Recherche uO Research Accueil

Recherche uO, le dépôt numérique de l'Université d'Ottawa, réunit le matériel de recherche et d'enseignement créé par notre communauté universitaire et nos partenaires. Le savoir de l'Université est ainsi disponible à long terme et en accès libre, ce qui lui procure de la visibilité et facilite sa diffusion.

Comment soumettre votre thèse

Comment déposer votre recherche

Communautés dans DSpace

Sélectionner une communauté pour parcourir les collections sous-jacentes.

Voici les éléments 1 - 5 sur 19

Nouveaux dépôts

Arcuate Nucleus Neurons Regulate Ventral Subregion Ventricular-Subventricular Zone Neural Stem Progenitor Cell Differentiation Through Endocannabinoid Signaling
(Université d'Ottawa | University of Ottawa, 2026-08-28) Sun, Yiren; Wang, Jing
Neural stem and progenitor cells in the ventricular-subventricular zone (V-SVZ) have been a long sought-after source of neurogenic potency. Although activation signals for NSPCs are well-described, difficulties arise in harnessing these NSPCS as isolating differentiation-specific signals remain elusive in vivo. Here, we report that monoacylglycerol lipase (Mgll), a homeostatic enzyme that attenuates synaptic endocannabinoid responses, is a physiological gatekeeper for NSPC differentiation. Remarkably, Mgll expression is non-cell autonomous, originating in axons from neurons innervating the V-SVZ. Furthermore, pathological conditions show early spatiotemporally-distinct overexpression of Mgll in the hypothalamic arcuate nucleus (ARC) of 3xTg Alzheimer’s disease mice (3xTg-AD). ARC Mgll overexpression is coupled to inhibition of differentiation and neurogenesis in the ventral V-SVZ subregion, culminating in olfactory behavioral deficits. Mechanistically, this spatiotemporal Mgll overexpression and subsequent ventral V-SVZ differentiation deficits originate from defective ARC-specific aPKC-CBP signaling. Conversely, spatial transcriptomics shows Mgll deletion in ARC POMC+ neurons increases ventral V-SVZ-specific expression of pro-differentiation transcription factors Nf1x and Nf1b, driving neurogenic and gliogenic lineage commitment. Finally, deleting Mgll in the ARC from mice with dysregulated aPKC-CBP signaling rescues ventral V-SVZ-derived neurogenesis deficits through Nf1x expression. Our study implicates a neuronal homeostatic mechanism in regulating V-SVZ NSPC differentiation and demonstrates that this mechanism is spatiotemporally dysregulated under pathological conditions. These findings show that interacting with neuronally-derived Mgll is a promising strategy to precisely restore neurogenic potency.
The Effects of Synthetic Sex Hormones on Cognitive Abilities, Affective State, the Gut-Brain Axis, and Acute Immune and Stress Reactivity During Puberty and Adulthood
(Université d'Ottawa | University of Ottawa, 2026-08-28) Kheloui, Sarah; Ismail, Nafissa
Combined oral contraceptives (COCs) are one of the most widely used forms of hormonal contraception by both adolescent and adult human females. While they are very effective at preventing pregnancy, they may also have effects on the central nervous system, cognition, and behaviour. However, there are a lot of inconsistencies reported on these effects. One possible explanation for these discrepancies could be that the effects of COCs on the brain are age-dependent and may be more pronounced during puberty and adolescence. The mechanisms underlying the effects of COCs on the brain and behaviour also remain unclear. The current thesis was designed to address these knowledge gaps and to investigate possible mechanisms through which COCs could impact the brain, cognitive abilities, and gut microbiome composition in an age-dependent manner in a mouse model (Article 1). Subsequently, we examined the effects of pubertal COC exposure on mental health outcomes such as depression-like and anxiety-like behaviors (Article 2). Lastly, we investigated whether COCs alter immune and stress responses in pubertal and adult CD-1 mice (Article 3). Together, the studies included in this dissertation furthers our understanding of the impact of combined oral contraceptives use during puberty and adulthood on women’s health including the brain, behaviour, gut microbiome as well as stress and immune systems.
Gobernar con IA: Cuatro acciones para construir una administración pública transformadora y resiliente
(2026-08-27) Régis, Catherine; Martin-Bariteau, Florian; Adams, Rachel; Bertrand, Brunessen; Effoduh, Jake Okechukwu; Parycek, Peter; de Souza, Carlos Affonso Pereira; Yoon, Hyesun Melissa
