bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delineating the relationship between immune system aging and myogenesis in muscle repair
Authors: Tobin Stephanie W. , Alibhai Faisal J. , Wlodarek Lukasz , Yeganeh Azadeh , Millar Sean , Wu Jun , Li Shu-hong , Weisel Richard D. , Li Ren-Ke 
Published: March 2020

AbstractHow aging affects the communication between immune cells and myoblasts during myogenesis is unclear. We therefore investigated how aging impacts the cellular synchronization of these two processes after muscle injury. Muscles of old mice (20 months) had chronic inflammation and fewer satellite cells compared to young mice (3 months). After injury, young mice developed a robust, but transient inflammatory response and a stepwise myogenic gene expression program. These responses were impaired with age. Replacement of old bone marrow (BM) via heterochronic bone marrow transplantation (BMT) increased muscle mass and performance on locomotive and behavioural tests. After injury, Y-O BMT restored the immune cell and cytokine profiles to a young phenotype and enhanced satellite cell activity while O-O BMT amplified a late-onset proinflammatory response.In vitro,conditioned media from young or old macrophages had no effect or impaired myoblast proliferation, respectively. Thus, BM age negatively affects myogenesis by inhibiting myoblast proliferation.
The importance of species interactions in spatially explicit eco-evolutionary community dynamics under climate change
Authors: Åkesson Anna , Curtsdotter Alva , Eklöf Anna , Ebenman Bo , Norberg Jon , Barabás György 
Published: March 2020

AbstractEco-evolutionary dynamics are essential in shaping the biological response of communities to ongoing climate change. Here we develop a spatially explicit eco-evolutionary framework which integrates evolution, dispersal, and species interactions within and between trophic levels. This allows us to analyze how these processes interact to shape species- and community-level dynamics under climate change. Additionally, we incorporate the heretofore unexplored feature that species interactions themselves might change due to increasing temperatures and affect the impact of climate change on ecological communities. The new modeling framework captures previously reported ecological responses to climate change, and also reveals two new key results. First, interactions between trophic levels as well as temperature-dependent competition within a trophic level mitigate the negative impact of climate change on global biodiversity, emphasizing the importance of understanding biotic interactions in shaping climate change impact. Second, using a trait-based perspective, we found a strong negative relationship between the within-community variation in preferred temperatures and the capacity to respond to climate change. Communities resulting from different ecological interaction structures form distinct clusters along this relationship, but varying species’ abilities to disperse and adapt to new temperatures leave it unaffected.
N-glycosylation blocks and simultaneously fosters different receptor-ligand binding sites: the chameleonic CD44–hyaluronan interaction
Authors: Vuorio Joni , Škerlová Jana , Fábry Milan , Veverka Václav , Vattulainen Ilpo , Řezáčová Pavlína , Martinez-Seara Hector 
Published: March 2020

ABSTRACTWhile DNA encodes protein structure, glycans provide a complementary layer of information to protein function. As a prime example of the significance of glycans, the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan, is modulated by N-glycosylation. However, the details of this modulation remain unclear. Based on atomistic simulations and NMR, we provide evidence that CD44 has multiple distinct binding sites for hyaluronan, and that N-glycosylation modulates their respective roles. We find that non-glycosylated CD44 favors the canonical sub-micromolar binding site, while glycosylated CD44 binds hyaluronan with an entirely different micromolar binding site. Our findings show (for the first time) how glycosylation can alter receptor affinity by shielding specific regions of the host protein, thereby promoting weaker binding modes. The mechanism revealed in this work emphasizes the importance of glycosylation in protein function and poses a challenge for protein structure determination where glycosylation is usually neglected.
Genetic and behavioral adaptation ofCandida parapsilosisto the microbiome of hospitalized infants revealed byin situgenomics, transcriptomics and proteomics
Authors: West Patrick T. , Peters Samantha L. , Olm Matthew R. , Yu Feiqiao B. , Lou Yue Clare , Firek Brian A. , Baker Robyn , Johnson Alexander D. , Morowitz Michael J. , Hettich Robert L. , Banfield Jillian F. 
Published: March 2020

