bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small-RNA sequencing reveals altered skeletal muscle microRNAs and snoRNAs signatures in weanling male offspring from mouse dams fed a low protein diet during lactation
Authors: Kanakis Ioannis , Alameddine Moussira , Folkes Leighton , Moxon Simon , Myrtziou Ioanna , Ozanne Susan E. , Peffers Mandy J. , Goljanek-Whysall Katarzyna , Vasilaki Aphrodite 
Published: February 2021

ABSTRACTNutrition plays a key role in pre- and postnatal growth of the musculoskeletal system. Maternal diet during gestation and lactation affects the development of skeletal muscles in the offspring and determines muscle health in later life, however, the molecular mechanisms that govern these effects are largely unknown. In this study, we aim to describe the association between maternal low protein diet-induced changes in offspring skeletal muscle and the differential expression (DE) of small non-coding RNAs (sncRNAs). We used a mouse model of maternal protein restriction to characterise the impact of early-life undernutrition on skeletal muscle morphology in male offspring at weaning. Mouse dams were fed either a normal (N, 20%) or a low protein (L, 8%) diet during gestation and newborn pups were cross-fostered to N or L lactating dams, resulting in the generation of NN, NL and LN offspring groups. Total body and tibialis anterior (TA) weights were decreased in NL males but not different in the LN group, as compared to NN, although neonates from low protein fed dams were smaller at birth than those born to dams fed a normal protein. However, histological evaluation of TA muscle revealed reduced muscle fibre size in both groups at the end of lactation. Small RNA-seq analysis demonstrated DE of multiple classes of sncRNAs, including miRs, snoRNAs and snRNAs. Bioinformatic analyses of miRs-15a, −34a, −122 and −199a, in combination with known myomiRs, confirmed their implication in key muscle-specific biological processes and cellular functions and suggest a promising set of miRs in muscle physiology studies. To our knowledge, this is the first comprehensive report for the DE of sncRNAs in nutrition-associated programming of skeletal muscle development, highlighting the need for further research.
Genetic mapping and identification of a QTL determining tolerance to freezing stress inFragaria vescaL.
Authors: Davik Jahn , Wilson Robert C. , Njah Relindis G. , Grini Paul E. , Randall Stephen K. , Alsheik Muath K. , Sargent Daniel James 
Published: February 2021

AbstractExtreme cold and frost cause significant stress to plants which can potentially be lethal. Low temperature freezing stress can cause significant and irreversible damage to plant cells and can induce physiological and metabolic changes that impact on growth and development. Low temperatures cause physiological responses including winter dormancy and autumn cold hardening in strawberry (Fragaria) species, and some diploidF. vescaaccessions have been shown to have adapted to low-temperature stresses. To study the genetics of freezing tolerance, aF. vescamapping population of 142 seedlings segregating for differential responses to freezing stress was raised. The progeny was mapped using ‘Genotyping-by-Sequencing’ and a linkage map of 2,918 markers at 851 loci was resolved. The mapping population was phenotyped for freezing tolerance response under controlled and replicated laboratory conditions and subsequent quantitative trait loci analysis using interval mapping revealed a single significant quantitative trait locus onFvb2in the physical interval 10.6 Mb and 15.73 Mb on theF. vescav4.0 genome sequence. This physical interval contained 896 predicted genes, several of which had putative roles associated with tolerance to abiotic stresses including freezing. Differential expression analysis of the 896 QTL-associated gene predictions in the leaves and crowns from ‘Alta’ and ‘NCGR1363’ parental genotypes revealed genotype-specific changes in transcript accumulation in response to low temperature treatment as well as expression differences between genotypes prior to treatment for many of the genes. The putative roles, and significant interparental differential expression levels of several of the genes reported here identified them as good candidates for the control of the effects of freezing tolerance at the QTL identified in this investigation and the possible role of these candidate genes in response to freezing stress is discussed.
Epigenetic rewriting at centromeric DNA repeats leads to increased chromatin accessibility and chromosomal instability
Authors: Decombe Sheldon , Loll François , Caccianini Laura , Affannoukoué Kévin , Izeddin Ignacio , Mozziconacci Julien , Escudé Christophe , Lopes Judith 
Published: February 2021