La IA no constituye un atajo para reformar el gobierno. En ausencia de una transformación institucional previa, de capacidades suficientes y de un marco de gobernanza claro, es más probable que su adopción consolide las disfunciones burocráticas, los sesgos y la opacidad, en lugar de mejorar el desempeño o promover la equidad. El éxito de la IA en el gobierno es, en última instancia, un desafío de gobernanza y no un reto técnico. Los resultados dependen menos del grado de sofisticación de la tecnología que de las capacidades institucionales, los mecanismos de rendición de cuentas, las relaciones de poder con los proveedores y la planificación para la resiliencia. Recomendamos cuatro acciones: rediseñar los servicios públicos en función de problemas reales antes de implementar la IA; invertir en capacidades institucionales mediante la capacitación y la creación de equipos interdisciplinarios; reequilibrar las relaciones de poder con los proveedores mediante mecanismos de contratación colectiva y colaboración; y sustentar el uso de la IA en el sector público sobre una infraestructura de confianza, basada en la transparencia, la rendición de cuentas, la supervisión y la resiliencia. * Original document in English: https://doi.org/10.20381/s959-yx05
From Conventional Methodologies to Error-Corrected Sequencing: High-Resolution Profiling of Dose-, Time-, and Tissue-Specific Benzo[b]fluoranthene-Induced Mutagenesis
(Université d'Ottawa | University of Ottawa, 2026-08-28) Schuster, David; Yauk, Carole; Marchetti, Francesco
Accurate assessment of in vivo somatic mutagenesis is essential for human health risk assessment. However, current regulatory testing guidelines rely heavily on short-term exposures and single-gene phenotypic reporter assays. This thesis characterizes the in vivo mutagenic dynamics of the priority polycyclic aromatic hydrocarbon (PAH) benzo[b]fluoranthene (BbF) across multiple tissues and extended exposure durations using Duplex Sequencing (DS). This approach simultaneously addresses existing knowledge gaps and validates DS as a promising tool to modernize in vivo mutagenicity assessments based on quantitative and mechanistic data. BbF exposure induced dose-dependent increases in micronucleus frequency in peripheral blood and mutation frequency (MF) in the liver and bone marrow (BM) of MutaMouse males after 28 days. Benchmark dose (BMD) modeling revealed comparable clastogenic and mutagenic potencies. Mutations were preferentially induced in intergenic loci, suggesting a protective activity of transcription-coupled nucleotide excision repair in transcribed regions. Furthermore, mutagenesis was characterized predominantly by C:G>A:T and secondary C:G>T:A mutations. Investigation of the trinucleotide mutation pattern revealed similarities towards human tobacco-associated cancer signatures, aligning with a canonical route of PAH exposure. Evaluating prolonged exposures up to 90 and 180 days demonstrated that mutation accumulation mechanisms are tissue-specific. The liver exhibited a higher maximum mutational burden than BM, reflecting its primary role in xenobiotic metabolic activation. In the highly proliferative BM, mutagenesis was heavily driven by the clonal expansion of mutant cells, whereas predominantly unique de novo mutations were detected in liver. This indicates that the physiological propagation of mutant cells contributes differently to the overall mutation burden depending on tissue characteristics. Despite these distinct tissue dynamics, the underlying mutation spectrum remained consistent over time, indicating a stable mutagenic mechanism. Furthermore, BMD modeling highlighted that prolonged exposures increase mutagenic potency and yield lower points of departure compared to standard 28-day designs. Direct comparisons revealed strong quantitative concordance, highlighted by robust Pearson correlations between DS-derived MF on the endogenous mouse mutagenesis panel or the exogenous lacZ transgene versus the conventional transgenic rodent (TGR) assay. These endpoints yielded overlapping potency estimates, validating sequence-resolved analysis as robust quantitative alternatives to the phenotypic TGR assay. Mutation spectrum analysis revealed comparable mutation subtypes between the MMP and lacZ loci, hinting towards endpoint independent mutagenic mechanisms. Conversely, targeted sequencing of the endogenous Pig-a locus was less informative and did not detect dose-related responses. Mutation spectrum analysis was predominantly driven by insertions and deletions in the Pig-a locus due to sequencing artifacts within homopolymeric sequences. This underscores the importance of distributed loci selection over single-gene sequencing. To address existing barriers to regulatory adoption, power analyses demonstrated that sample sizes of four animals per dose group provide sufficient statistical power, representing a reduction in animal use that supports 3Rs principles. Further collaborative efforts demonstrated the high inter-laboratory reproducibility of DS across eight laboratories and developed an open-source bioinformatic approach to harmonize mutation frequency calculations, statistical analysis and quantitative modeling. Collectively, this research defines the dose-, time-, and tissue-dependent determinants of BbF-induced mutagenesis and shows that these factors directly influence potency estimates. Sequence-resolved analyses confirm stable mutational mechanisms across endpoints and exposure durations. Concordance with OECD assays, together with reproducibility and standardized workflows, establishes Duplex Sequencing as a sensitive and quantitatively robust approach. It reduces animal use, integrates into existing toxicology study designs, and enables high-resolution mechanistic data generation. These features support its readiness for broader adoption in in vivo mutagenicity assessment.
