bluuebunny/crossref_metadata_2025_split huggingface dataset:
The methylome and comparative transcriptome after high intensity sprint exercise in human skeletal muscle
Authors: Maasar Mohd Firdaus , Turner Daniel C. , Gorski Piotr P. , Seaborne Robert A. , Strauss Juliette A. , Shepherd Sam O. , Cocks Matt , Pillon Nicolas J. , Zierath Juleen R. , Hulton Andrew T. , Drust Barry , Sharples Adam P. 
Published: September 2020

AbstractThe methylome and transcriptome signature following exercise that is physiologically and metabolic relevant to sporting contexts such as team sports or health prescription scenarios (e.g. high intensity interval training/HIIT) has not been investigated. To explore this, we undertook two different sport/exercise relevant high-intensity sprint running protocols in humans using a repeated measures design of: 1) Change of direction (COD) versus; 2) straight line (ST) sprint exercise. We took skeletal muscle biopsies from the vastus lateralis 30 minutes and 24 hours post exercise followed by 850K methylation arrays and comparative analysis with recent sprint and acute aerobic exercise meta-analysis transcriptomes. Despite matched intensity (speed x distance and number of accelerations/decelerations) between COD and ST exercise, COD exercise elicited greater movement (GPS Playerload™), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) loading compared with ST exercise. The exercise response alone across both conditions evoked extensive alterations in the methylome immediately post and 24 hrs after exercise, particularly in MAPK, AMPK and axon guidance pathways. COD evoked a considerably greater hypomethylated signature across the genome compared with ST sprint exercise, particularly enriched in: Protein binding, MAPK, AMPK, insulin, and axon guidance pathways. A finding that was more prominent immediately post exercise. Comparative methylome analysis with sprint running transcriptomes identified considerable overlap, with 49% of the genes altered at the expression level also differentially methylated after COD exercise. After differential methylated region analysis, we discovered that VEGFA and its downstream nuclear transcription factor, NR4A1 had enriched hypomethylation within their promoter regions. VEGFA and NR4A1 were also significantly upregulated in the sprint transcriptome and meta-analysis of exercise transcriptomes. We confirmed increased mRNA expression of VEGFA, and considerably larger increases in the expression of canonical metabolic genes, PGC1-α and NR4A3, 3 hrs post COD vs. ST exercise. Overall, we demonstrate that increased physiological load via change of direction sprint exercise in human skeletal muscle evokes considerable epigenetic modifications that are associated with changes in expression of genes responsible for adaptation to exercise. These data imply that introducing changes in direction into high intensity running protocols could serve as an important modulator of a favourable epigenomic and transcriptomic landscape in response to exercise in athletes and trigger greater skeletal muscle remodelling through enhanced gene expression.
Species- and strain-level assessment usingrrnlong-amplicons suggests donor’s influence on gut microbial transference via fecal transplants in metabolic syndrome subjects
Authors: Benítez-Páez Alfonso , Hartstra Annick V. , Nieuwdorp Max , Sanz Yolanda 
Published: September 2020

AbstractFecal microbiota transplantation (FMT) is currently used for treatingClostridium difficileinfection and explored for other clinical applications in experimental trials. However, the effectiveness of this therapy could vary, and partly depend on the donor’s bacterial species engraftment, whose evaluation is challenging because there are no cost-effective strategies for accurately tracking the microbe transference. In this regard, the precise identification of bacterial species inhabiting the human gut is essential to define their role in human health unambiguously. We used Nanopore-based device to sequence bacterialrrnoperons (16S-ITS-23S) and to reveal species-level abundance changes in the human gut microbiota of a FMT trial. By assessing the donor and recipient microbiota before and after FMT, we further evaluated whether this molecular approach reveals strain-level genetic variation to demonstrate microbe transfer and engraftment. Strict control over sequencing data quality and major microbiota covariates was critical for accurately estimating the changes in gut microbial species abundance in the recipients after FMT. We detected strain-level variation via single-nucleotide variants (SNVs) atrrnregions in a species-specific manner. We showed that it was possible to explore successfully the donor-bacterial strain (e.g.,Parabacteroides merdae)engraftment in recipients of the FMT by assessing the nucleotide frequencies at rrn-associated SNVs. Our findings indicate that the engraftment of donors’ microbiota is to some extent correlated with the improvement of metabolic health in recipients and that parameters such as the baseline gut microbiota configuration, sex, and age of donors should be considered to ensure the success of FMT in humans.Trial registrationThe study was prospectively registered at the Dutch Trial registry - NTR4488 (https://www.trialregister.nl/trial/4488).
Modelling illustrates that genomic selection provides new opportunities for intercrop breeding
Authors: Bančič Jon , Werner Christian , Gaynor Chris , Gorjanc Gregor , Odeny Damaris , Ojulong Henry F. , Dawson Ian K. , Hoad Steve , Hickey John M. 
Published: September 2020

