Caractérisation de la voie permettant la viabilité de Schizosaccharomyces pombe en l'absence de calnexine

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

Approche globale de prédiction d'adhésion au traitement et d'autogestion des soins chez des adultes diabétiques de type 2 : rôle des facteurs psychosociaux

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Unsettled Remains: Canadian Literature and the Postcolonial Gothic

Unsettled Remains: Canadian Literature and the Postcolonial Gothic examines how Canadian writers have combined a postcolonial awareness with gothic metaphors of monstrosity and haunting in their response to Canadian history. The essays gathered here range from treatments of early postcolonial gothic expression in Canadian literature to attempts to define a Canadian postcolonial gothic mode. Many of these texts wrestle with Canada’s colonial past and with the voices and histories that were repressed in the push for national consolidation but emerge now as uncanny reminders of that contentious history. The haunting effect can be unsettling and enabling at the same time. In recent years, many Canadian authors have turned to the gothic to challenge dominant literary, political, and social narratives. In Canadian literature, the “postcolonial gothic” has been put to multiple uses, above all to figure experiences of ambivalence that have emerged from a colonial context and persisted into the present. As these essays demonstrate, formulations of a Canadian postcolonial gothic differ radically from one another, depending on the social and cultural positioning of who is positing it. Given the preponderance, in colonial discourse, of accounts that demonize otherness, it is not surprising that many minority writers have avoided gothic metaphors. In recent years, however, minority authors have shown an interest in the gothic, signalling an emerging critical discourse. This “spectral turn” sees minority writers reversing long-standing characterizations of their identity as “monstrous” or invisible in order to show their connections to and disconnection from stories of the nation. [From the publisher\u27s website] ISBN: 9781554580545 Unsettled Remains: Canadian Literature and the Postcolonial Gothic has been shortlisted for the Gabrielle Roy Prize for Literary Criticism: Canada

Rest-activity disturbances and light exposure in myotonic dystrophy type 1 patients with apathy: An exploratory study using actigraphy

Background: Rest-activity rhythm disturbances have been reported in myotonic dystrophy type 1 (DM1) but no study has assessed its relationship with apathy and light exposure using actigraphy. Methods: Thirty-three DM1 patients wore an actigraph for two consecutive weeks. The Lille Apathy Rating Scale was used to assess apathy. Actigraphy was used to characterize sleep, activity, and light exposure and nonparametric analysis was performed to characterize intraday variability (IV), interday stability (IS), least active five-hour period (L5), most active ten-hour period (M10), and relative amplitude (RA). Results: Apathy was found in 42.4% of patients. Patients with apathy have a larger number of CTG repeat than those without (774 vs 381, p<0.01) Also, patients with apathy had higher IV values (0.98 vs 0.69, p<0.001) as well as lower IS (0.34 vs 0.47, p<0.05), RA (0.65 vs 0.83, p<0.05), and M10 (182.6 vs 493.8, p<0.001) values compared to patients without apathy. In addition, DM1 patients with apathy were exposed to less bright light (≥1000 lux) (41.4 vs 141.2 minutes p<0.01) than patients without. No difference was observed relatively to sleep quality and quantity. Conclusions: Daytime activity levels and bright light exposure were significantly lower in DM1 patients with apathy versus those without. The more fragmented, less stable, and lower amplitude rest-activity rhythm of DM1 patients with apathy, as revealed by non parametric analysis, can be partly ascribed to reduced daylight exposure. The use of bright light therapy as well as physical activity interventions should be explored to help prevent or reduce apathy levels in DM1

Immersion au cœur de l’invalidité : certificats médicaux et limitations fonctionnelles

Les assureurs exigent des certificats médicaux pour déterminer l’admissibilité à des prestations d’invalidité. Pourtant, les pratiques des médecins de famille en contexte de certification d’une incapacité au travail pour troubles mentaux varient. Par ailleurs, les certificats médicaux sont souvent incomplets ou ambigus, particulièrement la section relative aux limitations fonctionnelles. La présente étude vise à déterminer s’il existe une variabilité entre les médecins de famille quant à l’évaluation diagnostique, à la recommandation de traitement, à l’évaluation de l’incapacité au travail d’un même patient et de la durée d’une incapacité au travail et à analyser le type d’interprétation qu’ils font de la notion de limitations fonctionnelles. Vingt-trois médecins de famille du Québec ont complété quatre vignettes pour lesquelles ils doivent déterminer le diagnostic, le traitement, la nécessité ou non d’un arrêt de travail, la raison et dans l’affirmative les limitations fonctionnelles. Des analyses descriptives sont effectuées. Les résultats montrent que la décision de certifier une incapacité au travail ne fait pas bon consensus pour la moitié des vignettes contrairement à la catégorie diagnostique. La notion de limitations fonctionnelles semble confondue avec celle de symptômes. Ces résultats pourront servir à évaluer les pratiques actuelles en matière de certification d’une incapacité au travail

