NCube/papyrus huggingface dataset:
Ciblage exosomal et effet de HLA-DM sur la présentation antigénique par le complexe majeur d'histocompatibilité de classe II

Major histocompatibility class II (MHC II) molecules are expressed exclusively on the surface of antigen presenting cells and serve to stimulate CD4+ cells to initiate an immune response. Peptide loading on MHC II molecules occurs in late endosomal and lysosomal compartments by the catalytic action of HLA-DM. This non-classical class II molecule removes class-II-associated invariant-chain peptide (CLIP) from class II molecules and edits their repertoire of antigenic peptides loaded. Using a mutant form of HLA-DM (HLA-DMy) that is targeted to the plasma membrane, we observed in the case of HLA-DMy, there is an increase of the loading of exogenous peptides and also significantly increased T cell response in comparison with HLA-DM wild-type. It was found that some chemical molecules, like n-propanol, could mimic the effect of HLA-DM by removing peptides from cell surface class II molecules. Interestingly, HLA-DMy and n-propanol seem to have an additive effect on the exogenous peptide loading.   Some proteins of the endosomal pathway, like HLA-DR, HLA-DM, HLA-DO and Ii are targeted to microvesicules-containing compartments called MVB and they can be introduced into exosomes. Following the fusion between MVB and plasma membrane, exosomes are released in extracellular environment. We have determined that tyrosine motif of HLA-DMβ and interaction with HLA-DR does not affect HLA-DM targeting to exosomes, except for the HLA-DO molecule.   In conclusion, we showed that HLA-DMy increases the quantity and the quality of exogenous peptides loading on APC and HLA-DM and HLA-DMy are incorporated to exosomes.

Keyphrases: HLA-DM, HLA-DMy, Exosomes, MHC, Antigen presentation, Exogenous peptides, Endosomal targeting, Exosomes, HLA-DM, HLA-DMy
Études de cas sur l’impact de l’intégration du programme d’Agrément Canada sur le changement et l’apprentissage organisationnel : la Health Authority of Anguilla et la Ca’ Foncella Ospetale di Treviso

This research assesses whether integration of Accreditation Canada’s (previously known as Canadian Council on Health Services Accreditation) AIM (Achieving Improved Measurement) accreditation program brings about change and organizational learning.  It studies the case of two health organizations: the Health Authority of Anguilla (HAA) and the Ca’ Foncella Opetale de Treviso (CFOT).   The research consists of three levels of analysis for which qualitative and quantitative data were gathered: (1) members of the accreditation teams; (2) the accreditation teams; (3) the organization as a whole.  The techniques used to collect data consisted of individual questionnaires administered to team members, semi-formal interviews with team leaders and quality coordinators, a review of documentation and several periodic measurements of compliance with the AIM standards were the techniques used.      The findings indicate that the organizations made strategic, organizational and relational changes.  They improved their systems and management practices as well as their internal and external communications.     There was also useful learning by individuals, teams and the organizations.  Individual learning involved quality programs, the client-focused approach, risk management, professional ethics, participatory management and assessment of services.      The “self-assessment” and “make improvements and implement the recommendations” stages of the accreditation cycle contributed the most to change and organizational learning.  The interdisciplinary accreditation teams were the preferred vehicle for achieving these changes and this learning.       The HAA and CFOT have gradually improved their level of compliance with the standards in all quality dimensions, both at the accreditation team level and throughout the organization.  However, improvement in the overall compliance level was below the program’s minimum requirements to obtain accreditation status without major restrictions.   The scope of the changes and learning achieved raises the issue of the capacity of organizations to formalize this new knowledge throughout the organization.  CFOT might achieve this given the resources and skills available to it

Keyphrases: Compliance, Accreditation, Organizational, Change, Learning, Compliance
Dispositifs architecturaux et expérience spatiale de la ville: le cas de l'installation architecturale

