Éditeur(s) : HAL CCSD American Society of Hematology
Résumé : International audience
Polycythemia vera (PV) is characterized by an increased RBC mass, spontaneous erythroid colony formation, and the JAK2V617F mutation. PV is associated with a high risk of mesenteric and cerebral thrombosis. PV RBC adhesion to endothelial laminin is increased and mediated by phosphorylated erythroid Lu/BCAM. In the present work, we investigated the mechanism responsible for Lu/BCAM phosphorylation in the presence of JAK2V617F using HEL and BaF3 cell lines as well as RBCs from patients with PV. High levels of Rap1-GTP were found in HEL and BaF3 cells expressing JAK2V617F compared with BaF3 cells with wild-type JAK2. This finding was associated with increased Akt activity, Lu/BCAM phosphorylation, and cell adhesion to laminin that were inhibited by the dominant-negative Rap1S17N or by the specific Rap1 inhibitor GGTI-298. Surprisingly, knocking-down EpoR in HEL cells did not alter Akt activity or cell adhesion to laminin. Our findings reveal a novel EpoR-independent Rap1/Akt signaling pathway that is activated by JAK2V617F in circulating PV RBCs and responsible for Lu/BCAM activation. This new characteristic of JAK2V617F could play a critical role in initiating abnormal interactions among circulating and endothelial cells in patients with PV.
ISSN: 0006-4971

inserm-00821109
http://www.hal.inserm.fr/inserm-00821109
http://www.hal.inserm.fr/inserm-00821109/document
http://www.hal.inserm.fr/inserm-00821109/file/De_Grandis_Blood_2013.pdf
DOI : 10.1182/blood-2012-07-440487

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Chromatin modification enzymes are important regulators of gene expression and some are evolutionarily conserved from yeast to human. Saccharomyces cerevisiae is a major model organism for genome-wide studies that aim at the identification of target genes under the control of conserved epigenetic regulators. Ume6 interacts with the upstream repressor site 1 (URS1) and represses transcription by recruiting both the conserved histone deacetylase Rpd3 (through the co-repressor Sin3) and the chromatin-remodeling factor Isw2. Cells lacking Ume6 are defective in growth, stress response, and meiotic development. RNA profiling studies and in vivo protein-DNA binding assays identified mRNAs or transcript isoforms that are directly repressed by Ume6 in mitosis. However, a comprehensive understanding of the transcriptional alterations, which underlie the complex ume6Δ mutant phenotype during fermentation, respiration, or sporulation, is lacking. We report the protein-coding transcriptome of a diploid MAT a/α wild-type and ume6/ume6 mutant strains cultured in rich media with glucose or acetate as a carbon source, or sporulation-inducing medium. We distinguished direct from indirect effects on mRNA levels by combining GeneChip data with URS1 motif predictions and published high-throughput in vivo Ume6-DNA binding data. To gain insight into the molecular interactions between successive waves of Ume6-dependent meiotic genes, we integrated expression data with information on protein networks. Our work identifies novel Ume6 repressed genes during growth and development and reveals a strong effect of the carbon source on the derepression pattern of transcripts in growing and developmentally arrested ume6/ume6 mutant cells. Since yeast is a useful model organism for chromatin-mediated effects on gene expression, our results provide a rich source for further genetic and molecular biological work on the regulation of cell growth and cell differentiation in eukaryotes.
ISSN: 1617-4615

hal-01151619
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01151619
DOI : 10.1007/s00438-015-1051-5
PUBMED : 25957495

