Polyester layered silicate nanohybrids by controlled grafting polymerization

peer reviewedPoly( epsilon-caprolactone) (PCL) layered silicate nanohybrids were synthesized by ring opening polymerization of epsilon-caprolactone according to a well-controlled coordination-insertion mechanism. Montmorillonites were surface-modified by non functional (trimethylhexadecylammonium) and hydroxy functional alkylammonium cations, i.e., (2-hydroxyethyl) dimethylhexadecylammonium. The hydroxy functions available at the clay surface were activated into tin( II or IV) or Al(III) alkoxide initiators for lactone polymerization, thus yielding surface-grafted PCL chains. The surface-grafted PCL chains were recovered by an ionic exchange reaction with lithium chloride and they were analyzed by size exclusion chromatography. The PCL molar mass was measured as a function of the hydroxy content of the clay that was modulated by exchanging the Na cations with mixtures of non-functional and hydroxy functional ammonium cations of different compositions. Nanohybrids were also characterized by small-angle X-ray diffraction, transmission electron microscopy and thermogravimetry. The PCL molar mass and the nanocomposite morphology (i.e., exfoliation and/or intercalation) were readily tuned by the content of the hydroxy groups available at the clay surface. Surface-grafted aluminium trialkoxide species proved highly efficient in initiating polymerization that leads to PCL chains of controlled molar mass and narrow molecular weight distribution with polydispersity indices as low as 1.2

Multiple sclerosis risk variants alter expression of co-stimulatory genes in B cells.

The increasing evidence supporting a role for B cells in the pathogenesis of multiple sclerosis prompted us to investigate the influence of known susceptibility variants on the surface expression of co-stimulatory molecules in these cells. Using flow cytometry we measured surface expression of CD40 and CD86 in B cells from 68 patients and 162 healthy controls that were genotyped for the multiple sclerosis associated single nucleotide polymorphisms (SNPs) rs4810485, which maps within the CD40 gene, and rs9282641, which maps within the CD86 gene. We found that carrying the risk allele rs4810485*T lowered the cell-surface expression of CD40 in all tested B cell subtypes (in total B cells P ≤ 5.10 × 10-5 in patients and ≤4.09 × 10-6 in controls), while carrying the risk allele rs9282641*G increased the expression of CD86, with this effect primarily seen in the naïve B cell subset (P = 0.048 in patients and 5.38 × 10-5 in controls). In concordance with these results, analysis of RNA expression demonstrated that the risk allele rs4810485*T resulted in lower total CD40 expression (P = 0.057) but with an increased proportion of alternative splice-forms leading to decoy receptors (P = 4.00 × 10-7). Finally, we also observed that the risk allele rs4810485*T was associated with decreased levels of interleukin-10 (P = 0.020), which is considered to have an immunoregulatory function downstream of CD40. Given the importance of these co-stimulatory molecules in determining the immune reaction that appears in response to antigen our data suggest that B cells might have an important antigen presentation and immunoregulatory role in the pathogenesis of multiple sclerosis

Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients

Objective:to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods:We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results:HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10-7) outside the HLA region (65 Mb).Discussion:genetic factors predispose to the development of OCB

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Leveraging human genetics to inform intervention strategies for multiple sclerosis

status: Published onlin

Role of genetic factors in pathophysiology of multiple sclerosis

© 2016 Elsevier Inc. All rights reserved. Epidemiological studies have pointed to an important role of genetics in the susceptibility to multiple sclerosis. Large-scale collaborations have led to an enormous expansion of known susceptibility variants with a current list of more than 100 established risk loci. In this chapter, we review the identification of these risk variants and explore possible sources of additional genetic variation. Furthermore, we demonstrate the influence of these and additional genetic risk variants on disease phenotype and pathogenesis. © 2016 Copyrightedition: 1ststatus: publishe

Modélisation et outils logiciels pour une connaissance anatomo-fonctionnelle du Cerveau humain

Dans cette thèse, nous revisitons la méthode de la neuropsychologie définie comme l'étude des bases neurales des fonctions cognitives et comportementales par l'apport d'un modèle de représentation et d'organisation des données sur le cerveau et la création d'une base de données anatomo-fonctionnelles. Un Centre d'Anatomie Cognitive (C.A.C.) a été constitué afin de permettre le recueil et le traitement des données chez des patients présentant des lésions cérébrales. Des logiciels de mise en relation et de fusion des données anatomiques et fonctionnelles, ont été développés afin de produire des connaissances anatomo-fonctionnelles, notamment sous forme de règles anatomo-fonctionnelles. Nous décrivons les résultats des traitements appliqués à la base de données ; l'objectif étant de proposer aux experts une mise en perspective d 'utilisation du système informatique, montrant que des traitements appropriés sur des données modélisées de façon complexe constituent un outil de recherche. L'objectif général de cette thèse est de proposer un référentiel anatomo-fonctionnel pour aider à la compréhension du fonctionnement cérébral normal et pathologiqueLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Problématiques des hydrocarbures aromatiques polycycliques dans les corps gras

La présence des hydrocarbures aromatiques polycycliques (HAP) dans les huiles végétales peut provenir de différentes sources, mais généralement les huiles contaminées sont issues de matières premières nécessitant d’être séchées telles que les pépins de raisin, le coprah ou les grignons d’olive. Actuellement, il n’y a pas de réglementation européenne limitant la teneur en HAP dans les produits alimentaires mais un Code de Bonnes Pratiques a été établi par FEDIOL 1. La détermination de la totalité des HAP présents dans les corps gras est rendue délicate par le faible niveau de chaque PAH à quantifier et la complexité des étapes d’extraction et de purification. La seule méthode faisant l’objet d’une norme (NF EN ISO 15302) concerne la détermination de la teneur en benzo[a]pyrène. Un projet de méthode fourni par l’ITERG est en cours d’évaluation dans le cadre des travaux du Sous-Comité ISO\\TC34\\SC11 des « Corps gras d’origines animale et végétale ». Cette méthode permet la quantification de 12 HAP dans les corps gras, avec une limite de quantification de 0,2 μg\\kg pour tous les composés analysés, à l’exception des fluoranthène et benzo[g,h,i]pérylène où celle-ci est de 0,3 μg\\kg, ainsi que de l’indéno[1,2,3-cd]pyrène pour lequel la limite de quantification atteint 1 μg\\kg. Depuis quatre ans, les travaux de l’ITERG sur les HAP ont été centrés sur l’optimisation et la normalisation d’une procédure d’analyse (ISO\\CD 15753), sur l’estimation du niveau de contamination des huiles végétales produites en France et sur l’effet du raffinage sur le niveau en HAP. Chaque étape de ce travail est développée ici