87 research outputs found

    Sur le rapport du gouvernement de la Republika Srpska 

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    Cet article présente les origines, la mise en place, le travail et les suites du rapport par lequel le gouvernement de la Republika Srpska (RS) a, en juin 2004, reconnu la réalité du massacre de Srebrenica de juillet 1995. A l’origine, la Chambre des droits de l’Homme de Bosnie-Herzégovine a rendu en 2003 une décision qui ordonnait à la RS de faire une enquête sur les événements de Srebrenica. Suite à cette décision, le gouvernement de la RS a institué une commission aux travaux de laquelle un représentant de la Commission internationale pour les personnes portées disparues (ICMP) a été associée. Cet article présente d’abord le point de vue de la Chambre, puis celui de l’ICMP, institutions à la fois distinctes et complémentaires des juridictions pénales, qui, s’appuyant sur le principe de la défense des droits de l’Homme, considèrent les droits et le sort individuels des victimes de Srebrenica, morts et survivants, et la responsabilité collective du gouvernement de la RS.This article presents the origins, the establishment, the work and the consequences of the June 2004 report of the Government of the Republika Srpska (RS), whereby it formally acknowledged the Srebrenica massacre of July 1995. The Human Rights Chamber of Bosnia and Herzegovina delivered a decision in 2003 which ordered the RS to conduct an investigation into the events in Srebrenica. Following that decision, the RS Government created a commission with whose work a representative of the International Commission on Missing Persons (ICMP) was associated. This article first presents the point of view of the Human Rights Chamber, and then that of ICMP, two institutions that are at the same time distinct and complementary to criminal jurisdictions, which, resting on the principle of defending human rights, take into consideration the rights and the individual fate of the victims from Srebrenica, killed and surviving, and the collective responsibility of the RS Government

    Measurement of the Lateral Diffusion of Dipalmitoylphosphatidylcholine Adsorbed on Silica Beads in the Absence and Presence of Melittin: A 31P Two-Dimensional Exchange Solid-State NMR Study

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    Abstract31P two-dimensional exchange solid-state NMR spectroscopy was used to measure the lateral diffusion, DL, in the fluid phase of dipalmitoylphosphatidylcholine (DPPC) in the presence and absence of melittin. The use of a spherical solid support with a radius of 320±20nm, on which lipids and peptides are adsorbed together, and a novel way of analyzing the two-dimensional exchange patterns afforded a narrow distribution of DL centered at a value of (8.8±0.5)×10−8cm2/s for the pure lipid system and a large distribution of DL spanning 1×10−8 to 10×10−8cm2/s for the lipids in the presence of melittin. In addition, the determination of DL for nonsupported DPPC multilamellar vesicles (MLVs) suggests that the support does not slow down the lipid diffusion and that the radii of the bilayers vary from 300 to 800nm. Finally, the DPPC-melittin complex is stabilized at the surface of the silica beads in the gel phase, opening the way to further study of the interaction between melittin and DPPC

    Crosstalk between alternatively spliced UGT1A isoforms and colon cancer cell metabolism

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    Alternative splicing at the human glucuronosyltransferase 1 gene locus (UGT1) produces alternate isoforms UGT1A_i2s that control glucuronidation activity through protein-protein interactions. Here, we hypothesized that UGT1A_i2s function into a complex protein network connecting other metabolic pathways with influence on cancer cell metabolism. This is based on a pathway enrichment analysis of proteomic data that identified several high-confidence candidate interaction proteins of UGT1A_i2 proteins in human tissues, namely the rate-limiting enzyme of glycolysis pyruvate kinase (PKM), which plays a critical role in cancer cell metabolism and tumor growth. The partnership of UGT1A_i2 and PKM2 was confirmed by co-immunoprecipitation in the HT115 colon cancer cells and was supported by a partial co-localization of these two proteins. In support of a functional role for this partnership, depletion of UGT1A_i2 proteins in HT115 cells enforced the Warburg effect with higher glycolytic rate at the expense of mitochondrial respiration, and led to lactate accumulation. Untargeted metabolomics further revealed a significantly altered cellular content of 58 metabolites including many intermediates derived from the glycolysis and TCA cycle pathways. These metabolic changes were associated with a greater migration potential. The potential relevance of our observations is supported by the down-regulation of UGT1A_i2s mRNA in colon tumors compared to normal tissues. Alternate UGT1A variants may thus be part of the expanding compendium of metabolic pathways involved in cancer biology directly contributing to the oncogenic phenotype of colon cancer cells. Findings uncover new aspects of UGT functions diverging from their transferase activity

