parallel sharp numerical solver. The inherent multiple length scales present in the geometry and solution are reproduced using highly adaptive Octree grids. We analyze our results focusing on the electro-geometric properties of the receptor-binding domain and its vicinity. This work paves the way for a new class of hybrid computational and data-enabled approaches, where molecular dynamics simulations are combined with continuum modeling to produce high-fidelity computational measurements serving as a basis for protein bio-mechanism investigations.
Reconstructing genomes of carbon monoxide oxidisers in volcanic deposits including members of the class Ktedonobacteria
Authors: Hernández Marcela , Vera-Gargallo Blanca , Calabi-Floody Marcela , King Gary M , Conrad Ralf , Tebbe Christoph C. 
Published: October 2020

AbstractMicroorganisms can potentially colonize volcanic rocks using the chemical energy in reduced gases such as methane, hydrogen (H2) and carbon monoxide (CO). In this study, we analysed soil metagenomes from Chilean volcanic soils, representing three different successional stages with ages of 380, 269 and 63 years, respectively. A total of 19 metagenome-assembled genomes (MAGs) were retrieved from all stages with a higher number observed in the youngest soil (1640: 2 MAGs, 1751: 1 MAG, 1957: 16 MAGs). Genomic similarity indices showed that several MAGs had amino-acid identity (AAI) values >50% to the phyla Actinobacteria, Acidobacteria, Gemmatimonadetes, Proteobacteria and Chloroflexi. Three MAGs from the youngest site (1957) belonged to the class Ktedonobacteria (Chloroflexi). Complete cellular functions of all the MAGs were characterised, including carbon fixation, terpenoid backbone biosynthesis, formate oxidation and CO oxidation. All 19 environmental genomes contained at least one gene encoding a putative carbon monoxide dehydrogenase (CODH). Three MAGs had form IcoxLoperon (encoding the large subunit CO-dehydrogenase). One of these MAGs (MAG-1957-2.1, Ktedonobacterales) was highly abundant in the youngest soil. MAG-1957-2.1 also contained genes encoding a [NiFe]-hydrogenase andhypgenes encoding accessory enzymes and proteins. Little is known about the Ktedonobacterales through cultivated isolates, but some species can utilize H2and CO for growth. Our results strongly suggest that the remote volcanic sites in Chile represent a natural habitat for Ktedonobacteria and they may use reduced gases for growth.
Disentangling metacommunity processes using multiple metrics in space and time
Authors: Guzman Laura Melissa , Thompson Patrick L. , Viana Duarte S , Vanschoenwinkel Bram , Horváth Zsófia , Ptacnik Robert , Jeliazkov Alienor , Gascón Stéphanie , Lemmens Pieter , Anton-Pardo Maria , Langenheder Silke , De Meester Luc , Chase Jonathan M. 
Published: October 2020

AbstractMetacommunity ecology has focused on using observational and analytical approaches to disentangle the role of critical assembly processes, such as dispersal limitation and environmental filtering. Many methods have been proposed for this purpose, most notably multivariate analyses of species abundance and its association with variation in spatial and environmental conditions. These approaches tend to focus on few emergent properties of metacommunities and have largely ignored temporal community dynamics. By doing so, these are limited in their ability to differentiate metacommunity dynamics. Here, we develop a Virtual ecologist’ approach to evaluate critical metacommunity assembly processes based on a number of summary statistics of community structure across space and time. Specifically, we first simulate metacommunities emphasizing three main processes that underlie metacommunity dynamics (density-independent responses to abiotic conditions, density-dependent biotic interactions, and dispersal). We then calculate a number of commonly used summary statistics of community structure in space and time, and use random forests to evaluate their utility for understanding the strength of these three processes. We found that: (i) time series are necessary to disentangle metacommunity processes, (ii) each of the three studied processes is distinguished with different descriptors, (iii) each summary statistic is differently sensitive to temporal and spatial sampling effort. Some of the most useful statistics include the coefficient of variation of abundances through time and metrics that incorporate variation in the relative abundances (evenness) of species. Surprisingly, we found that when we only used a single snapshot of community variation in space, the most commonly used approaches based on variation partitioning were largely uninformative regarding assembly processes, particularly, variation in dispersal. We conclude that a combination of methods and summary statistics will be necessary to understand the processes that underlie metacommunity assembly through space and time.
Molecular and morphological analyses clarify species delimitation and reveal a newBetulaspecies in sectionCostatae
Authors: Wang Luwei , Ding Junyi , Borrell James S. , McAllister Hugh A. , Wang Feifei , Liu Lu , Wang Nian 
Published: October 2020