AbstractCentromeric regions of human chromosomes contain large numbers of tandemly repeated α-satellite sequences. These sequences are covered with constitutive heterochromatin which is enriched in trimethylation of histone H3 on lysine 9 (H3K9me3). Although well studied using artificial chromosomes and global perturbations, the contribution of this epigenetic mark to chromatin structure and genome stability remains poorly known in a more natural context. Using transcriptional activator-like effectors (TALEs) fused to a histone lysine demethylase (JMJD2B), we were able to reduce the level of H3K9me3 on the α-satellites repeats of human chromosome 7. We show that the removal of H3K9me3 affects chromatin structure by increasing the accessibility of DNA repeats to the TALE protein. Tethering TALE-demethylase to centromeric repeats impairs the recruitment of HP1α and proteins of Chromosomal Passenger Complex (CPC) on this specific centromere. Finally, the epigenetic re-writing by the TALE-JMJD2B affects specifically the stability of chromosome 7 upon mitosis, highlighting the importance of H3K9me3 in centromere integrity and chromosome stability, mediated by the recruitment of HP1α and the CPC.
Trends in community- and nosocomial-acquired infections of carbapenem resistant Enterobacteriaceae (CRE), carbapenemase producing Enterobacteriaceae (CPE) and vancomycin resistant Enterococcus (VRE): a 10-year prospective observational study
Authors: Ubillus Arriola Gloria Maritza , Araujo Banchon William , Patiño Gabriel Lilian , Kolevic Lenka , del Carmen Quispe Manco María , Olivo Lopez José María , Barrientos Achata Armando , Revilla Velasquez Maria Elena , Bouzid Donia , Casalino Enrique 
Published: February 2021

AbstractIntroductionCRE, CPE, and VRE are considered significant threats to public health.AimTo determine trends of nosocomial- and community-acquired infections.MethodsA 10-year prospective observational non-interventional study was conducted. We used time-series analysis to evaluate trends in infections number.FindingsInfection rate (%) were: CRE 2.48 (261/10,533), CPE 1.66 (175/10,533) and VRE 15.9 (121/761). We found diminishing trends for CRE (−19% [−31;−5], P=.03) and CPE (−22% [−30;−8], P=.04) but increasing trend for VRE (+48; [CI95% 34;75], P=.001). While we found decreasing trends for CRE and CPE in emergency (−71 [−122;−25], P=.001; −45 [−92;−27], P=.001) and hospitalization (−127 [−159; −85], P=.001; −56 [−98;−216], P=.01), we found increasing trends for VRE (+148 [113;192], P=.00001; +108[65;152], P=.003). Nosocomial-infections fell in CRE (−238 [−183;−316], P=.0001) and CPE (−163 [−96; −208], P=.001), but rose in VRE (+196 [151;242], P=.0001). We showed increasing trends in ambulatory and community-acquired infections in CRE (+134% [96;189]; P=.001; +77% [52;89]; P= .002), CPE (+288 [226;343]; P=.0001; +21% [−12;46]; P=.0.08) and VRE (+348 [295;458]; P=.0001; +66% [41;83]; P=.003). Direct admitted trends rose in all groups (CRE 16% [−8; 42]; P=.05), CPE 23% [−6; 48] (P=.05) and VRE (+241 [188; 301]; P=.0001).ConclusionsWe found a changing infection pattern with decreasing trends in in-hospital settings and nosocomial-acquired infections but increasing ambulatory and community-acquired infections. The observed increasing-trends in direct-admitted could be explained by community-onset infections diagnosed in the hospital. Our findings highlight the need to identify CRE/CPE/VRE community-acquired infections in ambulatory and in-hospital settings.
Analysing variations in pelage patterning among EuropeanFelis silvestris silvestrispopulations
Authors: Reher David , Stefen Clara 
Published: February 2021

AbstractThe pelage pattern of wildcats from six regions within the distribution range of the species is analysed to test the hypothesis that clear differences between different regions exist. In total, 98 furs were used, but with different distribution from the Eifel (Germany), Harz Mountains (Germany), Caucasus, Western Spain, Switzerland/France and Greece. Specimens were at least seven months old, sex was not considered. The characteristics used were adapted from the literature and included typical wildcat features like the tail and stripes on the neck. Polychoric correlations, as a binary version of Spearman’s rank correlation coefficient, were used as a measure of correlation between pelage characteristics. Pairwise tetrachoric correlations were computed with R 3.1.2., cluster analyses were conducted with SPSS 14.No clear relationship between the pelage characteristics and the geographic distribution of the six studied wildcat populations were found, the hypothesis needs to be rejected. It is however suggested, that coat patterning of Caucasian wildcats to some degree differ from other European wildcat. The results, however, do not clearly corroborate this hypothesis as Caucasian wildcats were not grouped into closed clusters in all the cluster analyses. To a lesser extent, pelage characteristic differences may also exist between wildcats from Western Spain as well as South-Western Greece and other European regions, but the samples are too small to draw conclusions. To test these refined hypotheses, more specimens from the Caucasus, Western Spain and South-Western Greece (but also Switzerland/North-Eastern France) need to be collected and compared according to our protocol.
Dual proteomics ofDrosophila melanogasterhemolymph infected with the heritable endosymbiontSpiroplasma poulsonii
Authors: Masson Florent , Rommelaere Samuel , Marra Alice , Schüpfer Fanny , Lemaitre Bruno 
Published: February 2021

