La valeur pronostique de la protéine S-100B et de l'énolase neurone-spécifique suivant un traumatisme craniocérébral modéré ou grave : revues systématiques et méta-analyses

Cette étude a pour objectif de déterminer la valeur pronostique de la protéine S-100ß et de l’énolase neurone-spécifique (NSE) chez les patients ayant subi un traumatisme craniocérébral (TCC) modéré ou grave. Deux revues systématiques et méta-analyses ont été effectuées afin de recenser les études présentant un dosage de ces biomarqueurs en lien avec la mortalité ou le pronostic fonctionnel évalué à l’aide du score du Glasgow outcome scale (GOS). Des 9228 résultats de la recherche, 41 et 26 études ont été incluses, respectivement, pour la protéine S-100ß et la NSE. Il existe une association entre le dosage sérique de la protéine S-100ß et de la NSE avec une issue clinique défavorable, c’est-à-dire la mortalité ou un score du GOS ≤ 3. Une concentration sérique entre 1,38 et 10,50 µg/L pour la protéine S-100ß est 100 % spécifique pour prédire le décès. La présence de lésions extracérébrales n’influençait pas cette association.The main objective of this study is to determine the prognostic value of S-100ß protein and neuron-specific enolase (NSE) following a moderate or severe traumatic brain injury (TBI). Two systematic reviews and meta-analysis were performed to find the studies having evaluated the link between a level of those biomarkers and the mortality or the Glasgow outcome scale (GOS). Of the 9228 citations, 41 and 26 studies were finally included respectively for S-100ß protein and NSE. We observed a significant association between blood levels of S-100ß protein and NSE and an unfavorable outcome such as the mortality or the GOS ≤ 3. A 100% specificity serum level threshold for mortality was between 1.38 to 10.50 µg/L for the S-100ß protein. The association showed consistent results despite the presence of significant extracranial injuries

Belief functions contextual discounting and canonical decompositions

AbstractIn this article, the contextual discounting of a belief function, a classical discounting generalization, is extended and its particular link with the canonical disjunctive decomposition is highlighted. A general family of correction mechanisms allowing one to weaken the information provided by a source is then introduced, as well as the dual of this family allowing one to strengthen a belief function

Requirements for the selective degradation of CD4 receptor molecules by the human immunodeficiency virus type 1 Vpu protein in the endoplasmic reticulum

BACKGROUND: HIV-1 Vpu targets newly synthesized CD4 receptor for rapid degradation by a process reminiscent of endoplasmic reticulum (ER)-associated protein degradation (ERAD). Vpu is thought to act as an adaptor protein, connecting CD4 to the ubiquitin (Ub)-proteasome degradative system through an interaction with beta-TrCP, a component of the SCFbeta-TrCP E3 Ub ligase complex. RESULTS: Here, we provide direct evidence indicating that Vpu promotes trans-ubiquitination of CD4 through recruitment of SCFbeta-TrCP in human cells. To examine whether Ub conjugation occurs on the cytosolic tail of CD4, we substituted all four Ub acceptor lysine residues for arginines. Replacement of cytosolic lysine residues reduced but did not prevent Vpu-mediated CD4 degradation and ubiquitination, suggesting that Vpu-mediated CD4 degradation is not entirely dependent on the ubiquitination of cytosolic lysines and as such might also involve ubiquitination of other sites. Cell fractionation studies revealed that Vpu enhanced the levels of ubiquitinated forms of CD4 detected in association with not only the ER membrane but also the cytosol. Interestingly, significant amounts of membrane-associated ubiquitinated CD4 appeared to be fully dislocated since they could be recovered following sodium carbonate salt treatment. Finally, expression of a transdominant negative mutant of the AAA ATPase Cdc48/p97 involved in the extraction of ERAD substrates from the ER membrane inhibited Vpu-mediated CD4 degradation. CONCLUSION: Taken together, these results are consistent with a model whereby HIV-1 Vpu targets CD4 for degradation by an ERAD-like process involving most likely poly-ubiquitination of the CD4 cytosolic tail by SCFbeta-TrCP prior to dislocation of receptor molecules across the ER membrane by a process that depends on the AAA ATPase Cdc48/p97.This work was performed by JB in partial fulfillment of her doctoral thesis and was supported by grants from the Canadian Institutes of Health Research (CIHR) (MOP-14228) and from the Fonds de la Recherche en Santé du Québec (FRSQ) to EAC. JB is the recipient of a studentship from the FRSQ and EAC holds the Canada Research Chair in Human Retrovirology