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: The filamentous fungus Trichoderma reesei is the main industrial cellulolytic enzyme producer. Several strains have been developed in the past using random mutagenesis, and despite impressive performance enhancements, the pressure for low-cost cellulases has stimulated continuous research in the field. In this context, comparative study of the lower and higher producer strains obtained through random mutagenesis using systems biology tools (genome and transcriptome sequencing) can shed light on the mechanisms of cellulase production and help identify genes linked to performance. Previously, our group published comparative genome sequencing of the lower and higher producer strains NG 14 and RUT C30. In this follow-up work, we examine how these mutations affect phenotype as regards the transcriptome and cultivation behaviour. Results: We performed kinetic transcriptome analysis of the NG 14 and RUT C30 strains of early enzyme production induced by lactose using bioreactor cultivations close to an industrial cultivation regime. RUT C30 exhibited both earlier onset of protein production (3 h) and higher steady-state productivity. A rather small number of genes compared to previous studies were regulated (568), most of them being specific to the NG 14 strain (319). Clustering analysis highlighted similar behaviour for some functional categories and allowed us to distinguish between induction-related genes and productivity-related genes. Cross-comparison of our transcriptome data with previously identified mutations revealed that most genes from our dataset have not been mutated. Interestingly, the few mutated genes belong to the same clusters, suggesting that these clusters contain genes playing a role in strain performance. Conclusions: This is the first kinetic analysis of a transcriptomic study carried out under conditions approaching industrial ones with two related strains of T. reesei showing distinctive cultivation behaviour. Our study sheds some light on some of the events occurring in these strains following induction by lactose. The fact that few regulated genes have been affected by mutagenesis suggests that the induction mechanism is essentially intact compared to that for the wild-type isolate QM6a and might be engineered for further improvement of T. reesei. Genes from two specific clusters might be potential targets for such genetic engineering.
ISSN: 1754-6834

Droits : http://creativecommons.org/licenses/by/
hal-01112360
http://hal.upmc.fr/hal-01112360
http://hal.upmc.fr/hal-01112360/document
http://hal.upmc.fr/hal-01112360/file/Poggi-Parodi_2014_Kinetic.pdf
DOI : 10.1186/s13068-014-0173-z

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Background: The impact of hepatitis B virus (HBV) genomic variability on the measurement of HBsAg level has been poorly evaluated. Objective: This study was designed to compare the performance of all the available assays measuring HBsAg level in this setting. Study design: A large selection of wild type HBV genotypes (n = 184) and HBsAg strains harboring mutations in the S gene (n = 81) from clinical samples was studied with three HBsAg quantification assays: Architect HBsAg (Abbott), LiaisonXL Murex HBsAg Quant (DiaSorin) and the Elecsys HBsAgII (Roche). Results: The overall percentage of positive results was 99.2% for Abbott, 98.9% for DiaSorin and 98.1% for Roche. Abbott and Roche assays provided an excellent concordance in HBsAg quantification (global mean bias of -0.006 logIU/mL). By contrast, DiaSorin underestimated HBsAg level with values 0.112 logIU/ml and 0.103 logIU/ml lower than Abbott and Roche, respectively. By contrast, DiaSorin slightly over quantified gtC(2.5% over the expected value) while Abbott provided values 6.2% lower than expected and 16.2% lower than what observed for the other genotypes. HBsAg quantitative assays were influenced by HBs protein substitutions irrespective to the genotype but no specific protein pattern that would particularly impair the quantification by one technique has been identified. However, Roche seemed to be particularly impacted by substitutions at 145 residue: 75% of under quantified samples carried a substituted 145 residue. Conclusion: This head-to-head comparison indicates a good correlation between all current systems used to quantify HBsAg but clearly shows an influence of both the genotype and the presence of "a" determinant variants in the absolute quantification of HBsAg. While these discrepancies may not translate into major clinical consequence, they may explain an absence of detection of weak concentration of HBsAg on some systems. (C) 2017 Elsevier B.V. All rights reserved.
ISSN: 1386-6532

hal-01588395
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01588395
DOI : 10.1016/j.jcv.2017.02.001
PUBMED : 28189936