AbstractInsects are frequently infected with heritable bacterial endosymbionts. Endosymbionts have a dramatic impact on their host physiology and evolution. Their tissue distribution is variable with some species being housed intracellularly, some extracellularly and some having a mixed lifestyle. The impact of extracellular endosymbionts on the biofluids they colonize (e.g. insect hemolymph) is however difficult to appreciate because biofluids composition can depend on the contribution of numerous tissues.Here we address the question ofDrosophilahemolymph proteome response to the infection with the endosymbiontSpiroplasma poulsonii. S. poulsoniiinhabits the fly hemolymph and gets vertically transmitted over generations by hijacking the oogenesis in females. Using dual proteomics on infected hemolymph, we uncovered a low level and chronic activation of the Toll immune pathway byS. poulsoniithat was previously undetected by transcriptomics-based approaches. Using Drosophila genetics, we also identified candidate proteins putatively involved in controllingS. poulsoniigrowth. Last, we also provide a deep proteome ofS. poulsonii, which, in combination with previously published transcriptomics data, improves our understanding of the post-transcriptional regulations operating in this bacterium.Summary statementWe report the changes inDrosophila melanogasterhemolymph proteome upon infection with the heritable bacterial endosymbiontSpiroplasma poulsonii.
Hierarchical cross-scale analysis identifies parallel ventral striatal networks coding for dynamic and stabilized olfactory reward predictions
Authors: Winkelmeier Laurens , Filosa Carla , Scheller Max , Hartig Renée , Sack Markus , Becker Robert , Wolf David , Reinwald Jonathan , Gerchen Martin Fungisai , Sartorius Alexander , Meyer-Lindenberg Andreas , Weber-Fahr Wolfgang , von Hohenberg Christian Clemm , Russo Eleonora , Kelsch Wolfgang 
Published: February 2021

SUMMARYThe unbiased identification of brain circuits responsible for behavior and their local cellular computations is a challenge for neuroscience. We establish here a hierarchical cross-scale approach from behavioral modeling and fMRI in task-performing mice to cellular network dynamics to identify how reward predictions are represented in the forebrain upon olfactory conditioning. fMRI identified functional segregation in reward prediction and error computations among olfactory cortices and subcortical circuits. Among them, the olfactory tubercle contributed both to dynamic reward predictions and prediction error. In this region, cellular recordings revealed two parallel neuronal populations for prediction coding. One population produced stabilized predictions as distributed stimulus-bound transient network activity; the other evolved during anticipatory waiting and fully reflected predicted value in single-units, dynamically integrating the recent cue-specific history of uncertain outcomes. Thus, the cross-scale approach revealed regional functional differentiation among the distributed forebrain circuits with a limbic hotspot for multiple non-redundant reward prediction coding.
Mutational sources oftrans-regulatory variation affecting gene expression inSaccharomyces cerevisiae
Authors: Duveau Fabien , Zande Petra Vande , Metzger Brian P. H. , Diaz Crisandra J. , Walker Elizabeth A. , Tryban Stephen , Siddiq Mohammad A. , Yang Bing , Wittkopp Patricia J. 
Published: February 2021

