NCube/papyrus huggingface dataset:
Localisation, mécanisme d’induction et rôle physiopathologique du récepteur B1 des kinines dans de modèles expérimentaux de douleur chez le rat

Kinins are vaso- and neuro-active peptides involved in hemodynamic, inflammatory and pain processes. Their biological effects are mediated by two G Protein Coupled Receptors (GPCR), termed B2R (constitutive) and B1R (inducible). B1R is expressed following tissue damage or exposure to bacterial endotoxin (LPS), pro-inflammatory cytokines (IL-1β, TNF-α) and increased reactive oxygen species (ROS) levels. The objectives of this doctoral thesis were to define 1) the localisation, 2) the mechanism of induction and 3) the pathophysiological role of B1R in experimental models of pain in rat. Our data showed that B1R is significantly upregulated on sensory C fibers, astrocytes and microglia in spinal cord of type 1 diabetic rat (paper #1). Moreover, pharmacological inhibition of microglia reversed diabetic pain neuropathy, reduced levels of pro-inflammatory mediators and prevented B1R pro-nociceptive activity (papers #2 and 3). Finally, our data showed that systemic stimulation of TRPV1 with capsaicin upregulated B1R expression, mainly on microglia, through the increase of ROS and possibly cytokines (paper #4). Altogether, these data increased our knowledge related to B1R mechanism of induction and B1R activity. Also, these data shed light on new strategies to prevent B1R expression (TRPV1 blockade) and B1R deleterious activity (inhibition of microglia activation) in inflammatory and neuropathic pain.

Keyphrases: TRPV1, kinin B1 receptor, pain, diabetes, microglia, capsaicin
Vers un approfondissement de l’évaluation des états mentaux : exploration de leurs propriétés et répercussions

Mental states refer to the quality of one’s capacity to mentally elaborate and open up to his/her subjective experience in the here-and-now moment. Mental states differ relatively to the availability of the representational and affective resources triggered in order to organize the experience, and in the type of defensive and self-regulatory strategies used. The aims of this thesis were 1) to deepen the evaluation of mental states through the creation and validation of a practical measure, the Mental States Task (MST), in order to evaluate differences in quality of mental states, and 2) to investigate the psychic properties and repercussions of the different mental states. The goal of the first article was to validate the MST. The first part of this article was dedicated to the validation of the French version of the MST, and the second part to the translation and validation of its English version. Results provide convincing evidence of validity and reliability, as well as an adequate predictive value with respect to a large range of related concepts, in both its French and English versions. The MST appears to well represent both low- and high-level mental states according to the reflective continuum, which were found to be linked to a large range of negative/immature and positive/mature constructs, respectively. In addition, each mental state measured by the MST appears to have particular characteristics relative to the mental and emotional processes used to deal with the experience. The purpose of the second article was to deepen the investigation of the predictive value of the MST, through the evaluation of the psychic costs generated by the different qualities of mental states—the costs presumably depending on the representational resources available and the regulatory strategies used. Results suggest that using low-level mental states generates higher energetic costs, resulting in a subsequent ego-depletion effect. Conversely, high-level mental states generate fewer costs, protecting from a subsequent ego-depletion effect. The MST appeared to be an efficient tool in the assessment of the energetic repercussions produced by the different mental sates.

Keyphrases: Mental States Task (MST), Validation, Mental states, Mentalization, Emotional regulation, Mental representations, Self regulation, Defense mechanisms, Mental organization, Ego depletion
Implication de la protéine tyrosine phosphatase DEP-1 dans la perméabilité vasculaire induite par le VEGF