ABSTRACTCandida parapsilosisis a common cause of invasive candidiasis, especially in newborn infants, and infections have been increasing over the past two decades.C. parapsilosishas been primarily studied in pure culture, leaving gaps in understanding of its function in microbiome context. Here, we reconstructed five uniqueC. parapsilosisgenomes from premature infant fecal samples and analyzed their genome structure, population diversity andin situactivity relative to reference strains in pure culture. All five genomes contain hotspots of single nucleotide variants, some of which are shared by strains from multiple hospitals. A subset of environmental and hospital-derived genomes share variants within these hotspots suggesting derivation of that region from a common ancestor. Four of the newly reconstructedC. parapsilosisgenomes have four to sixteen copies of the gene RTA3, which encodes a lipid translocase and is implicated in antifungal resistance, potentially indicating adaptation to hospital antifungal use. Time course metatranscriptomics and metaproteomics on fecal samples from a premature infant with aC. parapsilosisblood infection revealed highly variablein situexpression patterns that are distinct from those of similar strains in pure cultures. For example, biofilm formation genes were relatively less expressedin situ, whereas genes linked to oxygen utilization were more highly expressed, indicative of growth in a relatively aerobic environment. In gut microbiome samples,C. parapsilosiscoexisted withEnterococcus faecalisthat shifted in relative abundance over time, accompanied by changes in bacterial and fungal gene expression and proteome composition. The results reveal potentially medically relevant differences in Candida function in gut vs. laboratory environments, and constrain evolutionary processes that could contribute to hospital strain persistence and transfer into premature infant microbiomes.
Environmentally Induced Sperm RNAs Transmit Cancer Susceptibility to Offspring in a Mouse Model
Authors: da Cruz Raquel Santana , Dominguez Odalys , Chen Elaine , Gonsiewski Alexandra K. , Nasir Apsra , Cruz M. Idalia , Zou Xiaojun , Galli Susana , Makambi Kepher , McCoy Matthew , Schmidt Marcel O. , Jin Lu , Peran Ivana , de Assis Sonia 
Published: March 2020

AbstractDNA sequence accounts for the majority of disease heritability, including cancer. Yet, not all familial cancer cases can be explained by genetic factors. It is becoming clear that environmentally induced epigenetic inheritance occurs and that the progeny’s traits can be shaped by parental environmental experiences. In humans, epidemiological studies have implicated environmental toxicants, such as the pesticide DDT, in intergenerational cancer development, including breast and childhood tumors. Here, we show that the female progeny of males exposed to DDT in the pre-conception period have higher susceptibility to developing aggressive tumors in mouse models of breast cancer. Sperm of DDT-exposed males exhibited distinct patterns of small non-coding RNAs, with an increase in miRNAs and a specific surge in miRNA-10b levels. Remarkably, embryonic injection of the entire sperm RNA load of DDT-exposed males, or synthetic miRNA-10b, recapitulated the tumor phenotypes observed in DDT offspring. Mechanistically, miR-10b injection altered the transcriptional profile in early embryos with enrichment of genes associated with cell differentiation, tissue and immune system development. In adult DDT-derived progeny, transcriptional and protein analysis of mammary tumors revealed alterations in stromal and in immune system compartments. Our findings reveal a causal role for sperm RNAs in environmentally induced inheritance of cancer predisposition and, if confirmed in humans, this could help partially explain some of the “missing heritability” of breast, and other, malignancies.
Direct evidence of abortive lytic infection-mediated establishment of Epstein-Barr virus latency during B-cell infection
Authors: Inagaki Tomoki , Sato Yoshitaka , Ito Jumpei , Takaki Mitsuaki , Okuno Yusuke , Yaguchi Masahiro , Al Masud H. M. Abdullah , Watanabe Takahiro , Sato Kei , Iwami Shingo , Murata Takayuki , Kimura Hiroshi 
Published: March 2020

