Caractérisation de l’activité Nur77 et de ses complexes en essais BRET par complémentation

Dans le système nerveux central, la dopamine joue un rôle crucial dans de nombreuses fonctions physiologiques telles que : l’apprentissage, le mouvement volontaire, la motivation, la cognition et la production hormonale. Il a été aussi démontré que le système de signalisation dopaminergique est altéré dans plusieurs maladies neurologiques et psychiatriques comme la maladie de Parkinson et la schizophrénie. Des études, effectuées dans le laboratoire du Dr.Daniel Lévesque (laboratoire d’accueil), ont montré que les récepteurs nucléaires Nur77 (NR4A1, NGFI-B) et RXRγ (retinoid X receptors γ) sont impliqués dans la régulation des effets de la dopamine dans le système nerveux central. De plus, ces données suggèrent que le complexe Nur77 et RXR joueraient un rôle crucial dans l’effet des médicaments antipsychotiques et antiparkinsoniens. Toutefois, très peu de médicaments ciblant Nur77 ont été identifiés à ce jour et les médicaments agissant sur RXRγ restent mal caractérisés. En outre, les analyses actuellement disponibles ne peuvent pas résumer la complexité des activités des NRs et génèrent des mesures indirectes des activités des drogues. Afin de mieux comprendre comment est régulée l’interaction Nur77/RXRγ dans ces processus, mon projet a été de mettre au point un essai BRET (Bioluminescence Resonance Energy Transfer) et PCA-BRET (Protein Complementation Assay-BRET) basé sur le recrutement d'un motif mimant un co-activateur fusionné avec la YFP. Nos différents essais ont été validés par courbes dose-réponse en utilisant différents composés RXR . Les EC50 (concentration efficace médiane, qui permet de mesurer l'efficacité d'un composé) obtenues étaient très semblables aux valeurs précédemment rapportées dans la littérature. Nous avons aussi pu identifier un composé le SR11237 (BMS649) qui semble posséder une sélectivité pour le complexe Nur77/RXRγ par rapport aux complexes Nurr1/RXRγ et RXRγ /RXRγ. Nos résultats indiquent que ces essais de BRET peuvent être utilisés pour évaluer la sélectivité de nouveaux composés pour les complexes Nur77/RXRγ, Nurr1/RXRγ et RXRγ /RXRγ. Un autre aspect de mon projet de doctorat a été de mettre en évidence par BRET l’importance de la SUMOylation dans la régulation de l'activité de Nur77 dans sa forme monomèrique, homodimèrique et hétérodimèrique. Nous avons ainsi identifié que Nur77 recrute principalement SUMO2 sur sa lysine 577. Il est intéressant de noté que le recrutement de la SUMO2 à Nur77 est potentialisé en présence de la SUMO E3 Ligase PIASγ. Aussi, la perte de la SUMOylation sur la lysine 577 entraîne l'incapacité de Nur77 de recruter divers motifs de co-activation mais pas pour ses formes homo- et hétérodimèrique. Cependant, la présence de PIASγ ne potentialise pas le recrutement du co-activateur, suggérant que cette SUMO E3 Ligase est seulement impliqué dans le processus de recrutement de la SUMO mais pas dans celui du co-activateur. Nous avons ainsi déterminé une nouvelle modification post-traductionnelle sur Nur77 régulant spécifiquement son activité monomérique Ces projets pourraient donc apporter de nouvelles données cruciales pour l’amélioration du traitement de la maladie de Parkinson ou de la schizophrénie, ainsi que d'obtenir une meilleure compréhension sur les mécanismes permettant la régulation de la fonction de Nur77

Asymptomatic bacteriuria Escherichia coli strain 83972 carries mutations in the foc locus and is unable to express F1C fimbriae