AbstractIntercrop breeding programs using genomic selection can produce faster genetic gain than intercrop breeding programs using phenotypic selection. Intercropping is an agricultural practice in which two or more component crops are grown together. It can lead to enhanced soil structure and fertility, improved weed suppression, and better control of pests and diseases. Especially in subsistence agriculture, intercropping has great potential to optimise farming and increase profitability. However, breeding for intercrop varieties is complex as it requires simultaneous improvement of two or more component crops that combine well in the field. We hypothesize that genomic selection can significantly simplify and accelerate the process of breeding crops for intercropping. Therefore, we used stochastic simulation to compare four different intercrop breeding programs implementing genomic selection and an intercrop breeding program entirely based on phenotypic selection. We assumed three different levels of genetic correlation between monocrop grain yield and intercrop grain yield to investigate how the different breeding strategies are impacted by this factor. We found that all four simulated breeding programs using genomic selection produced significantly more intercrop genetic gain than the phenotypic selection program regardless of the genetic correlation with monocrop yield. We suggest a genomic selection strategy which combines monocrop and intercrop trait information to predict general intercropping ability to increase selection accuracy in early stages of a breeding program and to minimize the generation interval.
Analysis of Fox genes inSchmidtea mediterraneareveals new families and a conserved role ofSmed-foxOin controlling cell death
Authors: Pascual-Carreras Eudald , Herrera-Úbeda Carlos , Rosselló Maria , Garcia-Fernandez Jordi , Saló Emili , Adell Teresa 
Published: September 2020

AbstractThe forkhead box (Fox) genes encode transcription factors that control several key aspects of development. Present in the ancestor of all eukaryotes, Fox genes underwent several duplications followed by loss and diversification events that gave rise to the current 25 families. However, few Fox members have been identified from the Lophotrochozoa clade, and specifically from planarians, which are a unique model for understanding development, due to the striking plasticity of the adult. The aim of this study was to identify and perform evolutionary and functional studies of the Fox genes of lophotrochozoan species and, specifically, of the planarianSchmidtea mediterranea. Generating a pipeline for identifying Forkhead domains and using phylogenetics allowed us the phylogenetic reconstruction of Fox genes. We corrected the annotation for misannotated genes and uncover a new family, the QD, present in all metazoans. According to the new phylogeny, the 27 Fox genes found inSchmidtea mediterraneawere classified into 12 families. In Platyhelminthes, family losses were accompanied by extensive gene diversification and the appearance of specific families, the A(P) and N(P). Among the newly identified planarian Fox genes, we found a single copy offoxO, which shows an evolutionary conserved role in controlling cell death.Author summaryTranscription factors are the key elements that regulate gene expression in the nucleus. The forkhead box (Fox) transcription factors are one of the most numerous and they control key aspects of development. Fox genes were already present in the ancestor of all eukaryotes, and then underwent several duplications followed by loss and diversification events that gave rise to the current Fox families in the different species. The available data classifies Fox genes in 25 families, but they include few members corresponding to Lophotrocozoa, one of the two invertebrate phyla that includes annelids, molluscs or platyhelmintes. In this study we identify and perform evolutionary studies of the Fox genes of several lophotrochozoan species and, specifically, of the planarianSchmidtea mediterranea. The result is the correction of the annotation of Fox genes from many species, proposing a new nomenclature, and the identification of new families; the QD family, present in all metazoans, and the A(P) and N(P) families, specific of Platyhelminthes. We also study the function ofSchmidtea mediterranea foxO, a gene involved in aging and cancer in other species, showing its evolutionary conserved role in controlling cell death according to cell metabolism.
Rapid Development of Improved Data-dependent Acquisition Strategies
Authors: Davies Vinny , Wandy Joe , Weidt Stefan , van der Hooft Justin J. J. , Miller Alice , Daly Rónán , Rogers Simon 
Published: September 2020