AbstractViral infection induces dynamic changes in transcriptional profiles. Virus-induced and anti-viral responses are intertwined during the infection. Epstein-Barr virus (EBV) is a human gammaherpesvirus that provides a model of herpesvirus latency. To measure the transcriptome changes during the establishment of EBV latency, EBV-negative Akata cells were infected with EBV-EGFP and observed by transcriptome sequencing (RNA-seq) at 0, 2, 4, 7, 10, and 14 days after infection. We found transient downregulation of mitotic division-related genes, reflecting reprograming of cell growth by EBV. Moreover, a burst of viral lytic gene expression was detected in the early phase of infection. Experimental and mathematical investigations demonstrated that infectious virions were not produced in the pre-latent phase, suggesting the presence of an abortive lytic infection. Finally, we conducted fate mapping using recombinant EBV, enabling the noninvasive, continuous observation of infected cells during EBV infection. Our tracking analysis provided direct evidence that the abortive lytic infection in the pre-latent phase converges to latent infection during EBV infection of B-cells, shedding light on novel roles of viral lytic gene(s) in establishing latency.Author summaryViral infection is a complex process that activates both virus-triggered and host anti-viral responses. This process has classically been studied by snapshot analysis such as microarray and RNA-seq at discrete time points as population averages. Snapshot data lead to invaluable findings in host-pathogen interactions. However, these “snapshot” omics, even from a single cell, lack temporal resolution. Because the behavior of infected cells is highly dynamic and heterogenous, continuous analysis is required for deciphering the fate of infected cells during viral infection. Here, we exploited fate mapping techniques with recombinant Epstein-Barr virus (EBV) to track the infected cells and recorded a log of lytic gene expression during EBV infection. Our continuous observation of infected cells revealed that EBV established latency in B-cells via an abortive lytic infection in the pre-latent phase.
Atypical brain asymmetry in autism – a candidate for clinically meaningful stratification
Authors: Floris Dorothea L. , Wolfers Thomas , Zabihi Mariam , Holz Nathalie E. , Zwiers Marcel P. , Charman Tony , Tillmann Julian , Ecker Christine , Dell’Acqua Flavio , Banaschewski Tobias , Moessnang Carolin , Baron-Cohen Simon , Holt Rosemary , Durston Sarah , Loth Eva , Murphy Declan , Marquand Andre , Buitelaar Jan K. , Beckmann Christian F. ,   the EU-AIMS LEAP group
Published: March 2020

AbstractBackgroundAutism Spectrum Disorder (henceforth ‘autism’) is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, however its potential of lateralization as a neural stratification marker has not been widely examined.MethodsIn order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical (NT) controls as well as a replication dataset from ABIDE (513 autism, 691 NT) using a promising approach that moves beyond mean-group comparisons. We derived grey matter voxelwise laterality values for each subject and modelled individual deviations from the normative pattern of brain laterality across age using normative modeling.ResultsResults showed that individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language-, motor- and visuospatial regions, associated with symptom severity. Language delay (LD) explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged with individuals with autism with LD showing more pronounced rightward deviations than autism individuals without LD.ConclusionOur analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism, and indicate atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.
Transcriptional network analysis of transcriptomic diversity in resident tissue macrophages and dendritic cells in the mouse mononuclear phagocyte system
Authors: Summers Kim M. , Bush Stephen J. , Hume David A. 
Published: March 2020

