217 research outputs found

    DĂ©marches d’investigation en sciences et construction du savoir

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    National audienceDepuis plusieurs annĂ©es, les dĂ©marches dites «d’investigation» sont mises en avant dans les programmes scolaires en mathĂ©matiques et en sciences expĂ©rimentales. Depuis septembre 2013, les lycĂ©ens arrivant dans l’enseignement supĂ©rieur ont Ă©tĂ© initiĂ©s Ă  ces dĂ©marches, en particulier Ă  l’école primaire et au collĂšge. Lors du minicolloque «Enseignement» du congrĂšs gĂ©nĂ©ral de la SFP 2013, nous nous sommes centrĂ©s sur ce nouveau «profil» d’étudiant qui nĂ©cessite d’ĂȘtre connu des enseignants du supĂ©rieur, en particulier concernant les dĂ©marches scientifiques

    A thousand-genome panel retraces the global spread and adaptation of a major fungal crop pathogen

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    Human activity impacts the evolutionary trajectories of many species worldwide. Global trade of agricultural goods contributes to the dispersal of pathogens reshaping their genetic makeup and providing opportunities for virulence gains. Understanding how pathogens surmount control strategies and cope with new climates is crucial to predicting the future impact of crop pathogens. Here, we address this by assembling a global thousand-genome panel of Zymoseptoria tritici, a major fungal pathogen of wheat reported in all production areas worldwide. We identify the global invasion routes and ongoing genetic exchange of the pathogen among wheat-growing regions. We find that the global expansion was accompanied by increased activity of transposable elements and weakened genomic defenses. Finally, we find significant standing variation for adaptation to new climates encountered during the global spread. Our work shows how large population genomic panels enable deep insights into the evolutionary trajectory of a major crop pathogen

    Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

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    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3â€Č-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

    The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

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    Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

    Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    Get PDF
    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P = 9.2 x 10(-20)), ER-negative BC (P = 1.1 x 10(-13)), BRCA1-associated BC (P = 7.7 x 10(-16)) and triple negative BC (P-diff = 2 x 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 x 10(-3)) and ABHD8 (PPeer reviewe

    L’enclos cultuel latĂ©nien des « Jardins familiaux » Ă  Sin-le-Noble (Nord, France) : dĂ©pĂŽts mixtes de monnaies d’or et d’orfĂšvrerie celtique

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    International audienceL’amĂ©nagement d’un quartier au lieu-dit Le Raquet, sur les communes de Douai, Lambres et Sin-le-Noble (Nord) a conduit Ă  la fouille en2011/2012 par la CommunautĂ© d’agglomĂ©ration du Douaisis – Direction de l’archĂ©ologie prĂ©ventive, d’une superficie de 1,3 ha. À cette occasion fut dĂ©couvert un enclos quadrangulaire d’environ 40 m de cĂŽtĂ©, partiellement dĂ©truit par l’érosion. Le fossĂ© a livrĂ© diffĂ©rents dĂ©pĂŽts qui permettent d’avancer une destination au moins partiellement cultuelle pour cet enclos. On y a en effet dĂ©couvert la sĂ©pulture d’un individu en position contrainte ; trois (?) dĂ©pĂŽts soigneusement mis en scĂšne, associant des monnaies Ă  des bijoux en or ; un vase complet contenant des rĂ©sidus organiques (dĂ©pĂŽt n° 4), et finalement un dĂ©pĂŽt n° 5 constituĂ© de dix pesons en terre cuite. Les dĂ©pĂŽts ont Ă©tĂ© fouillĂ©s en laboratoire, et leur mise en scĂšne complexe a pu ĂȘtre mise en Ă©vidence. Ils associent des monnaies – statĂšres unifaces « ambiani » et quarts de statĂšres « au bateau » – Ă  des objets en or : dix statĂšres, sept quarts de statĂšres et un brassard en or (dĂ©pĂŽt n°1) ; sept statĂšres et quatre quarts de statĂšres (dĂ©pĂŽt n° 2) ; un statĂšre et un anneau en or (dĂ©pĂŽt n° 3). L’étude cĂ©ramologique pointe vers une date se situant vers le milieu du Ier s. av. J.-C. Les diffĂ©rents contextes rĂ©gionaux dans lesquels les monnaies apparaissent sont datables des annĂ©es 50/40-30 av. J.-C. et sont dĂšs lors postĂ©rieurs Ă  la Guerre des Gaules. Le remblaiement du fossĂ© est antĂ©rieur au rĂšgne d’Auguste
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