Escherichia coli is the most common organism associated with asymptomatic bacteriuria (ABU). In contrast to uropathogenic E. coli (UPEC), which causes symptomatic urinary tract infection (UTI), very little is known about the mechanisms by which these strains colonize the urinary tract. Bacterial adhesion conferred by specific surface-associated adhesins is normally considered as a prerequisite for colonization of the urinary tract. The prototype ABU E coli strain 83972 was originally isolated from a girl who had carried it asymptomatically for 3 years. This study characterized the molecular status of one of the primary adhesion factors known to be associated with UTI, namely F1C fimbriae, encoded by the foc gene cluster. F1C fimbriae recognize receptors present in the human kidney and bladder. Expression of the foc genes was found to be up-regulated in human urine. It was also shown that although strain 83972 contains a seemingly intact foc gene cluster, F1C fimbriae are not expressed. Sequencing and genetic complementation revealed that the focD gene, encoding a component of the F1C transport and assembly system, was non-functional, explaining the inability of strain 83972 to express this adhesin. The data imply that E. coli 83972 has lost its ability to express this important colonization factor as a result of host-driven evolution. The ancestor of the strain seems to have been a pyelonephritis strain of phylogenetic group B2. Strain 83972 therefore represents an example of bacterial adaptation from pathogenicity to commensalism through virulence factor loss.

Translation of the flavivirus Kunjin NS3 gene in cis but not its RNA sequence or secondary structure is essential for efficient RNA packaging

Our previous studies using trans-complementation analysis of Kunjin virus (KUN) full-length cDNA clones harboring in-frame deletions in the NS3 gene demonstrated the inability of these defective complemented RNAs to be packaged into virus particles (W. J. Liu, P. L. Sedlak, N. Kondratieva, and A. A. Khromykh, J. Virol. 76:10766-10775). In this study we aimed to establish whether this requirement for NS3 in RNA packaging is determined by the secondary RNA structure of the NS3 gene or by the essential role of the translated NS3 gene product. Multiple silent mutations of three computer-predicted stable RNA structures in the NS3 coding region of KUN replicon RNA aimed at disrupting RNA secondary structure without affecting amino acid sequence did not affect RNA replication and packaging into virus-like particles in the packaging cell line, thus demonstrating that the predicted conserved RNA structures in the NS3 gene do not play a role in RNA replication and/or packaging. In contrast, double frameshift mutations in the NS3 coding region of full-length KUN RNA, producing scrambled NS3 protein but retaining secondary RNA structure, resulted in the loss of ability of these defective RNAs to be packaged into virus particles in complementation experiments in KUN replicon-expressing cells. Furthermore, the more robust complementation-packaging system based on established stable cell lines producing large amounts of complemented replicating NS3-deficient replicon RNAs and infection with KUN virus to provide structural proteins also failed to detect any secreted virus-like particles containing packaged NS3-deficient replicon RNAs. These results have now firmly established the requirement of KUN NS3 protein translated in cis for genome packaging into virus particles.

Linguistic determinism and theory of mind in deaf children

DeVilliers and DeVilliers (2000, 2005) propose that deaf and hearing children acquire a theory of mind (or the understanding that human behaviour is the product of psychological states like true and false beliefs) as a consequence of their linguistic mastery of a rule of syntax. Specifically, they argue that the syntactic rule for sentential complementation with verbs of speech (e.g., “say”) precedes syntactic mastery of complementation for cognition (e.g., “think”) and both of these developmentally precede and promote conceptual mastery of a theory of mind (ToM), as indexed via success on standard false belief tests. The present study examined this proposition in groups of primary-school-aged deaf children and hearing preschoolers who took false belief tests and a modified memory for complements test that included control questions. Guttman scaling techniques indicated no support either for the prediction that syntactic skill precedes ToM understanding or for the earlier emergence of complementation for “say” than for “think”. Methodological issues and implications for deaf children's ToM development are discussed.

AS PRÁTICAS DE TREINAMENTO COMO MECANISMOS DISCIPLINARES E DE REGULAÇÃO EM ORGANIZAÇÃO DE DESENVOLVIMENTO E COMÉRCIO DE SOFTWARE DE RECURSOS HUMANOS

Este trabalho tem como objetivo investigar na prática organizacional as articulações e desarticulações entre as práticas de treinamento, vistas como mecanismo que disciplina o indivíduo (normas e padronização de procedimentos de trabalho), e as diretrizes de práticas de treinamento, vistas como mecanismo de regulação (normas, padrões de conduta), das relações entre a organização e os funcionários. A pesquisa permite trazer para o ambiente acadêmico científico um aprofundamento quanto aos mecanismos de poder disciplinar exercidos pela organização estudada sobre os funcionários e os mecanismos de regulação sobre o mesmo fenômeno práticas de treinamento , além de explorar a questão da distinção e complementaridade entre ambos. Foi utilizada pesquisa qualitativa e uma proposta teóricometodológica de análise de conteúdo e análise de discurso, a partir de uma amostra indicativa e intencional, sendo a empresa do ramo de desenvolvimento e comércio de software de recursos humanos. Utilizou-se de três instrumentos para a coleta de dados: a entrevista em profundidade, observações do pesquisador e pesquisa documental. As análises feitas entre a teoria e os dados empíricos comprovaram a existência de articulações e desarticulações entre os mecanismos, além de outros achados, confirmados através da norma de treinamento e dos depoimentos dos entrevistados.