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
EXOSC10 is a catalytic subunit of the exosome that processes biologically active transcripts, degrades aberrant mRNAs and targets certain long non-coding RNAs (lncRNAs). The yeast orthologue Rrp6 is required for efficient growth and gametogenesis, and becomes unstable during meiosis. However, nothing is known about the localization, stability and function of EXOSC10 in the rodent male germline. We detect the protein in nucleoli and the cytoplasm of mitotic and meiotic germ cells, and find that it transiently associates with the XY body, a structure targeted by meiotic sex chromosome inactivation (MSCI). Finally, EXOSC10 becomes unstable at later stages of gamete development. To determine Exosc10's meiotic function, we inactivated the gene specifically in male germ cells using cre recombinase controlled by Stra8 or Ddx4/Vasa promoters. Mutant mice have small testes, show impaired germ cell differentiation and are subfertile. Our results demonstrate that EXOSC10 is post-translationally regulated in germ cells, associate the protein with epigenetic chromosome silencing, and reveal its essential role in germ cell growth and development.
ISSN: 2045-2322

hal-01647082
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647082
DOI : 10.1038/s41598-017-14643-y
PUBMED : 29118343

Éditeur(s) : Université des Antilles Études caribéennes
Résumé : Introduction Le paysage est le produit de l’interaction entre un ordre de la nature et un ordre spatio-social qui expliquent ensemble sa genèse, son évolution, sa permanence ou ses mutations. En conséquence de sa nature même, le paysage « bouge ». Il mue au rythme des jours et des saisons qui modifient les conditions de lumière et la végétation. Le paysage se transforme également au cours des siècles en suivant les mutations économiques et sociales. Aux Antilles, des recherches de plus en plu...
Martinique

Droits : info:eu-repo/semantics/openAccess
urn:doi:10.4000/etudescaribeennes.763
http://journals.openedition.org/etudescaribeennes/763

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Archival Pneumocystis jirovecii specimens from 84 patients monitored at Rennes University Hospital (Rennes, France) were assayed at the dihydropteroate synthase (DHPS) locus. No patient was infected with mutants. The results provide additional data showing that P. jirovecii infections involving DHPS mutants do not represent a public health issue in Brittany, western France.
ISSN: 0732-8893

hal-00874675
https://hal.archives-ouvertes.fr/hal-00874675
DOI : 10.1016/j.diagmicrobio.2013.01.018
PUBMED : 23433532

Éditeur(s) : HAL CCSD Université des Antilles
Résumé : International audience
L’attrait généralisée des rivages et les pratiques qui les accompagnent ont entraîné des mutations des paysages et des écosystèmes. Dans le cadre étroit des îles, les milieux fragiles ne sont guère extensibles et souvent fractionnés. Les mutations récentes qui affectent les îles sont souvent irréversibles car les écosystèmes menacés n’ont pas toujours la taille suffisante pour reconquérir une zone. Avec la destruction d’un récif, c’est parfois l’unique espèce d’une variété de corail qui disparaît. La gestion et la préservation sont alors nécessaires. Elles doivent s’inscrire dans la durée et en lien avec les populations locales pour sauvegarder aux générations futures, ce cadre de vie qui nous y attire aujourd’hui.La mauvaise compréhension des mécanismes propres aux zones côtières se traduit souvent par des approches sectorielles et fréquemment à courte vue de l’aménagement. L’implantation d’un port de plaisance, d’un terminal à conteneurs peuvent entraîner des modifications du milieu et générer de nombreux conflits. Il est donc nécessaire de bien prendre en compte les principes élaborés par l’UNESCO pour le développement durable des zones côtières, principes qui renforcés dans le cadre étroit des petites îles.- Comprendre que l’aménagement des ressources côtières renouvelables revêt une importance stratégique pour le développement social et économique, et est donc rentable.- Reconnaître la nécessité de maintenir l’intégrité du système côtier et limiter l’exploitation des ressources côtières.- Elaborer des stratégies d’aménagement intégré autorisant des utilisations multiples des ressources côtières, intégrant des activités complémentaires et séparant nettement les activités ponctuelles.- Combiner un aménagement à grande échelle (niveau régional, international) avec un aménagement ciblé pour créer une réserve ou réhabiliter un écosystème dégradé.- Faire participer la population au processus de planification pour assurer l’efficacité des plans d’aménagement de la zone côtière.Les acteurs du littoral sont nombreux et leur capacité à intervenir dans sa protection et pour sa meilleure gestion, est variée selon l’intensité des pratiques de l’acteur isolé, du groupe de professionnels ou de l’association, du gestionnaire représentant l’Etat, de l’élu. La prise de conscience des atteintes des milieux et la nécessité du développement durable sont aujourd’hui généralisées dans toutes les îles. Le développement durable s’efforce de répondre aux besoins des générations présentes sans compromettre la capacité des générations futures à satisfaire les leurs. Les différents Etats multiplient les campagnes d’information à la télévision et dans la presse sur le développement durable, la nécessaire préservation, la lutte contre la pollution et contre la dégradation paysagère, la nécessité de respecter des normes architecturales (style, couleur, matériaux). Les particuliers identifient bien les problèmes : moins de poissons, des prises de petite taille, la mort de coraux, le trop grand nombre de pêcheurs, la pollution mal maîtrisée, le mitage progressif des paysages. Cependant, en fonction des niveaux de développement, la prise de conscience des dégradations ne débouche pas forcément sur une implication personnelle. Il est difficile de se sentir acteur participatif à la dégradation des écosystèmes insulaires.
ISSN: 1779-0980