La sécurité en escalade

Cet article présente les résultats d’un travail de recherche sur les conditions d’enseignement et d’apprentissage d’une activité physique et sportive de pleine nature, l’escalade, au sein d’institutions différentes. L’approche de la gestion des risques liés à cette pratique est comparative. Il s’agit de différencier ce qui relève de la généricité des institutions observées de ce qui dépend de la spécificité de certaines d’entre elles. Il ne s’agit donc pas d’un générique et d’un spécifique trans-disciplinaires comme il est coutume de le voir dans les travaux en didactique comparée, mais d’un générique et d’un spécifique trans-institutionnels. Nous avons appris de notre recherche (Mangeant, 2008), l’importance dans les dangers encourus par les pratiquants, de dimensions conventionnelles rarement mises en avant, et qui relèvent pour une part de l’action conjointe non didactique des membres d’une cordée, et pour l’autre part de l’action conjointe didactique de la cordée et du professeur.This article presents the results of Mangeant (2008) on the teaching and learning of a sport and physical outdoor activity, rock climbing, in different institutions. The approach to risks management associated with this practice is comparative. This is to differentiate what is the genericity of the institutions observed that depends on the specificity of some of them. It is therefore not a generic and a specific trans-disciplinary as it is customary to see into the works in teaching compared, but a generic and a specific trans-institutional. We learned from our research on weight in the dangers faced by climbers, of conventional dimensions rarely put forward, and falling for a share of the not didactical joint action of roped members and the other part of the joint didactical action of roped members and teacher

Les temps du soi. Bénévolat, identité et éthique

À partir d’une recherche empirique dans trois régions, l’articulation entre l’éthique et l’identité est analysée, ainsi que la façon dont l’engagement bénévole travaille l’identité. Des récits d’engagement de bénévoles québécois, oeuvrant dans le secteur scolaire, religieux ou culturel, nous dégageons quatre formes de parcours et de rapport à l’engagement, dans lesquelles nous reconnaissons d’abord quatre dimensions de l’identité, puis quatre postures éthiques. D’une pratique particulière, nous sommes ainsi conduits à une analyse plus générale touchant l’articulation entre identité et éthique dans le Québec contemporain.Based on empirical research in three regions, the interactions between ethics and identity are analysed, as well as the way in which volunteer involvement interacts with identity. From accounts of their involvement by Québec volunteers working in the school, religious and cultural sectors, the authors identify four forms of patterns and relationships with such involvement, in which four dimensions of identity are first recognized, followed by four ethical positionings. Thus, starting from one specific area of activity, we are led into a more general analysis focusing on the interactions between identity and ethics in contemporary Québec

Plate boundary segmentation in the northeastern Caribbean from geodetic measurements and Neogene geological observations

AbstractThe Caribbean–North America plate boundary in the northeastern Caribbean shows a remarkable example of along-strike transition from plate boundary–normal subduction in the Lesser Antilles, oblique subduction with no strain partitioning in Puerto Rico, and oblique subduction/collision with strain partitioning further west in Hispaniola. We show that this segmentation is well marked in the interseismic strain, as measured using space geodetic data, and in the Neogene deformation regime, as derived from geological observations. Hence, interseismic segmentation, which reproduces the geological segmentation persistent over a long time interval, is inherited from the geological history and long-term properties of the plate boundary. This result is relevant to the assessment of seismic hazard at convergent plate boundaries, where geodetic measurements often show interseismic segmentation between fully–and partially–coupled plate interface regions

Association between disruption of CD4 receptor dimerization and increased human immunodeficiency virus type 1 entry