O rádio FM e a propaganda em seu espaço on line

As emissoras de rádio não utilizam, de maneira eficiente, os espaços que possuem na internet. Foi baseado nesta hipótese que este trabalho foi construído. Trata-se de um estudo realizado a partir de sites de emissoras de rádio com sede na Capital Paulista, através do qual foi possível observar a maneira como as emissoras utilizam seus espaços on-line para a busca da interatividade com seus ouvintes e também a colocação de materiais publicitários de seus anunciantes. Após a etapa de pesquisa nos sites, especialistas divididos em professores universitários, anunciantes, profissionais de agências de propaganda e de veículos de comunicação foram procurados, com o intuito de verificar se acreditavam na possibilidade / capacidade de construção de uma relação interativa entre as emissoras de rádio, seus sites e seu público. Apesar da totalidade dos questionários apontar a crença nesta possibilidade, estes profissionais não mostraram caminhos possíveis para a utilização desta mídia audiovisual como complementação do processo comunicacional com o rádio. Assim, coube a este trabalho apresentar possibilidades de interação entre o mundo virtual e o rádio.(AU)

REPRESENTAÇÕES SOCIAIS DOS ALUNOS DO PROGRAMA ESPECIAL DE FORMAÇÃO PEDAGÓGICA: UM ESTUDO SOBRE A FORMAÇÃO DOCENTE DE PROFESSORES, QUE JÁ SÃO PROFESSORES

O objetivo desta pesquisa é investigar o Programa Especial de Formação Pedagógica (PEFP), na perspectiva das representações sociais. Foram convidados a participar da pesquisa 463 (quatrocentos e sessenta e três) alunos, integrantes de cinco turmas do curso, sendo que 102 (cento e dois) alunos aceitaram e responderam voluntariamente ao questionário colocado no ambiente virtual de aprendizagem. Em seguida, foram selecionados entre os alunos respondentes, aqueles que já exerciam a docência. Esses professores foram convidados a participar de uma entrevista sobre sua formação docente, por meio do programa especial e 9 (nove) professores aceitaram. Também foram entrevistados 4 (quatro) diretores de escolas e supervisores de ensino que atuam ou atuaram na região metropolitana de Santos. A investigação se completou com a análise da legislação educacional e mandados judiciais referentes ao Programa Especial de Formação Pedagógica. Os dados obtidos foram analisados pelo software ALCESTE e por meio de Análise de Conteúdo, numa metodologia de pesquisa qualitativa. Os resultados apontaram a seguinte representação social: ser professor é ter formação pedagógica, formação profissional e formação acadêmica, por meio de uma licenciatura. Esta representação quanto à formação docente converge para a themata: ser professor é ser licenciado. A díade licenciado/não licenciado enuncia uma tensão existente no centro da representação identificada. Alunos e egressos do curso manifestaram insegurança sobre a legitimidade da licenciatura obtida por meio da complementação pedagógica e, consequentemente, sobre sua inserção profissional no sistema educacional. Entretanto, entrevistas feitas com supervisores de ensino e diretores de escola mostram o outro lado da formação pedagógica, por meio do PEFP. Os relatos dos diretores e supervisores de ensino apontam para a legitimação do curso e para o envolvimento profissional destes professores, nas escolas onde atuam.