AbstractHeritable variation in a gene’s expression arises from mutations impactingcis- andtrans-acting components of its regulatory network, with expression variation often derived fromtrans-regulatory mutations within species. Here, we investigate howtrans-regulatory mutations are distributed within the genome and within a gene regulatory network by identifying and characterizing 69 mutations withtrans-regulatory effects on expression of the same focal gene inSaccharomyces cerevisiae. Relative to 1766 mutations without effects on expression of this focal gene, we found that thesetrans-regulatory mutations were enriched in coding sequences of transcription factors previously predicted to regulate expression of the focal gene. However, over 90% of thetrans-regulatory mutations identified mapped to other types of genes involved in diverse biological processes including chromatin state, metabolism and signal transduction. Finally, we find that the genomic distribution of these new regulatory mutations significantly overlaps with the genomic distribution oftrans-regulatory variants segregating withinS. cerevisiae.
Oncofusion-drivende novoenhancer assembly promotes malignancy in Ewing sarcomaviaaberrant expression of the stereociliary protein LOXHD1
Authors: Deng Qu , Natesan Ramakrishnan , Cidre-Aranaz Florencia , Arif Shehbeel , Liu Ying , Rasool Reyaz ur , Wang Pei , Cramer Zvi , Chou Margaret , Kumar-Sinha Chandan , Weber Kristy , Eisinger-Mathason T S Karin , Grillet Nicolas , Grünewald Thomas , Asangani Irfan A. 
Published: February 2021

AbstractEwing Sarcoma (EwS) is a highly aggressive tumor of bone and soft tissues that mostly affects children and adolescents. The pathognomonic oncofusion EWSR1-ETS (EWSR1-FLI1/EWSR1-ERG) transcription factors drive EwS by orchestrating an oncogenic transcription program throughde novoenhancers. Pharmacological targeting of these oncofusions has been challenged by unstructured prion-like domains and common DNA binding domains in the EWSR1 and ETS protein, respectively. Alternatively, identification and characterization of mediators and downstream targets of EWSR1-FLI1 dependent or independent function could offer novel therapeutic options. By integrative analysis of thousands of transcriptome datasets representing pan-cancer cell lines, primary cancer, metastasis, and normal tissues, we have identified a 32 gene signature (ESS32 - Ewing Sarcoma Specific 32) that could stratify EwS from pan-cancer. Of the ESS32, LOXHD1 – that encodes a stereociliary protein, was the most exquisitely expressed gene in EwS. CRISPR-Cas9 mediated deletion or silencing of EWSR1-FLI1 bound upstreamde novoenhancer elements in EwS cells led to the loss of LOXHD1 expression and altered the EWSR1-FLI1, MYC, and HIF1α pathway genes, resulting in decreased proliferation and invasionin vitroandin vivo. These observations implicate LOXHD1 as a novel biomarker and a major determinant of EwS metastasis and open up new avenues for developing LOXHD1-targeted drugs or cellular therapies for this deadly disease.
Engineering protease-resistant peptides to inhibit human parainfluenza viral respiratory infection
Authors: Outlaw Victor K. , Cheloha Ross W. , Jurgens Eric M. , Bovier Francesca T. , Zhu Yun , Kreitler Dale F. , Harder Olivia , Niewiesk Stefan , Porotto Matteo , Gellman Samuel H. , Moscona Anne 
Published: February 2021

ABSTRACTThe lower respiratory tract infections affecting children worldwide are in large part caused by the parainfluenza viruses (HPIVs), particularly HPIV3, along with human metapneumovirus and respiratory syncytial virus, enveloped negative-strand RNA viruses. There are no vaccines for these important human pathogens, and existing treatments have limited or no efficacy. Infection by HPIV is initiated by viral glycoprotein-mediated fusion between viral and host cell membranes. A viral fusion protein (F), once activated in proximity to a target cell, undergoes a series of conformational changes that first extend the trimer subunits to allow insertion of the hydrophobic domains into the target cell membrane, and then refold the trimer into a stable postfusion state, driving the merger of the viral and host cell membranes. Lipopeptides derived from the C-terminal heptad repeat (HRC) domain of HPIV3 F inhibit infection by interfering with the structural transitions of the trimeric F assembly. Clinical application of this strategy, however, requires improving thein vivostability of antiviral peptides. We show that the HRC peptide backbone can be modified via partial replacement of α-amino acid residues with β-amino acid residues to generate α/β-peptides that retain antiviral activity but are poor protease substrates. Relative to a conventional α-lipopeptide, our best α/β-lipopeptide exhibits improved persistencein vivoand improved anti-HPIV3 antiviral activity in animals.
A G protein-coupled receptor is required in cartilaginous and dense connective tissues to maintain spine alignment
Authors: Liu Zhaoyang , Hussien Amro A. , Wang Yunjia , Heckmann Terry , Gonzalez Roberto , Karner Courtney M. , Snedeker Jess G. , Gray Ryan S. 
Published: February 2021