Architectural installations, the central research object of this thesis, are a type of urban intervention eluding professional discourses as well as architectural research when the limits of the profession and of the discipline are put under question.  Taking a distance from the functionalism which dominates architectural thought and practice, this research shows that architectural installations are inscribed within a classical tradition anchored in the practice and theory of architecture and that their role in engaging architectural and urban projects in contemporary cities still occupies an important place.  The research therefore presents itself as an exploration guided by the desire of contributing to the recognition of this particular architectural practice.  Before posing the research hypothesis, it was presumed that architectural installations act as active constructions in public space, that they fulfill certain lacunae in the definition of contemporary urban issues, particularly in a context where freedom of choice, spheres of influences and opportunities are largely accompanied by organizational strategies, public control, technological constructions and efficiencies, whether they be functional or energy efficiency.  The research also supposed that the value of social and cultural agitation is associated with characteristics inherent to architecture, to the city and to the individual and that it represents an important object of research while opening on larger questions which cross the discipline.  Amongst those are particularly studied practices and discourses which stand outside usual definitions while presenting a critical stance towards the limits of the discipline, practices which put under light ideas such as uncertainty and event, notions of intervention, ethics, action and exploration.  This thesis wants to enlighten the potential contribution of architectural installations in urban and architectural questions and to show how the experience of the city, through architectural devices, can transform our ways of addressing built space.

Keyphrases: architecture, installation, experience, city, Cedric Price, Bernard Tschumi, pedagogy
L’impact d’une diète néonatale déficiente en nutriments essentiels à la défense antioxydante sur le métabolisme énergétique à long terme

Preterm infants are faced to oxidative stress resulting from a low antioxidant defence and/or a high oxidant load. Datas suggest that an oxidative stress may impair energy metabolism leading to metabolic syndrome development. Hypothesis: A weak antioxidant defence early in life such as observed in preterm newborns is sufficient to impair energy metabolism later in life. Methods: Four groups of guinea pigs (n=21) received between their 3rd and 7th days of life a control diet (C-1week, C-14weeks) or antioxidant deficient diet (DC-1week, DC-14weeks). At 7 day-old, 1week-groups were sacrificed for plasma and liver sampling whereas 14week-groups were fed with the control diet until 14 week-old. Blood glucose and plasma triacylglycerol were determined at 1, 3, 11 and 13-14 week-old. Glucose tolerance test was performed at 13 week-old. Hepatic antioxidant defences and key proteins regulating lipid and glucose metabolism were measured at 1 and 14 weeks. Results: The oxidized redox status of glutathione associated with the neonatal deficient diet was maintained until at least 14 week-old (p<0.01). The low plasma triacylglycerol, low blood glucose and better tolerance to glucose at 14 weeks (p<0.05) were associated with an oxidized redox status. Conclusion: The low glutathione observed in newborn preterm infants has been reproduced in our animal model. Since the oxidized redox state observed here seems to be protective against impaired energy metabolism and since the cellular redox environment is known to be an important rheostat of metabolism influencing development, it suggests being careful before adopting aggressive antioxidant treatments in preterm infants.

Keyphrases: Guinea pig, Antioxidant defence, Liver, Blood glucose, Energetic metabolism, Neonatal nutrition, Redox of glutathione, Neonatal oxidative stress, Metabolic syndrome, Plasma triacyglycerol
L'évaluation du rôle des facteurs génétiques dans la genèse des terreurs nocturnes chez l'enfant : étude prospective chez les jumeaux

For years, the contribution of genetic components to the pathology of sleep disorders has been increasingly recognised as important. There is growing evidence that genetic factors are involved in the occurrence of sleep terrors.  Twin studies provide invaluable information regarding genetic and environmental factors that can affect the manifestation of the disease. However, most previous twin studies on sleep terrors have been done retrospectively or with a sample that was too small to yield conclusive results.  The objective of this thesis was to determine the relative contribution of genetic and environmental factors to the manifestation of sleep terrors in a large cohort of early childhood twins followed prospectively.  The results of the present study confirm that sleep terrors are a partially hereditary parasomnia. Genetic factors play an important role in the manifestation of sleep terrors at a very young age. Of the total phenotypic variance in sleep terrors, the proportions due to genetic influences were over 40% for both 18 and 30 month old twins. At 18 months, the polychoric correlations were 0.63 for MZ and 0.36 for DZ twins. These values were 0, 68 (MZ) and 0, 24 (DZ) at 30 months. These results strongly support the heritability of sleep terrors. There also seems to be continuity in genetic effects with the persistence of sleep terror symptoms at the age of 30 months.