What is Arctic Sustainable Development? Pressuring Energy Development and Natural Resource Exploitation under Inuit Self-Determination in Nunavut and Kalaallit Nunaat
(Université d'Ottawa | University of Ottawa, 2026-08-27) Soer, Anna; Katz-Rosene, Ryan
As the media and states have picked up on the narrative of the Arctic as a goldmine for rare earths and minerals and resources, both Nunavut and Greenland are at the centre of international attention. The coming to power of President Trump of the United States of America in 2025 has started with a second heavy push to purchase Greenland from Denmark. Greenlandic officials however have reiterated that the answer to these pressures is not a debate on who would be a better colonizer between Denmark and the USA, but to remain focused on Greenland’s self-determination and path towards independence. Meanwhile, in the case of Canada’s Arctic, midst the threats to Canadian sovereignty by claiming the country as a 51st state, Inuit officials in Nunavut remain clear on their own path towards self-determination within the Canadian federacy. This thesis-by-article is situated within this complex social, political and economic ecosystem and asks the fundamental question: “How do global and national energy-transition resource exploitation pressures reconfigure environmental governance in Greenland and Nunavut?” The first article of the thesis-by-articles – published in the Arctic Yearbook - dissects the underpinning political dynamics in regional natural resource development and global decarbonization. The main research question for this article is “How are natural resource exploitation pressures during the global energy transition reshaping environmental governance in Greenland and Nunavut, and what do these dynamics reveal about the applicability of Arctic Exceptionalism as a defining concept for the region?” The second article – currently under review with The Polar Journal - continues with the topic of natural resource development in line with Inuit self-determination, zooming in in Greenland as an independent state-to-be. It asks “How do Greenland’s political–economic choices in resource and energy development shape its pursuit of energy sovereignty?” The third article – published at The Northern Review - zooms in on Nunavut at the municipal and territorial governance level and dives deeper in the question of Inuit knowledge advanced by the previous article. The study asks “In what ways are community consultation practices and Inuit Knowledge embedded in renewable-energy decision-making in Nunavut, and how effective are they under Nunavut, Canadian, and international frameworks?” The articles each identify key findings for the fields of International Relations and critical political geography in their applicability to Arctic studies. The thesis helps address theoretical gaps of epistemological nature and empirical gaps in this field through a multidisciplinary approach. The main findings of the first article point towards an enmeshment of regional securitization with imperatives of environmental (sustainable) governance. Specifically, natural resource development (especially mining) has become a powerful avenue for decolonial and ecological self-determination against the colonial state (Canada and Denmark) and international growing pressures. The main findings of the second article are situated at the conceptual refining of the tensions between agency and structure where energy sovereignty, under the ‘post’ of Greenland’s colonial era, is structured by a balancing act between extractivism and ecology. Global interests thereby underscore Greenland’s sustainable development paradigm. The results elaborated on in the third article how differences in (i) federal language versus territorial language, in (ii) the theory of centering Inuit knowledge versus its implementation, and in (iii) the theory of community consultation based in the Duty to Consult and the Free, Prior and Informed consent frameworks versus its implementation in federal and territorial policy on resource and energy development. These tensions between the federal, the territorial, and intra-territorial, showcase how Inuit self-determination becomes a maneuver against colonial imposition in defining sustainability.