Endothelial cell permeability is a crucial step of angiogenesis. The main actors behind permeability are endothelial cells who accomplish this in response to permeabilizing factors, most notably Vascular Endothelial Growth Factor (VEGF). In a pathological context, migrating tumor cells produce great quantities of VEGF that stimulate an increase of vascular permeability, which allows them to intravasate into the vasculature. Src has been shown to mediate this process. Our laboratory has previously shown that the protein tyrosine phosphatase DEP-1 is involved in the regulation of VEGF-dependant activation of Src. These data thus suggested that DEP-1 might play a role in endothelial cell permeability.  Here, we show through siRNA experiments that DEP-1 is important for the regulatory phosphorylation of VE-Cadherin which is critical for the induction of permeability. The impact of DEP-1 on intercellular junction dissociation is also demonstrated through immunofluorescence microscopy of endothelial cells. We further show that DEP-1 is  absolutely required for the VEGF-dependent increase of permeability as illustrated by in vitro permeability assay on siRNA-transfected endothelial cells. Finally, we show that tyrosine residues in DEP-1’s carboxy-terminal tail, which are crucial for mediating Src activity in response to VEGF, are implicated in VEGF-dependant increase in permeability by transfecting plasmids coding for DEP-1 mutants of these tyrosine residues. These findings shed light on a novel potential key regulator of in vivo permeability.

Keyphrases: Src, Vascular permeability, VEGF, DEP-1
Influence du milieu d'évaluation sur la réalisation de tâches liées à la préparation de repas auprès de personnes âgées fragiles

This thesis aims to advance the state of knowledge about the impact of assessment settings (home versus clinic) on meal preparation task performance in frail older adults. The thesis has three specific objectives and the results are presented in five articles. The first specific objective aims to review current knowledge about the concept of frailty in occupational therapy and the impact of assessment settings in frail older adults. First, a critical review about frailty was conducted. The results (article 1) demonstrate that a better understanding of the concept of frailty may help occupational therapists provide health care and services better tailored to the specific needs of this population. Second, a review of studies comparing performance of instrumental activities of daily living (IADL) between assessment settings was performed. The results (article 2) reveal that older adults without significant cognitive impairments tend to perform better in IADL tasks when assessed at home. Some factors, such as familiarity with the environment, may explain this difference. Based on this review, similar results might be expected with frail elders. The second specific objective aims to compare meal preparation task performance in home and clinical settings in a population of frail older adults. Thirty-seven frail older adults were thus assessed in home and clinical settings with the Assessment of Motor and Process Skills (AMPS) and the Performance Assessment of Self-Care Skills (PASS), using a counterbalanced design. The results (articles 3, 4, 5) globally demonstrate significantly better performance of participants when assessed at home. The third specific objective aims to identify demographic, physical, cognitive, psychological and environmental factors that may explain differences between assessment settings. The results (articles 3, 4, 5) indicate that a better performance in the home setting was mostly related to a decline in certain executive functions. Other cognitive, demographic, psychological, physical and environmental factors also contribute to explain the differences between assessment settings but to a lesser extent. Our findings may help occupational therapists identify frail older adults likely to present a different performance in the clinical setting and thus for whom home assessments would be advisable. Our findings could ultimately mean that frail clients are provided with services adapted to their needs, while ensuring an efficient allocation of health care resources.

Keyphrases: Frail older adults, Activity of daily living, Environment, Assessment, Executive functions
Fonctions de l'oncoprotéine LMO2 déterminées par ses interactions protéiques

Lymphoid leukemia represents about 30% of childhood cancer cases. It is often caused by chromosomal rearrangements involving genes coding for transcription factors, controlling complex genetic programs. As an example, the oncogenic transcription factor LMO2 (LIM-only 2) is often aberrantly expressed in T cell acute lymphoblastic leukemia (T-ALL). In normal hematopoiesis, LMO2 is essential for the generation of hematopoietic stem cells that give rise to all blood cells. Moreover, some leukemic cells possess properties normally reserved to hematopoietic stem cells. Thus, studying the role of LMO2 in hematopoietic stem cells could be relevant to the contexts of normal hematopoiesis and leukemogenesis.    To reveal new molecular functions for LMO2, I chose to identify its associated proteins. In addition to its known protein partners, I identified many proteins involved in transcription/chromatin remodeling, in agreement with its transcriptional role. In addition, several new potential functions have been revealed, indicating that this scaffold protein could be part of non-transcriptional protein complexes, regulating different cell processes. Oncogenes like LMO2 could be master regulators in normal hematopoietic and leukemic cells.  Particularly, I identified protein-protein interactions between LMO2 and DNA replication proteins. I demonstrated that LMO2 controls S phase progression in hematopoietic cells, independently of its association in transcriptional complexes. LMO2 overexpression in mice induces T-ALL and affects specifically the cell cycle status of thymocyte progenitors, which are targets of transformation by LMO2. Thus, LMO2 promotes DNA replication in hematopoietic cells, and possibly in leukemogenesis. Together, these studies allowed to reveal new functions for LMO2, and could serve as a paradigm for other oncogenic transcription factors, especially for other LMO proteins which are all potent oncogenes.