Background and AimsDelineating closely related and morphologically similar species with overlapping ranges can be difficult. Here, we use sectionCostatae(genusBetula) as a model to resolve species and subspecies boundaries in four morphologically similar trees:Betula ashburneri, Betula costata, Betula ermaniiandBetula utilis(including ssp.utilis,and diploid and tetraploid races of ssp.albosinensis).MethodsWe genotyped 298 individuals (20-80 per species) from 38 populations at 15 microsatellite markers and a subset of 34 individuals from 21 populations using restriction-site associated DNA sequencing (RAD-seq). Morphometric analysis was conducted to characterise leaf variation for a subset of 89 individuals.Key ResultsMolecular analyses and leaf morphology found little differentiation betweenB. ashburneri,diploidB. utilisssp.albosinensisand some samples ofB. utilisssp.utilissuggesting that these should be treated as a single species. By contrast, tetraploidBetula utilisssp.albosinensiswas divided into two groups with group I genetically similar toB. utilisssp.utilisbased on SNPs and group II, a very distinct cluster, which we propose as a new species, namely,Betula buggsii. Phylogenomic analysis based on 2,285,620 SNPs show a well-supported monophyletic clade ofB. buggsii,forming a sister with a well-supported clade ofB. ashburneri,diploidB. albosinensisand some samples ofB. utilisssp.utilis. Morphologically,Betula buggsiiis characterised by elongated lenticels and a distinct pattern of bark peeling.Betula buggsiiis geographically restricted to the Qinling-Daba Mountains.ConclusionsOur study reveals six genetically distinguishable species:B. ashburneri, B. buggsii, B. costata, B. utilisssp.utilis,B. utilisssp.albosinensisandB. ermanii. Our research demonstrates an integrative approach in delimitating species using morphological and genetic samples from their nearly entire distributions. Analyses based on subsets of species’ distributions may lead to erroneous species or subspecies delineation.
Genomic diversity and antimicrobial resistance among non-typhoidalSalmonellaassociated with human disease in The Gambia
Authors: Darboe Saffiatou , Bradbury Richard S. , Phelan Jody , Kanteh Abdoulie , Muhammad Abdul-Khalie , Worwui Archibald , Yang Shangxin , Nwakanma Davis , Perez-Sepulveda Blanca , Kariuki Samuel , Kwambana-Adams Brenda , Antonio Martin 
Published: October 2020

AbstractNon-typhoidalSalmonellaassociated with multidrug resistance cause invasive disease in sub-Saharan African. Specific lineages of serovarsS. Typhimurium andS. Enteritidis are implicated. We characterised the genomic diversity of 100 clinical Non-typhoidalSalmonellacollected from 93 patients in 2001 from the eastern and 2006 to 2018 in the western regions of The Gambia respectively. Phenotypic susceptibility applied Kirby Baur disk diffusion and whole genome sequencing utilized Illumina platforms. The predominant serovars wereS.Typhimurium ST19 (31/100) andS.Enteritidis ST11 (18/100) restricted to invasive disease with the notable absence ofS.Typhimurium ST313. Phylogenetic analysis performed in the context of 495 African strains from the European Nucleotide Archive confirmed the presence of theS. Enteritidis virulent epidemic invasive multidrug resistant West African clade. Multidrug resistance including chloramphenicol and azithromycin has emerged among the West AfricanS.Enteritidis clade 7/9 (78%) with potential for spread, thus having important implications for patient management warranting systematic surveillance and epidemiologic investigations to inform control.Data summarySequences are deposited in the NCBI sequence reads archive (SRA) under BioProject ID:PRJEB38968. The genomic assemblies are available for download from the European Nucleotide Archive (ENA):http://www.ebi.ac.uk/ena/data/view/. Accession numbers SAMEA6991082 to SAME6991180
BMPR-2 gates activity-dependent stabilization of dendrites during mitral cell remodeling
Authors: Aihara Shuhei , Fujimoto Satoshi , Sakaguchi Richi , Imai Takeshi 
Published: October 2020

