Langue et identité ethnique dans une communauté montagnaise bilingue

Le contact avec le français a entraîné des bouleversements linguistiques majeurs chez les Montagnais de Betsiamites où la fossilisation des habitudes d’alternance codique mène directement à l’émergence d’une langue mixte. Il est courant dans le domaine des langues mixtes d’invoquer le développement d’une identité métissée comme élément déclencheur de la mixité de la langue. Cet article présente les résultats d’une enquête menée à Betsiamites qui démontrent que l’hybridation de la langue ne s’accompagne pas d’une mutation dans l’identité. Ces résultats remettent en question l’hypothèse qui veut que les langues mixtes soient créées dans le but de satisfaire aux exigences d’une identité ethnique en voie de redéfinition.Language contact with French has brought about significant linguistic change in Betsiamites Montagnais where the fossilization of code-switching strategies leads to the development of a mixed language. A strong current in mixed language studies appeals to the development of a mixed identity in explaining the genesis of mixed languages. This article presents the results of a survey conducted in Betsiamites where the hybridization of Montagnais does not come with any mutation in ethnic identity. These results challenge the common assumption that mixed languages are created as a result of a mutation in ethnic identity

Inactive matriptase-2 mutants found in IRIDA patients still repress hepcidin in a transfection assay despite having lost their serine protease activity.

L'article final de l'éditeur contient 9 pages. Le manuscrit accepté contient 32 pages.International audienceMutations of the TMPRSS6 gene, which encodes Matriptase-2, are responsible for iron-refractory iron-deficiency anemia. Matriptase-2 is a transmembrane protease that downregulates hepcidin expression. We report one frameshift (p.Ala605ProfsX8) and four novel missense mutations (p.Glu114Lys, p.Leu235Pro, p.Tyr418Cys, p.Pro765Ala) found in IRIDA patients. These mutations lead to changes in both the catalytic and noncatalytic domains of Matriptase-2. Analyses of the mutant proteins revealed a reduction of autoactivating cleavage and the loss of N-Boc-Gln-Ala-Arg-p-nitroanilide hydrolysis. This resulted either from a direct modification of the active site or from the lack of the autocatalytic cleavage that transforms the zymogen into an active protease. In a previously described transfection assay measuring the ability of Matriptase-2 to repress the hepcidin gene (HAMP) promoter, all mutants retained some, if not all, of their transcriptional repression activity. This suggests that caution is called for in interpreting the repression assay in assessing the functional relevance of Matriptase-2 substitutions. We propose that Matriptase-2 activity should be measured directly in the cell medium of transfected cells using the chromogenic substrate. This simple test can be used to determine whether a sequence variation leading to an amino acid substitution is functionally relevant or not

PLoS Pathog

The low pathogenicity and replicative potential of HIV-2 are still poorly understood. We investigated whether HIV-2 reservoirs might follow the peculiar distribution reported in models of attenuated HIV-1/SIV infections, i.e. limited infection of central-memory CD4 T lymphocytes (TCM). Antiretroviral-naive HIV-2 infected individuals from the ANRS-CO5 (12 non-progressors, 2 progressors) were prospectively included. Peripheral blood mononuclear cells (PBMCs) were sorted into monocytes and resting CD4 T-cell subsets (naive [TN], central- [TCM], transitional- [TTM] and effector-memory [TEM]). Reactivation of HIV-2 was tested in 30-day cultures of CD8-depleted PBMCs. HIV-2 DNA was quantified by real-time PCR. Cell surface markers, co-receptors and restriction factors were analyzed by flow-cytometry and multiplex transcriptomic study. HIV-2 DNA was undetectable in monocytes from all individuals and was quantifiable in TTM from 4 individuals (median: 2.25 log10 copies/106 cells [IQR: 1.99-2.94]) but in TCM from only 1 individual (1.75 log10 copies/106 cells). HIV-2 DNA levels in PBMCs (median: 1.94 log10 copies/106 PBMC [IQR = 1.53-2.13]) positively correlated with those in TTM (r = 0.66, p = 0.01) but not TCM. HIV-2 reactivation was observed in the cells from only 3 individuals. The CCR5 co-receptor was distributed similarly in cell populations from individuals and donors. TCM had a lower expression of CXCR6 transcripts (p = 0.002) than TTM confirmed by FACS analysis, and a higher expression of TRIM5 transcripts (p = 0.004). Thus the low HIV-2 reservoirs differ from HIV-1 reservoirs by the lack of monocytic infection and a limited infection of TCM associated to a lower expression of a potential alternative HIV-2 co-receptor, CXCR6 and a higher expression of a restriction factor, TRIM5. These findings shed new light on the low pathogenicity of HIV-2 infection suggesting mechanisms close to those reported in other models of attenuated HIV/SIV infection models

Evaluer la santé psychologique d’une population adolescente scolarisée dans un territoire labellisé « Cité éducative »

International audienc

Dictionnaire de la résolution amiable des différends : RAD/ADR en matières civile, commerciale, familiale et sociale