Keyphrases: LMO2, leukemia, hematopoiesis, stem cell, DNA replication, protein-protein interactions
Genetics of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is the most common of motor neuron diseases, affecting 4-6 individuals per 100,000 individuals worldwide. ALS is characterized by muscle weakness and atrophy caused by the degeneration of neurons located in the motor cortex, brain stem and spinal cord. This fatal disease generally has an adult onset and progresses over a three to five year period. While 10% of patients affected have a family history of the disease, 90% of cases do not and are considered sporadic. The finding of mutations in the zinc/copper superoxide dismutase gene (SOD1) gene 19 years ago in about 15-20% of familial ALS (FALS) patients and approximately 2% of overall cases developed the interest of identifying rare genetics variants causing the disease. The ALS research field experienced a rapid progression during the last four years as mutations in new genes have been identified. While mutations in some of those new genes have been clearly linked to ALS, the role of others is still questionable and so far has not been positively replicated in other populations. Importantly, a significant portion of cases still need to be genetically explained and, unfortunately, there is still no effective treatment to cure, attenuate or prevent the disease.  The aim of this Ph.D research project was to identify new ALS mutated genes while analysing the causative role of other newly identified genes in a large familial and sporadic ALS cohort of different origins. The results presented here are categorized into three different sections. First, the contribution of FUS mutations to familial, sporadic and juvenile ALS is analysed. Specifically, new FUS mutations are reported in ALS cases and the proportions of variants present in the tested familial and sporadic ALS cohorts are assessed. In addition, a new mutation is reported in a juvenile ALS patient, and this interesting case is discussed. Second, new genetic avenues are explored for the SOD1 gene. Precisely, a new and complex SOD1 mutation is reported in a French ALS family. Moreover, the possibility that other ALS mutated genes influence SOD1 splicing events is evaluated. Third, the contribution of new candidate genes is evaluated. Precisely, the contribution of OPTN, SIGMAR1 and SORT1 genes to the ALS phenotype is assessed.  Hopefully, our different findings combined with recent developments in genetics and molecular biology will permit a better understanding of the pathological mechanisms involved in the disease and will lead to the identification of the right targets in order to develop appropriate therapeutics for ALS patients.

Keyphrases: mutations rares, SOD1, FUS, OPTN, SIGMAR1, SORT1, amyotrophic lateral sclerosis, motor neuron disease, neurodegeneration, human genetics, rare mutations, candidate genes sequencing
Le mouvement Tea Party aux États-Unis : une mobilisation expliquée par le cadre des opportunités politiques

This thesis looks at the emerging conditions of the Tea Party movement. Our main effort was to know if the mobilization has been facilitated by political opportunities, as theorized by the social movement framework. By using a content analysis method, it was possible to observe three opportunities in a period between February 2009 and October 2010. During this period, it was also possible to look at the frequency and the nature of the mobilization, which takes the form of protests and informal meetings. I find that these opportunities were there during the emerging phase of the Tea Party. It is reasonable to think that the presence of specific issues, division within political coalitions and support of allies explain the substantial increase of the mobilization. Those external conditions seem to have turned a protest-based movement into a traditional political movement, eager to win the 2010 midterm elections.