hal-01174352
https://hal.archives-ouvertes.fr/hal-01174352
https://hal.archives-ouvertes.fr/hal-01174352/document
https://hal.archives-ouvertes.fr/hal-01174352/file/acteurs%20de%20l%27environnement.pdf

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BOI1 and BOI2 are paralogs important for the actin cytoskeleton andpolar growth. BOI1 encodes a meiotic transcript isoform with an extended5-untranslated region predicted to impair protein translation. It is,however, unknown how the isoform is repressed during mitosis, and ifBoi1 is present during sporulation. By interpreting microarray data fromMATa cells, MATa/ cells, a starving MAT/ control, and a meiosis-impairedrrp6 mutant, we classified BOI1's extended isoform as earlymeiosis-specific. These results were confirmed by RNA-Sequencing, andextended by a 5-RACE assay and Northern blotting, showing that meioticcells induce the long isoform while the mitotic isoform remainsdetectable during meiosis. We provide evidence via motif predictions, anin vivo binding assay and genetic experiments that the Rpd3/Sin3/Ume6histone deacetylase complex, which represses meiotic genes duringmitosis, also prevents the induction of BOI1's 5-extended isoform inmitosis by direct binding of Ume6 to its URS1 target. Finally, we findthat Boi1 protein levels decline when cells switch from fermentation torespiration and sporulation. The histone deacetylase Rpd3 is conserved,and eukaryotic genes frequently encode transcripts with variable 5-UTRs.Our findings are therefore relevant for regulatory mechanisms involvedin the control of transcript isoforms in multi-cellular organisms.
ISSN: 0950-382X

hal-01122120
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122120
DOI : 10.1111/mmi.12976
PUBMED : 25708805

Éditeur(s) : HAL CCSD Portland Press
Résumé : International audience
Lutheran (Lu) blood group and Basal Cell Adhesion Molecule (BCAM) antigens both reside on two glycoprotein (gp) isoforms, Lu and Lu(v13), that differ by the size of their cytoplasmic tail. They are receptors of laminin-10/11 and are expressed in red blood cells (RBCs), epithelial cells of multiple tissues and vascular endothelial cells. To gain more insights into the biological function of Lu/BCAM gps, we looked for potential partners of their cytoplasmic tail. We isolated Ubc9 (Ubiquitin-conjugating enzyme 9) protein by screening a human kidney library using the yeast two-hybrid system. Lu/Ubc9 interaction was validated by GST pull-down and co-immunoprecipitation experiments. Endogenous Ubc9 formed a complex with endogenous or recombinant Lu gp in A498 and MDCK epithelial cells, respectively. Substitution of lysine 585 by alanine in the Lu gp, abolished in vitro and ex vivo interaction of Lu gp with Ubc9 protein. Lu K585A mutant transfected in MDCK cells exhibited a normal basolateral membrane expression but was overexpressed at the surface of polarized MDCK cells as compared to wild-type Lu. Pulse-chase experiments showed extended half-life of Lu K585A gp at the plasma membrane, suggesting an impaired endocytosis of this mutant leading to protein accumulation at the membrane. Furthermore, we showed that the ability of MDCK-Lu K585A cells to spread on immobilized laminin was dramatically decreased. Our data supports a physiological role for the direct interaction between Lu gp and Ubc9 protein, and reveals a role for this enzyme in regulating the stability of Lu gp at the cell membrane.
ISSN: 0264-6021