A INSERÇÃO DE BEBÊS EM CRECHES: UM OLHAR PARA AS POLÍTICAS PÚBLICAS

O presente trabalho propõe um estudo sobre a inserção de bebês em creches públicas no município de São Paulo. De acordo com Rosemberg (2010), a infância constitui fase importantíssima na formação da criança e embora a duração da primeira infância seja de curta duração, considerando-se a expectativa de vida de 70 anos, ela constitui a vida inteira dos bebês e das crianças pequenas. Nos dias atuais os bebês ingressam na creche a partir dos quatro meses de idade e lá permanecem por até dez horas. Nesse sentido, esta pesquisa buscou compreender as políticas públicas para esse atendimento, o qual, com a Constituição de 1988, foi considerado a primeira etapa da Educação Básica compondo a Educação Infantil brasileira, de oferta obrigatória e direito das crianças, garantindo, em complementação à família, o desenvolvimento integral da criança pequena. Desse contexto, alguns questionamentos foram trazidos para a discussão: quais as propostas de atendimento de bebês na creche e como funcionam as instituições que os recebem? Qual o olhar das políticas públicas para esse segmento de educação? A Constituição garante o ingresso dos bebês na creche, mas e seu desenvolvimento integral, está garantido? Recentemente atrelada à esfera educacional, a creche tem o desafio de compreender seu papel com essas crianças, desvinculando-se de práticas apenas assistencialistas e higienistas, e de construir novas concepções acerca desse atendimento. Tais concepções ficam explícitas não nas politicas públicas, mas efetivam-se na prática da creche, nas atividades desenvolvidas, nos espaços e processos pedagógicos pensados para receber o bebê. Em face do exposto, esta pesquisa possibilitou inferir que, apesar dos avanços acerca do atendimento educacional ofertado a primeira infância, falta ainda clareza por parte da sociedade em geral, sobre a importância de uma educação de qualidade para as crianças pequenas e seu impacto na formação humana. Essa lacuna merece o olhar das políticas públicas, uma vez que demanda ações nas diversas instâncias da creche, desde a formação e a valorização do professor de Educação Infantil, até a estrutura física e a escassez das vagas. Os poucos estudos que discutem tais políticas para a educação de bebês nas creches, justificam a realização deste trabalho.

Pseudomonas aeruginosa β-lactamase induction requires two permeases, AmpG and AmpP

Background In Enterobacteriaceae, β-lactam antibiotic resistance involves murein recycling intermediates. Murein recycling is a complex process with discrete steps taking place in the periplasm and the cytoplasm. The AmpG permease is critical to this process as it transports N-acetylglucosamine anhydrous N-acetylmuramyl peptides across the inner membrane. In Pseudomonadaceae, this intrinsic mechanism remains to be elucidated. Since the mechanism involves two cellular compartments, the characterization of transporters is crucial to establish the link. Results Pseudomonas aeruginosa PAO1 has two ampG paralogs, PA4218 (ampP) and PA4393 (ampG). Topology analysis using β-galactosidase and alkaline phosphatase fusions indicates ampP andampG encode proteins which possess 10 and 14 transmembrane helices, respectively, that could potentially transport substrates. Both ampP and ampG are required for maximum expression of β-lactamase, but complementation and kinetic experiments suggest they act independently to play different roles. Mutation of ampG affects resistance to a subset of β-lactam antibiotics. Low-levels of β-lactamase induction occur independently of either ampP or ampG. Both ampG and ampP are the second members of two independent two-gene operons. Analysis of the ampG and ampPoperon expression using β-galactosidase transcriptional fusions showed that in PAO1, ampGoperon expression is β-lactam and ampR-independent, while ampP operon expression is β-lactam and ampR-dependent. β-lactam-dependent expression of the ampP operon and independent expression of the ampG operon is also dependent upon ampP. Conclusions In P. aeruginosa, β-lactamase induction occurs in at least three ways, induction at low β-lactam concentrations by an as yet uncharacterized pathway, at intermediate concentrations by an ampPand ampG dependent pathway, and at high concentrations where although both ampP and ampGplay a role, ampG may be of greater importance. Both ampP and ampG are required for maximum induction. Similar to ampC, ampP expression is inducible in an ampR-dependent manner. Importantly, ampP expression is autoregulated and ampP also regulates expression of ampG. Both AmpG and AmpP have topologies consistent with functions in transport. Together, these data suggest that the mechanism of β-lactam resistance of P. aeruginosa is distinct from well characterized systems in Enterobacteriaceae and involves a highly complicated interaction between these putative permeases and known Amp proteins.

