Fréjus – Les Horts

Identifiant de l'opération archéologique : 8045 Date de l'opération : 2007 (EX) Inventeur(s) : Dumont Aurélie (INRAP) Une opération de diagnostic a été entreprise au 139 de la rue Einaudi, dans le quartier des Horts à Fréjus, à l’est du centre-ville. Le site est implanté dans la plaine au pied du rempart de la cité romaine et à une centaine de mètres du port romain, à une altitude de 3 m NGF. Les précédentes opérations réalisées dans ce secteur ont mis au jour des vestiges d’époque antique av..

Cavalaire-sur-Mer – Avenue Pierre et Marie Curie

Identifiant de l'opération archéologique : 8314 Date de l'opération : 2007 (EX) Inventeur(s) : Dumont Aurélie (INRAP) ; Michel Jean-Marie (INRAP) Une opération archéologique a été menée avenue Pierre-et-Marie-Curie dans le cadre d’un projet immobilier [ (Fig. n°1 : Localisation des découvertes antérieures (B : rue du Port ; C : rue Charles-de-Gaulle) et implantation des tranchées 2007 (A : avenue Pierre-et-Marie-Curie)), A]. Le terrain se situe en zone urbaine au sud-est du centre ville, à pr..

Draguignan – Parking Bontemps

Identifiant de l'opération archéologique : 8314 Date de l'opération : 2007 (EX) Inventeur(s) : Dumont Aurélie (INRAP) ; Michel Jean-Marie (INRAP) Une opération de diagnostic a été menée sur le parking Bontemps, rue Pierre-Clément à Draguignan, à l’occasion d’un projet de réaménagement du lieu et de la construction d’une partie souterraine. Le terrain se trouve hors des remparts de la ville médiévale dans les faubourgs alors qu’il se situe dans l’emprise de l’enceinte moderne (avenue Jean-Jaur..

Pratiques phytosanitaires en agriculture et environnement : des tensions irréductibles ?

La vulnérabilité croissante des ressources en eau et des milieux aquatiques aux pollutions a conduit au développement de dispositifs agri-environnementaux chargés en particulier de réduire et d’encadrer l’utilisation des pesticides (le plus récent étant le plan Ecophyto 2018 issu du Grenelle de l’environnement). Cette contribution analyse la tension entre les contraintes agricoles qui conditionnent les changements de pratiques phytosanitaires et les exigences environnementales désormais posées en termes d’obtention de résultats. L’observation d’un dispositif expérimental de diffusion de " pratiques améliorées " de traitement phytosanitaire, inscrit dans le Groupe d’action phytosanitaire de Midi-Pyrénées (Gramip), est mobilisée pour interroger, à partir d’une approche interdisciplinaire (économie, sociologie, agronomie), la permanence de logiques agricoles technico-économiques et l’émergence d’arguments sanitaires et commerciaux comme facteurs potentiels de diffusion de pratiques alternatives à l’utilisation des pesticides en agriculture. / The increasing vulnerability of water resources and aquatic pollution has led to the development of agrienvironmental tools in particular to reduce and control the use of pesticides. This paper explores the tension between the constraints that affect changes of phytosanitary practices and environmental requirements now posed in terms of environmental results. The observation of an experimental policy instrument of "better practices" in Midi-Pyrenees (Gramip), is mobilized to examine, from an interdisciplinary approach (economics, sociology, agronomy), the permanence of agricultural techno-economic logic and the emergence of health and commercial factors as potential diffusion of alternative practices to the use of pesticides in agriculture

Combined Mutation And Rearrangement Screening by Quantitative PCR High-Resolution Melting: Is It Relevant for Hereditary Recurrent Fever Genes?

The recent identification of genes implicated in hereditary recurrent fevers has allowed their specific diagnosis. So far however, only punctual mutations have been identified and a significant number of patients remain with no genetic confirmation of their disease after routine molecular approaches such as sequencing. The possible involvement of sequence rearrangements in these patients has only been examined in familial Mediterranean fever and was found to be unlikely. To assess the existence of larger genetic alterations in 3 other concerned genes, MVK (Mevalonate kinase), NLRP3 (Nod like receptor family, pyrin domain containing 3) and TNFRSF1A (TNF receptor superfamily 1A), we adapted the qPCR-HRM method to study possible intragenic deletions and duplications. This single-tube approach, combining both qualitative (mutations) and quantitative (rearrangement) screening, has proven effective in Lynch syndrome diagnosis. Using this approach, we studied 113 unselected (prospective group) and 88 selected (retrospective group) patients and identified no intragenic rearrangements in the 3 genes. Only qualitative alterations were found with a sensitivity similar to that obtained using classical molecular techniques for screening punctual mutations. Our results support that deleterious copy number alterations in MVK, NLRP3 and TNFRSF1A are rare or absent from the mutational spectrum of hereditary recurrent fevers, and demonstrate that a routine combined method such as qPCR-HRM provides no further help in genetic diagnosis. However, quantitative approaches such as qPCR or SQF-PCR did prove to be quick and effective and could still be useful after non contributory punctual mutation screening in the presence of clinically evocative signs

Muscle RANK is a key regulator of calcium storage, SERCA activity, and function of fast-twitch skeletal muscles

Receptor-activator of nuclear factor kB (RANK), its ligand RANKL and the soluble decoy receptor osteoprotegerin (OPG)are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion (RANKmko) has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscle preventing the loss of maximum specific force while promoting muscle atrophy, fatigability and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 (Stim1) content, a calcium sensor, and altered activity of the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) modulating Ca2+ storage. Muscle RANK deletion had no significant effects on the sham or denervated slow-twitch soleus (Sol) muscles. These data identify a novel role for RANK as a key regulator of calcium storage and SERCA activity, ultimately affecting denervated skeletal muscle function

Specific Oncogenic Activity of the Src-Family Tyrosine Kinase c-Yes in Colon Carcinoma Cells

c-Yes, a member of the Src tyrosine kinase family, is found highly activated in colon carcinoma but its importance relative to c-Src has remained unclear. Here we show that, in HT29 colon carcinoma cells, silencing of c-Yes, but not of c-Src, selectively leads to an increase of cell clustering associated with a localisation of β-catenin at cell membranes and a reduction of expression of β-catenin target genes. c-Yes silencing induced an increase in apoptosis, inhibition of growth in soft-agar and in mouse xenografts, inhibition of cell migration and loss of the capacity to generate liver metastases in mice. Re-introduction of c-Yes, but not c -Src, restores transforming properties of c-Yes depleted cells. Moreover, we found that c-Yes kinase activity is required for its role in β-catenin localisation and growth in soft agar, whereas kinase activity is dispensable for its role in cell migration. We conclude that c-Yes regulates specific oncogenic signalling pathways important for colon cancer progression that is not shared with c-Src

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

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

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers