10 research outputs found
Les enzymes de conjugaison Ă lâubiquitine dans lâautisme
Lâautisme est une pathologie neurodĂ©veloppementale impliquant des facteurs gĂ©nĂ©tiques. Nous utilisons une stratĂ©gie dâĂ©tude de gĂšnes candidats choisis pour leur rĂŽle clĂ© dans la voie de lâubiquitine, impliquĂ©e dans des mĂ©canismes de neurogĂ©nĂšse ou de plasticitĂ© synaptique mis en cause dans lâautisme.Lâidentification des 37 enzymes de conjugaison Ă lâubiquitine E2 humaines, groupĂ©es en 17 familles, a permis de sĂ©lectionner 6 enzymes pour mener une recherche de mutation chez 195 autistes : UBE2H, UBE2A, UBE2K, UBE2I, UBE2N, UBE2E3.Aucune mutation nâa Ă©tĂ© dĂ©tectĂ©e dans notre population dâautistes, et aucune preuve gĂ©nĂ©tique nâa pu impliquer les gĂšnes UBE2K, UBE2A et UBE2N. En revanche des associations significatives ont Ă©tĂ© mises en Ă©vidence avec des polymorphismes des gĂšnes UBE2E3, UBE2I et UBE2H.Des Ă©tudes in vitro ont mis en Ă©vidence les rĂŽles importants dâenzymes E2 lors de la neurogĂ©nĂšse : UBE2H favorise la prolifĂ©ration des CSN tout en empĂȘchant la diffĂ©renciation neuronale, tandis quâUBE2A modifie la diffĂ©renciation des CSN par une augmentation de la taille des neurites.Les recherches restent donc encouragĂ©es par ces premiers rĂ©sultats trĂšs prometteurs.Autism is a neurodevelopmental disorder involving genetic factors. We use a candidate genes strategy selected for their key role in the ubiquitin pathway involved in mechanisms of neurogenesis and synaptic plasticity implicated in autism.Identification of the 37 human ubiquitin conjugating enzymes E2, grouped into 17 families, helped to select 6 enzymes to conduct a mutation screening in 195 autistic patients: UBE2H, UBE2A, UBE2K, UBE2I, UBE2N, UBE2E3.No mutation was detected in our autistic population, and no genetic evidence could involve UBE2K, UBE2A and UBE2N genes. However significant associations were identified with polymorphisms from UBE2E3, UBE2I and UBE2H genes.In vitro studies highlighted the important role of E2 enzymes during neurogenesis: UBE2H promotes the proliferation of NSC while preventing neuronal differentiation, while UBE2A alters differentiation of NSC by increasing the neurites size.Researches therefore remain encouraged by these very promising initial results
Les enzymes de conjugaison Ă l'ubiquitine dans l'autisme
L autisme est une pathologie neurodĂ©veloppementale impliquant des facteurs gĂ©nĂ©tiques. Nous utilisons une stratĂ©gie d Ă©tude de gĂšnes candidats choisis pour leur rĂŽle clĂ© dans la voie de l ubiquitine, impliquĂ©e dans des mĂ©canismes de neurogĂ©nĂšse ou de plasticitĂ© synaptique mis en cause dans l autisme.L identification des 37 enzymes de conjugaison Ă l ubiquitine E2 humaines, groupĂ©es en 17 familles, a permis de sĂ©lectionner 6 enzymes pour mener une recherche de mutation chez 195 autistes : UBE2H, UBE2A, UBE2K, UBE2I, UBE2N, UBE2E3.Aucune mutation n a Ă©tĂ© dĂ©tectĂ©e dans notre population d autistes, et aucune preuve gĂ©nĂ©tique n a pu impliquer les gĂšnes UBE2K, UBE2A et UBE2N. En revanche des associations significatives ont Ă©tĂ© mises en Ă©vidence avec des polymorphismes des gĂšnes UBE2E3, UBE2I et UBE2H.Des Ă©tudes in vitro ont mis en Ă©vidence les rĂŽles importants d enzymes E2 lors de la neurogĂ©nĂšse : UBE2H favorise la prolifĂ©ration des CSN tout en empĂȘchant la diffĂ©renciation neuronale, tandis qu UBE2A modifie la diffĂ©renciation des CSN par une augmentation de la taille des neurites.Les recherches restent donc encouragĂ©es par ces premiers rĂ©sultats trĂšs prometteurs.Autism is a neurodevelopmental disorder involving genetic factors. We use a candidate genes strategy selected for their key role in the ubiquitin pathway involved in mechanisms of neurogenesis and synaptic plasticity implicated in autism.Identification of the 37 human ubiquitin conjugating enzymes E2, grouped into 17 families, helped to select 6 enzymes to conduct a mutation screening in 195 autistic patients: UBE2H, UBE2A, UBE2K, UBE2I, UBE2N, UBE2E3.No mutation was detected in our autistic population, and no genetic evidence could involve UBE2K, UBE2A and UBE2N genes. However significant associations were identified with polymorphisms from UBE2E3, UBE2I and UBE2H genes.In vitro studies highlighted the important role of E2 enzymes during neurogenesis: UBE2H promotes the proliferation of NSC while preventing neuronal differentiation, while UBE2A alters differentiation of NSC by increasing the neurites size.Researches therefore remain encouraged by these very promising initial results.TOURS-Bibl.Ă©lectronique (372610011) / SudocSudocFranceF
Developmental Cycle and Genome Analysis of Protochlamydia massiliensis sp nov a New Species in the Parachlamydiacae Family