hal-00478614
https://hal.archives-ouvertes.fr/hal-00478614
https://hal.archives-ouvertes.fr/hal-00478614/document
https://hal.archives-ouvertes.fr/hal-00478614/file/PEER_stage2_10.1042%252FBJ20060861.pdf
DOI : 10.1042/BJ20060861

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C. We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene. We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature. Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect.
ISSN: 1098-3600

hal-01134364
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134364
DOI : 10.1038/gim.2015.29
PUBMED : 25790162

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The Hedgehog (Hh) family of secreted proteins act as morphogens to control embryonic patterning and development in a variety of organ systems. Post-translational covalent attachment of cholesterol and palmitate to Hh proteins are critical for multimerization and long range signaling potency. However, the biological impact of lipid modifications on Hh ligand distribution and signal reception in humans remains unclear. In the present study, we report a unique case of autosomal recessive syndromic 46,XY Disorder of Sex Development (DSD) with testicular dysgenesis and chondrodysplasia resulting from a homozygous G287V missense mutation in the hedgehog acyl-transferase (HHAT) gene. This mutation occurred in the conserved membrane bound O-acyltransferase (MBOAT) domain and experimentally disrupted the ability of HHAT to palmitoylate Hh proteins such as DHH and SHH. Consistent with the patient phenotype, HHAT was found to be expressed in the somatic cells of both XX and XY gonads at the time of sex determination, and Hhat loss of function in mice recapitulates most of the testicular, skeletal, neuronal and growth defects observed in humans. In the developing testis, HHAT is not required for Sertoli cell commitment but plays a role in proper testis cord formation and the differentiation of fetal Leydig cells. Altogether, these results shed new light on the mechanisms of action of Hh proteins. Furthermore, they provide the first clinical evidence of the essential role played by lipid modification of Hh proteins in human testicular organogenesis and embryonic development.
ISSN: 1553-7390

hal-01063929
https://hal.archives-ouvertes.fr/hal-01063929
DOI : 10.1371/journal.pgen.1004340
PUBMED : 24784881

Éditeur(s) : HAL CCSD SAGE Publications (UK and US)
Résumé : International audience
Genetic approaches have shown that several genes could modify caries susceptibility; AmelogeninX (AMELX) has been repeatedly designated. Here, we hypothesized that AMELX mutations resulting in discrete changes of enamel microstructure may be found in children with a severe caries phenotype. In parallel, possible AMELX mutations that could explain resistance to caries may be found in caries-free patients. In this study, coding exons of AMELX and exon-intron boundaries were sequenced in 399 individuals with extensive caries (250) or caries-free (149) individuals from nine French hospital groups. No mutation responsible for a direct change of amelogenin function was identified. Seven single-nucleotide polymorphisms (SNPs) were found, 3 presenting a high allele frequency, and 1 being detected for the first time. Three SNPs were located in coding regions, 2 of them being non-synonymous. Both evolutionary and statistical analyses showed that none of these SNPs was associated with caries susceptibility, suggesting that AMELX is not a gene candidate in our studied population.
ISSN: 0022-0345

hal-01545481
https://hal.archives-ouvertes.fr/hal-01545481
DOI : 10.1177/0022034513482941

