NCube/papyrus huggingface dataset:
Modulation of nociception and pain by attention and stress

Psychological factors such as hypnosis, emotion, stress, and attention produce powerful modulatory effects on nociception and pain.  However, the influence of attention on nociception and pain and the underlying neural mechanism responsible are unclear. The current literature on attentional modulation of spinal nociceptive responses, as measured by the RIII reflex, and pain perception (pain intensity) is inconsistent and often contradictory. The present thesis provides a new component-based framework for the examination of attentional modulation of the RIII reflex and pain. A delayed-discrimination task was decomposed into the three components of attention – namely alerting, orienting, and executive control (sensory working memory). Previously, the multidimensional nature of attention was largely ignored in the pain literature. We show that each component of attention exerts a distinct modulatory effect on nociception and pain and suggest that this accounts for some of the confusion in the literature. By considering stress separately, we demonstrate for the first time that stress blocks attentional modulation of the RIII reflex, indicating an interaction and dissociation of attention- and stress-mediated modulation of spinal nociceptive responses. This important finding clarifies much of the disagreement in the literature, since cognitive tasks often induce increases in stress that consequently confound interpretation. Additionally, both visual and somatosensory stimuli were included in the discrimination task, revealing that the influence of attention on pain intensity is spatially-specific whereas attentional modulation of nociception is modality-specific, at least for the modalities investigated. From these findings a component-based model for the attentional modulation of pain processes is proposed. This model is substantially supported by the literature and provides a meaningful and cohesive explanation of the seemingly contradictory results across studies. Moreover, this model suggests potential neural mechanisms underlying the attentional modulation of pain.

Keyphrases: Pain, Nociception, RIII reflex, Attention, Stress, Pain modulation, Attentional components
L’identité en projets : ville, architecture et patrimoine. 
Analyse de concours à Québec et à Toronto

This thesis examines the concept of identity, its definitions and uses in the debates and practices of the city, architecture and heritage. Interventions on historic buildings reveal as much the relationship between the identity of society and its history as with the contemporary world. This research studies architectural competitions in two Canadian cities that aspire to be international, one focusing on the contemporary and global aspect (Toronto) and the other on the historical and local aspect (Quebec City). The objective of this research is on the one hand, to unravel the process of identity construction of the contemporary city through architectural projects. On the other hand, it is to analyze the process of identification and the architectural identity in its relation to history and contemporaneity in architectural practice of historic buildings.   The methodology used in this study combines discourse analysis and analysis of the architecture and its representation. The choice of the competition of Place-Royale Interpretation center in Quebec City (1996) and the competition for the expansion of Royal Ontario Museum (2001) in Toronto reveals the concept of identity’s different facets. The history of each competition and semantic analysis of the documentation clarify the relationship between processes and intentions and help to highlight local issues. The analysis of both textual and visual discourses of architects’ proposals reveals the process of identification of the projects, the different types of references involved and the communication strategies employed. The analysis of the projects reflects the identity characteristics of contemporary architecture.  This research reveals the importance of discourses and communication in the construction of cities’ identity, and the societal debates that these questions provoke. During the process of architectural identification, the specific approach of the brief, in the case of Quebec City, prompts a discourse with a historical focus by the architects. The proposed projects are presented within the historical setting and focus on the visual experience of visitors. In the Toronto case, the interest on the global and spectacular in the city’s identity construction generates enthusiasm for an attractive representation of the projects and for iconic architecture.

Keyphrases: Architecture, Discours, communication, Toronto, Identity, City, Heritage, Discourse, Royal Ontario Museum, Place-Royale interpretation center, Quebec City, Competition
Étude de l’expression de « Bcl-2 modifying factor » (Bmf) et son implication dans la néphropathie diabétique

Objective: To investigate the mechanisms underlying tubular apoptosis in diabetes by identifying pro-apoptotic genes that are differentially upregulated by reactive oxygen species in renal proximal tubular cells (RPTCs) in models of diabetes.  Research Design and Methods: Total RNAs isolated from renal proximal tubules (RPTs) of 20 week-old heterozygous db/m+, db/db and db/db catalase (CAT)-transgenic (Tg) mice were used for DNA chip microarray analysis. Real time-quantitative polymerase chain reaction assays, immunohistochemistry and mice rendered diabetic with streptozotocin were used to validate the pro-apoptotic gene expression in RPTs. Cultured rat RPTCs were used to confirm the apoptotic activity and regulation of pro-apoptotic gene expression. Additionally, studies in kidney tissues from patients with and without diabetes were employed to confirm enhanced pro-apoptotic gene expression in RPTs. Results: Bcl-2-modifying factor (Bmf) was differentially upregulated (p<0.01) in RPTs of db/db mice as compared to db/m+ and db/db CAT-Tg mice and in RPTs of streptozotocin-induced diabetic mice in which insulin reversed this finding. In vitro, Bmf cDNA overexpression in rat RPTCs co-immunoprecipated with Bcl-2, enhanced caspase-3 activity and promoted apoptosis. High glucose (HG, 25 mM) induced Bmf mRNA expression in RPTCs, while rotenone, catalase, diphénylèneiodonium and apocynin decreased it. Knockdown of Bmf with small interference RNA reduced HG-induced apoptosis in RPTCs. Importantly, enhanced Bmf expression was detected in RPTs of kidneys from patients with diabetes. Conclusion: These data demonstrate differential up-regulation of Bmf in diabetic RPTs and suggest a potential role for Bmf in regulating RPTC apoptosis and tubular atrophy in diabetes.

