bluuebunny/crossref_metadata_2025_split huggingface dataset:
Python nidoviruses, more than respiratory pathogens
Authors: Dervas Eva , Hepojoki Jussi , Smura Teemu , Prähauser Barbara , Windbichler Katharina , Blümich Sandra , Ramis Antonio , Hetzel Udo , Kipar Anja 
Published: April 2020

ABSTRACTIn recent years nidoviruses have emerged as an important respiratory pathogen of reptiles, affecting especially captive python populations. In pythons, nidovirus infection induces an inflammation of the upper respiratory and alimentary tract which can develop into a severe and often fatal proliferative pneumonia. We observed pyogranulomatous and fibrinonecrotic lesions in organ systems other than the respiratory tract during full post mortem examinations on 30 nidovirus RT-PCR positive pythons of varying species originating from Switzerland and Spain. The observations prompted us to study whether the atypical tissue tropism associates with previously unknown nidoviruses or changes in the nidovirus genome. RT-PCR and inoculation ofMorelia viridiscell cultures served to recruit the cases and to obtain virus isolates. Immunohistochemistry and immunofluorescence staining against nidovirus nucleoprotein demonstrated that the virus not only infects a broad spectrum of epithelial (respiratory and alimentary epithelium, hepatocytes, renal tubules, pancreatic ducts etc.), but also intravascular monocytes, intralesional macrophages and endothelial cells. By next-generation sequencing we obtained full length genome for a novel nidovirus species circulating in Switzerland. Analysis of viral genomes recovered from pythons showing nidovirus infection-associated respiratory or systemic disease did not explain the observed phenotypes. The results indicate that python nidoviruses have a broad cell and tissue tropism, further suggesting that the course of infection could vary and involve lesions in a broad spectrum of tissues and organ systems as a consequence of monocyte-mediated systemic spread of the virus.IMPORTANCEDuring the last years, python nidoviruses have become a primary cause of fatal disease in pythons. Nidoviruses represent a threat to captive snake collections, as they spread rapidly and can be associated with high morbidity and mortality. Our study indicates that, different from previously evidence, the viruses do not only affect the respiratory tract, but can spread in the entire body with blood monocytes, have a broad spectrum of target cells, and can induce a variety of lesions. Nidovirales is an order of animal and human viruses that compromise important zoonotic pathogens such as MERS-CoV and SARS-CoV, as well as the recently emerged SARS-CoV-2. Python nidoviruses belong to the same subfamily as the mentioned human viruses and show similar characteristics (rapid spread, respiratory and gastrointestinal tropism, etc.). The present study confirms the relevance of natural animal diseases to better understand the complexity of viruses of the order nidovirales.
Validating the use of bovine buccal sampling as a proxy for the rumen microbiota using a time course and random forest classification approach
Authors: Young Juliana , Skarlupka Joseph H. , Resende Rafael Tassinari , Fischer Amelie , Kalscheur Kenneth F. , McClure Jennifer C. , Cole John B. , Suen Garret , Bickhart Derek M. 
Published: April 2020