Keyphrases: Sleep terrors, Pediatrics, Genetics, Twins, Epidemiology
Le récepteur B1 des kinines : cible thérapeutique pour le choc septique dans le diabète

Death attributed to septic shock following severe infection increases in diabetic patients and occurs quite frequently in intensive care units. Diabetes mellitus and septic shock increase the production of reactive oxygen species and pro-inflammatory cytokines leading to higher kinin B1 receptor (RB1) expression that is mediated by the activation of the transcriptional nuclear factor Kappa B. Streptozotocin (STZ)-induced diabetes increased the expression of RB1 in rat peripheral tissues, brain and spinal cord. Bacterial lipopolysaccharides (LPS) commonly used to induce septic shock in animal models, also induce RB1. Our objective is to study the contribution of kinin RB1 in the increased morbidity and mortality associated with the combination of these two diseases. Sprague-Dawley rats (225-250g) treated with STZ (65 mg/kg, ip) or vehicle received four days later LPS (2 mg/kg, iv) or vehicle in the presence or absence of the RB1 antagonist, SSR240612 (10 mg/kg), administered by gavage. Body temperature was monitored for 24h after treatment. In addition, SSR240612 was administered twice (9h AM and 9h PM) and rats were sacrificed the following morning at 9h AM after 16 h of fasting to measure the impact on plasma insulin and glucose, oedema and vascular permeability in various tissues (with the technique of Evans Blue) and on the expression of  RB1 (real-time PCR) in heart and kidney. The increase in body temperature caused by treatment with LPS both in STZ-diabetic and non-diabetic rats was blocked by SSR240612. The antagonist normalized hyperglycaemia and improved insulin deficiency in STZ rats. SSR240612 inhibited oedema and reduced vascular permeability in all tissues from diabetic rats treated or not with LPS. The overexpression of RB1 induced by LPS and STZ was blocked by SSR240612. Pharmacological blockade of B1R with SSR240612 prevented the mortality induced by LPS and STZ plus LPS. Thus the anti-pyretic, anti-inflammatory and anti-diabetic effects of SSR240612 suggest that kinin RB1 is a promising therapeutic target for the treatment of co-morbidity associated with septic shock in diabetes.

Keyphrases: Diabetes, Kinin B1 receptor, Lipopolysaccharides, Vascular permeability, hyperthermie, diabetes, septic shock, hyperthemia, hyperglycemia, oedema, streptozotocin
Variabilité Génétique des Populations Ouest-Africaines

The unravelling of our genetic heritage has revealed a demogenetic segueway leading to an increased susceptibility of certain individuals to complex infectious diseases. In order to characterize genetic variability among the West African populations, we analyzed 659 X chromosomes at the dys44 locus which comprises 35 SNPs and a microsatellite spanning a region 2853 bp upstream and 5034 bp downstream of exon 44 of the dystrophine gene in Xp21.3. The resulting genotypes, obtained by dynamic allele specific oligonucleotide hybridization and acrylamide gel electrophoresis, were used for haplotype construction. Gene diversity parameters such as the haplotypic diversity (G) and fixation indexes (Fst) were estimated. Multidimensional analysis of the data, including principal component analysis was also performed. Of the 68 distinct haplotypes detected in our data set, 26 were novel. The mean haplotypic diversity (Gmoy) was 0.91 ± 0.03 for this West African region which was shown to be more heterogeneous than the rest of the continent (Gmoy = 0.85 ± 0.04). However, despite certain sub-regional differences in the distribution of dys44 variants, the analysis of molecular variance showed an overall decline in the genetic distance between Sub-Saharan populations (Fst = 1.5% ; p<10-5). Certain variants, such as the Eurasian-specific haplotype B006, appear to suggest a Trans-Saharan gene flux between North African and Sub-Saharan populations as exemplified by the observed genetic pool of one of the ubiquitous populations of the Nigerian-Congolese linguistic family: The Fulani. Our results are also in agreement with a phyletic heritage between the Biaka, the Afro-Americans and the populations of the Volta-Congo language subfamilies.