Keyphrases: Rein, Hypertension, Kidney, Transgenic mice, Renin-angiotensin system, Diabetic nephropathy, Hypertension, Microarrays, Apoptosis
L’immunoprotéasome : producteur de peptides-CMH I et régulateur de l’expression génique

The ubiquitin-proteasome system is the major mechanism by which intracellular proteins get degraded. Constitutive proteasomes (CPs) are thus essential for cellular homeostasis but also to regulate the majority of important cellular processes. However, the discovery of a second type of proteasome, named immunoproteasome (IP), raises new questions. Why are there more than one type of proteasome? Does the IP perform redundant or complementary roles with the CP? The IP is predominantly expressed in immune or cytokine-stimulated cells and several groups worked at defining its role during the immune response. Yet, the implication of its constitutive homolog in a variety of processes suggests that the IP may also have a much broader impact. The objective was to characterize cellular roles of the IP in dendritic cells. We first studied the global impact of the IP on class I antigen presentation. We discovered that the IP drastically increases the number and the diversity of peptide presented by class I major histocompatibility complexes. Cleavage differences between the CP and the IP are likely part of the explanation for this peptide repertoire diversity, notably due to IP’s apparent affinity for unstructured protein regions. Second, we discovered a new role for the IP in a process unrestricted to the immune system: transcription. We found that the IP affects transcript abundance mostly at the level of mRNA synthesis. The impact of IPs on the transcriptome is major and would be partly based on a different degradation of IRF, STAT and NF-kB transcription factor family members by the two types of proteasomes. IP-deficient dendritic cells are less potent activators of CD8+ T cells and we believe that this defect is at least partly caused by the transcriptome alterations induced by the absence of IPs. It is therefore important to understand the different molecular roles of the IP in order to better define its global contribution to cellular functions and to understand the evolutionary advantage, at the level of the organism, brought by such plasticity of the ubiquitin- proteasome system.

Keyphrases: Transcription, Immunoproteasome, Ubiquitin-proteasome system, Antigen presentation, Major histocompatibility complex of class I, Dendritic cell
Régulation de l’activité transcriptionnelle des récepteurs des estrogènes (ER) par le récepteur à chimiokine CXCR4 et les récepteurs à activité tyrosine kinase ErbB2 et ErbB3

Induction of estrogen-regulated gene transcription by estrogen receptors ERα and ERβ plays an important role in breast cancer development and growth. High expression of the chemokine receptor CXCR4 and its ligand CXCL12/SDF-1 has also been correlated with aggressive breast tumor phenotypes. Here, we describe a positive regulatory loop between CXCR4/SDF-1 signaling pathway and ER transcriptional competence in human breast cancer cells. Treatment of breast carcinoma MCF-7 cells with SDF-1 increased ER transcriptional activity and expression of ER target genes, including SDF-1 itself. These effects were blocked by the antiestrogen ICI-182780 and by CXCR4 silencing, and conversely, estrogen-induced gene expression and growth of MCF-7 cells were impaired upon CXCR4 inhibition. Growth factor signaling also plays an important role in breast cancer. Overexpression and deregulated signaling of receptor tyrosine kinase ErbB2 correlate with aggressive breast tumor phenotype and poor outcomes. However, how ErbB2 and CXCR4 signaling is functionally related to regulate ER response in breast cancer cells is not known. Here we show that steady-state levels of ErbB2 and its dimeric partner ErbB3, as well as ErbB2 tyrosine phosphorylation were negatively regulated with the expression of CXCR4. CXCR4 downregulated ErbB2/ErbB3 dimer activation of the PI3-K/Akt pathway in response to ErbB3 ligand heregulin-β, whereas addition of SDF-1 restored activation levels. We found that heregulin-β promoted CXCR4 phosphorylation at serine 339, an important site for CXCR4 internalization and signaling. In addition, ErbB2 recruitment to CXCR4 was enhanced by ErbB3 and heregulin-β. Transcriptional activity and gene expression measurement showed that the hormonal repression of ER was relieved with the expression of CXCR4 and partially recuperated with the addition of SDF-1. Together, these results show that CXCR4 recruitment to ErbB2 alters ErbB2/ErbB3 signaling pathway and downstream regulation of ER hormonal activity in in breast cancer cells. Our work has enabled us to identify and characterize the impact of membrane receptors signaling on ER transcriptionnal response in breast cancer cells. Membrane signaling is one of the factors involved in endocrine therapy resistance and targeting the receptors implicated could be benificial to improve existing treatments and to work on the creation of new ones.

