bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative abundance and diversity of populations of thePseudomonas syringaeand Soft RotPectobacteriaceaespecies complexes throughout the Durance River catchment from its French Alps sources to its delta
Authors: Morris C.E. , Lacroix C. , Chandeysson C. , Guilbaud C. , Monteil C. , Piry S. , Newall E. Rochelle , Fiorini S. , Van Gijsegem F. , Barny M.A. , Berge O. 
Published: September 2022

ABSTRACTRivers, creeks, streams are integrators of biological, chemical and physical processes occurring in a catchment linking land cover from the headwaters to the outlet. The dynamics of human and animal pathogens in catchments have been widely studied in a large variety of contexts allowing the optimization of disease risk reduction. In parallel, there is an emerging awareness that crop pathogens might also be disseminated via surface waters especially when they are used for irrigation. However, there are no studies on the extent to which potential plant pathogens are present – nor about their dynamics - along the full course of a catchment. Here we have compared the seasonal dynamics of populations of thePseudomonas syringae(Psy) and the Soft RotPectobacteriaceae(SRP) species complexes along a 270 km stretch of the Durance River from the upstream alpine reaches to the downstream agricultural production areas at the confluence with the Rhone River at Avignon. Among 168 samples collected at 21 sites in fall, winter, spring and summer of 2016 and 2017, Psy strains were detected at all sampling sites and in 156 of the samples at population densities up to 105bacteria L−1. In contrast, SRP strains were detected in 98 of the samples, mostly from the southern part of the river, at population densities that did not exceed 3 × 104bacteria L−1. Among the biological and chemical parameters that were characterized at each sampling site, temperature was the only factor that explained a significant amount of the variability in population size for both species complexes. Psy densities decreased with increasing temperature whereas SRP densities increased with increasing temperature. River-borne populations of SRP were composed mainly ofPectobacterium versatileandP. aquaticumthat have little known epidemiological importance. Only a few strains ofPectobacteriumandDickeyaspecies reputed for their epidemiological impact were observed. In contrast, Psy populations at all sites were dominated by a genetic lineage of phylogroup 2 known from other studies for its broad host range and its geographic and habitat ubiquity. Our observations suggest that surveillance of river water for SRP could be leveraged to signal diagnostic and management reactions to avoid disease outbreaks. In contrast, the constant presence of Psy throughout the catchment in absence of regular and widespread disease outbreaks due to this group of bacteria suggests that surveillance should focus on future changes in land use, river water conditions and agronomic practices that could destabilize the mechanisms currently holding Psy outbreaks in check.
Initial niche condition determines the aging speed and regenerative activity of quiescent cells
Authors: Liu Qi , Sheng Nan , Zhang Zhiwen , He Chenjun , Zhao Yao , Sun Haoyuan , Chen Jianguo , Yang Xiaojing , Tang Chao 
Published: September 2022

SUMMARYQuiescent cell ages with decline in both the survivability and regenerative activity. While most cellular quiescence/ageing research have focused on the survivability and from the population level, the question how the regenerative activity change with the quiescence time (i.e., chronological age) has rarely been addressed quantitatively. In this work, we systematically measured both features in ageing quiescent fission yeast cells at single cell level. We found that the regenerative activity declines linearly before survivability decline and the cellular chronological ageing speed is predetermined by the initial niche condition. Moreover, this linear ageing behavior is robust under various niche conditions and follows a common ageing trajectory in terms of gene expression. Furthermore, initial calorie restriction was found to improve not only the survivability but also the later regenerative activity. Our results reveal a continuous diverse spectrum of quiescence depth and ageing plasticity.
Inferring local molecular dynamics from the global actin network structure: a case study of 2D synthetic branching actin networks
Authors: Rostami Minghao W. , Bannish Brittany E. , Gasior Kelsey , Pinals Rebecca L. , Copos Calina , Dawes Adriana T. 
Published: September 2022

