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Molecular Control of Genome Architecture
No full textHeterochromatin (HC) tethering at the nuclear lamina (NL) is observed in almost every cell, and mutations in tethering proteins lead to a variety of diseases called laminopathies that have been the subject of intense study. Nonetheless, the importance of HC tethering for genome regulation and/or other cellular functions is not fully understood. Unlike most cells, murine rod photoreceptors have an inverted organization, in which euchromatin (EC) is localized to the nuclear periphery, and HC is untethered. Using rods as a model system devoid of any tethering proteins, two players were identified as crucial in HC tethering. The lamin B receptor (Lbr) is sufficient for HC tethering and is expressed during development, but Lbr levels decline upon rod photoreceptor differentiation. A second tether is the intermediate filament lamin A (LA), which is not normally expressed in murine rods. In my first published data chapter, I found that LA ectopically upregulates and reorganizes the genome during rod degeneration.
Using ATAC-seq to examine genome accessibility, we showed that LA and Lbr tethering proteins both lead to marked increases in genome accessibility at regions associated with stress responsive genes. However scRNA-seq on LA- and Lbr-expressing rods revealed relatively minor stress-responsive gene transcription. Together, our data reveal that HC tethers have a global effect on genome accessibility and suggest that HC tethering primes the photoreceptor genome to respond to stress.
In my next data chapter, I performed experiments designed to understand why LA upregulates during degeneration. Along with Jasmine Levesque , we found that in the rd1 model of retinitis pigmentosa, LA upregulation correlates with markers of DNA damage. Moreover, functional manipulations suggest that LA upregulation promotes rod photoreceptor survival. Together, these data imply that LA may upregulate as an adaptive response to DNA damage.
Next, to better understand the logic of HC tethering, I performed experiments designed to elucidate the tethering mechanism. I performed a structure/function study of LA-dependent HC tethering. More than 400 different LMNA gene mutations are associated with laminopathic disease. Studies have previously linked mutations to reduction of HC, abnormal nuclear morphology and DNA damage, but most experiments have been performed in conventionally organized cell types - many of which express wild-type LA/C and Lbr. It has therefore been difficult to determine whether genome disorganization is directly caused by specific LA mutations, or is a consequence of other pathological mechanisms. I expressed a panel of mutant LA constructs in rod photoreceptors to determine how mutations affect tethering competence.
I identified protein domains necessary for HC tethering within the LA C-terminus and IG-fold domain. Moreover, progeroid and non-progeroid laminopathic disease mutations exhibited a complete loss of tethering competence. However, defarnesylating these laminopathic mutants partially restored HC tethering. My results suggest that the LA C-terminus is necessary and sufficient for HC tethering, in part, due to the requirement for C-terminal processing.
In my final data chapter, since LA does not have an obvious chromatin binding domain, we evaluated the hypothesis that partner proteins act as a bridge between chromatin and LA. Using rod photoreceptors as a model for tethering sufficiency, I ectopically expressed a set of LA- interacting proteins. However, my results suggest that these partner proteins could not act in trans to restore tethering to versions of LA that were tethering-incompetent. Together with proteomic experiments profiling LA and molecular modelling, our results suggest that LA does not depend on known partner proteins to interact with HC, but interacts directly with nucleosomes. Our findings might impact the field of human disease genomics and provide insight into mechanisms regulating genome organization
A multi-centre, participant-blinded, randomized, 3-year study to compare the efficacy of Virtual Surgical Planning (VSP) to Freehand Surgery (FHS) on bony union and quality of life outcomes for mandibular reconstruction with fibular and scapular free flaps: study protocol for a randomized phase II/III trial
No full textAbstract Background Advanced head and neck malignancies with underlying bony involvement often require aggressive oncological resection of large segments of the oral cavity including the mandible. These patients require vascularized donor osseous free tissue transfer to reconstruct significant defects. Traditionally, the donor bone is harvested on its vascular supply and shaped to the defect in a free hand fashion (FHS). However, virtual surgical planning (VSP) has emerged as a method to optimize reconstructive outcomes and decrease operative time. The goals of this study are to assess superiority of VSP to FHS by comparing bony union rates at 12 months, short and long-term complication rates, reconstruction accuracy, quality of life (QOL), functional outcomes, and economic analysis. Methods This is a multicenter phase II/III study randomizing four hundred twenty head and neck patients undergoing mandibulectomy in a 1:1 ratio between VSP and FHS. Intention-to-treat analysis will be performed for patients enrolled but unable to undergo VSP-aided reconstruction. The primary endpoint is bony-union rates at 1 year post-operatively. Secondary outcomes include complication rates, QOL, functional outcomes, and economic burden. Discussion This study will provide an assessment of two different surgical approaches to the reconstructive methods of mandible defects using fibular or scapular free flaps on bony-union rates, complications, QOL and economics. Trial registration Clinicaltrials.gov identifier: NCT05429099. Date of registration: June 23, 2022. Current version: 1.0 on March 6, 2024