SUMMARYDeveloping neurons initially form excessive neurites and then remodel them based on molecular cues and neuronal activity. Developing mitral cells in the olfactory bulb initially extend multiple primary dendrites. They then stabilize single primary dendrites, while eliminating others. However, the mechanisms underlying the selective dendrite remodeling remain elusive. Using CRISPR/Cas9-based knockout screening combined within uteroelectroporation, we identified BMPR-2 as a key regulator for the selective dendrite stabilization.Bmpr2knockout and its rescue experiments show that BMPR-2 inhibits LIMK without ligands and thereby facilitates dendrite destabilization. In contrast, the overexpression of antagonists and agonists indicate that ligand-bound BMPR-2 stabilizes dendrites, most likely by releasing LIMK. Using genetic and FRET imaging experiments, we also demonstrate that free LIMK is activated by NMDARs via Rac1, facilitating dendrite stabilization through F-actin formation. Thus, the selective stabilization of mitral cell dendrites is ensured by concomitant inputs of BMP ligands and neuronal activity.
Highly Divergent Neuropeptide - non-coding RNA regulatory networks underpin variant host-finding behaviours inSteinernemaspecies infective juveniles
Authors: Warnock Neil D. , Atcheson Erwan , McCoy Ciaran , Dalzell Johnathan J. 
Published: October 2020

AbstractWe conducted a transcriptomic and small RNA analysis of infective juveniles (IJs) from three behaviourally distinctSteinernemaspecies. Substantial variation was found in the expression of shared gene orthologues, revealing gene expression signatures that correlate with behavioural states. 97% of predicted microRNAs are novel to each species. Surprisingly, our data provide evidence that isoform variation can effectively convert protein-coding neuropeptide genes into non-coding transcripts, which may represent a new family of long non-coding RNAs. These data suggest that differences in neuropeptide gene expression, isoform variation, and small RNA interactions could contribute to behavioural differences within theSteinernemagenus.
Differential patterns of gyral and sulcal morphological changes during normal aging process
Authors: Lin Hsin-Yu , Huang Chu-Chung , Chou Kun-Hsien , Yang Albert C. , Lo Chun-Yi Zac , Tsai Shih-Jen , Lin Ching-Po 
Published: October 2020

ABSTRACTThe cerebral cortex is a highly convoluted structure with distinct morphologic features, namely the gyri and sulci, which are associated with the functional segregation or integration in the human brain. During the lifespan, the brain atrophy that is accompanied by cognitive decline is a well-accepted aging phenotype. However, the detailed patterns of cortical folding change during aging, especially the changing trajectories of gyri and sulci, which is essential to brain functioning, remain unclear. In this study, we investigated the morphology of the gyral and sulcal regions from pial and white matter surfaces using MR imaging data of 417 healthy participants across the lifespan (21-92y). To elucidate the age-related changes in the cortical pattern, we fitted cortical thickness and intrinsic curvature of gyri and sulci using the quadratic model to evaluate their trajectories during normal aging. Our findings show that comparing to gyri, the sulcal thinning is the most prominent pattern during the aging process, and the gyrification of pial and white matter surfaces were also affected differently, which implies the vulnerability of functional segregation during aging. Taken together, we propose a morphological model of aging that may provide a framework for understanding the mechanisms underlying the gray matter degeneration.
Punctuated loci on chromosome IV determine natural variation in Orsay virus susceptibility ofCaenorhabditis elegansstrains Bristol N2 and Hawaiian CB4856
Authors: Sterken Mark G. , van Sluijs Lisa , Wang Yiru A. , Ritmahan Wannisa , Gultom Mitra L. , Riksen Joost A.G. , Volkers Rita J.M. , Snoek L. Basten , Pijlman Gorben P. , Kammenga Jan E. 
Published: October 2020