BACKGROUND: Human immunodeficiency virus (HIV) enters target cells by a membrane fusion process that involves a series of sequential interactions between its envelope glycoproteins, the CD4 receptor and CXCR4/CCR5 coreceptors. CD4 molecules are expressed at the cell surface of lymphocytes and monocytes mainly as monomers, but basal levels of CD4 dimers are also present at the cell surface of these cells. Previous evidence indicates that the membrane distal and proximal extracellular domains of CD4, respectively D1 and D4, are involved in receptor dimerization. RESULTS: Here, we have used A201 cell lines expressing two CD4 mutants, CD4-E91K, E92K (D1 mutant) and CD4-Q344E (D4 mutant), harboring dimerization defects to analyze the role of CD4 dimerization in HIV-1 entry. Using entry assays based on β-lactamase-Vpr or luciferase reporter activities, as well as virus encoding envelope glycoproteins derived from primary or laboratory-adapted strains, we obtained evidence suggesting an association between disruption of CD4 dimerization and increased viral entry efficiency. CONCLUSION: Taken together, our results suggest that monomeric forms of CD4 are preferentially used by HIV-1 to gain entry into target cells, thus implying that the dimer/monomer ratio at the cell surface of HIV-1 target cells may modulate the efficiency of HIV-1 entry

Simulations numériques de la multidiffusion acoustique en conduit, comparaison avec des modèles analytiques

National audienceNous nous intéressons à la caractérisation des effets de multi-diffusion dans les guides d'ondes. Nous considérons la propagation acoustique en régime harmonique dans un conduit horizontal 2D à parois rigides. Nous avons développé une approche numérique pour déterminer les propriétés effectives d'un milieu hétérogène aléatoire dans un conduit. A l'aide de simulations directes nous déterminons un champ cohérent en faisant la moyenne des champs sur de nombreuses réalisations différentes de désordre. En interprétant ce champ cohérent comme une onde se propageant dans un milieu homogène équivalent, les propriétés effectives de ce milieu sont extraites. Une comparaison avec des modèles analytiques de la littérature, développés en milieu infini et non en conduit, est effectuée. Une méthode d'éléments finis est choisie pour permettre de traiter des diffuseurs de formes arbitraires. Afin de réduire les temps de calcul, la méthode des éléments finis est couplée à une représentation intégrale du champ diffracté. Elle réduit la taille du maillage, mais nécessite l'évaluation de la fonction de Green du guide. Une réduction supplémentaire des temps de calcul est obtenue en considérant, non pas des configurations de diffuseurs complètement aléatoires, mais des configurations périodiques perturbées : les diffuseurs sont placés sur un réseau de référence périodique puis sont déplacés localement aléatoirement. Ceci permet de paralléliser les calculs, en divisant le domaine de calcul en tranches verticales. Pour chaque tranche, la matrice de diffusion est calculée. Enfin, la matrice de diffusion de la couche entière est obtenue par la combinaison des matrices de diffusion. Les calculs de transmissions effectives et de nombres d'ondes effectifs montrent un bon accord avec plusieurs modèles analytiques, sauf pour certaines fréquences, les fréquences de bandes interdites des réseaux périodiques sous-jacents. Dans ce cas, le réseau périodique perturbé se comporte en moyenne comme un réseau périodique

HIV-1 Vpr-Mediated G2 Arrest Involves the DDB1-CUL4AVPRBP E3 Ubiquitin Ligase

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) has been shown to cause G2 cell cycle arrest in human cells by inducing ATR-mediated inactivation of p34cdc2, but factors directly engaged in this process remain unknown. We used tandem affinity purification to isolate native Vpr complexes. We found that damaged DNA binding protein 1 (DDB1), viral protein R binding protein (VPRBP), and cullin 4A (CUL4A)—components of a CUL4A E3 ubiquitin ligase complex, DDB1-CUL4AVPRBP—were able to associate with Vpr. Depletion of VPRBP by small interfering RNA impaired Vpr-mediated induction of G2 arrest. Importantly, VPRBP knockdown alone did not affect normal cell cycle progression or activation of ATR checkpoints, suggesting that the involvement of VPRBP in G2 arrest was specific to Vpr. Moreover, leucine/isoleucine-rich domain Vpr mutants impaired in their ability to interact with VPRBP and DDB1 also produced strongly attenuated G2 arrest. In contrast, G2 arrest–defective C-terminal Vpr mutants were found to maintain their ability to associate with these proteins, suggesting that the interaction of Vpr with the DDB1-VPRBP complex is necessary but not sufficient to block cell cycle progression. Overall, these results point toward a model in which Vpr could act as a connector between the DDB1-CUL4AVPRBP E3 ubiquitin ligase complex and an unknown cellular factor whose proteolysis or modulation of activity through ubiquitination would activate ATR-mediated checkpoint signaling and induce G2 arrest