Processing a Mayan Corpus for Enhancing our Knowledge of Ancient Scripts

International audienceThe ancient Maya writing comprises more than 500 signs, either syllabic or semantic, and is largely deciphered, with a variable degree of reliability. We applied to the Dresden Codex, one of the only three manuscripts that reached us, encoded for LATEX with the mayaTEX package, our graded representation method of hybrid non-supervised learning, intermediate between clustering and oblique factor analysis, and following Hellinger metrics, in order to obtain a nuanced image of themes dealt with: the statistical entities are the 214 codex segments, and their attributes are the 1687 extracted bigrams of signs. For comparison, we introduced in this approach an exogenous element, i.e. the splitting of the composed signs into their elements, for a finer elicitation of the contents. The results are visualized as a set of "thematic concordances": for each homogeneous semantic context, the most salient bigrams or sequences of bigrams are displayed in their textual environment, which sheds a new light on the meaning of some little understood glyphs, placing them in clearly understandable contexts

Identification and characterization of a non-satellite cell muscle resident progenitor during postnatal development

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Nesprins are mechanotransducers that discriminate epithelial-mesenchymal transition programs

© 2020 Déjardin et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).LINC complexes are transmembrane protein assemblies that physically connect the nucleoskeleton and cytoskeleton through the nuclear envelope. Dysfunctions of LINC complexes are associated with pathologies such as cancer and muscular disorders. The mechanical roles of LINC complexes are poorly understood. To address this, we used genetically encoded FRET biosensors of molecular tension in a nesprin protein of the LINC complex of fibroblastic and epithelial cells in culture. We exposed cells to mechanical, genetic, and pharmacological perturbations, mimicking a range of physiological and pathological situations. We show that nesprin experiences tension generated by the cytoskeleton and acts as a mechanical sensor of cell packing. Moreover, nesprin discriminates between inductions of partial and complete epithelial-mesenchymal transitions. We identify the implicated mechanisms, which involve α-catenin capture at the nuclear envelope by nesprin upon its relaxation, thereby regulating β-catenin transcription. Our data thus implicate LINC complex proteins as mechanotransducers that fine-tune β-catenin signaling in a manner dependent on the epithelial-mesenchymal transition program.This material is based on work supported by the Centre national de la recherche scientifique (CNRS), Agence nationale de la recherche (ANR; grants ANR-13-JSV5-0007 and ANR-14-CE09-0006), France BioImaging (ANR-10-INBS-04), la Ligue contre le Cancer (REMX17751 to P.M. Davidson), and the Fondation ARC pour la Recherche sur le Cancer (PDF20161205227 to P.M. Davidson). P.S. Carollo has received funding from the European Union’s Horizon 2020 Framework Programme for Research and Innovation (Marie Skłodowska-Curie grant agreement 665850-INSPIRE) and acknowledges the Ecole Doctorale Frontières de l'Innovation en Recherche et Éducation (FIRE) Programme Bettencourt. E.R. Gomes was supported by a European Research Council consolidator grant (617676).info:eu-repo/semantics/publishedVersio

Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations

Publisher Copyright: © 2022, The Author(s).Mutations in the lamin A/C gene (LMNA) cause dilated cardiomyopathy associated with increased activity of ERK1/2 in the heart. We recently showed that ERK1/2 phosphorylates cofilin-1 on threonine 25 (phospho(T25)-cofilin-1) that in turn disassembles the actin cytoskeleton. Here, we show that in muscle cells carrying a cardiomyopathy-causing LMNA mutation, phospho(T25)-cofilin-1 binds to myocardin-related transcription factor A (MRTF-A) in the cytoplasm, thus preventing the stimulation of serum response factor (SRF) in the nucleus. Inhibiting the MRTF-A/SRF axis leads to decreased α-tubulin acetylation by reducing the expression of ATAT1 gene encoding α-tubulin acetyltransferase 1. Hence, tubulin acetylation is decreased in cardiomyocytes derived from male patients with LMNA mutations and in heart and isolated cardiomyocytes from Lmnap.H222P/H222P male mice. In Atat1 knockout mice, deficient for acetylated α-tubulin, we observe left ventricular dilation and mislocalization of Connexin 43 (Cx43) in heart. Increasing α-tubulin acetylation levels in Lmnap.H222P/H222P mice with tubastatin A treatment restores the proper localization of Cx43 and improves cardiac function. In summary, we show for the first time an actin-microtubule cytoskeletal interplay mediated by cofilin-1 and MRTF-A/SRF, promoting the dilated cardiomyopathy caused by LMNA mutations. Our findings suggest that modulating α-tubulin acetylation levels is a feasible strategy for improving cardiac function.Peer reviewe

Supramolecular assembly of gelatin and inorganic polyanions: Fine-tuning the mechanical properties of nanocomposites by varying their composition and microstructure

