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Neural Regeneration Research 2025年第8期20卷 2302-2303页

作者： Asma Boulksibat Alessandra Tempio Barbara Bardoni Institut de Pharmacologie Moléculaire et cellulaire CNRS UMR7275Inserm U1323ValbonneFrance

The second messengers 3',5'-cyclic adenosine monophosphate(cAMP)and 3',5'-cyclic guanosine monophosphate(cGMP)modulate molecular pathways that are involved in a large variety of cellular *** the brain,these processes include neurogenesis,neuronal differentiation,activation and function of microglia,and synaptic plasticity,finally resulting in memory formation.

关键词： formation processes finally

Charcot-Marie-Tooth-1A and sciatic nerve crush rat models:insights from proteomics

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Neural Regeneration Research 2023年第6期18卷 1354-1363页

作者： Zeina Msheik Stephanie Durand Emilie Pinault Martial Caillaud laetitia Vignaud Fabrice Billet Mohamed El Massry Alexis desmoulière UR20218 NeurIT(NEURopathies périphériques et Innovation Thérapeutique) University of LimogesLimogesFrance BISCEm(Biologie Intégrative SantéChimie Environnement)Platform US 42 Inserm/UAR 2015 CNRSUniversity of LimogesLimogesFrance umr 1308 inserm/chu–captur(contrôle de l’activation cellulaire Progression Tumorale et Résistance thérapeutique)University of LimogesLimogesFrance inserm umr1235–TENS(The Enteric Nervous System in Gut and Brain Diseases) University of NantesNantesFrance

The sensorimotor and histological aspects of peripheral neuropathies were already studied by our team in two rat models:the sciatic nerve crush and the Charcot-Marie-Tooth-1A *** this study,we sought to highlight and compare the protein signature of these two pathological ***,the identification of protein profiles in diseases can play an important role in the development of pharmacological *** fact,Charcot-Marie-Tooth-1A rats develop motor impairments that are more severe in the hind ***,for the first time,protein expression in sciatic nerve of Charcot-Marie-Tooth-1A rats was ***,distal sciatic nerves were collected from Charcot-Marie-Tooth-1A and uninjured wild-type rats aged 3 *** protein extraction,sequential window acquisition of all theoretical fragment ion spectra liquid chromatography and mass spectrometry was employed.445 proteins mapped to Swiss-Prot or trEMBl Uniprot databases were identified and *** these,153 proteins showed statistically significant differences between Charcot-Marie-Tooth-1A and wild-type *** majority of these proteins were overexpressed in *** clustering and functional enrichment using Gene Ontology were used to group these proteins based on their biological effects concerning Charcot-Marie-Tooth-1A ***,proteomic characterization of wild-type rats subjected to sciatic nerve crush was performed sequential window acquisition of all theoretical fragment ion spectra liquid chromatography and mass *** month after injury,distal sciatic nerves were collected and analyzed as described *** of 459 identified proteins,92 showed significant differences between sciatic nerve crush and the uninjured wild-type rats used in the first *** results suggest that young adult Charcot-Marie-Tooth-1A rats(3 months old)develop compensatory mechanisms at the level of redox balance,protein folding,myelination,and

关键词： Charcot-Marie-Tooth-1A endoplasmic reticulum Gene Ontology neurogenesis oxidative stress proteomics rat repair sciatic nerve crush SWATH-MS

Mechanical Properties of living Adherent Cells :Relationship with Structure and Function

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生物医学工程学杂志 2005年第S1期22卷 9-10页

