50 research outputs found
Sciences et Ătat de droit
Marie-AngĂšle Hermitte, directrice dâĂ©tudesOlivier Beauvallet, magistrat Naissance du droit pĂ©nal international Cet enseignement a Ă©tĂ© rĂ©alisĂ© en coopĂ©ration avec deux autres sĂ©minaires pour montrer, Ă travers trois thĂšmes distincts, les diffĂ©rents instruments que le droit mobilise pour mettre en Ćuvre ce que lâon recouvre du terme gĂ©nĂ©ral de globalisation. La dynamique de lâenseignement a conduit Ă traiter Ă©galement de « dĂ©globalisation ». Lâobjectif du sĂ©minaire Ă©tait de montrer par la diver..
Sciences et Ătat de droit
Marie-AngĂšle Hermitte, directrice dâĂ©tudesOlivier Beauvallet, magistrat Naissance du droit pĂ©nal international Cet enseignement a Ă©tĂ© rĂ©alisĂ© en coopĂ©ration avec deux autres sĂ©minaires pour montrer, Ă travers trois thĂšmes distincts, les diffĂ©rents instruments que le droit mobilise pour mettre en Ćuvre ce que lâon recouvre du terme gĂ©nĂ©ral de globalisation. La dynamique de lâenseignement a conduit Ă traiter Ă©galement de « dĂ©globalisation ». Lâobjectif du sĂ©minaire Ă©tait de montrer par la diver..
Bacterial protein signals are associated with Crohn's disease
Objective No Crohnâs disease (CD) molecular maker has advanced to clinical use, and independent lines of evidence support a central role of the gut microbial community in CD. Here we explore the feasibility of extracting bacterial protein signals relevant to CD, by interrogating myriads of intestinal bacterial proteomes from a small number of patients and healthy controls.
Design We first developed and validated a workflowâincluding extraction of microbial communities, two-dimensional difference gel electrophoresis (2D-DIGE), and LC-MS/MSâto discover protein signals from CD-associated gut microbial communities. Then we used selected reaction monitoring (SRM) to confirm a set of candidates. In parallel, we used 16S rRNA gene sequencing for an integrated analysis of gut ecosystem structure and functions.
Results Our 2D-DIGE-based discovery approach revealed an imbalance of intestinal bacterial functions in CD. Many proteins, largely derived from Bacteroides species, were over-represented, while under-represented proteins were mostly from Firmicutes and some Prevotella members. Most overabundant proteins could be confirmed using SRM. They correspond to functions allowing opportunistic pathogens to colonise the mucus layers, breach the host barriers and invade the mucosae, which could still be aggravated by decreased host-derived pancreatic zymogen granule membrane protein GP2 in CD patients. Moreover, although the abundance of most protein groups reflected that of related bacterial populations, we found a specific independent regulation of bacteria-derived cell envelope proteins.