AbstractCells rely on their cytoskeleton for key processes including division and directed motility. Actin filaments are a primary constituent of the cytoskeleton. Although actin filaments can create a variety of network architectures linked to distinct cell functions, the microscale molecular interactions that give rise to these macroscale structures are not well understood. In this work, we investigate the microscale mechanisms that produce different branched actin network structures using an iterative classification approach. First, we employ a simple yet comprehensive agent-based model that produces synthetic actin networks with precise control over the microscale dynamics. Then we apply machine learning techniques to classify actin networks based on measurable network density and geometry, identifying key mechanistic processes that lead to particular branched actin network architectures. Extensive computational experiments reveal that the most accurate method uses a combination of supervised learning based on network density and unsupervised learning based on network symmetry. This framework can potentially serve as a powerful tool to discover the molecular interactions that produce the wide variety of actin network configurations associated with normal development as well as pathological conditions such as cancer.
Fusion-negative Rhabdomyosarcoma 3D-organoids as an innovative model to predict resistance to cell death inducers
Authors: Savary Clara , Huchedé Paul , Luciana Léa , Tourbez Arthur , Deligne Clémence , Picard Cécile , Diot Thomas , Coquet Claire , Meynard Nina , Grand Marion Le , Tonon Laurie , Gadot Nicolas , Degletagne Cyril , Léon Sophie , Attignon Valéry , Bomane Alexandra , Rochet Isabelle , Müller Kevin , Mournetas Virginie , Bergeron Christophe , Rinaudo Paul , Dutour Aurélie , Cordier-Bussat Martine , Dijoud Frédérique , Corradini Nadège , Maucort-Boulch Delphine , Pasquier Eddy , Blay Jean-Yves , Castets Marie , Broutier Laura 
Published: September 2022

AbstractRhabdomyosarcoma (RMS) is the main form of soft-tissue sarcoma in children and adolescents. For 20 years, and despite international clinical trials, its cure rate has not really improved, and remains stuck at 20% in case of relapse. The definition of new effective therapeutic combinations is hampered by the lack of reliable models, which complicate the transposition of promising results obtained in pre-clinical studies into efficient solutions for young patients. Inter-patient heterogeneity, particularly in the so-called fusion-negative group (FNRMS), adds an additional level of difficulty in optimizing the clinical management of children and adolescents with RMS.Here, we describe an original 3D-organoid model derived from relapsed FNRMS and show that it finely mimics the characteristics of the original tumor, including inter- and intra-tumoral heterogeneity. Moreover, we have established the proof-of-concept of their preclinical potential by re-evaluating the therapeutic opportunities of targeting apoptosis in FNRMS from a streamlined approach based on the exploitation of bulk and single-cell omics data.
Heritability enrichment in context-specific regulatory networks improves phenotype-relevant tissue identification
Authors: Feng Zhanying , Duren Zhana , Xin Jingxue , Yuan Qiuyue , He Yaoxi , Su Bing , Wong Wing Hung , Wang Yong 
Published: September 2022

AbstractSystems genetics holds the promise to decipher complex traits by interpreting their associated SNPs through gene regulatory networks derived from comprehensive multi-omics data of cell types, tissues, and organs. Here, we propose SpecVar to integrate paired chromatin accessibility and gene expression data into context-specific regulatory network atlas and regulatory categories, conduct heritability enrichment analysis with GWAS summary statistics, identify relevant tissues, and depict shared heritability and regulations by relevance correlation. Our method improves power upon existing approaches by associating SNPs with context-specific regulatory elements to assess heritability enrichments and by explicitly prioritizing gene regulations underlying relevant tissues. Experiments on GWAS of six phenotypes show that SpecVar can improve heritability enrichment, accurately detect relevant tissues, and reveal causal regulations. Furthermore, SpecVar correlates the relevance patterns for pairs of phenotypes and better reveals shared heritability and regulations of phenotypes than existing methods. Studying GWAS of 206 phenotypes in UK-Biobank demonstrates that SpecVar leverages the context-specific regulatory network atlas to prioritize phenotypes’ relevant tissues and shared heritability for biological and therapeutic insights. SpecVar provides a powerful way to interpret SNPs via context-specific regulatory networks and is available at https://github.com/AMSSwanglab/SpecVar.
Coordinated and distinct LD-transpeptidase-independent roles of peptidoglycan carboxypeptidases DacC and DacA in stress adaptation and cell shape maintenance
Authors: Choi Umji , Park Si Hyoung , Lee Han Byeol , Lee Chang-Ro 
Published: September 2022