ABSTRACTAnalysis of the cow microbiome, as well as host genetic influences on the establishment and colonization of the rumen microbiota, is critical for development of strategies to manipulate ruminal function toward more efficient and environmentally friendly milk production. To this end, the development and validation of noninvasive methods to sample the rumen microbiota at a large-scale is required. Here, we further optimized the analysis of buccal swab samples as a proxy for direct microbial samples of the rumen of dairy cows. To identify an optimal time for sampling, we collected buccal swab and rumen samples at six different time points relative to animal feeding. We then evaluated several biases in these samples using a machine learning classifier (random forest) to select taxa that discriminate between buccal swab and rumen samples. Differences in the Simpson’s diversity, Shannon’s evenness and Bray-Curtis dissimilarities between methods were significantly less apparent when sampling was performed prior to morning feeding (P<0.05), suggesting that this time point was optimal for representative sampling. In addition, the random forest classifier was able to accurately identify non-rumen taxa, including 10 oral and feed-associated taxa. Two highly prevalent (> 60%) taxa in buccal and rumen samples had significant variance in absolute abundance between sampling methods, but could be qualitatively assessed via regular buccal swab sampling. This work not only provides new insights into the oral community of ruminants, but further validates and refines buccal swabbing as a method to assess the rumen microbiota in large herds.IMPORTANCEThe gastrointestinal tract of ruminants harbors a diverse microbial community that coevolved symbiotically with the host, influencing its nutrition, health and performance. While the influence of environmental factors on rumen microbes is well-documented, the process by which host genetics influences the establishment and colonization of the rumen microbiota still needs to be elucidated. This knowledge gap is due largely to our inability to easily sample the rumen microbiota. There are three common methods for rumen sampling but all of them present at least one disadvantage, including animal welfare, sample quality, labor, and scalability. The development and validation of non-invasive methods, such as buccal swabbing, for large-scale rumen sampling is needed to support studies that require large sample sizes to generate reliable results. The validation of buccal swabbing will also support the development of molecular tools for the early diagnosis of metabolic disorders associated with microbial changes in large herds.
Glucosamine-6P and glucosamine-1P, respectively an activator and a substrate of rhodococcal ADP-glucose pyrophosphorylases, show a hint to ascertain (actino)bacterial glucosamine metabolism
Authors: Cereijo AE , Alvarez HM , Iglesias AA , Asencion Diez MD 
Published: April 2020

AbstractRhodococcusspp. are important microorganisms for biotechnological purposes, such as bioremediation and biofuel production. The latter, founded on the oleaginous characteristic (high lipid accumulation) exhibited by manyRhodococcusspecies when grown in certain carbon sources under low nitrogen availability. These bacteria accumulate glycogen during exponential growth, and the glucan plays a role as an intermediary metabolite for temporary carbon storage related to lipid metabolism. The kinetic and regulatory properties of the ADP-glucose pyrophosphorylase (ADP-GlcPPase) fromRhodococcus jostiisupports this hypothesis. The enzyme was found able to use glucosamine-1P as an alternative substrate. Curiously, the activity with glucosamine-1P was sensitive to glucose-6P, the main activator of actinobacterial ADP-GlcPPases. Herein, we report the study of glucosamine-1P related to the activity and regulation of ADP-GlcPPases fromR. jostiiandR. fascians, with the finding that glucosamine-6P is also a significant activator. Glucosamine-6P, belonging to a node between carbon and nitrogen metabolism, was identified as a main regulator in Actinobacteria. Thus, its effect on rhodococcal ADP-GlcPPases reinforces the function proposed for glycogen as temporary carbon storage. Results indicate that the activity of the studied enzymes using glucosamine-1P as a substrate responds to the activation by several metabolites that improve their catalytic performance, which strongly suggest metabolic feasibility. Then, studying the allosteric regulation exerted on an alternative activity would open two scenarios for consideration: (i) the existence of new molecules/metabolites yet undescribed, and (ii) evolutionary mechanisms underlying enzyme promiscuity that give rise new metabolic features in bacteria.
Vegetation and Microbes Interact to Preserve Organic Matter in Wooded Peatlands
Authors: Wang Hongjun , Tian Jianqing , Chen Huai , Ho Mengchi , Vilgalys Rytas , Liu Xingzhong , Richardson Curtis J. 
Published: April 2020

AbstractPeatlands have persisted as massive carbon sinks over millennia, even during past periods of climate change. The commonly accepted theory of abiotic controls (mainly anoxia and low temperature) over carbon decomposition cannot explain how vast low-latitude wooded peatlands consistently accrete peat under warm and seasonally unsaturated conditions. Similarly, that theory cannot accurately project the decomposition rate in boreal peatlands where warming and drought have decreasedSphagnumand increased shrub expansion. Here, by comparing composition and ecological traits of microbes betweenSphagnum- and shrub-dominated peatlands, we present a previously unrecognized natural course that curbs carbon loss against climate change. Slow-growing microbes decisively dominate the studied wooded peatlands, concomitant with plant-induced, high recalcitrant carbon and phenolics. The slow-growing microbes inherently metabolize organic matter slowly. However, the fast-growing microbes that dominate ourSphagnumsite (most boreal peatlands as well) decomposed labile carbon >30 times faster than the slow-growing microbes. We show that the high-phenolic shrub/tree induced shifts in microbial composition may compensate for positive effects of temperature and/or drought on metabolism over time in peatlands. This biotic self-sustaining process that modulates abiotic controls on carbon cycling may help better project long-term climate-carbon feedbacks in peatlands.
Involvement of thedoublesexgene in body color masculinization of the blue-tailed damselfly,Ischnura senegalensis
Authors: Takahashi Michihiko , Okude Genta , Futahashi Ryo , Takahashi Yuma , Kawata Masakado 
Published: April 2020