AbstractTandem mass spectrometry (LC-MS/MS) is widely used to identify unknown ions in untargeted metabolomics. Data Dependent Acquisition (DDA) chooses which ions to fragment based upon intensity observed in MS1 survey scans and typically only fragment a small subset of the ions present. Despite this inefficiency, relatively little work has addressed the development of new DDA methods, partly due to the high overhead associated with running the many extracts necessary to optimise approaches in busy MS facilities. In this work, we firstly provide theoretical results that show how much improvement is possible over current DDA strategies. We then describe anin silicoframework for fast and cost efficient development of new DDA acquisition strategies using a previously developed Virtual Metabolomics Mass Spectrometer (ViMMS). Additional functionality is added to ViMMS to allow methods to be used both in simulation and on real samples via an instrument application programming interface (API).We demonstrate this framework through the development and optimisation of two new DDA methods which introduce new advanced ion prioritisation strategies. Upon application of the here developed methods to two complex metabolite mixtures, our results show that they are able to fragment more unique ions than standard DDA acquisition strategies.
Phylogeny of docks and sorrels (Rumex, Polygonaceae) reveals plasticity of reproductive systems
Authors: Grant Kirstie D. , Koenemann Daniel , Mansaray Janet , Ahmed Aisha , Khamar Hamid , Oualidi Jalal El , Burke Janelle M. 
Published: September 2020

AbstractThe genusRumexis a unique member of the Polygonaceae (Buckwheat) family of plants. A source of intrigue forRumexlies in the diversity of the reproductive systems associated with the subgenera, species, and subspecies within this genus. Four previously circumscribed subgenera, some 200 species, and a number of subspecies comprise the collectiveRumexgenus. These species exhibit monoecious, dioecious, synoecious (hermaphroditic), and polygamous reproductive systems. Moreover, some of the dioecious species contain sex chromosomes, a phenomenon that is very rare in angiosperms. Apart from the confirmed morphological and phytogeographical distinctions, two of the four described subgenera,AcetosaandAcetosella, are distinctive in their exhibited sex chromosome systems. For this study, we used three chloroplast markers,rbcL, trnH-psbA, trnL-F, and dense taxon sampling, to reconstruct a molecular phylogeny forRumex.The reconstructed phylogeny for this work resolves six major clades and one large grade inRumex. In addition, the species with known dioecious reproductive systems derived from unique sex chromosome systems are resolved in two different clades nested within “the dioecious clade”. These results suggest that the species with divergent sexual systems are more closely related to each other than to other species comprising the rest of theRumexgenus. Furthermore, some species with known synoecious reproductive systems are resolved in a single clade which is also nested within “the dioecious clade”. These results imply a possible reversal occurring over time which suggests the highly plastic nature of reproductive systems amongRumexspecies.
Reorganization of the neurobiology of language after sentence overlearning
Authors: Skipper Jeremy I , Aliko Sarah , Brown Stephen , Jo Yoon Ju , Lo Serena , Molimpakis Emilia , Lametti Daniel R 
Published: September 2020

AbstractThere is a widespread assumption that there are a static set of ‘language regions’ in the brain. Yet, people still regularly produce familiar ‘formulaic’ expressions when those regions are severely damaged. This suggests that the neurobiology of language varies with the extent of word sequence learning and might not be fixed. We test the hypothesis that perceiving sentences is mostly supported by sensorimotor regions involved in speech production and not ‘language regions’ after overlearning. Twelve participants underwent two sessions of behavioural testing and functional magnetic resonance imaging (fMRI), separated by 15 days. During this period, they repeated two sentences 30 times each, twice a day. In both fMRI sessions, participants ‘passively’ listened to those two sentences and novel sentences. Lastly, they spoke novel sentences. Behavioural results confirm that participants overlearned sentences. Correspondingly, there was an increase or recruitment of sensorimotor regions involved in sentence production and a reduction in activity or inactivity for overlearned sentences in regions involved in listening to novel sentences. The global network organization of the brain changed by ∼45%, mostly through lost connectivity. Thus, there was a profound reorganization of the neurobiology of speech perception after overlearning towards sensorimotor regions not considered in most contemporary models and away from the ‘language regions’ posited by those models. These same sensorimotor regions are generally preserved in aphasia and Alzheimer’s disease, perhaps explaining residual abilities with formulaic language. These and other results warrant reconsidering static neurobiological models of language.
Molecular Characterization, Phylogenetic and Variation Analyzes of SARS-CoV-2 strains in Turkey
Authors: Murat Karamese , Didem Ozgur , Ediz Tutuncu Emin 
Published: September 2020