AbstractHost-pathogen interactions play a major role in evolutionary selection and shape natural genetic variation. The genetically distinctCaenorhabditis elegansstrains, Bristol N2 and Hawaiian CB4856, are differentially susceptible to the Orsay virus (OrV). Here we report the dissection of the genetic architecture of susceptibility to OrV infection. We compare OrV infection in the relatively resistant wild-type CB4856 strain to the more susceptible canonical N2 strain. To gain insight into the genetic architecture of viral susceptibility, 52 fully sequenced recombinant inbred lines (CB4856 x N2 RILs) were exposed to OrV. This led to the identification of two loci on chromosome IV associated with OrV resistance. To verify the two loci and gain additional insight into the genetic architecture controlling virus infection, introgression lines (ILs) that together cover chromosome IV, were exposed to OrV. Of the 27 ILs used, 17 had an CB4856 introgression in an N2 background and 10 had an N2 introgression in a CB4856 background. Infection of the ILs confirmed and fine-mapped the locus underlying variation in OrV susceptibility and we found that a single nucleotide polymorphism incul-6contributes to the difference in OrV susceptibility between N2 and CB4856. An allele swap experiment showed the strain CB4856 became more susceptible by having an N2cul-6allele, although having the CB4856cul-6allele did not increase resistance in N2. Additionally, we found that multiple strains with non-overlapping introgressions showed a distinct infection phenotype from the parental strain, indicating that there are punctuated locations on chromosome IV determining OrV susceptibility. Thus, our findings reveal the genetic complexity of OrV susceptibility inC. elegansand suggest that viral susceptibility is governed by multiple genes.
Irradiated mesenchymal stromal cells induce genetic instability in human CD34+ cells
Authors: Kohl Vanessa , Drews Oliver , Costina Victor , Bierbaum Miriam , Jawhar Ahmed , Roehl Henning , Weiss Christel , Brendel Susanne , Kleiner Helga , Flach Johanna , Spiess Birgit , Seifarth Wolfgang , Nowak Daniel , Hofmann Wolf-Karsten , Fabarius Alice , Popp Henning D. 
Published: October 2020

AbstractRadiation-induced bystander effects (RIBE) in human hematopoietic stem and progenitor cells may initiate myeloid neoplasms (MN). Here, the occurrence of RIBE caused by genotoxic signaling from irradiated human mesenchymal stromal cells (MSC) on human bone marrow CD34+ cells was investigated. For this purpose, healthy MSC were irradiated in order to generate conditioned medium containing potential genotoxic signaling factors. Afterwards, healthy CD34+ cells from the same donors were grown in conditioned medium and RIBE were analyzed. Increased DNA damage and chromosomal instability were detected in CD34+ cells grown in MSC conditioned medium when compared to CD34+ cells grown in control medium. Furthermore, reactive oxygen species and distinct proteome alterations, e.g., heat-shock protein GRP78, that might be secreted into the extracellular medium, were identified as potential RIBE mediators. In summary, our data provide evidence that irradiated MSC induce genetic instability in human CD34+ cells potentially resulting in the initiation of MN. Furthermore, the identification of key bystander signals, such as GRP78, may lay the framework for the development of next-generation anti-leukemic drugs.