French Institute of Health and Medical Research

About: French Institute of Health and Medical Research is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Receptor. The organization has 109367 authors who have published 174236 publications receiving 8365503 citations.

The visual word form area: spatial and temporal characterization of an initial stage of reading in normal subjects and posterior split-brain patients.

Abstract: A standard model of word reading postulates that visual information is initially processed by occipitotemporal areas contralateral to the stimulated hemifield, from whence it is subsequently transferred to the visual word form (VWF) system, a left inferior temporal region specifically devoted to the processing of letter strings. For stimuli displayed in the left visual field, this transfer proceeds from the right to the left hemisphere through the posterior portion of the corpus callosum. In order to characterize the spatial and temporal organization of these processes, reading tasks with split-field presentation were performed by five control subjects and by two patients suffering from left hemialexia following posterior callosal lesions. The subjects' responses were studied using behavioural measures and functional brain imaging techniques, providing both high spatial resolution (functional MRI, fMRI) and high temporal resolution (high-density event-related potentials, ERPs). Early visual processing was revealed as activations contralateral to stimulation, located by fMRI in the inferior occipitotemporal region and presumably coincident with area V4. A negative wave occurring 150-160 ms post-stimulus, also strictly contralateral to stimulation, was recorded over posterior electrodes. In contrast with these hemifield-dependent effects, the VWF system was revealed as a strictly left-hemispheric activation which, in control subjects, was identical for stimuli presented in the left or in the right hemifield and was located in the middle portion of the left fusiform gyrus. The electrical signature of the VWF system consisted of a unilateral sharp negativity, recorded 180-200 ms post-stimulus over left inferior temporal electrodes. In callosal patients, due to the inability of visual information to pass across the posterior part of the corpus callosum, the VWF system was activated only by stimuli presented in the right visual field. Similarly, a significant influence of the word/non-word status on ERPs recorded over the left hemisphere was discernible for either hemifield in controls, while it affected only right-hemifield stimuli in callosal patients. These findings provide direct support for the main components of the classical model of reading and help specify their timing and cerebral substrates.

Biology of Oligodendrocyte and Myelin in the Mammalian Central Nervous System

Abstract: Oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), and astrocytes constitute macroglia. This review deals with the recent progress related to the origin and differentiation of the oligodendrocytes, their relationships to other neural cells, and functional neuroglial interactions under physiological conditions and in demyelinating diseases. One of the problems in studies of the CNS is to find components, i.e., markers, for the identification of the different cells, in intact tissues or cultures. In recent years, specific biochemical, immunological, and molecular markers have been identified. Many components specific to differentiating oligodendrocytes and to myelin are now available to aid their study. Transgenic mice and spontaneous mutants have led to a better understanding of the targets of specific dys- or demyelinating diseases. The best examples are the studies concerning the effects of the mutations affecting the most abundant protein in the central nervous myelin, the p...

Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

Abstract: We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55–4.30; P = 2 × 10−16). We also show six risk loci associated with proximal gene expression or DNA methylation.

Inhibition of macroautophagy triggers apoptosis.

Abstract: Mammalian cells were observed to die under conditions in which nutrients were depleted and, simultaneously, macroautophagy was inhibited either genetically (by a small interfering RNA targeting Atg5, Atg6/Beclin 1-1, Atg10, or Atg12) or pharmacologically (by 3-methyladenine, hydroxychloroquine, bafilomycin A1, or monensin). Cell death occurred through apoptosis (type 1 cell death), since it was reduced by stabilization of mitochondrial membranes (with Bcl-2 or vMIA, a cytomegalovirus-derived gene) or by caspase inhibition. Under conditions in which the fusion between lysosomes and autophagosomes was inhibited, the formation of autophagic vacuoles was enhanced at a preapoptotic stage, as indicated by accumulation of LC3-II protein, ultrastructural studies, and an increase in the acidic vacuolar compartment. Cells exhibiting a morphology reminiscent of (autophagic) type 2 cell death, however, recovered, and only cells with a disrupted mitochondrial transmembrane potential were beyond the point of no return and inexorably died even under optimal culture conditions. All together, these data indicate that autophagy may be cytoprotective, at least under conditions of nutrient depletion, and point to an important cross talk between type 1 and type 2 cell death pathways.

Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson's Disease

Abstract: Background Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson's disease. Methods Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson's disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel–Haenszel procedure used to estimate odds ratios across centers. Results All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of p...