    PARPs database: A LIMS systems for protein-protein interaction data mining or laboratory information management system

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    <p>Abstract</p> <p>Background</p> <p>In the "post-genome" era, mass spectrometry (MS) has become an important method for the analysis of proteins and the rapid advancement of this technique, in combination with other proteomics methods, results in an increasing amount of proteome data. This data must be archived and analysed using specialized bioinformatics tools.</p> <p>Description</p> <p>We herein describe "PARPs database," a data analysis and management pipeline for liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomics. PARPs database is a web-based tool whose features include experiment annotation, protein database searching, protein sequence management, as well as data-mining of the peptides and proteins identified.</p> <p>Conclusion</p> <p>Using this pipeline, we have successfully identified several interactions of biological significance between PARP-1 and other proteins, namely RFC-1, 2, 3, 4 and 5.</p

    De la bête au non-humain : perspectives et controverses autour de la condition animale

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    À la croisée de l’anthropologie, de l’histoire, de la géographie et de la sociologie, cet ouvrage donne à voir un panorama des relations entre l’animal et l’homme de l’époque médiévale à nos jours, en différents endroits du monde. Témoins de l’évolution des statuts et du mouvement des frontières ontologiques, les contributions explorent la question animale dans ses dimensions mythiques, symboliques, idéologiques, environnementales, sociales, morales et éthiques. Le Congrès national des sociétés historiques et scientifiques rassemble chaque année universitaires, membres de sociétés savantes et jeunes chercheurs. Ce recueil est issu de travaux présentés lors du 141e Congrès sur le thème « L’animal et l’homme »

    A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling

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    Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. De novo dominant mutations in different members of the SWI/SNF chromatin remodeling complex have recently been described in individuals with Coffin-Siris (CSS) and Nicolaides-Baraitser (NCBRS) syndromes. Using a combination of whole-exome sequencing, NGS-based sequencing of 23 SWI/SNF complex genes, and molecular karyotyping in 46 previously undescribed individuals with CSS and NCBRS, we identified a de novo 1-bp deletion (c.677delG, p.Gly226Glufs*53) and a de novo missense mutation (c.914G>T, p.Cys305Phe) in PHF6 in two individuals diagnosed with CSS. PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex implicating dysfunction of a second chromatin remodeling complex in the pathogenesis of CSS-like phenotypes. Altogether, we identified mutations in 60% of the studied individuals (28/46), located in the genes ARID1A, ARID1B, SMARCB1, SMARCE1, SMARCA2, and PHF6. We show that mutations in ARID1B are the main cause of CSS, accounting for 76% of identified mutations. ARID1B and SMARCB1 mutations were also found in individuals with the initial diagnosis of NCBRS. These individuals apparently belong to a small subset who display an intermediate CSS/NCBRS phenotype. Our proposed genotype-phenotype correlations are important for molecular screening strategie

    La sculpture romaine en Occident

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    Cet ouvrage réunit les résultats de deux manifestations complémentaires  : d’une part, la table ronde intitulée «  Rendre à César  », organisée le mercredi 20 juin 2012, à Paris, au Musée du Louvre et, d’autre part, les «  Rencontres autour de la sculpture romaine conservée en France  » qui ont eu lieu du 18 au 20 octobre 2012 au Musée départemental Arles antique. La richesse des interventions lors de ces deux manifestations permet de restituer un ouvrage composé de trente-huit articles, répartis en trois parties et une conclusion. La première partie, en écho et en développement de la table ronde du Louvre, porte sur le portrait du «  César du Rhône  », aussi bien que sur «  Le portrait romain en Gaule  ». La deuxième partie publie cinq études autour des «  nouvelles techniques d’investigations scientifiques  » et présente l’analyse des matériaux des sculptures en pierre et en bronze, découvertes dans le Rhône à Arles, ainsi qu’une étude ethnoarchéologique sur les techniques de production du portrait. Enfin une troisième partie présente les «  découvertes récentes et les nouvelles recherches  », déclinées en seize études qui sont consacrées à des études de cas (Autun, Vaison-la-Romaine, Nîmes, Metz-Divodurum, Apt), ainsi qu’à des relectures novatrices de sculptures méconnues (Plouarzel, Langres, Avignonet-Lauragais, Vernègues, vallée de l’Ubaye, Besançon, Lyon). Robert Turcan signe la conclusion. Ainsi, «  La sculpture romaine en Occident. Nouveaux regards   » reflète la variété et l’intérêt des questionnements actuels dans ce domaine

    A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

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    Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock
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