Keyphrases: SNP, haplotype, dys44, populations, variability, West-Africa
Rôle du test génétique dans la cardiomyopathie arythmogène du ventricule droit. Étude sur une cohorte prospective unicentrique

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetic disorder characterized by the presence of fibro-fatty replacement of the myocardium in the right ventricle. The disease is thought responsible for an important percentage of sudden cardiac death in the young. Hence the disease is usually difficult to diagnose with present clinical tools. ARVC/D is it caused in greater part by mutations in desmosomal proteins. The diagnosis of the genetic carriers bears important implications in family members, who unknowingly may be at risk for sudden death. In order to improve the diagnosis, a new tool, genetic testing, is increasingly being used. Hypothesis: In order to assess the value of genetic testing in complementing clinical testing in ARVC/D, we undertook the project to collect and perform clinical and genetic investigation in 23 probands with the disease. Methods: The probands were usually identified either after the death of a family member or after their clinical investigation for arrhythmias. The diagnosis of ARVC was made with clinical tools according to accepted criteria. Genetic analysis of desmosomal proteins previously associated with the disease was performed by sequencing the exons and intron-exon boundaries. Results: The clinical diagnosis was clear in 18/23 and suspicious in 5/23 individuals. We identified 15 different mutations in 10 probands. 64% of the mutations were not previously described. Interestingly we also observed the presence of double or triple mutants in 40% of the positive individuals. Individuals with mutations were younger and had more symptoms than individuals with no mutation. Conclusion: Genetic testing is useful in 43% of patients with ARVC. The use of mutation-based genetic technology has a very limited value due to the high percentage of previously unknown mutations in this disease. The presence of double and even triple mutants is not associated with a more severe phenotype but it indicates the need to have genetic testing performed for all genes for familial screening. Genetic testing is a useful tool to add to the clinical testing for the diagnosis of patients who do not completely fulfill the clinical criteria for the disease. Key words: genetic, ARVC/D, sudden death, desmosome

Keyphrases: ARVC/D, Desmosome, Sudden death, ARVC/D, Desmosome, Genetic
Caractérisation de la sous-unité bêta du translocon chez la levure Schizosaccharomyces pombe

Protein secretion is an essential biological process.  In eukaryotes, secreted proteins transit into the endoplasmic reticulum through the translocon pore.  The core of the translocation channel is composed of three subunits called Sec61α, β and γ in mammals, or Sec61p, Sbh1p and Sss1p in yeasts.  While the role of the α and γ subunit is well understood, the function of the β subunit remains ill-defined.  Although numerous species-specific phenotypes have been reported for this protein, the striking sequence conservation among species argue in favour of a universal role.  Recently, Feng et al. (2007) reported the surprising finding that the transmembrane domain (TMD) of Sbh1p was sufficient to complement different functions of the entire protein in Saccharomyces cerevisiae, suggesting an important role for this region.  The aim of my project was to explore the biological function of the translocon β subunit and its TMD in Schizosaccharomyces pombe.  In this yeast, we found that the sbh1+ gene is unessential for viability at 30oC, but is required for growth at low temperature.  Knockout of sbh1+ results in sensitivity to cell-wall stress and reduced protein secretion at 23oC.  Overexpression of Sbh1p also diminishes protein secretion and results in an elongated cell shape.  These phenotypes contrast with those observed S. cerevisiae, as deletion of both Sec61β paralogs in this yeast results in heat sensitivity instead of cold sensitivity.  Nevertheless, Sec61β homologs from both S. pombe and S. cerevisiae complement the respective temperature sensitivity of either yeast.  This functional complementation can also be accomplished by the human homolog of the translocon β subunit, indicating that a fundamental function of Sec61β is conserved from yeast to human. Remarkably, the TMD of Sec61β homologs from S. pombe, S. cerevisiae and human are sufficient to complement the gene knockout in both fission and budding yeasts.  Together, these observations indicate that the TMD of Sec61β exerts a cellular function that is conserved across species.