Keyphrases: Tea party, Social movement, Political opportunity, Mobilization, Conservatism, Libertarianism, Political parties, United States, Tea party
Le potentiel antioxydant de l’alimentation tel qu'estimé par le score ORAC : une comparaison des apports des personnes âgées avec démence du type Alzheimer avec ceux des témoins sans problèmes cognitifs

Oxidative stress and the formation of free radicals are involved in several mechanisms of neuronal death that are characteristic of Alzheimer's disease. Antioxidants are known to help defend against oxidative stress and may protect against the development of Alzheimer's disease. This study aims to evaluate the antioxidant potential, using the “oxygen radical absorbance capacity” (ORAC) score of the diet of older adults people with Alzheimer's disease compared with cognitively-intact age-matched controls. It was hypothesized that the antioxidant potential of the diet of elderly people with Alzheimer's disease will be lower than that of controls without cognitive problems. The current study is a secondary analysis of data obtained from the "Nutrition-Memory study" (NMS). The NMS study recruited forty-two patients with probable Alzheimer’s disease, and their caregivers, and followed them over a period of eighteen months. The current study focuses on three days of dietary data collection, compiled at the beginning (T0) of the NMS study. The antioxidant potential of the diet was determined using the list of ORAC scores highlighted in the USDA database for the oxygen radical absorbance capacity of selected foods. Our results showed that the diet of patients (13784.07 ± 7372.70 μmol TE/100g) had a lower antioxidant potential than that of controls (± 23220.54 10862.55 μmol TE/100g). Moreover, BMI, education and group-status were factors that influenced the total ORAC score. Eating foods rich in antioxidants is a low risk preventative behaviour that could benefit individuals susceptible to developing Alzheimer’s disease.

Keyphrases: ORAC score, oxidative stress, antioxidant potential, dietary intake, free radicals, Alzheimer’s disease, antioxidants, older adults
Dietary patterns associated with diet quality among First Nations women living on reserves in British Columbia

Indigenous Canadians are going through a rapid nutrition transition marked by an increased consumption of market foods and a decreased intake of traditional products. The aim of this research is to identify dietary patterns associated with a better diet quality among Indigenous female adults living on reserve in British Columbia. The sample (n=493) was selected from the First Nations Food, Nutrition, and Environment Study. The study used 24-hour food recalls. To identify dietary patterns, individuals were classified in three groups (tertiles) according to points obtained on a dietary score (based on Dietary Reference Intakes for dietary fiber, total fat, saturated fat, folate, magnesium, calcium, iron, vitamins A, C, D). The tertiles were compared for their consumption of 25 food groups (FGs) using statistical non-parametric tests (i.e. Kruskal-Wallis and ANCOVA tests).  A discriminant analysis was used to confirm the FGs significantly associated with diet quality.   Generally, subjects had poor diet quality since no food recall met the recommended intakes for all selected nutritional elements. The discriminant analysis confirmed that the FGs significantly associated with diet quality were “vegetables and vegetable products”, “fruits”, “traditional foods”, “low-fat dairy products”, “soups and broth”, and “other market meat” (standardized discriminant function coefficient= 0.324, 0.295, 0.292, 0.282, 0.157, -0.189 respectively). The percentage of correct classifications was 83.8%.  In conclusion, our findings support the promotion of dietary choices according to the “Eating well with the Canadian Food Guide – First Nations, Inuit, and Métis”. It is greater use of vegetables, fruits, low-fat dairy products, and traditional foods that characterizes better dietary patterns.

Keyphrases: Dietary patterns, Diet quality, Dietary score, Discriminant analysis, Indigenous Canadians
L’évolution de l’argument contre l’idéalisme dans la Critique de la raison pure

Each edition of the Critique of Pure Reason contains a proof for the reality of the external world: the first is located in the “Fourth Paralogism”, the second, in the “Refutation of Idealism.” This work examines the evolution from the first argument to the second, taking into account two significant criticisms of the first edition which influenced Kant’s second attempt. The latter half of this work treats topics particular to the Refutation only, focusing again on the issues which were stumbling blocks, namely the structure of determined empirical consciousness, the role of the permanent in establishing objectivity, as well as a secondary argument found in the footnotes of the main text and preface.