Are Myokines Linked to Metabolic Improvements with Increased Physical Activity in Subjects with Type 2 Diabetes: How Acute and Chronic Exercise Regulate Myokine Secretion in this Population
No full textSkeletal muscle is the main site of post-prandial glucose uptake and in patients with type 2 diabetes (T2D), it is affected with metabolic dysfunctions. Muscle cells secrete peptides called myokines that positively modulate muscle metabolism. In patients with T2D, myokine secretion is altered. As physical activity is an efficient method for the management of T2D that can also regulate myokine secretion, regular practice of exercise could be beneficial to patients with T2D in restoring myokine secretion. To study this potential relationship, we explored the regulation of myokines in humans with or without T2D in response to acute and chronic exercise.
We first compared peripheral myokines in subjects with or without obesity in response to an exercise bout, and found that plasma FGF21, interleukin (IL)-6, IL-8, IL-15, and IL-18 were regulated by acute exercise, while obesity was associated with elevated plasma IL-13, but lower IL-8 and FGF21. Chronic inflammation is a common driver of both coronary artery disease (CAD) and T2D. The comparison of peripheral cytokines (candidate myokines) in subjects with CAD with or without T2D in response to interventions consisting of either high intensity interval training (HIIT) or moderate intensity continuous training (MICT) showed that the co-morbidity was associated with increased plasma IL-8 and training further reduced plasma FGF21 and IL-6 in this group. No differences were found between HIIT and MICT on cytokine secretion. Finally, we compared the effect of chronic exercise on peripheral and local myokine secretion in healthy subjects and patients with T2D with or without resistance to exercise training and found no differences as a function of T2D status or response to exercise, with the exception of modest differences in expression patterns for certain myokines (IL-1β, IL-8, IL-10, and IL-15).
This research serves as comparative reference of how autocrine/paracrine and endocrine signaling by skeletal muscle is altered by exercise in patients with T2D. Most studies concerning myokines and their role in modulating energy metabolism mostly focus on a single candidate at a time, the results of my doctoral research are novel in considering the myokine network without neglecting the potential interactions in action of these peptides
Synthesis and Application of Photoactive Nanomaterials for Antimicrobial and Catalytic Activity
No full textIn this work we sought to investigate the fascinating and powerful interactions between light and metal nanoparticles of silver (AgNPs) and palladium (PdNPs) to enhance their applications in photobiology and catalysis. This work begins with the synthesis of citrate capped silver NPs using in-flow irradiation of various Norrish Type-1 photoinitiators with AgNO3 to generate AgNP “seeds” rapidly, and at relatively large scale. Using these seeds, we can take advantage of their high sensitivity to light to further drive the growth of these small AgNPs into larger, more complex structures such as triangles and decahedra without having to add bulky surfactants or polymers. In this approach, we can control nanoparticle shape using different wavelengths of LED illumination, while adjusting citrate concentration can allow for the fine tuning of AgNP absorbance throughout the visible spectrum, and into the NIR region. Using our light-generated AgNPs, we observe potent light-activated antibacterial effects when irradiating the NPs with light wavelengths corresponding to their plasmonic absorbance. These particles are able to totally wipe out bacterial cultures in batch at high bacterial concentrations at AgNP concentrations as low as 10 ppm. These highly antibacterial NPs can also be fixed to a heterogenous support, glass wool (AgNPs@GW), to act as a heterogenous antibacterial agent, effectively killing bacteria under white light irradiation for effective in-flow treatment of bacteria contaminated water. We show that the antibacterial effects from these particles may be derived from a combined light-activated heating effect, along with light-induced reactive oxygen species (ROS) generation. Applying these same lessons to industrially relevant reactions, in our final chapter we utilize the same versatile support, glass wool, to fix PdNPs, making an effective heterogenous nitro-to-amine photocatalyst. Using a broad range of characterization methods, we demonstrate the effectiveness of high-resolution light microscopy techniques (confocal, TIRF, FLIM) at visualizing the catalytic sites on PdNP coated GW fibres. Under these conditions, we show that Pd on GW is a stable and robust catalyst for the nitro-to-amine reaction, showing little catalyst migration or loss of activity, even after several hours on continuous flow.