Keyphrases: ERβ, ERα, SDF-1, CXCR4, MAPK/ERK, ErbB2/Her-2/Neu, ErbB3, PI3-K/Akt, Heregulin, breast cancer
Approches bio-informatiques appliquées aux technologies émergentes en génomique

Genetic studies, such as linkage and association studies, have contributed greatly to a better understanding of the etiology of several diseases. Nonetheless, despite the tens of thousands of genetic studies performed to date, a large part of the heritability of diseases and traits remains unexplained. The last decade experienced unprecedented progress in genomics. For example, the use of microarrays for high-density comparative genomic hybridization has demonstrated the existence of large-scale copy number variations and polymorphisms. These are now detectable using DNA microarray or high-throughput sequencing. In addition, high-throughput sequencing has shown that the majority of variations in the exome are rare or unique to the individual. This has led to the design of a new type of DNA microarray that is enriched for rare variants that can be quickly and inexpensively genotyped in high throughput capacity. In this context, the general objective of this thesis is the development of methodological approaches and bioinformatics tools for the detection at the highest quality standards of copy number polymorphisms and rare single nucleotide variations. It is expected that by doing so, more of the missing heritability of complex traits can then be accounted for, contributing to the advancement of knowledge of the etiology of diseases. We have developed an algorithm for the partition of copy number polymorphisms, making it feasible to use these structural changes in genetic linkage studies with family data. We have also conducted an extensive study in collaboration with the Wellcome Trust Centre for Human Genetics of the University of Oxford to characterize rare copy number definition metrics and their impact on study results with unrelated individuals. We have conducted a thorough comparison of the performance of genotyping algorithms when used with a new DNA microarray composed of a majority of very rare genetic variants. Finally, we have developed a bioinformatics tool for the fast and efficient processing of genetic data to increase quality, reproducibility of results and to reduce spurious associations.

Keyphrases: Bioinformatics, Single nucleotide variants and polymorphisms, Copy number variations and polymorphisms, DNA microchip, Genetic data quality control
La nature des représentations sociales des enseignantes du primaire à l’égard du domaine de l’univers social et de son enseignement : étude de cas à la Commission scolaire de l’Or-et-des-Bois

This research is intended to bring to light the nature of elementary school teach-ers’ social representations in regard to the disciplines related to the social studies field, as well as the teaching of these disciplines within a provincial school board. This project came to exist following a number of interventions in elementary school classes as a practicum supervisor, and after discussions with teachers about the teaching of social studies. The foundations of this project are based on the following observation: at the elementary level, the teaching of knowledge and competencies in the social studies field is lacking and does not completely meet the expectations prescribed by the ministère de l’Éducation, du Loisir et du Sport. Teachers at the elementary level teach very little of the knowledge and competencies in the social studies field in Quebec. As such, students are poorly equipped when they enter secondary school. Previous research targeted some of the factors, allowing an explanation of this observation. However, the researcher supposed that there were other reasons that could explain this phenomenon, and the researcher believed that the analysis of teachers’ social representations could contribute important information to the analysis of this issue. This analysis of social representations is based on the works and on the theories of Abrics’ central core theory (Abric, 1994a). It was constructed around an exploratory research done within a regional school board, where 21 teachers were interviewed. Using a qualitative methodology, with an approach specifically intended for the educational sciences (Merriam, 1998), the results of the research enable us to identify three determining factors in the creation of teachers’ social representations, with regard to history, geography and citizenship education. These factors also lead teachers to modify their teaching and didactic approaches. Moreover, this research allowed for a better understanding of the creation of teachers’ social representations as regards to the disciplines related to social studies and allowed several determining factors in the reluctance to teach this material to students.