Over-Expression of Endothelin 3 Sensitizes Mice to Uv-Induced Melanoma Metastasis

Melanomagenesis is influenced by environmental and genetic factors. In normal cells, ultraviolet (UV) induced photoproducts are successfully repaired by the nucleotide excision repair (NER) pathway. Mice carrying mutations in the xeroderma pigmentosum (Xp) complementation group of genes (Xpa-Xpg) lack the NER pathway and are therefore highly sensitive to UV light; however, they do not develop melanoma after UV exposure. In humans, the Endothelin 3 signaling pathway has been linked to melanoma progression and its metastatic potential. Transgenic mice that over-express Edn3 under the control of the Keratin 5 promoter (K5-Edn3) and exhibit a hyperpigmentation phenotype, were crossed with Xp deficient mice. Because melanoma is highly metastatic and many primary malignancies spread via the lymphatic system, analyzing the lymph nodes may serve useful in assessing the possible spread of tumor cells to other tissues. This study aimed to determine whether the over-expression of Edn3 is sufficient to lead to melanoma metastasis to the lymph nodes. Mice were exposed to UV radiation and analyzed for the presence of skin lesions. Mice presenting skin lesions were sacrificed and the nearest lymph nodes were excised and examined for the presence of metastasis. Mice with melanoma skin lesions presented enlarged and hyperpigmented lymph nodes. Diagnosis of melanoma was established by immunostaining with melanocyte and melanoma cell markers, and while UV radiation caused the development of skin lesions in both K5-Edn3 transgenic and control mice, only those mice carrying the K5-Edn3 transgene were found to develop melanoma metastasis to the lymph nodes. These results indicate that over-expression of Edn3 is sufficient to lead to lymph node metastasis in mice exposed to at least one dose of UV radiation.

Caractérisation de l’activité Nur77 et de ses complexes en essais BRET par complémentation

Dans le système nerveux central, la dopamine joue un rôle crucial dans de nombreuses fonctions physiologiques telles que : l’apprentissage, le mouvement volontaire, la motivation, la cognition et la production hormonale. Il a été aussi démontré que le système de signalisation dopaminergique est altéré dans plusieurs maladies neurologiques et psychiatriques comme la maladie de Parkinson et la schizophrénie. Des études, effectuées dans le laboratoire du Dr.Daniel Lévesque (laboratoire d’accueil), ont montré que les récepteurs nucléaires Nur77 (NR4A1, NGFI-B) et RXRγ (retinoid X receptors γ) sont impliqués dans la régulation des effets de la dopamine dans le système nerveux central. De plus, ces données suggèrent que le complexe Nur77 et RXR joueraient un rôle crucial dans l’effet des médicaments antipsychotiques et antiparkinsoniens. Toutefois, très peu de médicaments ciblant Nur77 ont été identifiés à ce jour et les médicaments agissant sur RXRγ restent mal caractérisés. En outre, les analyses actuellement disponibles ne peuvent pas résumer la complexité des activités des NRs et génèrent des mesures indirectes des activités des drogues. Afin de mieux comprendre comment est régulée l’interaction Nur77/RXRγ dans ces processus, mon projet a été de mettre au point un essai BRET (Bioluminescence Resonance Energy Transfer) et PCA-BRET (Protein Complementation Assay-BRET) basé sur le recrutement d'un motif mimant un co-activateur fusionné avec la YFP. Nos différents essais ont été validés par courbes dose-réponse en utilisant différents composés RXR . Les EC50 (concentration efficace médiane, qui permet de mesurer l'efficacité d'un composé) obtenues étaient très semblables aux valeurs précédemment rapportées dans la littérature. Nous avons aussi pu identifier un composé le SR11237 (BMS649) qui semble posséder une sélectivité pour le complexe Nur77/RXRγ par rapport aux complexes Nurr1/RXRγ et RXRγ /RXRγ. Nos résultats indiquent que ces essais de BRET peuvent être utilisés pour évaluer la sélectivité de nouveaux composés pour les complexes Nur77/RXRγ, Nurr1/RXRγ et RXRγ /RXRγ. Un autre aspect de mon projet de doctorat a été de mettre en évidence par BRET l’importance de la SUMOylation dans la régulation de l'activité de Nur77 dans sa forme monomèrique, homodimèrique et hétérodimèrique. Nous avons ainsi identifié que Nur77 recrute principalement SUMO2 sur sa lysine 577. Il est intéressant de noté que le recrutement de la SUMO2 à Nur77 est potentialisé en présence de la SUMO E3 Ligase PIASγ. Aussi, la perte de la SUMOylation sur la lysine 577 entraîne l'incapacité de Nur77 de recruter divers motifs de co-activation mais pas pour ses formes homo- et hétérodimèrique. Cependant, la présence de PIASγ ne potentialise pas le recrutement du co-activateur, suggérant que cette SUMO E3 Ligase est seulement impliqué dans le processus de recrutement de la SUMO mais pas dans celui du co-activateur. Nous avons ainsi déterminé une nouvelle modification post-traductionnelle sur Nur77 régulant spécifiquement son activité monomérique Ces projets pourraient donc apporter de nouvelles données cruciales pour l’amélioration du traitement de la maladie de Parkinson ou de la schizophrénie, ainsi que d'obtenir une meilleure compréhension sur les mécanismes permettant la régulation de la fonction de Nur77