Increased missense mutation burden of Fatty Acid metabolism related genes in nunavik inuit population.

Nunavik Inuit (northern Quebec, Canada) reside along the arctic coastline where for generations their daily energy intake has mainly been derived from animal fat. Given this particular diet it has been hypothesized that natural selection would lead to population specific allele frequency differences and unique variants in genes related to fatty acid metabolism. A group of genes, namely CPT1A, CPT1B, CPT1C, CPT2, CRAT and CROT, encode for three carnitine acyltransferases that are important for the oxidation of fatty acids, a critical step in their metabolism.Exome sequencing and SNP array genotyping were used to examine the genetic variations in the six genes encoding for the carnitine acyltransferases in 113 Nunavik Inuit individuals.Altogether ten missense variants were found in genes CPT1A, CPT1B, CPT1C, CPT2 and CRAT, including three novel variants and one Inuit specific variant CPT1A p.P479L (rs80356779). The latter has the highest frequency (0.955) compared to other Inuit populations. We found that by comparison to Asians or Europeans, the Nunavik Inuit have an increased mutation burden in CPT1A, CPT2 and CRAT; there is also a high level of population differentiation based on carnitine acyltransferase gene variations between Nunavik Inuit and Asians.The increased number and frequency of deleterious variants in these fatty acid metabolism genes in Nunavik Inuit may be the result of genetic adaptation to their diet and/or the extremely cold climate. In addition, the identification of these variants may help to understand some of the specific health risks of Nunavik Inuit

Second generation sequencing of the mesothelioma tumor genome.

The current paradigm for elucidating the molecular etiology of cancers relies on the interrogation of small numbers of genes, which limits the scope of investigation. Emerging second-generation massively parallel DNA sequencing technologies have enabled more precise definition of the cancer genome on a global scale. We examined the genome of a human primary malignant pleural mesothelioma (MPM) tumor and matched normal tissue by using a combination of sequencing-by-synthesis and pyrosequencing methodologies to a 9.6X depth of coverage. Read density analysis uncovered significant aneuploidy and numerous rearrangements. Method-dependent informatics rules, which combined the results of different sequencing platforms, were developed to identify and validate candidate mutations of multiple types. Many more tumor-specific rearrangements than point mutations were uncovered at this depth of sequencing, resulting in novel, large-scale, inter- and intra-chromosomal deletions, inversions, and translocations. Nearly all candidate point mutations appeared to be previously unknown SNPs. Thirty tumor-specific fusions/translocations were independently validated with PCR and Sanger sequencing. Of these, 15 represented disrupted gene-encoding regions, including kinases, transcription factors, and growth factors. One large deletion in DPP10 resulted in altered transcription and expression of DPP10 transcripts in a set of 53 additional MPM tumors correlated with survival. Additionally, three point mutations were observed in the coding regions of NKX6-2, a transcription regulator, and NFRKB, a DNA-binding protein involved in modulating NFKB1. Several regions containing genes such as PCBD2 and DHFR, which are involved in growth factor signaling and nucleotide synthesis, respectively, were selectively amplified in the tumor. Second-generation sequencing uncovered all types of mutations in this MPM tumor, with DNA rearrangements representing the dominant type

Pairwise linkage disequilibrium (LD) diagram for <i>CPT1B</i> and <i>CPT2</i> in Inuit.

<p>LD block was delineated using confidence intervals (Gabriel et al), and 0.6–0.98 for strong LD. Variants of MAF<0.05 were indicated with dashed-line. Variants were extracted from exome sequencing and SNP array data, with the asterisk indicated variants only genotyped by the SNP array. D value <1 was shown in the box, with red color indicated LOD ≥2.</p