AbstractPeptidoglycan (PG) is an essential bacterial architecture pivotal for shape maintenance and adaptation to osmotic stress. Although PG synthesis and modification are tightly regulated under harsh environmental stresses, few related mechanisms have been investigated. In this study, we aimed to investigate the coordinated and distinct roles of the PG carboxypeptidases DacC and DacA, in adaptation to alkaline and salt stresses and shape maintenance in Escherichia coli. We found that DacC is an alkaline PG carboxypeptidase, whose enzyme activity and protein stability are significantly enhanced under alkaline stress. Both DacC and DacA were required for bacterial growth under alkaline stress, whereas only DacA was required for the adaptation to salt stress. Under normal growth conditions, only DacA was necessary for cell shape maintenance, while under alkaline stress conditions, both DacA and DacC were necessary for cell shape maintenance, but their roles were distinct. Notably, all these roles of DacC and DacA were independent of LD-transpeptidases, which are necessary for the formation of PG 3-3 crosslinks and covalent bonds between PG and the outer membrane lipoprotein Lpp. Instead, DacC and DacA interacted with penicillin-binding proteins (PBPs), DD-transpeptidases, mostly in a C-terminal domain-dependent manner, and these interactions were necessary for most of their roles. Collectively, our results demonstrate the coordinated and distinct novel roles of PG carboxypeptidases in stress adaptation and shape maintenance and provide novel insights into the cellular functions of PG carboxypeptidases associated with PBPs.
Comparing the signaling and transcriptome profiling landscapes of human iPSC-derived and primary rat neonatal cardiomyocytes
Authors: Bourque Kyla , Jones-Tabah Jace , Pétrin Darlaine , Martin Ryan D. , Hébert Terence E. 
Published: September 2022

AbstractThe inaccessibility of human cardiomyocytes significantly hindered years of cardiovascular research efforts. Post-mortem tissue or biopsies from diseased patients, which remain scarcely available, rendered it possible to study end-stage heart disease yet the inclusion of healthy human cardiac materials for basic science research was beyond reach. To overcome these limitations, non-human cell sources were used as proxies to study heart function and associated diseases. Rodent models became increasingly acceptable surrogates to model the human heart either in vivo or through in vitro cultures. More recently, due to concerns regarding animal to human translation, including cross-species differences, the use of human inducible stem cell derived cardiomyocytes presented a renewed opportunity. We think it necessary to conduct a comparative study, assessing cellular signalling through cardiac G protein-coupled receptors and bulk transcriptomics of traditional rat neonatal cardiomyocytes and human iPSC-CMs. Genetically-encoded biosensors were used to interrogate nuclear protein kinase A (PKA) and extracellular signal-regulated kinase 1/ 2 (ERK1/2) in rat and human-derived cardiomyocyte populations. To increase data granularity, a single-cell analytical approach was conducted for an in-depth examination of existing differences between both in vitro cardiomyocyte models. Using automated high content microscopy, our analyses of nuclear PKA and ERK1/2 signaling revealed distinct response clusters in rat and human CMs. In line with this, bulk RNA-seq demonstrated key differences regarding the expression patterns of GPCRs, G proteins and effectors. Overall, our study demonstrates that human stem cell derived models of the cardiomyocyte do provide significant advantages and should be taken advantage of.
Omicron-induced interferon signalling prevents influenza A virus infection
Authors: Bojkova Denisa , Bechtel Marco , Rothenburger Tamara , Kandler Joshua D. , Hayes Lauren , Olmer Ruth , Ulrich Martin , Jonigk Danny , Ciesek Sandra , Wass Mark N. , Michaelis Martin , Cinatl Jindrich 
Published: September 2022