Éditeur(s) : HAL CCSD Ivyspring International Publisher
Résumé : International audience
Mullerian duct regression is a complex process which involves the AMH signalling pathway. We have previously demonstrated that besides AMH and its specific type II receptor (AMHRII), BMPR-IA and Smad5 are two essential factors implicated in this mechanism. Mothers against decapentaplegic homolog 4 (Smad4) is a transcription factor and the common Smad (co-Smad) involved in transforming growth factor beta (TGF-beta) signalling pathway superfamily. Since Smad4 null mutants die early during gastrulation, we have inactivated Smad4 in the Mullerian duct mesenchyme. Specific inactivation of Smad4 in the urogenital ridge leads to the partial persistence of the Mullerian duct in adult male mice. Careful examination of the urogenital tract reveals that the Mullerian duct retention is randomly distributed either on one side or both sides. Histological analysis shows a uterus-like structure, which is confirmed by the expression of estrogen receptor alpha. As previously described in a beta-catenin conditional mutant mouse model, beta-catenin contributes to Mullerian duct regression. In our mutant male embryos, it appears that beta-catenin expression is locally reduced along the urogenital ridge as compared to control mice. Moreover, the expression pattern is similar to those observed in control female mice. This study shows that reduced Smad4 expression disrupts the Wnt/beta-catenin signalling leading to the partial persistence of Mullerian duct
ISSN: 1449-2288

hal-01319890
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01319890
DOI : 10.7150/ijbs.12300
PUBMED : 27194944

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
The main familial focal epilepsies are autosomal dominant nocturnal frontal lobe epilepsy, familial temporal lobe epilepsy and familial focal epilepsy with variable foci. A frameshift mutation in the DEPDC5 gene (encoding DEP domain-containing protein 5) was identified in a family with focal epilepsy with variable foci by linkage analysis and exome sequencing. Subsequent pyrosequencing of DEPDC5 in a cohort of 15 additional families with focal epilepsies identified 4 nonsense mutations and 1 missense mutation. Our findings provided evidence of frequent (37%) loss-of-function mutations in DEPDC5 associated with a broad spectrum of focal epilepsies. The implication of a DEP (Dishevelled, Egl-10 and Pleckstrin) domain-containing protein that may be involved in membrane trafficking and/or G protein signaling opens new avenues for research.
ISSN: 1061-4036

hal-01544763
https://hal.archives-ouvertes.fr/hal-01544763
DOI : 10.1038/ng.2601

Éditeur(s) : HAL CCSD Portland Press
Résumé : International audience
CP12 is a small chloroplastic protein involved in the Calvin cycle that was shown to bind copper, a metal ion involved in modulation of its transition from reduced to oxidized state. In order to describe CP12 copper binding properties, copper-IMAC experiments and site-directed mutagenesis based on computational modeling, were coupled to top-down mass spectrometry (ESI-MS and MSMS). Copper-IMAC experiments allowed the primary characterization of mutation effects upon copper binding. Top-down MSMS experiments carried out under non-denaturing conditions on wild-type and mutant CP12/Cu2+ complexes then allowed fragment ions specifically liganding the copper ion to be determined. Comparison of MSMS datasets defined three regions involved in metal ion binding: residues D16 to D23, D38 to K50 and D70 to E76, with the two first regions containing selected residues for mutation. These data confirmed that copper ligands involved glutamic and aspartic residues in contrast to typical protein copper chelators. We propose that copper might play a role in regulation of CP12 biological activity.
ISSN: 0264-6021

hal-00479106
https://hal.archives-ouvertes.fr/hal-00479106
https://hal.archives-ouvertes.fr/hal-00479106/document
https://hal.archives-ouvertes.fr/hal-00479106/file/PEER_stage2_10.1042%252FBJ20082004.pdf
DOI : 10.1042/BJ20082004

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein (MAP) kinase pathway has been involved in the positive and negative regulation of cell proliferation. Upon mitogen stimulation, ERK1/ERK2 activation is necessary for G1- to S-phase progression whereas when hyperactived, this pathway could elicit cell cycle arrest. The mechanisms involved are not fully elucidated but a kinase-independent function of ERK1/2 has been evidenced in the MAPK-induced growth arrest. Here, we show that p70S6K, a central regulator of protein biosynthesis, is essential for the cell cycle arrest induced by overactivation of ERK1/2. Indeed, whereas MEK1 silencing inhibits cell cycle progression, we demonstrate that active mutant form of MEK1 or MEK2 triggers a G1 phase arrest by stimulating an activation of p70S6K by ERK1/2 kinases. Silencing of ERK1/2 activity by shRNA efficiently suppresses p70S6K phosphorylation on Thr421/Ser424 and S6 phosphorylation on Ser240/244 as well as p21 expression, but these effects can be partially reversed by the expression of kinase-dead mutant form of ERK1 or ERK2. In addition, we demonstrate that the kinase p70S6K modulates neither the p21 gene transcription nor the stability of the protein but enhances the translation of the p21 mRNA. In conclusion, our data emphasizes the importance of the translational regulation of p21 by the MEK1/2-ERK1/2-p70S6K pathway to negatively control the cell cycle progression. J. Cell. Physiol. 229: 903-915, 2014. © 2013 Wiley Periodicals, Inc.
ISSN: 0021-9541

hal-01061238
https://hal.archives-ouvertes.fr/hal-01061238
https://hal.archives-ouvertes.fr/hal-01061238/document
https://hal.archives-ouvertes.fr/hal-01061238/file/MEK12_OveractivationArticle_GUEGAN_JCP_2014.pdf
DOI : 10.1002/jcp.24521

Éditeur(s) : Inter-Research
Résumé : The marine environment is of special interest for studying hybridization between closely related taxa because of the high dispersal potential of planktonic larvae, such as those of most bivalve species. The oysters Crassostrea angulata and C. gigas are known to be very close genetically and entirely inter-fertile under controlled conditions. However, hybridization in the wild had not been investigated, mainly due to the lack of nuclear diagnostic markers. In the present paper, we first estimated genetic differentiation between these 2 closely related taxa using 8 microsatellite markers. Interestingly, 5 markers displayed significant differences of allele size between taxa. The subsequent sequencing of alleles of one of these microsatellites showed several mutational events, which suggested null alleles and homoplasy. The presence of 1 insertion/deletion event in its 5' flanking sequence enabled us to design a new bi-allelic ('C' and 'NC') nuclear PCR-restriction fragment length polymorphism (-RFLP) marker (CG44R). This, together with a mitochondrial DNA marker, was used to analyze populations of C. angulata and C. gigas. The CG44R allele frequencies were very different between C. angulata (f[C] = 0.91) and C. gigas (f[NC] = 0.92) populations. This analysis also provided evidence for hybridization between C. angulata and C. gigas in a wild Portuguese population where the 2 taxa are in contact due to recent transportation of C. gigas stocks for aquacultural production. Our results represent the first indication of hybridization between these 2 taxa in the natural environment, and contribute to knowledge of the evolutionary history of the Crassostrea genus.
Marine Ecology Progress Series (0171-8630) (Inter-Research), 2004 , Vol. 272 , P. 141-152

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/2004/publication-3355.pdf
http://archimer.ifremer.fr/doc/00000/3355/