This work demonstrates the utilization of visible and NIR irradiation to control nanoparticle synthesis, enhance antibacterial activity, develop in-flow water treatments, and drive flow-photoreactors. Altogether, this thesis aims to demonstrate the enhanced capabilities of materials when they interact with light, effectively enhancing their already fascinating properties
Explorer le modèle d'intervention Niikaniganaw comme méthodologie d'apprentissage à la sécurisation culturelle en contexte urbain avec des personnes autochtones vivant ou affectées par le VIH
No full textContexte : malgré les avancées médicales et les programmes de prévention innovants, les peuples autochtones au Canada (Premières Nations, Inuit, Métis) continuent d’être affectés de manière disproportionnelle par des taux élevés d’infections transmissibles sexuellement et par le sang (ITSS), y compris le VIH, comparativement à la population générale. Les facteurs historiques et actuels liés à la colonisation, incluant l’absence de soins de santé et de services sociaux de santé culturellement sécuritaires, semblent être la cause de cette disparité.
But : explorer la le projet Niikaniganaw « Toutes mes relations » comme intervention potentielle d’apprentissage à la sécurisation culturelle pour décrire l’impact des pratiques culturelles autochtones à l’apprentissage à la sécurisation culturelle avec des personnes autochtones vivant ou affectées par le VIH, des intervenants de première ligne, ainsi que des personnes autochtones porteuses des savoirs traditionnels.
Méthodes : l’étude a fait appel à la recherche communautaire participative relationnelle comme approche méthodologique, à laquelle ont été associées trois méthodes stratégiques qui sont complémentaires et interreliées, (1) l’ethnographie expérimentale, (2) l’analyse de données secondaires et (3) l’analyse d’un questionnaire quantitatif ont été utilisées pour décrire l’impact des pratiques culturelles autochtones à l’apprentissage à la sécurisation culturelle.
Résultats : l’ethnographie expérimentale a mené à une transformation intellectuelle et personnelle qui ont conduit à la définition de la posture identitaire dans le cadre de l’intervention Niikaniganaw à titre de jeune chercheure francophone noire. Cette posture identitaire de chercheure influencera l’analyse de données secondaires de laquelle douze thématiques différentes permettent de décrire une perception des participants centrée sur l’individu à une compréhension collective de l’intervention. Cette compréhension collective repose sur le désir collectif d’être des alliés potentiels ou effectifs pour promouvoir et favoriser des soins de santé et des services sociaux de santé culturellement sécuritaires. Enfin, le questionnaire quantitatif montre que le changement structurel dans les milieux organisationnels pour une approche de sécurisation culturelle peut se révéler difficile. Toutefois, les participants issus de ces organisations peuvent agir comme outil de transmission et de mobilisation des connaissances développé dans le cadre de l’intervention Niikaniganaw.