A series of bionanocomposites has been synthesized through a complex coacervation process inducing the assembly of gelatin with a wide range of inorganic polyanions (IPyAs) differing by their diameter and charge and including polyoxometalates (POMs) and a polythiomolybdate cluster. The microstructure and stoichiometry of these hybrid coacervates, which are strongly dependent on the charge matching between both components, have been studied by combining Fourier transform infrared (FT-IR) spectroscopy, solid-state nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), elemental analysis, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and energy-dispersive X-ray (EDX) elemental mapping. The mechanical properties of these materials were deeply characterized by tensile measurements at large deformation, revealing different behaviors (i.e., elastomer and ductile), depending on the nature of the IPyA. It is noteworthy that the mechanical properties of these bionanocomposites are strongly enhanced, compared to pure gelatin hydrogels. When attempting to connect structure and properties in these bionanocomposites, we have demonstrated that the density of cross-links (gelatin triple helices and IPyA) is the key parameter to control the extensibility of these materials

Severe ACTA1-related nemaline myopathy: intranuclear rods, cytoplasmic bodies, and enlarged perinuclear space as characteristic pathological features on muscle biopsies.

peer reviewedNemaline myopathy (NM) is a muscle disorder with broad clinical and genetic heterogeneity. The clinical presentation of affected individuals ranges from severe perinatal muscle weakness to milder childhood-onset forms, and the disease course and prognosis depends on the gene and mutation type. To date, 14 causative genes have been identified, and ACTA1 accounts for more than half of the severe NM cases. ACTA1 encodes α-actin, one of the principal components of the contractile units in skeletal muscle. We established a homogenous cohort of ten unreported families with severe NM, and we provide clinical, genetic, histological, and ultrastructural data. The patients manifested antenatal or neonatal muscle weakness requiring permanent respiratory assistance, and most deceased within the first months of life. DNA sequencing identified known or novel ACTA1 mutations in all. Morphological analyses of the muscle biopsy specimens showed characteristic features of NM histopathology including cytoplasmic and intranuclear rods, cytoplasmic bodies, and major myofibrillar disorganization. We also detected structural anomalies of the perinuclear space, emphasizing a physiological contribution of skeletal muscle α-actin to nuclear shape. In-depth investigations of the nuclei confirmed an abnormal localization of lamin A/C, Nesprin-1, and Nesprin-2, forming the main constituents of the nuclear lamina and the LINC complex and ensuring nuclear envelope integrity. To validate the relevance of our findings, we examined muscle samples from three previously reported ACTA1 cases, and we identified the same set of structural aberrations. Moreover, we measured an increased expression of cardiac α-actin in the muscle samples from the patients with longer lifespan, indicating a potential compensatory effect. Overall, this study expands the genetic and morphological spectrum of severe ACTA1-related nemaline myopathy, improves molecular diagnosis, highlights the enlargement of the perinuclear space as an ultrastructural hallmark, and indicates a potential genotype/phenotype correlation

Nuclear positioning: A matter of life

International audienceCell organization, and in particular how organelles are distributed in the cell, is often used by physio-pathologists to visually identify cell types in an organism. Behind this simple fact, it suggests that the positioning of sub-cellular structures is not occurring randomly but by active manners. Three hundred years ago, Leeuwenhoek reported the existence of a structure which will be then called the nucleus. It is the biggest organelle in eukaryotic cells, and has been described to be actively displaced in a large range of organisms and tissues. One of the first nuclear movements in an organism life occurs just after fecondation, when the two pronuclei moves towards each other in the egg [1]. After this first discovery, other nuclear movements has been described, such as in plants in 1903 [2] or occurring during neuroepithelium development in 1935 [3]. The latter was called interkinetic nuclear movement (INM). Whether nuclear movement has a function for cell fate and also how this is achieved needed to be further investigated. Several groups have tackled this question in different organisms and cell systems; it reveals similarities in the modus operandi between them but also particularities that could be associated with specific requirements for cell function. INM, for example, has been observed in other tissues and organisms, and defects in this movement lead to severe developmental defects, such as Lissencephaly. In Drosophila, inhibiting nuclear movement in the oocyte affects the polarity and therefore the future segmentation of the embry

Actin on and around the Nucleus

International audienceActin plays roles in many important cellular processes, including cell motility, organelle movement, and cell signaling. The discovery of transmembrane actin-binding proteins at the outer nuclear membrane (ONM) raises the exciting possibility that actin can play a role in direct force transmission to the nucleus and the genome at its interior. Actin-dependent nucleus displacement was first described a decade ago. We are now gaining a more detailed understanding of its mechanisms, as well as new roles for actin during mitosis and meiosis, for gene expression, and in the cell's response to mechanical stimuli. Here we review these recent developments, the actin-binding proteins involved, the tissue specificity of these mechanisms, and methods developed to reconstitute and study this interaction in vitro

L’Atlas du Muscle : une banque d’images de biopsies musculaires

L’analyse des biopsies musculaires constitue un outil essentiel dans le domaine de la recherche et pour le diagnostic. La biopsie musculaire est régulièrement utilisée dans le diagnostic et l’évaluation de nombreuses maladies neuromusculaires survenant chez l’enfant ou chez l’adulte, ainsi que dans l’étude des modèles animaux correspondants. Nous décrivons ici l’Atlas du Muscle, une banque d’images de biopsies musculaires saines et pathologiques, dont les objectifs sont de documenter les données morphologiques d’une myopathie donnée bien caractérisée, de faciliter le diagnostic des différentes myopathies, et de fournir du matériel pour des approches faisant appel à l’intelligence artificielle (IA)