AbstractOdonata (dragonflies and damselflies) display remarkable color pattern diversity including sexual dimorphism and intrasexual polymorphism. We previously found that expression of a sex-determining transcription factor, thedoublesex(dsx) gene, is associated with female color polymorphism (gynomorph for female-specific color and andromorph for male mimicking color) in the blue-tailed damselfly,Ischnura senegalensis. Here we investigate the function of dsx gene on thoracic coloration by electroporation-mediated RNA interference (RNAi). RNAi of thedsxcommon region changed color patterns of males and andromorphic females to patterns of gynomorphic females. Further, gynomorphic color pattern was not affected bydsxRNAi. The long isoform ofdsxRNAi produced no effects, suggesting that the short isoform ofdsxis important for body color masculinization in both males and andromorphic females. Expression pattern changes were also examined in five genes with different expression levels between sexes and female morphs. Among these genes are two melanin suppressing genes,blackandebony, that were upregulated in thedsx-RNAi region compared to a control region. Upregulation coincides with a gynomorphic orange color instead of the black stripe observed in males and andromorphic females.dsxmay regulate male color differentiation by suppressingblackandebonyin the thoracic region ofI. senegalensis.Results add to the understanding of molecular mechanisms underlying the evolution of female polymorphism in Odonata.
Complete Coding Genome Sequence for a Novel Multicomponent Kindia Tick Virus Detected from Ticks Collected in Guinea
Authors: Ternovoi Vladimir A. , Protopopova Elena V. , Shvalov Alexander N. , Kartashov Mikhail Yu. , Bayandin Roman B. , Tregubchak Tatyana V. , Yakovlev Sergey A. , Nikiforov Konstantin A. , Konovalova Svetlana N. , Loktev Valery B. , Agafonov Alexander P. , Maksyutov Rinat A. , Popova Anna Yu. 
Published: April 2020

ABSTRACTKindia tick virus (KITV) is a novel multicomponent virus first detected by direct sequencing ofRhipicephalus geigyiticks in Guinea in 2017. Here, we present a complete coding genome sequence for all four segments of KITV/2017/1. This virus appears to be evolutionarily related to unclassified flaviviruses, such as Alongshan virus.
An Algorithm to Build aMulti-genomeReference
Authors: Rabbani Leily , Müller Jonas , Weigel Detlef 
Published: April 2020

1AbstractMotivationNew DNA sequencing technologies have enabled the rapid analysis of many thousands of genomes from a single species. At the same time, the conventional approach of mapping sequencing reads against a single reference genome sequence is no longer adequate. However, even where multiple high-quality reference genomes are available, the problem remains how one would integrate results from pairwise analyses.ResultTo overcome the limits imposed by mapping sequence reads against a single reference genome, or serially mapping them against multiple reference genomes, we have developed theMGRmethod that allows simultaneous comparison against multiple high-quality reference genomes, in order to remove the bias that comes from using only a single-genome reference and to simplify downstream analyses. To this end, we present theMGRalgorithm that creates a graph (MGRgraph) as amulti-genomereference. To reduce the size and complexity of themulti-genomereference, highly similar orthologous1and paralogous2regions are collapsed while more substantial differences are retained. To evaluate the performance of our model, we have developed a genome compression tool, which can be used to estimate the amount of shared information between genomes.Availabilityhttps://github.com/LeilyR/Multi-genome-Reference.gitContactweigel@tue.mpg.de
Metabolite genome-wide association study (mGWAS) and gene-metabolite interaction network analysis reveal potential biomarkers for feed efficiency in pigs
Authors: Wang Xiao , Kadarmideen Haja N. 
Published: April 2020