Conclusion : selon la perspective décoloniale de l’intervention Niikaniganaw, la création d’un espace culturellement sécuritaire est nécessaire pour accroître les capacités à offrir des soins de santé et services sociaux culturellement sécuritaires aux personnes autochtones vivant ou affectées par le VIH. Il est important d’innover la manière d’exposer les professionnels de la santé à l’apprentissage à la sécurisation culturelle avec des pratiques expérientielles, notamment les pratiques culturelles. Enfin, l’intervention Niikaniganaw montre la nécessité d’une transformation individuelle ancrée dans une approche collective pour promouvoir l’approche de sécurisation culturelle. Toutefois, la responsabilité de la transformation collective ne doit pas reposer uniquement sur la transformation individuelle
Parcours de vie et imprévisibilité du social : les expériences de l’infertilité par les citadines camerounaises
No full textLes études sur les femmes africaines infertiles suggèrent qu’elles sont, plus que les autres, à risque de vivre un divorce ou la polygamie. De plus, les femmes sont, plus que les hommes, les premières pointées du doigt en cas d’infertilité, et celles qui en subissent le plus les conséquences. De nombreux travaux documentent ainsi divers aspects des expériences de l’infertilité en se concentrant sur les relations de couple, sur les expériences des traitements de l’infertilité. Seulement, les expériences des citadines, notamment celles des camerounaises sont peu explorées, de même que peu de travaux tentent de saisir l’expérience de l’infertilité dans sa globalité. Pour combler cette lacune, j’adopte une approche qualitative, se concentrant principalement sur les récits de vie des femmes infertiles, complétés par quelques conversations avec des hommes. La méthodologie de recherche repose sur des récits de vie et des observations effectuées sur Facebook, et les données produites sont analysées à la lumière d’un assemblage théorique combinant les concepts de genre, de stigmate (Goffman, 1975) mais aussi la théorie des conjonctures vitales (Johnson-Hanks, 2017) et la sociologie de l’imprévisible (Grossetti, 2004).
Les résultats de recherche mettent en lumière les différents aspects socioculturels, économiques, et médicaux, liés à l'infertilité chez les femmes camerounaises. Ils examinent l'influence des normes sociales, du désir d’enfant, des attentes familiales, et des pressions communautaires sur les parcours de vie des citadines camerounaises infertiles. Les récits de vie recueillis révèlent les tensions émotionnelles, les parcours étiologiques et thérapeutiques souvent complexes, et les implications psychologiques de l'infertilité au Cameroun. Par ailleurs, l'analyse des données met en lumière des stratégies d'adaptation et des formes de résilience développées par les femmes pour faire face à l'infertilité, et se construire en marge de la reproduction. En intégrant des observations sur les interactions en ligne via Facebook, cette recherche offre également un aperçu unique des façons dont les femmes utilisent les réseaux sociaux pour obtenir un soutien émotionnel et des informations médicales, tout en naviguant dans la stigmatisation associée à l'infertilité
L'apport du mentorat facultaire au processus d'adaptation psychosociale aux études universitaires : une recherche qualitative conduite auprès d'étudiant.e.s inscrit.e.s aux études de premier cycle à l'Université d'Ottawa
No full textSelon l'état actuel des connaissances, de nombreux défis et enjeux confrontent les étudiant.e.s qui débutent leurs études universitaires. Ces défis et enjeux à relever peuvent être de nature académique, sociale, psychologique et/ou vocationnelle. Par exemple, la transition de l'école secondaire vers l'université provoque souvent un processus d'adaptation à un environnement social inconnu et à de nouvelles exigences académiques. Dans ce contexte, le mentorat a le potentiel de faciliter le processus d'adaptation psychosociale aux études universitaires. D'où notre question de recherche: comment est-ce que le mentorat facultaire participe au processus d'adaptation psychosociale aux études universitaires chez les étudiant.e.s inscrit.e.s à un programme de premier cycle. L'analyse qualitative des résultats indique que l'apport du mentorat facultaire audit processus est à la fois de nature relationnelle ainsi que de nature informative
A Study Based on the Knowledge, Attitudes, and Practices Regarding COVID-19, Vaccines and Non-pharmaceutical Interventions (NPIs): An International Survey
No full textAbstract
Background
The COVID-19 outbreak posed a significant global threat, necessitating the swift deployment of stringent measures to mitigate its spread and impact. Central to effectively managing such crises thorough assessments of population health must be performed and should be underpinned by the recognition that knowledge acquisition plays a pivotal role in shaping behavioral responses. In this context, the Knowledge, Attitudes, and Practices (KAP) model emerges as a robust diagnostic framework. This study aims to assess residents' understanding, attitudes, and behaviors regarding the 2019 coronavirus, vaccines, and non-pharmaceutical interventions in Cameroon and Canada. Using the KAP model, we seek to explore how knowledge, attitudes, and practices interact, providing insights for future targeted interventions and disease control measures.