AbstractRecent findings in permanent cell lines suggested that SARS-CoV-2 Omicron BA.1 induces a stronger interferon response than Delta. Here, we show that BA.1 and BA.5 but not Delta induce an antiviral state in air-liquid interface (ALI) cultures of primary human bronchial epithelial (HBE) cells and primary human monocytes. Both Omicron subvariants caused the production of biologically active type I (α/β) and III (λ) interferons and protected cells from super-infection with influenza A viruses. Notably, abortive Omicron infection of monocytes was sufficient to protect monocytes from influenza A virus infection. Interestingly, while influenza-like illnesses surged during the Delta wave in England, their spread rapidly declined upon the emergence of Omicron. Mechanistically, Omicron-induced interferon signalling was mediated via double-stranded RNA recognition by MDA5, as MDA5 knock-out prevented it. The JAK/ STAT inhibitor baricitinib inhibited the Omicron-mediated antiviral response, suggesting it is caused by MDA5-mediated interferon production, which activates interferon receptors that then trigger JAK/ STAT signalling. In conclusion, our study 1) demonstrates that only Omicron but not Delta induces a substantial interferon response in physiologically relevant models, 2) shows that Omicron infection protects cells from influenza A virus super-infection, and 3) indicates that BA.1 and BA.5 induce comparable antiviral states.
A novel cancer-associated cassette exon in TLN1 alters Talin 1 mechanosensitivity
Authors: Gallego-Paez Lina M. , Edwards William J.S. , Guo Yanyu , Chanduri Manasa , Koorman Thijs , Lee Chieh-Yu , Grexa Nina , Derksen Patrick W. B. , Yan Jie , Schwartz Martin A. , Mauer Jan , Goult Benjamin T. 
Published: September 2022

AbstractTalin 1 is the core mechanosensitive adapter protein linking integrins to the cytoskeleton. The TLN1 gene is comprised of 57 exons that encode the 2541 amino acid TLN1 protein. TLN1 was previously considered to be expressed as a single isoform. However, through differential pre-mRNA splicing analysis, we discovered a cancer-enriched, non-annotated 51-nucleotide exon in TLN1 between exons 17 and 18, which we refer to as exon 17b. TLN1 is comprised of an N-terminal FERM domain, linked to 13 force-dependent switch domains, R1-R13. Inclusion of exon 17b results in an in-frame insertion of 17 amino acids immediately after Gln665 in the region between R1-R2 which lowers the force required to open the R1-R2 switches potentially altering downstream mechanotransduction. Biochemical analysis of this isoform revealed enhanced vinculin binding, and cells expressing this variant show altered adhesion dynamics. Finally, we show that the TGF-β/SMAD3 signaling pathway regulates this isoform switch. Future studies will need to consider the balance of these two TLN1 isoforms.
Evaluation of noninvasive biospecimens for transcriptome studies
Authors: Martorella Molly , Kasela Silva , Garcia-Flores Renee , Gokden Alper , Castel Stephane E. , Lappalainen Tuuli 
Published: September 2022

ABSTRACTTranscriptome studies disentangle functional mechanisms of gene expression regulation and may elucidate the underlying biology of disease processes. However, the types of tissues currently collected typically assay a single post-mortem timepoint or are limited to investigating cell types found in blood. Noninvasive tissues may improve disease-relevant discovery by enabling more complex longitudinal study designs, by capturing different and potentially more applicable cell types, and by increasing sample sizes due to reduced collection costs and possible higher enrollment from vulnerable populations. Here, we develop methods for sampling noninvasive biospecimens, investigate their performance across commercial and in-house library preparations, characterize their biology, and assess the feasibility of using noninvasive tissues in a multitude of transcriptomic applications. We collected buccal swabs, hair follicles, saliva, and urine cell pellets from 19 individuals over three to four timepoints, for a total of 300 unique biological samples, which we then prepared with replicates across three library preparations, for a final tally of 472 transcriptomes. Of the four tissues we studied, we found hair follicles and urine cell pellets to be most promising due to the consistency of sample quality, the cell types and expression profiles we observed, and their performance in disease-relevant applications. This is the first study to thoroughly delineate biological and technical features of noninvasive samples and demonstrate their use in a wide array of transcriptomic and clinical analyses. We anticipate future use of these biospecimens will facilitate discovery and development of clinical applications.
Climate change has affected the spillover risk of bat-borne pathogens
Authors: Van de Vuurst P , Qiao H , Soler-Tovar D , Escobar LE 
Published: September 2022

