La participation des représentants patronaux et syndicaux dans les comités de santé et sécurité du travail

Ce memoire porte sur les mecanismes de participation dans les comites paritaires de sante et securite du travail. L'hypothese initiale de cette recherche exploratoire est qu'une relation existe entre le statut specifique de l'acteur dans l'organisation et son type de participation au sein de ces comites. L'enquete sur le terrain a ete realisee dans deux organisations situees au Quebec. Differents moyens ont ete utilises afin de recueillir les donnees: entrevues avec les principaux acteurs, observations de reunions et cueillette des documents pertinents et disponibles. L'analyse des donnees nous amene a constater la presence d'une relation entre le statut dans l'organisation et le type de participation au comite. Toutefois, notre analyse nous permet de mettre egalement en lumiere le role de variable intermediaire que joue le modele de repartition du pouvoir a l'interieur duquel cette relation se concretise

Osteopontin: an early innate immune marker of Escherichia coli mastitis harbors genetic polymorphisms with possible links with resistance to mastitis

<p>Abstract</p> <p>Background</p> <p>Mastitis is the most important disease in dairy cows and it causes significant lost of profit to producers. Identification of the genes, and their variants, involved in innate immune responses is essential for the understanding of this inflammatory disease and to identify potential genetic markers for resistance to mastitis. The progeny of dairy cows would benefit from receiving favourable alleles that support greater resistance to infection, thus reducing antibiotic use. This study aims to identify a key gene in the innate immune response to mastitis, led us to evaluate its genetic association with somatic cell score (SCS), which is an indicator of clinical mastitis, and to evaluate its impact on other traits related to milk production.</p> <p>Results</p> <p>The osteopontin transcript (<it>SPP1</it>) was identified in the somatic cells from cows experimentally infected with <it>Escherichia coli</it>. By selecting bulls with extreme estimated breeding values (EBVs) for SCS, which is an indicator of mammary gland health, four DNA polymorphisms in the <it>SPP1 </it>genomic sequence were found. Statistical analysis revealed that the SNP <it>SPP1c.-1301G>A </it>has an impact on EBV for SCS (<it>P </it>< 0.001) Using an allele substitution model, <it>SPP1c.-1251C>T</it>, <it>SPP1c.-430G>A</it>, and <it>SPP1c.*40A>C </it>have an impact on SCS whereas <it>SPP1c.-1301G>A </it>has an effect on the EBVs for milk yield (second and third lactations), fat and protein percentages (all three lactations). Analysis revealed statistically significant differences between haplotype groups at a comparison-wise level with sire EBVS for SCS for the first (<it>P </it>= 0.012), second (<it>P </it>< 0.001), and third (<it>P </it>< 0.001) lactations.</p> <p>Conclusion</p> <p>This study reports the link between DNA polymorphisms of <it>SPP1</it>, the number of milk immune cells and, potentially, the susceptibility to mastitis. These SNPs were identified by <it>in silico </it>search to be located in transcription factor recognition sites which factors are presumably involved in the Th1 immune response and in the Th2 regulation pathway. Indeed, one SNP abolished the SP1 recognition site, whereas another SNP affected the transcription binding factor IKAROS. All together, these findings support the genetic potential of these variants in terms of selection for the improvement of mastitis resistance in dairy cows.</p

Acquired MET Expression Confers Resistance to EGFR Inhibition In a Mouse Model of Glioblastoma Multiforme

Glioblastoma Multiforme (GBM) is an aggressive brain tumor for which there is no cure. Overexpression of wild-type EGFR and loss of the tumor suppressor genes Ink4a/Arf and PTEN are salient features of this deadly cancer. Surprisingly, targeted inhibition of EGFR has been clinically disappointing, demonstrating an innate ability for GBM to develop resistance. Efforts at modeling GBM in mice using wild-type EGFR have proven unsuccessful to date, hampering endeavors at understanding molecular mechanisms of therapeutic resistance. Here, we describe a unique genetically engineered mouse model of EGFR-driven gliomagenesis that uses a somatic conditional overexpression and chronic activation of wild-type EGFR in cooperation with deletions in the Ink4a/Arf and PTEN genes in adult brains. Using this model, we establish that chronic activation of wild-type EGFR with a ligand is necessary for generating tumors with histopathological and molecular characteristics of GBMs. We show that these GBMs are resistant to EGFR kinase inhibition and we define this resistance molecularly. Inhibition of EGFR kinase activity using tyrosine kinase inhibitors in GBM tumor cells generates a cytostatic response characterized by a cell cycle arrest, which is accompanied by a substantial change in global gene expression levels. We demonstrate that a key component of this pattern is the transcriptional activation of the MET receptor tyrosine kinase and that pharmacological inhibition of MET overcomes the resistance to EGFR inhibition in these cells. These findings provide important new insights into mechanisms of resistance to EGFR inhibition and suggest that inhibition of multiple targets will be necessary to provide therapeutic benefit for GBM patients

Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren’s syndrome

Sjögren’s syndrome is a common autoimmune disease (~0.7% of European Americans) typically presenting as keratoconjunctivitis sicca and xerostomia. In addition to strong association within the HLA region at 6p21 (Pmeta=7.65×10−114), we establish associations with IRF5-TNPO3 (Pmeta=2.73×10−19), STAT4 (Pmeta=6.80×10−15), IL12A (Pmeta =1.17×10−10), FAM167A-BLK (Pmeta=4.97×10−10), DDX6-CXCR5 (Pmeta=1.10×10−8), and TNIP1 (Pmeta=3.30×10−8). Suggestive associations with Pmeta<5×10−5 were observed with 29 regions including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2, and PHIP amongst others. These results highlight the importance of genes involved in both innate and adaptive immunity in Sjögren’s syndrome