Keyphrases: Social representations, Social science, History, Geography, Citizenship education, Teaching, Didactics
Accompagnement de l'élève de 16 à 24 ans en formation générale des adultes du Québec et réussite au sein de l'école

With a view to developing and refining the tools needed to better solve the problem of school drop-out rates, this research interests itself in the accompaniment of the student and the resulting success in the school. It is addressed to the 16 to 24 year old students that are attending Québec’s FGA Education Centres. The general objective is describing what practices are used to accompany the student toward success while also identifying and describing the characteristics and objectives of said practices. In order to achieve this goal, three research questions have been studied, namely: 1) what are the accompaniment methods used in FGA; 2) what are the objectives sought with the use of these methods, and; 3) what are the characteristics of these methods?  This research leans on the approach of sociology of education developed by François Dubet (1994), and proposes to examine three dimensions (pedagogical, personal, and social) as well as seven methods of student accompaniment: tutoring, counselling, pair work, assistance between peers, mentoring, cyber-mentoring, and teacher pedagogical methods. The undertaking is aimed at establishing a group of accompaniment practices for the student in his environment. All of these practices, prior to our research, had never been tabulated. The results obtained permit us to observe an important deployment of several accompaniment methods in use in FGA, including the teachers’ own pedagogical methods. In fact, tutoring and counselling are two methods that score high marks. In addition, this research has helped make it possible to document in a rather complete manner the teachers’ pedagogical methods in said student accompaniment, and to understand the dynamics of these methods in student successes at school. Upon the completion of this research, two sources of knowledge stand out. The first one emanates from the components of the theoretical model presently being studied, while the second relates to the specificity of the teachers’ pedagogical methods. In both cases the results, as well as the analyses, reveal the importance of the pedagogical dimension with respect to accompanying the FGA student, which in turn leads us back to the important contribution made by the teacher in student accompaniment in FGA, as in fact the teacher includes student accompaniment in the actual practice of teaching.

Keyphrases: Scholar accompaniment, Guidance, Follow-up, Support-help, Guardian-support, Tutoring-guide-frame of work, Success, High school drop-out, Adult education, Social inequalities
Programme en partenariat pour la prévention des troubles musculosquelettiques dans une pharmacie communautaire: étude exploratoire

Introduction Health is regarded as an ideal, a goal to improve and to achieve; in order to enhance it some therapists using enabling approaches. The latter show positive results for the prevention of musculoskeletal disorders (MSD's). Objective The objective of this research is to measure the effects of a partnership program in a community pharmacy for the prevention of MSD's. Methodology A mixed design (quantitative, qualitative and descriptive) before and after with a non-equivalent control group is used. Participant recruitment is done on a voluntary basis. They are aged 18 years and over (experimental group (n = 18) and control (n = 17)) and occupy three distinct job titles. Different measures through questionnaires and interviews are taken before and after the intervention. The intervention, meanwhile, includes three session developed from the concepts of ergonomics. Results Results are related to the acquired knowledge and mobilization, and there is a decreased of pain sensation is measured among the participants of the experimental group. Similarly, for these participants, a disposition or proneness to generalize knowledge is observed. Conclusion Inspired by the principles of prevention, ergonomics and empowerment, this study, despite its limitations, allows to better document the effects of a program in partnership with business services for MSD's prevention.

Keyphrases: Formation, Ergonomics, Occupational therapy, Prevention, Training, Empowerment, Occupational health, Musculoskeletal disorders
La performance diagnostique des marqueurs tumoraux messagers dans le diagnostic et le suivi du cancer du sein

According to several evidences, the presence of occult tumor cells in blood circulation in the early stages of breast cancer could be the origin of metastatic lesions. Recent research studies have shown that the use of qRT-PCR for the detection of circulating tumor cells CTC offers the best sensitivity in the quantification of tumor markers. Currently routine monitoring of breast cancer is performed by immunoassay of serum markers CA15.3 and CEA. However, the low sensitivity of these markers in the early stages of the disease and the lack of tissue specificity does not allow their use in diagnosis and prognosis of breast cancer. The diagnosis of the disease is rather based on the analysis of biopsies of the tumor or lymph nodes. This is an invasive procedure, expensive and not suitable for routine monitoring of the risk of relapse and response to treatment. Despite these studies, detection of these cells in hospital laboratories is rare.  Our objective is to set up a new RT-PCR assay for the detection of malignant breast cancer cells in the circulation. The specificity and sensitivity of some potential markers will be compared. The ultimate goal of this project is to routinely offer the detection of one or of a combination of these markers routinely to patients with breast cancer.            Our results show a positive correlation between the expression of CK19 and HER2 mRNA with clinical data of patients. Furthermore, the sensitivity and specificity of our RT-PCR tests are similar to the recent literature. Finally, the comparison of our test with the immunoassay of serum tumor markers CEA and CA15.3 showed that the detection of HER2 and CK19 by RT-PCR is more sensitive in patients with metastatic breast cancer

Keyphrases: Her2, cancer, qrt-pcr, Ck19, routine, monitoring, breast, Rt-Pcr