AbstractMetabolites represent the ultimate response of biological systems, so metabolomics is considered to link the genotypes and phenotypes. Feed efficiency is one of the most important phenotypes in sustainable pig production and is the main breeding goal trait. We utilized metabolic and genomic datasets from a total of 108 pigs from our own previously published studies that involved 59 Duroc and 49 Landrace pigs with data on feed efficiency (residual feed intake or RFI), genotype (PorcineSNP80 BeadChip) data and metabolomic data (45 final metabolite datasets derived from LC-MS system). Utilizing these datasets, our main aim was to identify genetic variants (single-nucleotide polymorphisms or SNPs) that affect 45 different metabolite concentrations in plasma collected at the start and end of the performance testing of pigs categorized as high or low in their feed efficiency (based on RFI values). Genome-wide significant genetic variants could be then used as potential genetic or biomarkers in breeding programs for feed efficiency. The other objective was to reveal the biochemical mechanisms underlying genetic variations for pigs’ feed efficiency. In order to achieve these objectives, we firstly conducted a metabolite genome-wide association study (mGWAS) based on mixed linear models and found 152 genome-wide significant SNPs (P-value < 1.06E-06) in association with 17 metabolites that included 90 significant SNPs annotated to 52 genes. On chromosome one alone, 51 significant SNPs associated with isovalerylcarnitine and propionylcarnitine were found to be in strong linkage disequilibrium (LD). SNPs in strong LD annotated toFBXL4andCCNCconsisted of two haplotype blocks where three SNPs (ALGA0004000, ALGA0004041 and ALGA0004042) were in the intron regions ofFBXL4andCCNC. The interaction network revealed thatCCNCandFBXL4were linked by the hub geneN6AMT1that was associated with isovalerylcarnitine and propionylcarnitine. Moreover, three metabolites (i.e., isovalerylcarnitine, propionylcarnitine and pyruvic acid) were clustered in one group based on the low-high RFI pigs.This study performed a comprehensive metabolite-based GWAS analysis for pigs with differences in feed efficiency and provided significant metabolites for which there is a significant genetic variation as well as biological interaction networks. The identified metabolite genetic variants, genes and networks in high versus low feed efficient pigs could be considered as potential genetic or biomarkers for feed efficiency.
GeneDMRs: an R package for Gene-based Differentially Methylated Regions analysis
Authors: Wang Xiao , Hao Dan , Kadarmideen Haja N. 
Published: April 2020

AbstractDNA methylation in gene or promoter or gene body could restrict/promote the gene transcription. Moreover, methylation in the gene regions along with CpG island regions could modulate the transcription to undetectable gene expression levels. Therefore, it is necessary to investigate the methylation levels within the gene, gene body, CpG island regions and their overlapped regions and then identify the gene-based differentially methylated regions (GeneDMRs). Here, R packageGeneDMRsaims to facilitate computing gene based methylation rate using next generation sequencing (NGS)-based methylome data. The user-friendly R packageGeneDMRsis presented to analyze the methylation levels in each gene/promoter/exon/intron/CpG island/CpG island shore or each overlapped region (e.g., gene-CpG island/promoter-CpG island/exon-CpG island/intron-CpG island/gene-CpG island shore/promoter-CpG island shore/exon-CpG island shore/intron-CpG island shore). Here, we used the public reduced representation bisulfite sequencing (RRBS) data of mouse (GSE62392) for evaluating software and found novel biologically significant results to supplement the previous research. The R packageGeneDMRscan facilitate computing gene based methylation rate to interpret complex interplay between methylation levels and gene expression differences or similarities across physiological conditions or disease states.
lncRNA Mediated Hijacking of T-cell Hypoxia Response Pathway byMycobacterium tuberculosisPredicts Latent to Active Progression in Humans
Authors: Mehra Jyotsana , Kumar Vikram , Srivastava Priyansh , Sethi Tavpritesh 
Published: April 2020