AbstractThe mononuclear phagocyte system (MPS) is a family of cells including progenitors, circulating blood monocytes, resident tissue macrophages and dendritic cells (DC) present in every tissue in the body. To test the relationships between markers and transcriptomic diversity in the MPS, we collected from NCBI-GEO >500 quality RNA-seq datasets generated from mouse MPS cells isolated from multiple tissues. The primary data were randomly down-sized to a depth of 10 million reads and requantified. The resulting dataset was clustered using the network analysis toolGraphia. A sample-to-sample matrix revealed that MPS populations could be separated based upon tissue of origin. Cells identified as classical DC subsets, cDC1 and cDC2, and lackingFcgr1(CD64), were centrally-located within the MPS cluster and no more distinct than other MPS cell types. A gene-to-gene correlation matrix identified large generic co-expression clusters associated with MPS maturation and innate immune function. Smaller co-expression gene clusters including the transcription factors that drive them showed higher expression within defined isolated cells, including macrophages and DC from specific tissues. They include a cluster containingLyve1that implies a function in endothelial cell homeostasis, a cluster of transcripts enriched in intestinal macrophages and a generic cDC cluster associated withCcr7. However, transcripts encoding many other putative MPS subset markers includingAdgre1, Itgax, Itgam, Clec9a, Cd163, Mertk, RetnlaandH2-a/e(class II MHC) clustered idiosyncratically and were not correlated with underlying functions. The data provide no support for the concept of markers of M2 polarization or the specific adaptation of DC to present antigen to T cells. Co-expression of immediate early genes (e.g.Egr1, Fos, Dusp1) and inflammatory cytokines and chemokines (Tnf, Il1b, Ccl3/4) indicated that all tissue disaggregation protocols activate MPS cells. Tissue-specific expression clusters indicated that all cell isolation procedures also co-purify other unrelated cell types that may interact with MPS cellsin vivo. Comparative analysis of public RNA-seq and single cell RNA-seq data from the same lung cell populations showed that the extensive heterogeneity implied by the global cluster analysis may be even greater at a single cell level with few markers strongly correlated with each other. This analysis highlights the power of large datasets to identify the diversity of MPS cellular phenotypes, and the limited predictive value of surface markers to define lineages, functions or subpopulations.
Genome-wide locus sequence typing (GLST) of eukaryotic pathogens
Authors: Schwabl Philipp , Sánchez Jalil Maiguashca , Costales Jaime A. , Ocaña Sofía , Segovia Maikell , Carrasco Hernán J. , Hernández Carolina , Ramírez Juan David , Lewis Michael D. , Grijalva Mario J. , Llewellyn Martin S. 
Published: March 2020

AbstractAnalysis of genetic polymorphism is a powerful tool for epidemiological surveillance and research. Powerful inference from pathogen genetic variation, however, is often restrained by limited access to representative target DNA, especially in the study of obligate parasitic species for whichex vivoculture is resource-intensive or bias-prone. Modern sequence capture methods enable pathogen genetic variation to be analyzed directly from vector/host material but are often too complex and expensive for resource-poor settings where infectious diseases prevail. This study proposes a simple, cost-effective ‘genome-wide locus sequence typing’ (GLST) tool based on massive parallel amplification of information hotspots throughout the target pathogen genome. The multiplexed polymerase chain reaction amplifies hundreds of different, user-defined genetic targets in a single reaction tube, and subsequent agarose gel-based clean-up and barcoding completes library preparation at under 4 USD per sample. Approximately 100 libraries can be sequenced together in one Illumina MiSeq run. Our study generates a flexible GLST primer panel design workflow forTrypanosoma cruzi, the parasitic agent of Chagas disease. We successfully apply our 203-target GLST panel to direct, culture-free metagenomic extracts from triatomine vectors containing a minimum of 3.69 pg/μlT. cruziDNA and further elaborate on method performance by sequencing GLST libraries fromT. cruzireference clones representing discrete typing units (DTUs) TcI, TcIII, TcIV, and TcVI. The 780 SNP sites we identify in the sample set repeatably distinguish parasites infecting sympatric vectors and detect correlations between genetic and geographic distances at regional (< 150 km) as well as continental scales. The markers also clearly separate DTUs. We discuss the advantages, limitations and prospects of our method across a spectrum of epidemiological research.
Endosomal free fatty acid receptor 2 signaling is essential for propionate-induced anorectic gut hormone release
Authors: Caengprasath Natarin , Gonzalez-Abuin Noemi , Shchepinova Maria , Ma Yue , Inoue Asuka , Tate Edward W. , Frost Gary , Hanyaloglu Aylin C. 
Published: March 2020

