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

Le bouvier dans la poésie hellénistique et le roman grec

Dans la poésie bucolique, le bouvier est avec les autres pâtres un personnage essentiel et éminent – à partir de la figure légendaire et fondatrice de Daphnis. La présence du bouvier ne se limite toutefois pas à cet univers générique précis, on le voit peupler l’espace de différents autres genres littéraires depuis Homère et la poésie archaïque. Les textes réunis dans ce volume mettent en relation deux représentations concurrentes du bouvier dans la poésie hellénistique et dans le roman de l’époque impériale ; ils visent à mettre en lumière les potentialités poétiques, dramatiques et anthropologiques de cette figure pastorale. In bucolic poetry, the cowherd is with the other herdsmen an essential and eminent character—starting with the legendary and founding figure of Daphnis. But the presence of the cowherd is not limited to this precise generic universe, but he is also populating the space of various other literary genres since Homer and archaic poetry. The texts in this volume relate two competing representations of the cowherd in Hellenistic poetry and in the novel of the imperial period; they aim to highlight the poetic, dramatic and anthropological potentialities of this pastoral figure. A partire da Daphnis, figura leggendaria e fondatrice, il bovaro è, insieme agli altri pastori, un personaggio essenziale ed eminente nella poesia bucolica. Tuttavia, la presenza del bovaro non si limita soltanto a questo preciso ambito letterario, ma si estende a vari altri generi dopo Omero e la poesia arcaica. I testi raccolti in questo volume mettono in relazione due rappresentazioni contrapposte del pastore nella poesia ellenistica e nel romanzo di età imperiale; essi mirano ad evidenziare le potenzialità poetiche, drammatiche e antropologiche di questa figura

The forestry & wood sector and climate change mitigation: From carbon sequestration in forests to the development of the bioeconomy

While the main challenge in intertropical and boreal regions is tackling deforestation and forest resource degradation, forests and forestry in temperate regions face what may appear to be contradictory goals: to increase atmospheric carbon capture through sequestration in biomass and soils, while providing a growing share of the resources needed to produce essential material goods and energy for human societies as well as gradually renewing forests to enable them to adapt to future climate conditions. Creating a balance between these potentially competing priorities has been the subject of intense societal and scientific debate in recent years, which has prompted us to examine all aspects of these issues in greater depth. INRAE and IGN, at the request of the French Ministries responsible for agriculture and forestry, have jointly undertaken a scientific assessment to shed light on the details of this debate, using the example of forests and the forestry & wood sectors in metropolitan France. The results of this important exercise are presented in this book

The forestry & wood sector and climate change mitigation: From carbon sequestration in forests to the development of the bioeconomy

International audienceWhile the main challenge in intertropical and boreal regions is tackling deforestation and forest resource degradation, forests and forestry in temperate regions face what may appear to be contradictory goals: to increase atmospheric carbon capture through sequestration in biomass and soils, while providing a growing share of the resources needed to produce essential material goods and energy for human societies as well as gradually renewing forests to enable them to adapt to future climate conditions. Creating a balance between these potentially competing priorities has been the subject of intense societal and scientific debate in recent years, which has prompted us to examine all aspects of these issues in greater depth. INRAE and IGN, at the request of the French Ministries responsible for agriculture and forestry, have jointly undertaken a scientific assessment to shed light on the details of this debate, using the example of forests and the forestry & wood sectors in metropolitan France. The results of this important exercise are presented in this book

Quel rôle pour les forêts et la filière forêt-bois françaises dans l’atténuation du changement climatique? Une étude des freins et leviers forestiers à l’horizon 2050

La présente étude a été réalisée par l’INRA et l’IGN et financée par le Ministère de l’Agriculture et de l’Alimentation (MAA). Le CGAAER avait en amont de ce travail pris l’initiative de solliciter l’INRA pour mener une réflexion de ce type dans les suites du rapport du Conseil général analysant la façon dont l’agriculture et la forêt françaises pouvaient contribuer à la lutte contre le changement climatique (Madignier et al., 2014). L’étude a été conduite par la Délégation à l’Expertise scientifique collective, à la Prospective et aux Etudes (DEPE) de l’INRA et selon les principes et les règles de conduite des expertises et des études qui régissent les travaux menés par cette structure

CDCP1 enhances Wnt signaling in colorectal cancer promoting nuclear localization of β-catenin and E-cadherin

Elevated CUB-domain containing protein 1 (CDCP1) is predictive of colorectal cancer (CRC) recurrence and poor patient survival. While CDCP1 expression identifies stem cell populations that mediate lung metastasis, mechanisms underlying the role of this cell surface receptor in CRC have not been defined. We sought to identify CDCP1 regulated processes in CRC using stem cell populations, enriched from primary cells and cell lines, in extensive in vitro and in vivo assays. These experiments, demonstrating that CDCP1 is functionally important in CRC tumor initiation, growth and metastasis, identified CDCP1 as a positive regulator of Wnt signaling. Detailed cell fractionation, immunoprecipitation, microscopy, and immunohistochemical analyses demonstrated that CDCP1 promotes translocation of the key regulators of Wnt signaling, β-catenin, and E-cadherin, to the nucleus. Of functional importance, disruption of CDCP1 reduces nuclear localized, chromatin-associated β-catenin and nuclear localized E-cadherin, increases sequestration of these proteins in cell membranes, disrupts regulation of CRC promoting genes, and reduces CRC tumor burden. Thus, disruption of CDCP1 perturbs pro-cancerous Wnt signaling including nuclear localization of β-catenin and E-cadherin

Harmonised projections of future forest resources in Europe

• Key message A dataset of forest resource projections in 23 European countries to 2040 has been prepared for forest-related policy analysis and decision-making. Due to applying harmonised definitions, while maintaining country-specific forestry practices, the projections should be usable from national to international levels. The dataset can be accessed at https://doi.org/10.5061/dryad.4t880qh . The associated metadata are available at https://metadata-afs.nancy.inra.fr/geonetwork/srv/eng/catalog.search#/metadata/8f93e0d6-b524-43bd-bdb8-621ad5ae6fa9