Éditeur(s) : HAL CCSD European Respiratory Society
Résumé : International audience
Telomerase reverse transcriptase (TERT) or telomerase RNA (TERC) gene mutation is a major monogenic cause of pulmonary fibrosis. Sequencing of TERT/TERC genes is proposed to patients with familial pulmonary fibrosis. Little is known about the possible predictors of this mutation and its impact on prognosis. We retrospectively analysed all the genetic diagnoses made between 2007-2014 in patients with pulmonary fibrosis. We evaluated the prevalence of TERT/TERC disease-Associated variant (DAV), factors associated with a DAV, and the impact of the DAV on survival. 237 patients with pulmonary fibrosis (153 with familial pulmonary fibrosis, 84 with telomere syndrome features without familial pulmonary fibrosis) were tested for TERT/TERC DAV. DAV was diagnosed in 40 patients (16.8%), including five with non-idiopathic interstitial pneumonia. Prevalence of TERT/TERC DAV did not significantly differ between patients with familial pulmonary fibrosis or with only telomere syndrome features (18.2% versus 16.4%). Young age, red blood cell macrocytosis, and low platelet count were associated with the presence of DAV; the probability of DAV was increased for patients 40-60 years. Transplant-free survival was lower with than without TERT/TERC DAV (4.2 versus 7.2 years; p=0.046). TERT/TERC DAV were associated with specific clinical and biological features and reduced transplantfree survival. ©ERS 2016.
ISSN: 0903-1936

hal-01467555
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555/file/Prevalence%20and%20characteristics%20of%20TERT.pdf
DOI : 10.1183/13993003.02115-2015

Éditeur(s) : HAL CCSD
Résumé : This thesis falls within the scope of social and human geography and more exactly of« disability studies ». Understanding the disability like a « social object », the thesis analyzes the societal consideration of disabled people in non-urbanized areas with a high issue of touristic, recreational and patrimonial development. In the first place, it's the recent construction of disability as a social object that is discussed by reminding the history of the societal consideration of the disabled person in our occidental world. The French model and his fundamental rule of global accessibility for ail the domains of the social life are explained and the « Nature and Disability » thematic is more precisely analyzed as a development of an active living ideal for people who are in a disability situation. Secondly, the thesis develops this thematic on the particular field of the Reunion Island and tries to answer to a question which is both simple and complicated: « Today, how we live with a disability on the Reunion Island? ». ln a last time and on the basis of this study of the disability inside a Reunion Island society with accelerated transformations, the thesis specifies the current tendencies with the emergence of new public policies for the welcome of disabled people on natural and touristic areas of the island. To conclude and referring to an original survey, the thesis suggests some tools of evaluation and decision-making aids to these areas.
Cette thèse s'inscrit dans le champ de la géographie humaine et sociale et plus précisément dans celui des « disability studies ». En positionnant le handicap comme une « figure du social », la thèse analyse la prise en compte sociétale des personnes à mobilité réduite (PMR) dans des environnements non urbanisés, à très fort enjeu de développement touristique, récréatif et patrimonial. Dans un premier temps, c'est la construction récente du handicap en tant que figure du social qui est abordée, en rappelant l'historique de la considération de la personne handicapée dans nos sociétés occidentales. Le modèle français et son principe fondamental d'accessibilité généralisée à tous les domaines de la vie sociale sont détaillés et la thématique « Nature et Handicap » est analysée plus précisément, en tant que développement d'un idéal de vie active pour les personnes en situation de handicap. Dans un second temps, la thèse développe cette thématique sur le terrain particulier de l'Île de La Réunion et tente de répondre à une question à la fois simple et complexe : « comment vit-on avec une déficience aujourd'hui à La Réunion ? ». Dans un dernier temps et sur la base de cette analyse du handicap au sein d'une société réunionnaise aux mutations accélérées, la thèse précise les tendances actuelles avec l'apparition de nouvelles politiques publiques d'accueil des PMR dans les espaces naturels et touristiques de l'île. S'appuyant sur une enquête originale, la thèse propose enfin des outils d'évaluation et d'aide à la décision spécifiques à ces espaces.
https://tel.archives-ouvertes.fr/tel-01279042

NNT : 2012LARE0025
tel-01279042
https://tel.archives-ouvertes.fr/tel-01279042
https://tel.archives-ouvertes.fr/tel-01279042/document
https://tel.archives-ouvertes.fr/tel-01279042/file/2012lare0025_AGuenat.pdf