SummaryThe ability of propionate, a short chain fatty acid produced from the fermentation of non-digestible carbohydrates in the colon, to stimulate the release of anorectic gut hormones, such as glucagon like peptide-1 (GLP-1), is an attractive approach to enhance appetite regulation, weight management and glycaemic control. Propionate induces GLP-1 release via its G protein-coupled receptor (GPCR), free fatty acid receptor 2 (FFA2); a GPCR that activates Gαi and Gαq/11 pathways. However, how pleiotropic GPCR signaling mechanisms in the gut regulates appetite is poorly understood. Here, we identify propionate-mediated G protein signaling is spatially directed within the cell via the targeting of FFA2 to very early endosomes. Furthermore, propionate activates an endosomal Gαi/p38 signaling pathway, which is essential for propionate-induced GLP-1 release in enteroendocrine cells and colonic crypts. Our study reveals that intestinal metabolites can engage membrane trafficking pathways and endosomal signaling platforms to orchestrate complex GPCR pathways within the gut.
Full-length genome sequence of segmented RNA virus from ticks was obtained using small RNA sequencing data
Authors: Xu Xiaofeng , Bei Jinlong , Xuan Yibo , Chen Jianyuan , Chen Defu , Barker Stephen C. , Kelava Samuel , He Bingjun , Gao Shan , Chen Ze 
Published: March 2020

AbstractIn 2014, A novel tick-borne virus of the genusFlaviviruswas first reported from the Mogiana region in Brazil. This virus was named the Mogiana tick virus (MGTV). Later, MGTV was also named as Jingmen tick virus (JMTV), Kindia tick virus (KDTV), Guangxi tick virus (GXTV) etc. In the present study, we used small RNA sequencing (sRNA-seq) to detect viruses in ticks and detected MGTV inAmblyomma testudinariumticks, which had been captured in Yunnan province of China in the year of 2016. The full-length genome sequence of a new MGTV strain Yunnan2016 (GenBank:MT080097,MT080098,MT080099andMT080100) was obtained and recommended to be included into the NCBI RefSeq database for the future studies of MGTV. Our phylogenetic analyses showed that viruses named MGTV, JMTV, KDTV and GXTV are monophyletic: the MGTV group (lineage) of viruses. We show, for the first time, that 5′ and 3′ sRNAs can be used to obtain full-length sequences of the 5’ and 3’ ends of, but not limited to genome sequences of RNA viruses. And we proved the feasibility of using the sRNA-seq based method for the detection of viruses in a sample containing miniscule RNA.
Chikungunya virus requires an intact microtubule network for efficient viral genome delivery
Authors: Hoornweg Tabitha E. , Bouma Ellen M. , van de Pol Denise P.I. , Rodenhuis-Zybert Izabela A. , Smit Jolanda M. 
Published: March 2020

AbstractChikungunya virus (CHIKV) is a re-emerging mosquito-borne virus, which has rapidly spread around the globe thereby causing millions of infections. CHIKV is an enveloped virus belonging to theTogaviridaefamily and enters its host cell primarily via clathrin-mediated endocytosis. Upon internalization, the endocytic vesicle containing the virus particle moves through the cell and delivers the virus to early endosomes where membrane fusion is observed. Thereafter, the nucleocapsid dissociates and the viral RNA is translated into proteins. In this study, we examined the importance of the microtubule network during the early steps of infection and dissected the intracellular trafficking behavior of CHIKV particles during cell entry. We observed two distinct CHIKV intracellular trafficking patterns prior to membrane hemifusion. Whereas half of the CHIKV virions remained static during cell entry and fused in the cell periphery, the other half showed fast-directed microtubule-dependent movement prior to delivery to Rab5-positive early endosomes and predominantly fused in the perinuclear region of the cell. Disruption of the microtubule network reduced the number of infected cells. At these conditions, membrane hemifusion activity was not affected yet fusion was restricted to the cell periphery. Furthermore, follow-up experiments revealed that disruption of the microtubule network impairs the delivery of the viral genome to the cell cytosol. We therefore hypothesize that microtubules may direct the particle to a cellular location that is beneficial for establishing infection or aids in nucleocapsid uncoating.Author SummaryChikungunya virus (CHIKV) is an alphavirus that is transmitted to humans by infected mosquitoes. Disease symptoms can include fever, rash, myalgia, and long-lasting debilitating joint pains. Unfortunately, there is currently no licensed vaccine or antiviral treatment available to combat CHIKV. Understanding the virus:host interactions during the replication cycle of the virus is crucial for the development of effective antiviral therapies. In this study we elucidated the trafficking behavior of CHIKV particles early in infection. During cell entry, CHIKV virions require an intact microtubule network for efficient delivery of the viral genome into the host cell thereby increasing the chance to productively infect a cell.