AbstractBat-borne viruses are a threat to global health and have in recent history had major impacts to human morbidity and mortality. Examples include diseases such as rabies, Ebola, SARS-Cov-1, and SARS-Cov-2 (COVID-19). Climate change could exacerbate the emergence of bat-borne pathogens by affecting the distribution and abundance of bats in tropical ecosystems. Here we report an assessment of historical climate and vampire bat occurrence data for the last century, which revealed a relationship between climatic variation and risk of disease spillover triggered by changes in bat distributions. This report represents one of the first examples of empirical evidence of global change effects on continental patterns of bat-borne pathogen transmission risk. We therefore recommend that more research is necessary on the impacts of climate change on bat-borne pathogen spillover risk, and that climate change impacts on bat-borne disease should be considered in global security initiatives.HighlightsBat-borne viruses are a threat to global health and include diseases such as rabies, Ebola, SARS-Cov-1, and SARS-Cov-2 (COVID-19).Climate change could exacerbate the emergence of bat-borne pathogens by affecting the distribution and abundance of bats.Here we report an assessment of historical climate and vampire-bat occurrence data for the last century, which reveals a relationship between climatic variation and risk of disease spillover triggered by changes in bat distributions.
Deregulations of miR-1 and its target Multiplexin promote dilated cardiomyopathy associated with myotonic dystrophy type 1
Authors: Souidi Anissa , Nakamori Masayuki , Zmojdzian Monika , Jagla Teresa , Renaud Yoan , Jagla Krzysztof 
Published: September 2022

AbstractMyotonic dystrophy type 1 (DM1) is the most common muscular dystrophy. It is caused by the excessive expansion of non-coding CTG repeat, which when transcribed affect functions of RNA-binding factors. Specifically, MBNL1 is sequestered in nuclear foci while CELF1 is stabilised, with adverse effects on alternative splicing, processing and stability of a large set of muscular and cardiac transcripts. Among these effects, inefficient processing and down-regulation of muscle- and heart-specific miRNA, miR-1, has been reported in DM1 patients, but the impact of reduced miR-1 on DM1 pathogenesis was unknown. Here, we used Drosophila DM1 models to explore miR-1 involvement in cardiac dysfunction in DM1. We found that miR-1 down-regulation in the heart led to dilated cardiomyopathy (DCM), a DM1-associated phenotype. We then combined in silico screening for miR-1 targets with transcriptional profiling of DM1 cardiac cells to identify miR-1 target genes with potential roles in DCM. We identified Multiplexin (Mp) as a new cardiac miR-1 target involved in DM1. Mp and its human ortholog Col15A1 were both highly enriched in cardiac cells of DCM-developing DM1 flies and in heart samples from DM1 patients with DCM, respectively. Importantly, when overexpressed in the heart, Mp induced DCM, whereas its attenuation ameliorated the DCM phenotype in aged DM1 flies. Reduced levels of miR-1 and consecutive up-regulation of its target Mp/Col15A1 are thus critical in DM1-associated DCM.
One-step generation of a conditional allele in mice using a short artificial intron
Authors: Cassidy Annelise M , Thomas Destinée B , Kuliyev Emin , Chen Hanying , Pelletier Stephane 
Published: September 2022

AbstractDespite tremendous advances in genome editing technologies, generation of conditional alleles in mice has remained challenging. Recent studies in cells have successfully made use of short artificial introns to engineer conditional alleles. The approach consists of inserting intronic sequences flanked by two loxP sites within an exon of a gene using CRISPR-Cas9 technology. Under normal conditions, the artificial intron is removed by the splicing machinery, allowing for expression of the gene product. Following Cre-mediated recombination of the two loxP sites, the intron is disabled, and splicing can no longer occur. The remaining intronic sequences create a frameshift and early translational termination. Here we describe the application of this technology to engineer conditional alleles in mice using Scyl1 as a model gene. Insertion of the cassette occurred in 17% of edited mice obtained from pronuclear stage zygote microinjection. Mice homozygous for the insertion expressed SCYL1 at levels comparable to wild-type mice and showed no overt abnormalities associated with the loss of Scyl1 function, indicating the proper removal of the artificial intron. Deletion of the cassette via Cre-mediated recombination in vivo occurred at high frequency, abrogated SCYL1 protein expression, and resulted in loss-of-function phenotypes. Our results broaden the applicability of this approach to engineering conditional alleles in mice.