Cartographe dynamique des voies de signalisation MAPK chez la levure Saccharomyces cerevisiae

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Interpreting Human Genetic Variation through Genomics and In Vivo Models

Improvements in genomic technology, both in the increased speed and reduced cost of sequencing, have expanded the appreciation of the abundance of human genetic variation. However the sheer amount of variation, as well as the varying type and genomic content of variation, poses a challenge in understanding the clinical consequence of a single mutation. This work uses several methodologies to interpret the observed variation in the human genome, and presents novel strategies for the prediction of allele pathogenicity.

Using the zebrafish model system as an in vivo assay of allele function, we identified a novel driver of Bardet-Biedl Syndrome (BBS) in CEP76. A combination of targeted sequencing of 785 cilia-associated genes in a cohort of BBS patients and subsequent in vivo functional assays recapitulating the human phenotype gave strong evidence for the role of CEP76 mutations in the pathology of an affected family. This portion of the work demonstrated the necessity of functional testing in validating disease-associated mutations, and added to the catalogue of known BBS disease genes.

Further study into the role of copy-number variations (CNVs) in a cohort of BBS patients showed the significant contribution of CNVs to disease pathology. Using high-density array comparative genomic hybridization (aCGH) we were able to identify pathogenic CNVs as small as several hundred bp. Dissection of constituent gene and in vivo experiments investigating epistatic interactions between affected genes allowed for an appreciation of several paradigms by which CNVs can contribute to disease. This study revealed that the contribution of CNVs to disease in BBS patients is much higher than previously expected, and demonstrated the necessity of consideration of CNV contribution in future (and retrospective) investigations of human genetic disease.

Finally, we used a combination of comparative genomics and in vivo complementation assays to identify second-site compensatory modification of pathogenic alleles. These pathogenic alleles, which are found compensated in other species (termed compensated pathogenic deviations [CPDs]), represent a significant fraction (from 3 – 10%) of human disease-associated alleles. In silico pathogenicity prediction algorithms, a valuable method of allele prioritization, often misrepresent these alleles as benign, leading to omission of possibly informative variants in studies of human genetic disease. We created a mathematical model that was able to predict CPDs and putative compensatory sites, and functionally showed in vivo that second-site mutation can mitigate the pathogenicity of disease alleles. Additionally, we made publically available an in silico module for the prediction of CPDs and modifier sites.

These studies have advanced the ability to interpret the pathogenicity of multiple types of human variation, as well as made available tools for others to do so as well.

Argument structure and specific language impairment: retrospect and prospect

This article reflects a collaboration between the Universities of Groningen and Reading of which Frans Zwarts was the promoter. One of the outcomes was a close attention to the learning of various aspects of argument structure by children with specific language impairment (SLI) in Dutch and English. At that time and since, the focus on deficits in grammatical morphology in these children has left verb complementation as something of a syntactic Cinderella. Here we review the findings from our studies in the 1990s. We confirm that children with SLI in both languages have problems with verb specificity, with argument structure alternations and with resultative verb predicates. The very limited number of subsequent studies on verb syntax appear to support our findings. We conclude that this is an area which will repay further scrutiny – it is high time argument structure received an invitation to the ball.

Cartographe dynamique des voies de signalisation MAPK chez la levure Saccharomyces cerevisiae

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.