作者： R. FODIl S. Féréol E. PlANUS V.M. lAURENT B. lOUIS D. ISABEY inserm umr 651 Fonctions Cellulaire et Moléculaire de l'Appareil Respiratoire et des Vaisseaux Equipe Biomécanique Cellulaire et Respiratoire Faculté de Médecine Créteil 94 010 FranceInserm UMR 651 Fonctions Cellulaire et Moléculaire de l'Appareil Respiratoire et des Vaisseaux Equipe Biomécanique Cellulaire et Respiratoire Faculté de Médecine Créteil 94 010 FranceInserm UMR 651 Fonctions Cellulaire et Moléculaire de l'Appareil Respiratoire et des Vaisseaux Equipe Biomécanique Cellulaire et Respiratoire Faculté de Médecine Créteil 94 010 FranceInserm UMR 651 Fonctions Cellulaire et Moléculaire de l'Appareil Respiratoire et des Vaisseaux Equipe Biomécanique Cellulaire et Respiratoire Faculté de Médecine Créteil 94 010 FranceInserm UMR 651 Fonctions Cellulaire et Moléculaire de l'Appareil Respiratoire et des Vaisseaux Equipe Biomécanique Cellulaire et Respiratoire Faculté de Médecine Créteil 94 010 FranceInserm UMR 651 Fonctions Cellulaire et Moléculaire de l'Appareil Respiratoire et des Vaisseaux Equipe Biomécanique Cellulaire et Respiratoire Faculté de Médecine Créteil 94 010 France

Mediator contributes to IgH locus VDJ rearrangements by promoting usage of most distal V segments

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Cellular & Molecular Immunology 2020年第4期17卷 407-409页

作者： Iman Dalloul Zeinab Dalloul Sandrine le Noir François Boyer Bernardo Reina-San-Martin Jeanne Cook-Moreau Michel Cogné umr CNRS 7276 INSERM U1262Universite de LimogesLimoges 87025France inserm U1258 UMR CNRS 7104Institut de Genetique et de Biologie Moleculaire et CellulaireUniversitéde StrasbourgIllkirch 67400France

INTRODUCTION The immunoglobulin heavy(IgH)chain locus includes a large cluster of V,D and J segments spanning thousands of kilobases in mammals and its expression implies long-range 3D-regulation of various gene modifications.1 V(D)J recombination occurs during early B-cell ontogeny.2 It is regulated by multiple transcription factors and cis-regulatory elements,and most notably by the intronic 5′Eμelement located in the JH to Cμintron.3 The intergenic control region 1(IGCR1)located between the VH and D gene clusters inhibits rearrangement of the most DH-proximal VH gene segments,while promoting usage of distal VH gene segments.4 Other downstream elements of the locus,flanking its 3′end might have more subtle roles:while the large 3′regulatory region(3′RR)shows strong internal synergies2 and behaves as a superenhancer in mature B *** deletion showed no influence on the VDJ repertoire and rather increased transcription of unrearranged V segments.3–5 Insulators binding CTCF farther downstream of the 3′RR were shown,however,to promote usage of distal VH segments.6 Altogether,there are strong indications that elements involved in long-distance regulation of transcription might also influence VDJ ***-frame splicing of VDJ exons is also needed for full Ig expression.7 Given the functional importance of gene architecture and long-range interactions for the IgH locus physiology,we explored the dependence of the VDJ repertoire on Med1,a known actor of long-range enhancer interactions.

关键词： B cells mediator VDJ repertoire

Molecular Evolution of the Substrate Specificity of Chloroplastic Aldolases/Rubisco lysine Methyltransferases in Plants

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Molecular Plant 2016年第4期9卷 569-581页

作者： Sheng Ma Jacqueline Martin-laffon Morgane Mininno Oceane Gigarel Sabine Brugiere Olivier Bastien Marianne Tardift Stephane Ravanel Claude Alban Universite Grenoble Alpes Laboratoire de Physiologie Cellulaire & Vegetale 38041 Grenoble France CNRS UMR5168 38054 Grenoble France CEA iRTSV Laboratoire de Physiologie Cellulaire & Vegetale 38054 Grenoble France INRA USC1359 38054 Grenoble France Universite Grenoble Alpes 38041 Grenoble France CEA iRTSV Biologie & Grande Echelle 38054 Grenoble France inserm U1038 38054 Grenoble France