AbstractCytosolic functions of Long non-coding RNAs including mRNA translation masking and sponging are major regulators of biological pathways. Formation of T cell-bounded hypoxic granuloma is a host immune defence for containing infected Mtb-macrophages. Our study exploits the mechanistic pathway of Mtb-induced HIF1A silencing by the antisense lncRNA-HIF1A-AS2 in T cells. Computational analysis of in-vitro T-cell stimulation assays in progressors (n=119) versus non-progressor (n=221) tuberculosis patients revealed the role of lncRNA mediated disruption of hypoxia adaptation pathways in progressors. We found 291 upregulated and 227 downregulated DE lncRNAs that were correlated at mRNA level with HIF1A and HILPDA which are major players in hypoxia response. We also report novel lncRNA-AC010655 (AC010655.4 and AC010655.2) in cis with HILPDA, both of which contain binding sites for the BARX2 transcription factor, thus indicating a mechanistic role. Detailed comparison of infection with antigenic stimulation showed a non-random enrichment of lncRNAs in the cytoplasmic fraction of the cell in TB progressors. The lack of this pattern in non-progressors replicates indicates the hijacking of the lncRNA dynamics by Mtb. The in-vitro manifestation of this response in the absence of granuloma indicates pre-programmed host-pathogen interaction between T-cells and Mtb regulated through lncRNAs, thus tipping this balance towards progression or containment of Mtb. Finally, we trained multiple machine learning classifiers for reliable prediction of latent to the active progression of patients, yielding a model to guide aggressive treatment.
Low tolerance for transcriptional variation at cohesin genes is accompanied by functional links to disease-relevant pathways
Authors: Schierding William , Horsfield Julia , O’Sullivan Justin 
Published: April 2020

AbstractVariants in DNA regulatory elements can alter the regulation of distant genes through spatial-regulatory connections. In humans, these spatial-regulatory connections are largely set during early development, when the cohesin complex plays an essential role in genome organisation and cell division. A full complement of the cohesin complex and its regulators is important for normal development, since heterozygous mutations in genes encoding these components are often sufficient to produce a disease phenotype. The implication that genes encoding the cohesin complex and cohesin regulators must be tightly controlled and resistant to variability in expression has not yet been formally tested. Here, we identify spatial-regulatory connections with potential to regulate expression of cohesin loci, including linking their expression to that of other genes. Connections that centre on the cohesin ring subunits (Mitotic: SMC1A, SMC3, STAG1, STAG2, RAD21/RAD21-AS; Meiotic: SMC1B, STAG3, REC8, RAD21L1), cohesin-ring support genes (NIPBL, MAU2, WAPL, PDS5A and PDS5B), and CTCF provide evidence of coordinated regulation that has little tolerance for perturbation. We identified transcriptional changes across a set of genes co-regulated with the cohesin loci that include biological pathways such as extracellular matrix production and proteasome-mediated protein degradation. Remarkably, many of the genes that are co-regulated with cohesin loci are themselves intolerant to loss-of-function. The results highlight the importance of robust regulation of cohesin genes, indicating novel pathways that may be important in the human cohesinopathy disorders.
Isolation, sequence, infectivity and replication kinetics of SARS-CoV-2
Authors: Banerjee Arinjay , Nasir Jalees A. , Budylowski Patrick , Yip Lily , Aftanas Patryk , Christie Natasha , Ghalami Ayoob , Baid Kaushal , Raphenya Amogelang R. , Hirota Jeremy A. , Miller Matthew S. , McGeer Allison J. , Ostrowski Mario , Kozak Robert A. , McArthur Andrew G. , Mossman Karen , Mubareka Samira 
Published: April 2020

ABSTRACTSARS-CoV-2 emerged in December 2019 in Wuhan, China and has since infected over 1.5 million people, of which over 107,000 have died. As SARS-CoV-2 spreads across the planet, speculations remain about the range of human cells that can be infected by SARS-CoV-2. In this study, we report the isolation of SARS-CoV-2 from two cases of COVID-19 in Toronto, Canada. We determined the genomic sequences of the two isolates and identified single nucleotide changes in representative populations of our virus stocks. More importantly, we tested a wide range of human immune cells for productive infection with SARS-CoV-2. Here we confirm that human primary peripheral blood mononuclear cells (PBMCs) are not permissive for SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor single nucleotide polymorphisms in the virus and to continue to isolate circulating viruses to determine viral genotype and phenotype usingin vitroandin vivoinfection models.