ABSTRACTIntroductionWe present the sequence analysis for 47 complete genomes for SARS-CoV-2 isolates on Turkish patients. To identify their genetic similarity, phylogenetic analysis was performed by comparing the worldwide SARS-CoV-2 sequences, selected from GISAID, to the complete genomes from Turkish isolates. In addition, we focused on the variation analysis to show the mutations on SARS-CoV-2 genomes.MethodsIllumina MiSeq platform was used for sequencing the libraries. The raw reads were aligned to the known SARS-CoV-2 genome (GenBank:MN908947.3) using the Burrows-Wheeler aligner (v.0.7.1). The phylogenetic tree was constructer using Phylip v.3.6 with Neighbor-Joining and composite likelihood method. The variants were detected by using Genome Analysis Toolkit-HaplotypeCaller v.3.8.0 and were inspected on GenomeBrowse v2.1.2.ResultsAll viral genome sequences of our isolates was located in lineage B under the different clusters such as B.1 (n=3), B.1.1 (n=28), and B.1.9 (n=16). According to the GISAID nomenclature, all our complete genomes were placed in G, GR and GH clades. Five hundred forty-nine total and 53 unique variants were detected. All 47 genomes exhibited different kinds of variants. The distinct variants consist of 274 missense, 225 synonymous, and 50 non-coding alleles.ConclusionThe results indicated that the SARS-CoV-2 sequences of our isolates have great similarity with all Turkish and European sequences. Further studies should be performed for better comparison of strains, after more complete genome sequences will be released. We also believe that collecting and sharing any data about SARS-CoV-2 virus and COVID-19 will be effective and may help the related studies.
Functional binding dynamics relevant to the evolution of zoonotic spillovers in endemic and emergentBetacoronavirusstrains
Authors: Rynkiewicz Patrick , Babbitt Gregory A. , Cui Feng , Hudson André O. , Lynch Miranda L. 
Published: September 2020

ABSTRACTComparative functional analysis of the dynamic interactions between variousBetacoronavirusmutant strains and broadly utilized target proteins such as ACE2 and CD26, is crucial for a more complete understanding of zoonotic spillovers of viruses that cause diseases such as COVID-19. Here, we employ machine learning to replicated sets of nanosecond scale GPU accelerated molecular dynamics simulations to statistically compare and classify atom motions of these target proteins in both the presence and absence of different endemic and emergent strains of the viral receptor binding domain (RBD) of the S spike glycoprotein. Machine learning was used to identify functional binding dynamics that are evolutionarily conserved from bat CoV-HKU4 to human endemic/emergent strains. Conserved dynamics regions of ACE2 involve both the N-terminal helices, as well as a region of more transient dynamics encompassing K353, Q325 and a novel motif AAQPFLL 386-92 that appears to coordinate their dynamic interactions with the viral RBD at N501. We also demonstrate that the functional evolution ofBetacoronaviruszoonotic spillovers involving ACE2 interaction dynamics are likely pre-adapted from two precise and stable binding sites involving the viral bat progenitor strain’s interaction with CD26 at SAMLI 291-5 and SS 333-334. Our analyses further indicate that the human endemic strains hCoV-HKU1 and hCoV-OC43 have evolved more stable N-terminal helix interactions through enhancement of an interfacing loop region on the viral RBD, whereas the highly transmissible SARS-CoV-2 variants (B.1.1.7, B.1.351 and P.1) have evolved more stable viral binding via more focused interactions between the viral N501 and ACE2 K353 alone.
Itk promotes the integration of TCR and CD28 costimulation, through its direct substrates, SLP-76 and Gads
Authors: Hallumi Enas , Shalah Rose , Lo Wan-Lin , Corso Jasmin , Oz Ilana , Beach Dvora , Wittman Samuel , Isenberg Amy , Sela Meirav , Urlaub Henning , Weiss Arthur , Yablonski Deborah 
Published: September 2020