Methods
An anonymous online survey was randomly administered amongst 166 participants in Cameroon and Canada via SurveyMonkey between October 25, 2022, and February 25, 2023. Descriptive and stratified analyses quantified residents’ responses to KAP. The data was analyzed through both qualitative and quantitative approaches. The analytical protocol included descriptive data analyses followed by an assessment of independent factors associated with KAP. Correlations were assessed between the dependent variables. A linear regression was employed to identify predictors related to KAP scores. A scoping review was conducted to map existing evidence on COVID-19, KAP, vaccines, and NPIs using Cochrane guidelines, including 35 international studies published between December 2019 and September 2022. The review aimed to examine factors influencing COVID-19 vaccine acceptance, intention, and hesitancy, and to develop a conceptual framework for these factors and NPIs globally. Covidence was used for screening articles following inclusion and exclusion criteria.
Results
73.5% of participants identified as youths within 18-25 years of age. Data analysis revealed that there was a significant correlation between knowledge and practices (r = 0.249, p<.001). Further, residence, marital status, and educational level were identified as significant predictors of KAP. These findings also demonstrated that Canadians displayed higher knowledge levels and adherence to recommended guidelines, whereas Cameroonians exhibited better attitudes, yet less adherence to COVID-19 protocols, non-pharmaceutical interventions (NPIs), and vaccination.
Conclusion
Conclusively, our observations revealed that the level of public knowledge was significantly correlated to the level of practices. The higher the level of knowledge of the participants, the better the practices. In addition, the level of education and marital status were identified as strong predictors of KAP. These data underscore that importance of knowledge dissemination for the spread of communicable diseases related to COVID outbreaks, as it will help with adherence to disease prevention strategies.
Abstrait
Introduction
L’épidémie de la COVID-19 a constitué une menace mondiale importante, suivie de la mise en œuvre de mesures rigoureuses adoptées par l’urgence nationale pour contrôler sa propagation massive. L’évaluation de la santé d’une population est primordiale pour faciliter l’éradication des maladies, l’acquisition de connaissances est un facteur primordial dans le changement de comportement, et le modèle CAP a été identifié comme un outil de diagnostic puissant. Cette étude vise à évaluer la compréhension, les attitudes et les comportements des résidents concernant le coronavirus 2019, les vaccins et les interventions non-pharmaceutiques au Cameroun et au Canada. À l’aide du modèle CAP, nous cherchons à explorer comment les connaissances, les attitudes et les pratiques interagissent, en fournissant des informations pour des interventions ciblées et des mesures de contrôle des maladies. Une revue de la portée a été effectuée pour améliorer la robustesse de la thèse en cartographiant systématiquement les preuves existantes sur le terrain.
Méthode
Un sondage anonyme en ligne a été administré au hasard à 166 participants au
Cameroun et au Canada via Survey Monkey entre le 25 octobre 2022 et le 25 février 2023. Des analyses descriptives et stratifiées ont permis de quantifier les réponses des résidents au CAP. Les données ont été analysées à l’aide d’approches qualitatives et quantitatives à l’aide de Survey Monkey et de SPSS. Le protocole d’analyse comprenait des analyses de données descriptives. Une corrélation a été évaluée entre les variables dépendantes et indépendantes. Un modèle de régression linéaire a été utilisé pour identifier les prédicteurs liés aux scores CAP. Une revue a été menée pour cartographier les données probantes existantes sur la COVID-19, les CAP, les vaccins et les INPs à l’aide des lignes directrices Cochrane. L’examen visait à examiner les facteurs influençant l’acceptation, l’intention et l’hésitation du vaccin contre la COVID-19, et à élaborer un cadre conceptuel pour ces facteurs et les INPs à l’échelle mondiale. Covidence a été utilisé pour filtrer les articles selon des critères d’inclusion et d’exclusion et 35 études internationales ont été identifier
Résultats
73.5% des participants s’identifiaient comme des jeunes-adultes. Le test statistique réalisé a révélé qu’il existait une corrélation significative entre les connaissances et les pratiques (r=0,249, p<,001). Le lieu de résidence, l’état matrimonial et le niveau de scolarité ont été identifiés comme de bons prédicteurs de la CAP à la signification à p<. 001. Les résultats ont montré que les Canadiens affichaient des niveaux de connaissances et de respect des lignes directrices recommandées plus élevés, tandis que les Camerounais affichaient de meilleures attitudes, mais des niveaux inférieurs de connaissances et d’adhésion aux protocoles COVID-19, aux interventions non pharmaceutiques (INPs) et à la vaccination.