Rubisco and fructose-1,6-bisphosphate aldolases （FBAs） are involved in CO2 fixation in chloroplasts. Both enzymes are trimethylated at a specific lysine residue by the chloroplastic protein methyltransferase lSMT. Genes coding lSMT are present in all plant genomes but the methylation status of the substrates varies in a species-specific manner. For example, chloroplastic FBAs are naturally trimethylated in both Pisum sati- vum and Arabidopsis thaliana, whereas the Rubisco large subunit is trimethylated only in the former spe- cies. The in vivo methylation status of aldolases and Rubisco matches the catalytic properties of AtlSMT and PslSMT, which are able to trimethylate FBAs or FBAs and Rubisco, respectively. Here, we created chimera and site-directed mutants of monofunctional AtlSMT and bifunctional PslSMT to identify the molecular determinants responsible for substrate specificity. Our results indicate that the His-Ala/Pro- Trp triad located in the central part of lSMT enzymes is the key motif to confer the capacity to trimethylate Rubisco. Two of the critical residues are located on a surface loop outside the methyltransferase catalytic site. We observed a strict correlation between the presence of the triad motif and the in vivo methylation status of Rubisco. The distribution of the motif into a phylogenetic tree further suggests that the ancestral function of lSMT was FBA trimethylation. In a recent event during higher plant evolution, this function evolved in ancestors of Fabaceae, Cucurbitaceae, and Rosaceae to include Rubisco as an additional substrate to the archetypal enzyme. Our study provides insight into mechanisms by which SET-domain protein methyltransferases evolve new substrate specificity.

关键词： SET-domain protein methyltransferase site-directed mutagenesis chimeric enzyme methylation,molecular evolution green lineage

Chloroplast Proteomics and the Compartmentation of Plastidial Isoprenoid Biosynthetic Pathways

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Molecular Plant 2009年第6期2卷 1154-1180页

作者： Jacques Joyard Myriam Ferro Christophe Masselon Daphne Seigneurin-Berny Daniel Salvi Jerome Garin Norbert Rolland laboratoire de Physiologie cellulaire Vegetale umr 5168 CEA CNRS INRA Universite Joseph Fourier iRTSV CEA-Grenoble 38054 Grenoble-cedex 9 France laboratoirre Etude de la Dynamique des Proteomes U880 CEA inserm Universite Joseph Fourrier iRTSV CEA-Grenoble 38054 Grenoble-cedex 9 France

Recent advances in the proteomic field have allowed high-throughput experiments to be conducted on chloroplast samples. Many proteomic investigations have focused on either whole chloroplast or sub-plastidial fractions. To date, the Plant Protein Database （PPDB, Sun et al., 2009） presents the most exhaustive chloroplast proteome available online. However, the accurate localization of many proteins that were identified in different sub-plastidial compartments remains hypothetical. Ferro et al. （2009） went a step further into the knowledge of Arabidopsis thaliana chloroplast proteins with regards to their accurate localization within the chloroplast by using a semi-quantitative proteomic approach known as spectral counting. Their proteomic strategy was based on the accurate mass and time tags （AMT） database approach and they built up AT_CHlORO, a comprehensive chloroplast proteome database with sub-plastidial localization and curated information on envelope proteins. Comparing these two extensive databases, we focus here on about 100 enzymes involved in the synthesis of chloroplast-specific isoprenoids. Well known pathways （i.e. compartmentation of the methyl erythritol phosphate biosynthetic pathway, of tetrapyrroles and chlorophyll biosynthesis and breakdown within chloroplasts） validate the spectral counting-based strategy. The same strategy was then used to identify the precise localization of the biosynthesis of carotenoids and prenylquinones within chloroplasts （i.e. in envelope membranes, stroma, and/or thylakoids） that remains unclear until now.