Conclusions This study provides the first evidence that quantifiable bacterial protein signals are associated with CD, which can have a profound impact on future molecular diagnosis
Le Royaume-Uni Ă lâheure de la coalition
Dans lâhistoire politique britannique, la coalition constitue un mode de gouvernance atypique, provisoire et a priori instable. Or aprĂšs dix-huit annĂ©es dâhĂ©gĂ©monie nĂ©oconservatrice puis treize de domination politique du New Labour, le Royaume-Uni est dirigĂ© depuis quatre ans par une coalition politique rĂ©unissant, sous le leadership de David Cameron, les partis consservateur et libĂ©ral-dĂ©mocrate. Lâobjet de ce numĂ©ro est de faire un large tour dâhorizon de cette situation exceptionnelle, et de dresser un bilan critique de lâaction politique menĂ©e depuis 2010. Quelles sont les influences et les sources dâinspiration de la coalition ? Quels sont les Ă©lĂ©ments de continuitĂ© et de rupture par rapport aux politiques de la troisiĂšme voie ? Quâest-il advenu du projet de « Big Society » ? Quelle est la filiation idĂ©ologique avec le nĂ©o-libĂ©ralisme thatchĂ©rien ? Les articles prĂ©sentĂ©s abordent les diffĂ©rents aspects des politiques mises en Ćuvre, quâil s'agisse des domaines Ă©conomique, social ou sociĂ©tal ou des relations internationales. Ils interrogent aussi le fonctionnement de la coalition au quotidien, les tensions et rapports de force internes au sein des institutions, lâarticulation entre la cohĂ©rence du projet politique et la prĂ©servation dâidentitĂ©s partisanes. La situation actuelle est-elle pĂ©renne ? Traduit-ellle une Ă©volution durable du systĂšme britannique ? Comment ce mode de gouvernement est-il perçu par les militants, les mĂ©dias et lâopinion publique
Abstract P6-08-12: Feasibility of a nation-wide family-based study to assess cancer risks in families with a predicted pathogenic variant identified through hereditary breast and ovary multi-gene panel testing: The TUMOSPEC study
International audienceBackground. Assessment of the age-dependent cancer risk conferred by germline predicted pathogenic variants (PPV) in cancer susceptibility genes is often hampered by the way the data are collected. Cohort-based data frequently contain an overrepresentation of patients carrying a gene variant of interest and an underrepresentation of cancer-free gene variant carriers. In order to overcome this problem, penetrance estimates can be grounded on family-based study designs, through the evaluation of index patients (IP) and their family relatives. The purpose of the TUMOSPEC study is to estimate the penetrance of PPV in genes whose literature data are currently inaccurate or limited and to determine their associated tumour spectrum. This will lead to an appropriate assessment of the clinical utility of testing these genes. Methods. IP are enrolled consecutively among patients who are being offered a germline genetic test in a hereditary breast and ovary cancer (HBOC) context in a participating cancer genetics clinics. A panel of 24 genes (ATM, BAP1, BARD1, BRIP1, CHEK2, FANCM, FAM175A, MRE11A, NBN, STK11, RINT1, XRCC2, PALB2, MLH1, MSH2, MSH6, PMS2, CDH1, PTEN, RAD50, RAD51B, RAD51C, RAD51D, TP53) is tested in parallel of BRCA1 and BRCA2. If a PPV is identified, the IP is asked to give her/his first- and second-degree relatives and cousins address, regardless of their health status. Each relative is then contacted by the study coordinating centre (CC) to be invited. Each participant completes an epidemiological questionnaire addressing personal medical history and exposure to various risk factors, and provides a saliva sample to determine if he/she carries the familial PPV. The CC collects questionnaires, family history, clinical and genetic data. Results. Enrolment for the feasibility study takes place between Sep. 2017 and Dec. 2019 at each of the 46 participating french clinics. In June 2019, the study included 3,298 IP. So far, the CC received 1,241 TUMOSPEC panel results (37.6%) with a mean delay of 5 months [0.7 -17.5]. Among them, 169 carried a PPV in at least one of the genes (totalizing 183 PPV). Additionally, 44 IP with PPV identified beforehand were enrolled (table 1). Relativesâ invitation of these 213 IP began in June 2018. Among the relatives of the first 29 index cases contacted so far, 4.6 relatives per family consented