International audienc

Can physicians and schools mitigate social inequalities in human papillomavirus vaccine awareness, uptake and vaccination intention among adolescents? A cross-sectional study, France, 2021 to 2022

International audienceBackground:In France, human papillomavirus (HPV) vaccination coverage varies across socioeconomic levels. Aim We aimed at assessing HPV vaccine awareness, uptake and vaccination intention among adolescents in France. Methods In a cluster-randomised study, 13–15-year-old students in 61 French middle schools completed a web-based questionnaire. We used multivariable logistic regression to evaluate determinants of HPV vaccine awareness, self-reported uptake and vaccination intention among unvaccinated students and interaction terms to explore effects of visits to family physician and remembering school lessons on vaccination. The French deprivation index of school municipalities served as proxy for socioeconomic levels. Results Among 6,992 participants, awareness was significantly associated with parental education (odds ratio (OR) = 0.82; 95% confidence interval (CI): 0.71–0.95), language spoken at home (OR = 0.59; 95% CI: 0.52–0.66) and deprivation level (OR = 0.57; 95% CI: 0.44–0.71), regardless of physician visit or school lessons. Vaccine uptake was associated with parental education without a recent physician visit (OR = 0.31; 95% CI: 0.16–0.59, vs OR = 0.64; 95% CI: 0.52–0.78 with a visit, interaction p = 0.045). Vaccination intention among unvaccinated was associated with deprivation level (moderate-low vs low) among students not remembering school lessons on vaccination (OR = 0.17; 95% CI: 0.05-0.62, vs OR = 0.93; 95% CI: 0.51–1.67 remembering school lessons, interaction p = 0.022). Parental education was associated with vaccination intention among students reporting a physician visit (OR = 0.41; 95% CI: 0.26–0.64 vs OR = 1.05; 95% CI: 0.50–2.20 without a visit, interaction p = 0.034). Conclusion Our results suggest that healthcare and school could promote vaccination and mitigate social inequalities in HPV vaccination coverage

AN1-type zinc finger protein 3 (ZFAND3) is a transcriptional regulator that drives Glioblastoma invasion

The infiltrative nature of Glioblastoma (GBM), the most aggressive primary brain tumor, critically prevents complete surgical resection and masks tumor cells behind the blood brain barrier reducing the efficacy of systemic treatment. Here, we use a genome-wide interference screen to determine invasion-essential genes and identify the AN1/A20 zinc finger domain containing protein 3 (ZFAND3) as a crucial driver of GBM invasion. Using patient-derived cellular models, we show that loss of ZFAND3 hampers the invasive capacity of GBM, whereas ZFAND3 overexpression increases motility in cells that were initially not invasive. At the mechanistic level, we find that ZFAND3 activity requires nuclear localization and integral zinc-finger domains. Our findings indicate that ZFAND3 acts within a nuclear protein complex to activate gene transcription and regulates the promoter of invasion-related genes such as COL6A2, FN1, and NRCAM. Further investigation in ZFAND3 function in GBM and other invasive cancers is warranted

Single- vs double-unit cord blood transplantation for children and young ă adults with acute leukemia or myelodysplastic syndrome

International audienceTransplantation of 2 unrelated cord blood (UCB) units instead of 1 has been proposed to increase the cell dose. We report a prospective randomized study, designed to compare single- vs double-UCB transplantation in children and young adults with acute leukemia in remission or myelodysplasia. Eligible patients had at least two 4-6 HLA-identical UCBs with >3 × 10(7) nucleated cells/kg for the first and >1.5 × 10(7) for the second. The primary end point was the 2-year cumulative incidence of transplantation strategy failure, a composite end point including transplant-related mortality (TRM), engraftment failure, and autologous recovery. Randomized patients who did not proceed to transplantation due to refractory disease were considered transplantation failures. A total of 151 patients were randomized and included in the intent-to-treat analysis; 137 were transplanted. Double-UCB transplantation did not decrease transplantation strategy failure (23.4% ± 4.9% vs 14.9% ± 4.2%). Two-year posttransplant survival, disease-free survival, and TRM were 68.8% ± 6.0%, 67.6% ± 6.0%, and 5.9% ± 2.9% after single-unit transplantation compared with 74.8% ± 5.5%, 68.1% ± 6.0%, and 11.6% ± 3.9% after double-unit transplantation. The final relapse risk did not significantly differ, but relapses were delayed after double-unit transplantation. Overall incidences of graft-versus-host disease (GVHD) were similar, but chronic GVHD was more frequently extensive after double-UCB transplantation (31.9% ± 5.7% vs 14.7% ± 4.3%, P = .02). In an exploratory subgroup analysis, we found a significantly lower relapse risk after double-unit transplantation in patients receiving total body irradiation without antithymocyte globulin (ATG), whereas the relapse risk was similar in the group treated with busulfan, cyclophosphamide, and ATG. Single-UCB transplantation with adequate cell dose remains the standard of care and leads to low TRM. Double-unit transplantation should be reserved for patients who lack such units. This trial was registered at www.clinicaltrials.gov as #NCT01067300