International audienceAmoeba-associated microorganisms (AAMs) are frequently isolated from water networks. In this paper, we report the isolation and characterization of Protochlamydia massiliensis, an obligate intracellular Gram-negative bacterium belonging to the Parachlamydiaceae family in the Chlamydiales order, from a cooling water tower. This bacterium was isolated on Vermamoeba vermiformis. It has a multiple range of hosts among amoeba and is characterized by a typical replication cycle of Chlamydiae with a particularity, recently shown in some chlamydia, which is the absence of inclusion vacuoles in the V. vermiformis host, adding by this a new member of Chlamydiae undergoing developmental cycle changes in the newly adapted host V. vermiformis. Draft genome sequencing revealed a chromosome of 2.86 Mb consisting of four contigs and a plasmid of 92 Kb
Protochlamydia phocaeensis sp nov., a new Chlamydiales species with host dependent replication cycle
International audienceChlamydiae are pathogenic and symbiotic bacteria, which form an important part of amoeba-associated microorganisms. In this paper, we report the isolation, developmental cycle and genome analysis of Protochlamydia phocaeensis sp. nov., an obligate intracellular parasite with a large host spectrum, able to infect Acanthamoeba castellanii, Acanthamoeba polyphaga, and Vermamoeba vernnformis. The genome size is 3,424,182 bp with a GC content of 42%. This bacterium displayed a particular developmental cycle depending on the infected host. The P. phocaeensis showed typical inclusion vacuoles in A. castellanii, while these were absent in V vernnformis. Since ``Chlamydiae amoebae'' interactions are supposed to depend on the chlamydial species, our findings speculate that variations in the developmental cycle of certain Chlamydiae are also host dependent. (C) 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved
Developmental Cycle and Genome Analysis of ``Rubidus massiliensis,'' a New Vermamoeba vermiformis Pathogen
International audienceThe study of amoeba-associated Chlamydiae is a dynamic field in which new species are increasingly reported. In the present work, we characterized the developmental cycle and analyzed the genome of a new member of this group associated with Vermarnoeba vermiforrnis, we propose to name ``Rubidus rnassiliensis.'' This bacterium is well-adapted to its amoeba host and do not reside inside of inclusion vacuoles after phagocytosis. It has a developmental cycle typical of this family of bacteria, with a transition from condensed elementary bodies to hypodense replicative reticulate bodies. Multiplication occurs through binary fission of the reticulate bodies. The genome of ``R. massiliensis'' consists of a 2.8 Mbp chromosome and two plasmids (pRml, pRm2) consisting of 39,075 bp and 80,897 bp, respectively, a feature that is unique within this group. The Re-analysis of the Chlamydiales genomes including the one of ``R. massiliensis'' slightly modified the previous phylogeny of the tic gene encoding the ADP/ATP translocase. Our analysis suggested that the tic gene could have been transferred to plant and algal plastids before the transfer to Rickettsiales, and that this gene was probably duplicated several times
Divergent Gemycircularvirus in HIV-Positive Blood, France
International audienceWe retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII-IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09-2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00-1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT
High-quality draft genome sequence and description of Haemophilus massiliensis sp nov.
International audienceStrain FF7(T) was isolated from the peritoneal fluid of a 44-year-old woman who suffered from pelvic peritonitis. This strain exhibited a 16S rRNA sequence similarity of 94.8 % 16S rRNA sequence identity with Haemophilus parasuis, the phylogenetically closest species with a name with standing in nomenclature and a poor MALDI-TOF MS score (1.32 to 1.56) that does not allow any reliable identification. Using a polyphasic study made of phenotypic and genomic analyses, strain FF7(T) was a Gram-negative, facultatively anaerobic rod and member of the family Pasteurellaceae. It exhibited a genome of 2,442,548 bp long genome (one chromosome but no plasmid) contains 2,319 protein-coding and 67 RNA genes, including 6 rRNA operons. On the basis of these data, we propose the creation of Haemophilus massiliensis sp. nov. with strain FF7(T) (= CSUR P859 = DSM 28247) as the type strain
Additional file 1: Table S1. of High-quality draft genome sequence and description of Haemophilus massiliensis sp. nov.
Antimicrobial susceptibility and minimum inhibitory concentrations (MIC) of Haemophilus massiliensis strain FF7T sp nov. (DOC 30 kb
Additional file 2: Table S2. of High-quality draft genome sequence and description of Haemophilus massiliensis sp. nov.
Differential characteristics of Haemophilus massiliensis strain FF7T (data from this study), H. influenzae strain ATCC 33391T [1, 33], H. sputorum strain CCUG 13788T [38, 39], H. pittmaniae strain HK 85T [40, 41], Haemophilus felis strain TI189T [42, 43] and H. parasuis strain ATCC 19417T [33, 41]. na = data not available. (DOC 57 kb