Conclusion
En conclusion, le niveau de connaissance était significativement corrélé au niveau des pratiques. Plus le niveau de connaissance des participants est élevé, plus le niveau de pratiques est élevé. De plus, le niveau d’éducation et l’état matrimonial ont été identifiés comme de puissants prédicteurs de la CAP. Il est nécessaire de comprendre la propagation des maladies transmissibles d’un pays à l’autre, car cela facilitera la prise de décision et la mise en œuvre de stratégies de prévention des maladies
Evaluating Elderly Perceptions of Green Space in Ottawa Using Deep Learning
No full textThis thesis investigates the degree to which advanced GeoAI techniques, particularly deep learning models, and how these models can reproduce older adults perceptions of urban green spaces and to map the quality of green spaces across the city using street-level imagery. The study compares three popular deep-learning feature extractors to predict and map seniors' perceptual responses to green spaces in Ottawa, utilizing data derived from Mapillary street-level images. In these images, senior citizen volunteers were seated in front of a computer and selected between images based on perceptual dimensions such as safety and aesthetics. A few AI ranking models are constructed for the purpose of identifying how well street-level photographs are valued by seniors within Ottawa’s green spaces. Our focus is mainly on finding the best-performing model and backbone training dataset via experimentation with various generations of deep learning architectures and using statistics to determine how such differences affect human perceptual modelling. Experimentation included the determination of the best ranking loss function for our data, comparing different loss functions, effects of hidden layers and how different pre-trained weights from different domains affect model performance. The RankNet algorithm demonstrated superior performance compared to RankSVM in a range of architectural configurations, including ViT-B16, VGG16, and ResNet50, with an average difference of 8.45% in accuracy for each perceptual attribute. The model deemed most effective overall adopted ViT-B16 as its foundation, providing the highest absolute accuracy despite the accuracy not being statistically different from VGG19 or ResNet50. Contrary to previous research we did not find the addition of Softmax to be of any significance in model preformance. Finally, we found that there is no statistically significant differences in using different-object-domain training weights in the transfer learning. Detailed prediction maps were predicted on park photographs from Mapillary that indicated how seniors perceive public spaces across the city. By combining deep learning, image segmentation, and spatial analysis, the research offers an empirical contribution of how AI can contribute insights into how urban planning can be enhanced to meet the needs of an ageing population and creates a foundation for further investigation into age-friendly environments
Analysis of Time-Periodic Navier-Stokes Equations in a Moving Domain and Numerical Computations with Radial Basis Neural Networks: Application to Artificial Hearts Blood Flow
No full textThe dynamics of blood flow within an artificial heart (AH) chamber are governed by the time-periodic Navier-Stokes (NS) equations. These equations are coupled with a hyperbolic partial differential equation (PDE) that describes the dynamic behavior of the membrane (diaphragm). This coupled system of PDEs is subject to a moving boundary.
In this work, we decouple the system by assuming that the solution of the membrane equation is known within a well-defined Banach space. Subsequently, we solve only the NS problem and not the coupled fluid-structure problem. We conduct an analysis, specifically examining the existence and uniqueness of a time-periodic strong solution for the Navier-Stokes (NS) problem in dimensions = 2, 3 within a moving domain. The moving domain Ωₜ is supposed to be a ^∞(^{2,2̂*}) ∩ ^1(^2) ∩ ^2(^2) local perturbation of a ^{1,1} reference domain Ω₀ where 2̂* = 2 + {4 / }, > 0 if = 2 and 2̂* = 3 + { / (4 - )}, ∈ (0, 3] if = 3. Typically, our moving domain Ωₜ is of class ^∞(^{2, 2̂*}) ∩ ^1(^2) ∩ ^2(^2), which is weaker that the ^3 in space regularity presented in the literature.
Subsequently, we proceed to numerically solve the problem in dimension = 2 using radial basis neural network (RBNN) functions. To validate our computational framework, we compare our results against existing literature, particularly by solving benchmark-driven cavity problems up to a Reynolds number = 10,000$. Finally, we solve numerically the time-periodic NS equations for different AH geometries. The results we obtain demonstrate the strong dependence of the blood flow behavior on the AH geometry and motivate the optimal shape design of AH, which we plan to address in future work