to participate. Conclusions. The feasibility study showed that inclusion process is well adapted and that the communication between the various partners (clinicians, biologists, investigators and study participants) is quite smooth. Rates of inclusion for invited relatives (50%), for IP questionnaire completion (45%) and relatives biological sample collection (50%) are also very satisfactory and yet underestimated due to the recent start of relatives inclusions. Overall, this study shows that it is feasible to conduct a large-scale study to gather sufficient number of positive families for each gene included in the panel in a reasonable interval of time. This on-going national effort will allow to appropriately assess cancer risks cancer in families with a PPV in a gene often included in HBOC multi-gene panels. This is an essential step to optimize clinical management guidelines specific to each gene, and will represent a valuable resource for future research on the genetics of breast and ovary cancers
Co-invalidation of Prnp and Sprn in FVB/N mice affects reproductive performances and highlight complex biological relationship between PrP and Shadoo
International audienceShadoo and PrP belongs to the same protein family, whose biological function remains poorly understood. Previous experiments reported potential functional redundancies or antagonisms between these two proteins, depending on the tissue analysed. While knockdown experiments suggested the requirement of Shadoo in the absence of PrP during early mouse embryogenesis, knockout ones, on the contrary, highlighted little impact, if any, of the double-knockout of these two loci. In the present study, we reinvestigated the phenotype associated with the concomitant knockout of these two genes using newly produced FVB/N Sprn knockout mice. In this genetic background, the combined two genes & rsquo; knockout induces intra-uterine growth retardations, likely resulting from placental failures highlighted by transcriptomic analyses that revealed potential redundant or antagonist roles of these two proteins in different developmental-related pathways. It also induced an increased perinatal-lethality and ascertained the role of these two loci in the lactation process
Etude Genesis : trois ans d'inclusion en France
AbstractNational audienceIntroduction.â Le cancer du sein (CS) concerne environ 10% des femmes. Des mutations dans les gĂšnes BRCA1/2 sont impliquĂ©es dans environ 5% des CS et seulement 15 Ă 20%des cas familiaux testĂ©s. LâĂ©tude GENESIS a pour objectifs dâidentifier et de caractĂ©riser de nouveaux gĂšnes de prĂ©disposition et dâĂ©valuer le rĂŽle de facteurs non gĂ©nĂ©tiques qui pourraient modifier lâeffet de ces gĂšnes. Ceci permettra une meilleure prise en charge des femmes Ă risque.MĂ©thodes.â GENESIS combine une Ă©tude de liaison gĂ©nĂ©tique non paramĂ©trique chez des paires de soeurs atteintes de CS, non porteuses dâune mutation des gĂšnes BRCA et une Ă©tude dâassociation avec deux groupes tĂ©moins : soeurs indemnes et proches non apparentĂ©es. Lâeffectif attendu est 1000 paires de soeurs et 4000 tĂ©moins. Les cas index sont invitĂ©s par les consultants en gĂ©nĂ©tiquedu Groupe gĂ©nĂ©tique et cancer de la FĂ©dĂ©ration nationale des Centres de lutte contre le cancer. Des caractĂ©ristiques phĂ©notypiques des cas (caractĂ©ristiques tumorales, densitĂ© mammaire. . .) permettront de dĂ©finir des endophĂ©notypes et de diminuer ainsi lâhĂ©tĂ©rogĂ©nĂ©itĂ© gĂ©nĂ©tique de la population dâĂ©tude. Le centre coordonateur organise le recueil et la gestion des donnĂ©es Ă©pidĂ©miologiques et des mammographies, le centre de ressources biologiques ceux des Ă©chantillonssanguins.RĂ©sultats.â Fin 2010, 1493 cas index, 740 soeurs atteintes, 520 soeurs indemnes et 1289 amies ont acceptĂ© de participer et ont recžu un dossier dâinclusion ; 75% ont renvoyĂ© leur questionnaire, 76%ont fait leur prĂ©lĂšvement sanguin, 74% ont fourni des mammographies qui ont Ă©tĂ© numĂ©risĂ©es et anonymisĂ©es.Discussion/conclusion.â AprĂšs trois ans dâinclusions, 630 paires de soeurs atteintes participent Ă lâĂ©tude. Le protocole a Ă©tĂ© Ă©tendu aux index sans soeur atteinte disponible afin dâaugmenter la puissance des Ă©tudes dâassociation. Remerciements.âGENESIS est soutenue par la Ligue Nationale Contre le Cancer depuis 2006 et par lâINCa depuis 2008