SummaryAdolescent idiopathic scoliosis (AIS) is the most common spine disorder affecting children worldwide, yet little is known about the pathogenesis of this disorder. Here, we demonstrate that genetic regulation of structural components of the axial skeleton, the intervertebral discs and dense connective tissues (e.g., ligaments and tendons), are essential for maintenance of spinal alignment. We show that the G-coupled protein receptorAdgrg6, previously implicated in human AIS association studies, is required in these tissues to maintain typical spine morphology. We show thatAdgrg6regulates biomechanical properties of tendon and stimulates CREB signaling governing gene expression in cartilaginous tissues of the spine. Treatment with an cAMP agonist was able to mirror aspects of receptor function in culture defining core pathways for regulation of these axial connective tissues. AsADGRG6is a key gene involved in human AIS, these findings open up novel therapeutic opportunities for human scoliosis.HighlightsKnockout mice lackingAdgrg6function in the tendons and ligaments of the spine develop perinatal-onset thoracic scoliosis.Loss ofAdgrg6function in cartilaginous tissues of the discs contribute to the incidence and severity of scoliosis.The loss ofAdgrg6function in spine tissues provide a model of construct validity for human adolescent idiopathic scoliosisFine tuning of the biomechanical properties of dense connective tissues is essential for maintaining spine alignment.
Dominance shifts increase the likelihood of soft selective sweeps
Authors: Muralidhar Pavitra , Veller Carl 
Published: February 2021

AbstractGenetic models of adaptation to a new environment have typically assumed that the alleles involved maintain a constant fitness dominance across the old and new environments. However, theories of dominance suggest that this should often not be the case. Instead, the alleles involved should frequently shift from recessive deleterious in the old environment to dominant beneficial in the new environment. Here, we study the consequences of these expected dominance shifts for the genetics of adaptation to a new environment. We find that dominance shifts increase the likelihood that adaptation occurs from the standing variation, and that multiple alleles from the standing variation are involved (a soft selective sweep). Furthermore, we find that expected dominance shifts increase the haplotypic diversity of selective sweeps, rendering soft sweeps more detectable in small genomic samples. In cases where an environmental change threatens the viability of the population, we show that expected dominance shifts of newly beneficial alleles increase the likelihood of evolutionary rescue and the number of alleles involved. Finally, we apply our results to a well-studied case of adaptation to a new environment: the evolution of pesticide resistance at theAcelocus inDrosophila melanogaster. We show that, under reasonable demographic assumptions, the expected dominance shift of resistant alleles causes soft sweeps to be the most frequent outcome in this case, with the primary source of these soft sweeps being the standing variation at the onset of pesticide use, rather than recurrent mutation thereafter.
Human basigin (CD147) does not directly interact with SARS-CoV-2 spike glycoprotein
Authors: Ragotte Robert J. , Pulido David , Donnellan Francesca R. , Gorini Giacomo , Davies Hannah , Brun Juliane , King Lloyd D. W. , Skinner Katherine , Draper Simon J. 
Published: February 2021

AbstractBasigin, or CD147, has been reported as a co-receptor used by SARS-CoV-2 to invade host cells. Basigin also has a well-established role inPlasmodium falciparummalaria infection of human erythrocytes where it is bound by one of the parasite’s invasion ligands, reticulocyte binding protein homolog 5 (RH5). Here, we sought to validate the claim that the receptor binding domain (RBD) of SARS-CoV-2 spike glycoprotein can form a complex with basigin, using RH5-basigin as a positive control. Using recombinantly expressed proteins, size exclusion chromatography and surface plasmon resonance, we show that neither RBD nor full-length spike glycoprotein bind to recombinant human basigin (either expressed inE. colior mammalian cells). Given the immense interest in SARS-CoV-2 therapeutic targets, we would caution the inclusion of basigin in this list on the basis of its reported direct interaction with SARS-CoV-2 spike glycoprotein.ImportanceReducing the mortality and morbidity associated with COVID-19 remains a global health priority. Critical to these efforts is the identification of host factors that are essential to viral entry and replication. Basigin, or CD147, was previously identified as a possible therapeutic target based on the observation that it may act as a co-receptor for SARS-COV-2, binding to the receptor binding domain of the spike protein. Here, we show that there is no direct interaction between the RBD and basigin, casting doubt on its role as a co-receptor and plausibility as a therapeutic target.