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The 37/67 kDa laminin receptor (LR) is a non-integrin protein, which binds both laminin-1 of the extracellular matrix and prion proteins, that hold a central role in prion diseases. The 37/67 kDa LR has been identified as interactor for the prion protein (PrPC) and to be required for pathological PrP (PrPSc) propagation in scrapie-infected neuronal cells, leading to the possibility that 37/67 kDa LR-PrPC interaction is related to the pathogenesis of prion diseases. A relationship between 37/67 kDa LR and PrPC in the presence of specific LR inhibitor compounds has not been investigated yet. We have characterized the trafficking of 37/67 kDa LR in both neuronal and non-neuronal cells, finding the receptor on the cell surface and nuclei and identified the 67 kDa LR as the almost exclusive isoform interacting with PrPC. Here, we show that the treatment with the 37/67 kDa LR inhibitor, NSC47924, affects both the direct 37/67 kDa LR-PrPC interaction in vitro and the formation of the immunocomplex in live cells, inducing a progressive internalization of 37/67 kDa LR and stabilization of PrPC on the cell surface. These data reveal NSC47924 as a useful tool to regulate PrPC and 37/67 kDa LR trafficking and degradation, representing a novel small molecule to be tested against prion diseases.

Based on a pluridisciplinary research programme on New Caledonia's lagoon (2004-2008), this paper addresses economic, ecological and political issues in order to implement integrated coastal zone management (ICZM) in this French Pacific territory. The nickel mining industry constitutes the core of the re-balancing economic and social strategy between the Northern and Southern provinces. But major impacts on the coastal environment of metal-processing plants, harbours, and decades of mine exploitation have released a controversy. A short diachronic analysis suggests that such environmental concerns prompted the emergence of collective actions to among civil society, customary and institutional stakeholders. The inscription of New Caledonia lagoon and reef areas in the UNESCO World Heritage List in 2008 would be both an outcome and a catalyst of this on-going process. Looking beyond the reefs towards the mainland and watersheds for the construction of local socio-ecological systems, we assume that the current stakes could result in the initiation of ICZM in New Caledonia.

International audience; This study examined the association between long working hours and cognitive function in middle age. Data were collected in 1997-1999 (baseline) and 2002-2004 (follow-up) from a prospective study of 2,214 British civil servants who were in full-time employment at baseline and had data on cognitive tests and covariates. A battery of cognitive tests (short-term memory, Alice Heim 4-I, Mill Hill vocabulary, phonemic fluency, and semantic fluency) were measured at baseline and at follow-up. Compared with working 40 hours per week at most, working more than 55 hours per week was associated with lower scores in the vocabulary test at both baseline and follow-up. Long working hours also predicted decline in performance on the reasoning test (Alice Heim 4-I). Similar results were obtained by using working hours as a continuous variable; the associations between working hours and cognitive function were robust to adjustments for several potential confounding factors including age, sex, marital status, education, occupation, income, physical diseases, psychosocial factors, sleep disturbances, and health risk behaviors. This study shows that long working hours may have a negative effect on cognitive performance in middle age.

International audience; Socioeconomic status (SES) is related to health in every industrialized society where it has been studied. Indicators include educational attainment, occupational status, and income. Subjective social status (SSS), a summative judgment of one's socioeconomic position across these dimensions, also appears to be associated with health status. The current study examines whether SSS has similar associations with SES indicators and with health outcomes among British civil servants (participants in the Whitehall-II study), and U.S. whites and blacks (participants in the CARDIA study). The comparisons shed light on social status in the U.S. and England and on the applicability of findings from Whitehall-II to both whites and blacks in the U.S. Parallel analyses in each group examined (1) the extent to which income, education, and occupational status determine SSS ratings, (2) the association of SSS with hypertension, depression, and global health, and (3) the extent to which adjustment for education, occupation and income individually and collectively reduce the association of SSS and health outcomes. As predicted, occupation is a more important determinant of SSS in Whitehall-II than in CARDIA; adjustment for occupation reduces the association between SSS and health outcomes more for the Whitehall-II participants -- especially males -- than for CARDIA participants. Among the latter, education and income play relatively greater roles. Socioeconomic factors do not predict SSS scores for blacks as well as they do for the other two groups. SSS is significantly related to global health and depression in all groups and to hypertension in all groups except black males. Overall, relationships of SSS and health were stronger for Whitehall-II and white CARDIA participants than for blacks in CARDIA.