Flexural isostatic response of the Alps to increased Quaternary erosion recorded by foreland basin remnants, SE France

International audienceWe test the hypothesis that flexural isostatic compensation of the mass removed by enhanced Quaternary erosion is responsible for uplift of the Western European Alps and their forelands. We use two well-preserved and well-dated (1.8 Ma) abandonment surfaces of foreland basin remnants in SE France (the Chambaran and Valensole plateaux) as passive benchmarks for tilting of the foreland. Estimating their initial slope from morphometric scaling relationships, we determine bulk post-depositional tilting of 0.5–0.8% for these surfaces. The calculated isostatic response of the Alpine lithosphere to erosional unloading, using the method recently proposed by Champagnac et al. [Geology 35 (2007) 195–198], yields a predicted tilting of 0.3–0.4% in the considered areas, explaining approximately half of the determined post-depositional tilting. Such long-term deformation being insensitive to cyclic loading/unloading because of glaciations, we suspect the other half to be related to as yet undetermined long-wavelength and long-lived tectonic process(es)

L'enseignement de la phonologie pour améliorer les processus de bas niveau en compréhension de l'oral

Listening comprehension is a major domain in which students are trained for when learning a foreign language in high school. The French national syllabus sets as objectives reference levels of the CEFR but international surveys highlight the poor performances of French students particularly in listening comprehension activities. A bibliographical review shows that a lack of automatisation in the decoding of speech constitutes a limiting threshold for the intermediate student who is then unable to compensate the faulty perception by interpretation strategies. In two experiments, we attempt to demonstrate that the teaching of phonology is a high yield approach to perception issues at the intermediate level. The second experiment on the weak forms of grammatical words produces promising results, albeit statistically under-sized groups.La compréhension de l’oral (CO) est une des cinq activités langagières auxquelles les élèves sont formés et entraînés en LVE, de la 6e à la terminale. Les programmes scolaires fixent comme objectifs à atteindre des niveaux du CECRL en fin de troisième et au bac mais les comparaisons internationales indiquent que les élèves français en majorité ne les atteignent pas, obtenant leurs plus mauvais résultats en CO. Une revue des études scientifiques sur le sujet montre que le manque d’automatisation du décodage du message provoque un nivellement par le bas chez l’élève de niveau intermédiaire, l’empêchant de compenser efficacement ses lacunes de perception par des stratégies d’interprétation plus larges. Une première hypothèse avançant que « ce que l’on prononce mal, on ne l’entend pas » n’est pas corroborée par l’expérimentation. En mettant à l’épreuve l’hypothèse 2 selon laquelle l’enseignement de la phonologie améliore la perception orale des apprenants, un enseignement ciblé sur les formes faibles des mots grammaticaux produit des résultats très positifs lors d’une évaluation de la CO portant spécifiquement sur l’identification de mots grammaticaux,mais la taille réduite des groupes ne permet pas de conclure définitivement à un effet significatif

Osteocyte apoptosis and lipid infiltration as mechanisms of alcohol-induced bone loss

AIMS: We carried out an in vivo study to assess the relationship between increase in adiposity in the marrow and osteocyte apoptosis in the case of alcohol-induced bone loss. METHODS AND RESULTS: After alcohol treatment, the number of apoptotic osteocytes was increased and lipid droplets were accumulated within the osteocytes, the bone marrow and the cortical bone micro-vessels. At last, we found an inverse correlation between bone mineral density and osteocyte apoptosis and strong significant correlations between the osteocyte apoptotic number and lipid droplet accumulation in osteocyte and bone micro-vessels. CONCLUSION: These data show that alcohol-induced bone loss is associated with osteocyte apoptosis and lipid accumulation in the bone tissue. This lipid intoxication, or ‘bone steatosis’, is correlated with lipid accumulation in bone marrow and blood micro-vessels.Delphine B. Maurel, Stéphane Pallu, Christelle Jaffré, Nicola L. Fazzalari, Nathalie Boisseau, Rustem Uzbekov, Claude-Laurent Benhamou and Gaël Y. Rochefor

Penetrance estimation of Alzheimer disease in SORL1 loss-of-function variant carriers using a family-based strategy and stratification by APOE genotypes

International audienceAbstract Background Alzheimer disease (AD) is a common complex disorder with a high genetic component. Loss-of-function (LoF) SORL1 variants are one of the strongest AD genetic risk factors. Estimating their age-related penetrance is essential before putative use for genetic counseling or preventive trials. However, relative rarity and co-occurrence with the main AD risk factor, APOE -ε4, make such estimations difficult. Methods We proposed to estimate the age-related penetrance of SORL1 -LoF variants through a survival framework by estimating the conditional instantaneous risk combining (i) a baseline for non-carriers of SORL1- LoF variants, stratified by APOE-ε4 , derived from the Rotterdam study ( N = 12,255), and (ii) an age-dependent proportional hazard effect for SORL1- LoF variants estimated from 27 extended pedigrees (including 307 relatives ≥ 40 years old, 45 of them having genotyping information) recruited from the French reference center for young Alzheimer patients. We embedded this model into an expectation-maximization algorithm to accommodate for missing genotypes. To correct for ascertainment bias, proband phenotypes were omitted. Then, we assessed if our penetrance curves were concordant with age distributions of APOE -ε4-stratified SORL1- LoF variant carriers detected among sequencing data of 13,007 cases and 10,182 controls from European and American case-control study consortia. Results SORL1- LoF variants penetrance curves reached 100% (95% confidence interval [99–100%]) by age 70 among APOE -ε4ε4 carriers only, compared with 56% [40–72%] and 37% [26–51%] in ε4 heterozygous carriers and ε4 non-carriers, respectively. These estimates were fully consistent with observed age distributions of SORL1- LoF variant carriers in case-control study data. Conclusions We conclude that SORL1- LoF variants should be interpreted in light of APOE genotypes for future clinical applications