The Metallo-β-Lactamase/β-CASP Domain of Artemis Constitutes the Catalytic Core for V(D)J Recombination

The V(D)J recombination/DNA repair factor Artemis belongs to the metallo-β-lactamase (β-Lact) superfamily of enzymes. Three regions can be defined within the Artemis protein sequence: (a) the β-Lact homology domain, to which is appended (b) the β-CASP region, specific of members of the β-Lact superfamily acting on nucleic acids, and (c) the COOH-terminal domain. Using in vitro mutagenesis, here we show that the association of the β-Lact and the β-CASP regions suffices for in vivo V(D)J recombination of chromosome-integrated substrates. Single amino acid mutants point to critical catalytic residues for V(D)J recombination activity. The results presented here define the β-Lact/β-CASP domain of Artemis as the minimal core catalytic domain needed for V(D)J recombination and suggest that Artemis uses one or two Zn(II) ions to exert its catalytic activity, like bacterial class B β-Lact enzymes hydrolyzing β-lactam compounds

Chronique de jurisprudence constitutionnelle française 2015

Désormais traditionnelle dans cette revue, la chronique de jurisprudence constitutionnelle vise à faire un état des lieux annuel des décisions rendues par le Conseil constitutionnel. Sous un angle critique, les auteurs présentent les continuités et ruptures de jurisprudence, ainsi que la variabilité du contrôle exercé par le Conseil selon les droits en cause.Now traditional in this journal, the chronicle of constitutional jurisprudence aims to make an annual inventory of the Constitutional Council’s decisions. The authors present, from a critical point of view, the continuity and discontinuity of case law, and the variability of the control exercised by the Council according to the rights in question

Systemic epigenetic response to recombinant lentiviral vectors independent of proviral integration

Background: Lentiviral vectors (LV) are widely used for various gene transfer or gene therapy applications. The effects of LV on target cells are expected to be limited to gene delivery. Yet, human hematopoietic CD34+ cells respond to functional LVs as well as several types of non-integrating LVs by genome-wide DNA methylation changes. Results: A new algorithm for the analysis of 450K Illumina data showed that these changes were marked by de novo methylation. The same 4126 cytosines located in islands corresponding to 1059 genes were systematically methylated. This effect required cellular entry of the viral particle in the cells but not the genomic integration of the vector cassette. Some LV preparations induced only mild sporadic changes while others had strong effects suggesting that LV batch heterogeneity may be related to the extent of the epigenetic response. Conclusion: These findings identify a previously uncharacterized but consistent cellular response to viral components and provide a novel example of environmentally modified epigenome. © 2016 The Author(s)

The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage

The CHD4 helicase is identified as a new component of the genome surveillance machinery in a proteomic screen for factors enriched on chromatin after ionizing radiation (see also related paper by Smeenk et al. in this issue)

Contribution à l'analyse et à la réalisation d'un système de CAO à base de caractéristiques de forme

Modelling represents a large part of CAD/CAM systems. The work presented in this thesis is concerned with product modelling and consists in proposing a form feature-based design system. This system has main functions : features insertion in the designed part and their management all along the product evolution (modification, removal ...) ; creation of user-defined generic features and their insertion in the form feature library. A data structure able to model form features is presented first. Then a modification management method in the design model is proposed ; it avoids re-evaluating the whole design history. Finally, interactive and convivial tools allow the user to integrate new features into the software. The last part is concerned with the computer implementation of these proposalsLa modélisation représente une partie très importante des systèmes de conception et fabrication assistées par ordinateur. Les travaux présentés dans ce mémoire s'inscrivent dans la cadre de la modélisation produit et consistent plus précisément à proposer un système de conception basé sur les caractéristiques de forme. Le système propose remplit deux fonctions principales : - l'insertion de caractéristiques dans la pièce en cours de conception et leur maintenance pendant toute l'évolution du produit (modification, suppression) ; - la création par l'opérateur de nouvelles caractéristiques génériques et leur insertion dans la bibliothèque de caractéristiques de forme. Une structure de données permettant de modéliser les caractéristiques de forme est tout d'abord présentée. Puis une méthode de gestion des modifications dans le modèle de conception, qui évite de réévaluer tout l'historique de construction de la scène, est proposée. Enfin, des outils interactifs et conviviaux permettent à l'utilisateur d'intégrer de nouvelles caractéristiques au logiciel. Une dernière partie est consacrée à la mise en œuvre informatique des proposition

La sphère oro-faciale dans la trisomie 21 (pathologies et traitements)

NANCY1-SCD Pharmacie-Odontologie (543952101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Chronique de jurisprudence constitutionnelle française 2015

International audienc

Mycobacterium tuberculosis prosthetic joint infections a case series and literature review

International audienceObjectives - We aimed to characterize diagnosis, management, and outcome of Mycobacterium tuberculosis prosthetic joint infections (PJI).Methods - Cases of M. tuberculosis PJI documented in 7 referral French centers were retrospectively reviewed. Data were collected from medical files on a standardized questionnaire. We performed a literature review using the keywords 'prosthetic joint', and 'tuberculosis'. Results - During years 1997-2016, 13 patients (8 males, 5 females, median age 79 years [range, 60-86]) had documented M. tuberculosis PJI, involving hip (n = 6), knee (n = 6), or shoulder (n = 1). Median time from arthroplasty to diagnosis was 9 years [0.4-20]. The diagnosis was obtained on joint aspirates (n = 9), or synovial tissue (n = 4). PCR was positive in all cases tested (5/5). Median duration of antituberculosis treatment was 14 months [6-32]). Nine patients underwent surgery: debridement (n = 4), resection arthroplasty (n = 3), and revision arthroplasty (1-stage exchange, n = 2). PJI was controlled in 12 patients. Seventeen additional cases of documented M. tuberculosis PJI have been reported, with a favorable outcome in 79% (11/14) of patients with no surgery, 85% (11/13) with debridement, 86% (19/22) with revision arthroplasty, and 81% (17/21) with resection (NS). Conclusions - M. tuberculosis PJI can be controlled with prolonged antituberculosis treatment in most cases, with or without surgical treatment

Lentiviral transduction of CD34(+) cells induces genome-wide epigenetic modifications.

Epigenetic modifications may occur during in vitro manipulations of stem cells but these effects have remained unexplored in the context of cell and gene therapy protocols. In an experimental model of ex vivo gene modification for hematopoietic gene therapy, human CD34(+) cells were cultured shortly in the presence of cytokines then with a gene transfer lentiviral vector (LV) expected to transduce cells but to have otherwise limited biological effects on the cells. At the end of the culture, the population of cells remained largely similar at the phenotypic level but some epigenetic changes were evident. Exposure of CD34(+) cells to cytokines increased nuclear expression of epigenetic regulators SIRT1 or DNMT1 and caused genome-wide DNA methylation changes. Surprisingly, the LV caused additional and distinct effects. Large-scale genomic DNA methylation analysis showed that balanced methylation changes occurred in about 200 genes following culture of CD34(+) cells in the presence of cytokines but 900 genes were modified following addition of the LV, predominantly increasing CpG methylation. Epigenetic effects resulting from ex vivo culture and from the use of LV may constitute previously unsuspected sources of biological effects in stem cells and may provide new biomarkers to rationally optimize gene and cell therapy protocols