AbstractThe costimulatory receptor, CD28, synergizes with the T cell antigen receptor (TCR) to promote IL-2 production, cell survival and proliferation. Despite their profound synergy, the obligatory interdependence of the signaling pathways initiated by these two receptors is not well understood. Upon TCR stimulation, Gads, a Grb2-family adaptor, bridges the interaction of two additional adaptors, LAT and SLP-76, to form a TCR-induced effector signaling complex. SLP-76 binds the Tec-family tyrosine kinase, Itk, which phosphorylates SLP-76 at Y173 and PLC-γ1 at Y783. Here we identified Gads Y45 as an additional TCR-inducible, Itk-mediated phosphorylation site. Y45 is found within the N-terminal SH3 domain of Gads, an evolutionarily conserved domain with no known binding partners or signaling function. Gads Y45 phosphorylation depended on the interaction of Gads with SLP-76 and on the preferentially-paired binding of Gads to phospho-LAT. Three Itk-related features, Gads Y45, SLP-76 Y173, and a proline-rich Itk SH3-binding motif on SLP-76, were selectively required for activation of the CD28 RE/AP transcriptional element from the IL-2 promoter, but were not required to activate NFAT. This study illuminates a new regulatory module, in which Itk-targeted phosphorylation sites on two adaptor proteins, SLP-76 and Gads, control the transcriptional response to TCR/CD28 costimulation, thus enforcing the obligatory interdependence of the TCR and CD28 signaling pathways.
Site-specific lipidation enhances IFITM3 membrane interactions and antiviral activity
Authors: Garst Emma , Lee Hwayoung , Das Tandrila , Bhattacharya Shibani , Percher Avital , Wiewiora Rafal , Witte Isaac P. , Li Yumeng , Goger Michael , Peng Tao , Im Wonpil , Hang Howard C. 
Published: September 2020

ABSTRACTInterferon-induced transmembrane proteins (IFITMs) areS-palmitoylated proteins in vertebrates that restrict a diverse range of viruses.S-palmitoylated IFITM3 in particular directly engages incoming virus particles, prevents their cytoplasmic entry, and accelerates their lysosomal clearance by host cells. However, the precise molecular mechanisms of action for IFITM-mediated viral restriction are still unclear. To investigate how site-specificS-palmitoylation controls IFITM3 antiviral activity, here we employed computational, chemical, and biophysical approaches to demonstrate that site-specific lipidation of IFITM3 at highly conserved cysteine 72 modulates its conformation and interaction with lipid membranes leading to enhanced antiviral activity of IFITM3 in mammalian cells. Collectively, our results demonstrate that site-specificS-palmitoylation of IFITM3 directly alters its biophysical properties and activity in cells to prevent virus infection.
NuMorph: tools for cellular phenotyping in tissue cleared whole brain images
Authors: Krupa Oleh , Fragola Giulia , Hadden-Ford Ellie , Mory Jessica T. , Liu Tianyi , Humphrey Zachary , Rees Benjamin W. , Krishnamurthy Ashok , Snider William D. , Zylka Mark J. , Wu Guorong , Xing Lei , Stein Jason L. 
Published: September 2020

AbstractTissue clearing methods allow every cell in the mouse brain to be imaged without physical sectioning. However, the computational tools currently available for cell quantification in cleared tissue images have been limited to counting sparse cell populations in stereotypical mice. Here we introduce NuMorph, a group of image analysis tools to quantify all nuclei and nuclear markers within the mouse cortex after tissue clearing and imaging by a conventional light-sheet microscope. We applied NuMorph to investigate two distinct mouse models: aTopoisomerase 1(Top1) conditional knockout model with severe neurodegenerative deficits and aNeurofibromin 1(Nf1) conditional knockout model with a more subtle brain overgrowth phenotype. In each case, we identified differential effects of gene deletion on individual cell-type counts and distribution across cortical regions that manifest as alterations of gross brain morphology. These results underline the value of 3D whole brain imaging approaches and the tools are widely applicable for studying 3D structural deficits of the brain at cellular resolution in animal models of neuropsychiatric disorders.