关键词： Non-mevalonate pathway chlorophyll biosynthesis chlorophyll degradation carotenoid biosynthesis prenylquinone biosynthesis envelope stroma thylakoids.

A novel regulatory region controls IgH locus transcription and switch recombination to a subset of isotypes

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Cellular & Molecular Immunology 2019年第11期16卷 887-889页

作者： Rocío Amoretti-Villa Mélanie Rogier Isabelle Robert Vincent Heyer Bernardo Reina-San-Martin Institut de Génétique et de Biologie Moléculaire et cellulaire(IGBMC) IllkirchFrance Institut National de la Santéet de la Recherche Médicale(inserm) U1258IllkirchFrance Centre National de la Recherche Scientifique(CNRS) UMR7104IllkirchFrance Universitéde Strasbourg IllkirchFrance

Class switch recombination(CSR)occurs at the IgH locus and replaces the immunoglobulin(Ig)isotype expressed from IgM to IgG,IgE or IgA,endowing the B cell receptor with novel effector *** is triggered by activation-induced cytidine deaminase(AID),1 an enzyme that deaminates cytosines to uracils in single-stranded DNA exposed by *** distinct antibody isotypes are encoded in the IgH locus in individual transcription units composed of a cytokine-inducible promoter,an intronic exon,and a switch region(Sx),followed by the exons encoding the constant region(Cx)(Fig.S1a).During CSR,the choice of recombination to a particular isotype is determined by the stimulation-dependent activation of specific promoters,triggering the generation of noncoding germline transcripts(GlTs).2 Thus far,the transcriptional regulation of the IgH locus is known to be controlled by the Eμenhancer,located downstream of the variable region and upstream of the donor switch region(Sμ),and the 3′regulatory region(3′RR)super-enhancer located downstream of Cα.

关键词： IgH stimulation replace

Potential Use of Polyelectrolyte Multilayer thin Films in Vascular Tissue Engineering:Evaluation of the Viability and Adhesion of Endothelial Cells

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生物医学工程学杂志 2005年第S1期22卷 117-118页

作者： Cédric BOURA Halima KERDJOUDJ Vanessa MOBY Pierre SCHAAJ Jean Claude VOEGEl Jean-Fran·ois STOlTZ Patrick MENU Mécanique et Ingénierie cellulaire et Tissulaire LEMTA-UMR CNRS 7563Facultéde Médecine54505 Vandoeuvre-lès-NancyFrance Institut Charles Sadron(CNRS-UlP) UPR 22 CNRS67083 StrasbourgFrance inserm U 595 Facultéde Médecine67085 StrasbourgFrance

1 Introduction A method in vascular tissue engineering to obtain hemocompatible synthetic prosthesis consist s to cover the luminal surface by a monolayer of endothelial cell s(ECs).Nevertheless,the surface of current prosthesi s does not favour the development of an ECs ***,a new versatile method of self2assembled archi2 tectures based on the alternate adsorption of polycations and polyanions has been developed to lead to the build2up of multilayered polyelectrolyte films(MPF).This new type of surface modification offers also large possibilities for varying the physico2chemical properties such as rough2 ness or surface charges,film thickness and viscoelastic properties.

关键词： Tissue Engineering thin Films viscoelastic properties surface modification tissue engineering endothelial cells method of type of

Mechanobiology and Cartilage Tissue Engineering

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生物医学工程学杂志 2005年第S1期22卷 33-34页

作者： Céline HUSElSTEIN Natalia de ISlA Jing-Wei YANG Yun WANG Sylvaine MUlleR Jean-Fran·ois STOlTZ Research Group of Cell and Tissue Engineering LEMTA-CNRS UMR 7563 et IFR 111 BioingénierieFacultéde Médecine54505 Vandoeuvre-lès-Nancy CedexFrance Unitéde Thérapie cellulaire et Tissulaire(UTCT)-CHRU-54500 Vandoeuvre-lès-Nancy Cedex France

1 Introduction The cartilage i s a hydrated connective tissue in joint s that withstands and distributes mechanical *** utilize mechanical signals to maintain tissue *** regulate their metabolic activity through complex biological and biophysical interactions with the extracellular matrix(ECM).Although some of the mechanisms of mechanotransduction are known today,there are certainly many others left *** topics of chondrocytes mechanobiology have led to the development of tissue *** is the concept of substitute tissue developed in vitro,from bioresorbable or non2bioresorbable scaffolds and from cells harvested in a physiologic mechanical environment.

