Immune Response and Mitochondrial Metabolism Are Commonly Deregulated in DMD and Aging Skeletal Muscle

Duchenne Muscular Dystrophy (DMD) is a complex process involving multiple pathways downstream of the primary genetic insult leading to fatal muscle degeneration. Aging muscle is a multifactorial neuromuscular process characterized by impaired muscle regeneration leading to progressive atrophy. We hypothesized that these chronic atrophying situations may share specific myogenic adaptative responses at transcriptional level according to tissue remodeling. Muscle biopsies from four young DMD and four AGED subjects were referred to a group of seven muscle biopsies from young subjects without any neuromuscular disorder and explored through a dedicated expression microarray. We identified 528 differentially expressed genes (out of 2,745 analyzed), of which 328 could be validated by an exhaustive meta-analysis of public microarray datasets referring to DMD and Aging in skeletal muscle. Among the 328 validated co-expressed genes, 50% had the same expression profile in both groups and corresponded to immune/fibrosis responses and mitochondrial metabolism. Generalizing these observed meta-signatures with large compendia of public datasets reinforced our results as they could be also identified in other pathological processes and in diverse physiological conditions. Focusing on the common gene signatures in these two atrophying conditions, we observed enrichment in motifs for candidate transcription factors that may coordinate either the immune/fibrosis responses (ETS1, IRF1, NF1) or the mitochondrial metabolism (ESRRA). Deregulation in their expression could be responsible, at least in part, for the same transcriptome changes initiating the chronic muscle atrophy. This study suggests that distinct pathophysiological processes may share common gene responses and pathways related to specific transcription factors

Meta-analysis of muscle transcriptome data using the MADMuscle database reveals biologically relevant gene patterns

<p>Abstract</p> <p>Background</p> <p>DNA microarray technology has had a great impact on muscle research and microarray gene expression data has been widely used to identify gene signatures characteristic of the studied conditions. With the rapid accumulation of muscle microarray data, it is of great interest to understand how to compare and combine data across multiple studies. Meta-analysis of transcriptome data is a valuable method to achieve it. It enables to highlight conserved gene signatures between multiple independent studies. However, using it is made difficult by the diversity of the available data: different microarray platforms, different gene nomenclature, different species studied, etc.</p> <p>Description</p> <p>We have developed a system tool dedicated to muscle transcriptome data. This system comprises a collection of microarray data as well as a query tool. This latter allows the user to extract similar clusters of co-expressed genes from the database, using an input gene list. Common and relevant gene signatures can thus be searched more easily. The dedicated database consists in a large compendium of public data (more than 500 data sets) related to muscle (skeletal and heart). These studies included seven different animal species from invertebrates (<it>Drosophila melanogaster, Caenorhabditis elegans</it>) and vertebrates (<it>Homo sapiens, Mus musculus, Rattus norvegicus, Canis familiaris, Gallus gallus</it>). After a renormalization step, clusters of co-expressed genes were identified in each dataset. The lists of co-expressed genes were annotated using a unified re-annotation procedure. These gene lists were compared to find significant overlaps between studies.</p> <p>Conclusions</p> <p>Applied to this large compendium of data sets, meta-analyses demonstrated that conserved patterns between species could be identified. Focusing on a specific pathology (Duchenne Muscular Dystrophy) we validated results across independent studies and revealed robust biomarkers and new pathways of interest. The meta-analyses performed with MADMuscle show the usefulness of this approach. Our method can be applied to all public transcriptome data.</p

Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

Data for: Role of rift maturity on the architecture and shortening distribution in mountain belts

Equations sovled by the code used for numerical simulations and extended results of the numerical models showing the evolution of the viscosity, strain rate and strain of the presented models in the main articleTHIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Epipalaeolithic and Neolithic gazelle hunting in the Badia of north-east Jordan. Reconstruction of seasonal movements of herds by stable isotope and dental microwear analyses

In the north-east Jordan steppe, gazelle were of considerable economic importance to human groups during the Epipalaeolithic and Neolithic. An influential model argues that gazelle herds migrated through the region and were only seasonally available to hunters. This study tests that model, asking whether gazelle were indeed highly seasonally mobile during these time frames, or whether they could have remained more local, adapted to periodically resource-rich habitats, and thus been available to hunters throughout the year. Interpretation of animal location, diet and season, through stable isotope analyses and microwear studies of archaeological gazelle teeth from ten chronologically and spatially varied sites, suggests herds did not migrate. Rather, gazelle appear to have had relatively local year-round habitats in the steppe during the Epipalaeolithic at least, while possibly ranging further and becoming more mobile in the Neolithic

Topographic and Tectonic Evolution of Mountain Belts Controlled by Salt Thickness and Rift Architecture

International audienceThe role of the heterogeneous rheological architecture of rifted margins in the building of mountain belts has challenged our view of how a collisional orogen formed. We show, using two-dimensional numerical experiments of collision built by the inversion of rifted margins, that a weak pre-extensional evaporitic layer delays the growth of topography and the onset of syn-orogenic sedimentary record in foreland basins. In tectonic models lacking a weak décollement layer, the orogen grows by progressive accretion of basement thrusts. With a 2-km-thick salt layer, the orogen develops an antiformal stack in the deep crust that is kinematically connected to a shallow thin-skin thrust belt in the foreland as observed in many orogens. A 5-km-thick weak layer leads to the quasi-absence of topography and widespread salt tectonics and obliterates thrusts propagation while promoting crust and mantle underthrusting. During convergence, the preservation of a marine seaway emphasizes that collision may involve a significant period of submarine continental accretion, which duration is controlled by the thickness of the weak décollement layer. From these experiments we infer that the thicker the salt layer, the longer the delay between the onset of far-field shortening and the formation of the orogen. Our study explains first-order features recognized in many orogens controlled by variable salt thickness and extension

Robustness and reliability achievements for direct hybrid bonding integration: a review

International audienc