Keyphrases: Sec61 beta, Sbh1p, Translocon, Transmembrane domain, Yeast, Complementation, Secretion, Schizosaccharomyces pombe, Saccharomyces cerevisiae, sbh1
Exploration sur l'existence et la nature de la bioéthique en Asie

This research study represents an incursion into Asian bioethics. The goal is to verify whether a specific bioethics approach is attributed to Asia and, if so, to identify its most obvious distinctiveness. This research was based on a corpus of articles published between 2001 and 2005 in electronic versions from acknowledged scientific magazines. This research infers the existence of an Asian bioethics which allows for a specific predominance to certain human values as well as unique and distinct meaning. On one hand, the cultural and local moral traditions relationship and, on the other hand, the predominance and interpretation of ethical values, must be recognized and considered so bioethics become relevant and applicable to those affected by the assessed issues in Asia. This study also identifies four distinctiveness in ‘Asian bioethics’ which represent the beginning of an endeavor to define their nature: The correlation between ‘the self’ and the others, compassion, harmony and a spiritual idea of the world based upon interdependence and networking in an intertwined and participative universal order.

Keyphrases: compassion, Asian bioethics, Asia, cultures and traditions, person in relation, compassion, harmony, interdependance, networking
La protéine majeure de la capside de l’HSV-1 est ubiquitinée

Herpes simplex virus type 1 (HSV-1) is the human pathogen responsible for herpetic lesion such as cold sores. On a yearly basis, it is responsible for many cases of encephalitis and infections of the eye that are the most common cause of blindness in North America. Antiviral treatments exist, but no vaccines or drugs are able to prevent or cure the diseases caused by this virus. Today, infections caused by HSV-1 are present all around the world.  Recently a proteomics approach was used to study mature extracellular viruses. This study highlighted the presence in the virus of free ubiquitin and ubiquitin related enzymes. Furthermore, the virus exploits this machinery during the course of infection. Also, it is known that certain virally encoded proteins are ubiquitinated and that the virus mimics some ubiquitin related enzymes.   Our researches focused on identifying ubiquitinated viral proteins that could be present in mature extracellular viruses and their potential roles. The major capsid protein, VP5, an important virus component, was identified. We characterised the type of ubiquitination, a monoubiquitination of lysine K810 and/or K1275 of VP5. The role that could play the ubiquitination of VP5 in the viral cell cycle and in mature virions has yet to be identified.

Keyphrases: VP5, Herpes simplex virus 1, Major protein, VP5, Ubiquitin, Proteasome
Cloning and Characterisation of the human gene gremlin promoter

Osteoarthritis (OA) is a disease that affects the integrity of the articular cartilage which leads to serious health issues for many individuals. Research is focused on understanding the molecular mechanisms which lead to this loss in integrity in the hopes of finding a way to turn the tide. The bone morphogenetic proteins (BMPs) have been shown to play a role in the progression of this disease and this study focuses on one of their antagonists, gremlin.                          We therefore decided to study what affects the expression of this protein through the cloning and characterization of its promoter region. We also studied the role of this protein in the disease, can it influence gene expression and can it initiate a signalling cascade within the cell on its own.                           The results identified a region important for basal and induced activity of its promoter .The results also demonstrated that the main role of this protein in the progression of OA is through BMP antagonism. Gremlin does not initiate a signalling cascade and affect gene expression on its own.

Keyphrases: Gremlin, Gremlin, Osteoarthritis, Cartilage, Cartilage, BMP antagonist, Bone morphogenetic proteins, Chondrocyte, Chondrocyte