Keyphrases: Kant, Critique of Pure Reason, Refutation of Idealism, Fourth Paralogism, Transcendental Idealism
Vers un cinéma immatériel : réminiscences du cinématographique dans l’œuvre d'Olafur Eliasson

It is now common to acknowledge that cinema, today, is emancipated from its traditional media figure, adopting various forms related to the cultural fields that welcome it : video games, web, portable medias, etc. However, it is perhaps the visual and media contemporary arts that have morphed it, since the late sixties, into the most disembodied forms, even sometimes beyond recognition. To this end, some contemporary sculptures and installations only composed of light and steam seem, by their own means, to have adopted, and simultaneously put to the test, some characteristics of the cinematographic medium. Based on this observation, this paper aims to analyze, on an aesthetic level, this relationship between media-cinema and the nature of these immaterial artworks. To do so, our analysis will be divided into three chapters focusing respectively on : 1) the expansion of the cinema and its requalification as seen by intermedial theories, 2) the cinema’s loss of its images and materials in some visual art practices since the last fifty years, and 3) the artistic corpus of Danish artist Olafur Eliasson, and more precisely his work entitled Din Blinde Passenger (2010), which is intimately related to our subject matter. Finally, our reflection will mainly be guided by the aesthetic and philosophical approaches of Georges Didi-Huberman and Jacques Rancière.

Keyphrases: Art contemporain, Installation, Olafur Eliasson, Contemporary art, Cinema, Intermediality, Immateriality
Fabrication, caractérisation et étude électrochimique de microcapsules conductrices à base de dérivés carbazole aminés pour la conception de biopiles enzymatiques

The main objective of this thesis is the development of a conductive enzyme immobilisation template for laccase through microencapsulation allowing an efficient electron transfer between the enzyme and the electrode for application in biofuel cells. First, p-phenylenediamine was used as substrate for the characterisation of the microencapsulated laccase. The diffusion of this substrate through the microcapsules was studied under various conditions by means of its electrochemical and enzymatic oxidation processes in order to assess its reversibility and stability. Cyclic voltammetry, rotating disk electrode and Clark electrode were the techniques used in this study. Moreover, poly(aminocarbazole) compounds and their derivatives were identified to replace poly(ethyleneimine) in the fabrication of the microcapsules. These polymers exhibit primary amines (mono- or di-amino) that could be available for an interfacial polymerisation using a cross-linker agent. Also, the monomer 1,8-diaminocarbazole presents the desired electrochemical propreties for an efficient electron transfer between the enzyme and the electrode. Therefore, a synthetic pathway was developed in order to synthesise this monomer since the available literature protocol was considered inappropriate for large scale synthesis. As for the direct synthesis of the poly(1,8-diaminocarbazole), to our knowledge, there is no protocol currently available. Two structural isomers (1,6 and 1,8-diaminocarbazole) were thus synthesised in two steps. The first step consists in the electrophilic substitution of 3,6-dibromocarbazole in 1,8 and/or 1,6 positions by nitro groups. This step was followed by a dehydrodehalogenation reaction that comes along with reduction of nitro to amino functions using Et3N and 10% Pd/C as the catalyst in methanol under H2 flux. During the first step, the 3,6-dibromo-1-nitro-carbazole was also obtained and appeared to be an efficient monomer in the synthesis of the desired conductive copolymer. Finally, the fabrication of the conductive microcapsules was realised by adding the copolymer poly[(9H-octylcarbazol-3,6-diyl)-alt-co-(2-amino-9H-carbazol-3,6-diyl)] to the PEI. This copolymer was synthesised in large quantities, which allowed its use in the design of microcapsules. Its electrochemical behaviour was similar in many ways to the one of poly(1,8-diaminocarbazole). These conductive microcapsules were then used to modify the surface of a platinum electrode to fabricate the bioelectrode. The main objective of this project was achieved through this final step.

Keyphrases: laccase, microcapsules, 1,8-diaminocarbazole, 3,6-dibromo-1-nitro-carbazole, poly[(9H-octylcarbazol-3,6-diyl)-alt-co-(2-amino-9H-carbazol-3,6-diyl)], p-phenylenediamine, poly(ethyleneimine), cyclic voltammetry, microcapsules, Clark electrode, bioelectrode