关键词： Ca MSCs Mechanobiology and Cartilage Tissue Engineering

Characterization of two rat models of cystic fibrosis—KO and F508del CFTR—Generated by Crispr-Cas9

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Animal Models and Experimental Medicine 2019年第4期2卷 297-311页

作者： Elise Dreano Marc Bacchetta Juliette Simonin louise Galmiche Claire Usal lotfi Slimani Jérémy Sadoine laurent Tesson Ignacio Anegon Jean-Paul Concordet Aurélie Hatton lucile Vignaud Danielle Tondelier Isabelle Sermet-Gaudelus Marc Chanson Charles-Henry Cottart inserm 1151 INEMUniversitéde ParisParisFrance Département de Pédiatrie Gynécologie&Obstétrique et Département de Physiologie Cellulaire&MétabolismeUniversitéde GenèveGenèveSwitzerland Département de Pathologie APHPCHU Necker-Enfants MaladesParisFrance Centre de Recherche en Transplantation&Immunologie UMR 1064INSERMUniversitéde NantesNantesFrance Plateforme Trangénèse Rat&ImmunoPhénomique INSERM 1064&SFR François BonamyCNRS UMS3556NantesFrance Pathologie Imagerie&Biothérapies OrofacialesMontrougeFrance Plateforme Imageries du vivant Facultéde chirurgie dentaireUniversitéde ParisParisFrance inserm U1154 CNRS UMR7196MNHNTACGENEParisFrance AP-HP Centre Maladie Rare Mucoviscidose et Maladies du CFTRAssistance Publique Hôpitaux de ParisHôpital Necker-Enfants MaladesParisFrance Facultéde Médecine de Paris Universitéde ParisParisFrance Facultéde Pharmacie de Paris Universitéde ParisParisFrance

Background: Genetically engineered animals are essential for gaining a proper understanding of the disease mechanisms of cystic fibrosis(CF). The rat is a relevant laboratory model for CF because of its zootechnical capacity, size, and airway characteristics, including the presence of submucosal ***: We describe the generation of a CF rat model(F508 del) homozygous for the ***508 del mutation in the transmembrane conductance regulator(Cftr) gene. This model was compared to new Cftr-/-rats(CFTR KO). Target organs in CF were examined by histological staining of tissue sections and tooth enamel was quantified by micro-computed tomography. The activity of CFTR was evaluated by nasal potential difference(NPD) and short-circuit current measurements. The effect of VX-809 and VX-770 was analyzed on nasal epithelial primary cell cultures from F508 del ***: Both newborn F508 del and Knock out(KO) animals developed intestinal obstruction that could be partly compensated by special diet combined with an osmotic laxative. The two rat models exhibited CF phenotypic anomalies such as vas deferens agenesis and tooth enamel defects. Histology of the intestine, pancreas, liver, and lungs was normal. Absence of CFTR function in KO rats was confirmed ex vivo by short-circuit current measurements on colon mucosae and in vivo by NPD, whereas residual CFTR activity was observed in F508 del rats. Exposure of F508 del CFTR nasal primary cultures to a combination of VX-809 and VX-770 improved CFTR-mediated ***: The F508 del rats reproduce the phenotypes observed in CFTR KO animals and represent a novel resource to advance the development of CF therapeutics.

关键词： animal models CFTR channel activity CFTR modulators cystic fibrosis primary cultures rat