Life Sciences Commons^™

Characterizing The Function Of B Cells That Accumulate In The Inflamed Central Nervous System In Anti-Myelin Autoimmunity, Lika Chowdhury

Electronic Thesis and Dissertation Repository

While the role of autoimmune T cells has been extensively studied in anti-myelin

autoimmunity, little is known about the function of B cells in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS). B cells form clusters with T cells in the meninges directly adjacent to demyelinating lesions. Previous studies have shown that disease progression is dependent on the depletion of specific populations of B cells, but it is not clear which contributes to pathology or how. The purpose of this thesis is to characterize the population of meningeal B cells to determine how they differ …

Postexercise Executive Function Benefits And Cerebral Blood Flow: In The Lab And At Home, Benjamin Tari

Electronic Thesis and Dissertation Repository

A single bout of aerobic exercise improves executive function; however, the mechanism, or mechanisms, supporting this improvement remain unclear. One candidate mechanism is an exercise-mediated increase in cerebral blood flow (CBF) that enhances the efficiency of executive-related frontoparietal networks. To evaluate the link between exercise, CBF and executive function, three separate experiments were conducted. In the first study, separate 10-min sessions of moderate-to-heavy-intensity aerobic exercise, and a hypercapnic environment (i.e., 5% CO₂) were implemented. The hypercapnic condition was included because it increases CBF independent of the metabolic demands of exercise. The second study investigated whether exercise intensity-specific changes …

The Clinical Value Of Oculomotor Assessments Across The Continuum Of Concussion, Dillon Richards

Electronic Thesis and Dissertation Repository

Concussions are complex conditions that are difficult to manage medically. Variations in symptom presentation, intricate neurophysiological processes, and the availability of a variety of possible assessment tools may contribute to this complexity. Clinicians must use a broad approach, employing both subjective symptom assessment and objective assessments to confirm a diagnosis and/or monitor progression and recovery. Oculomotor function after concussion may be an important indicator of injury, given the interconnectedness of oculomotor function, vestibulo-ocular and visual systems, and even cognition. Oculomotor function may be assessed objectively or indirectly using patient-reported symptom checklists as part of subjective assessments. One way of objectively …

Using A One Health Approach For The Assessment Of Rabies Control In Rural Victoria Falls, Zimbabwe, Ryan Lapenna

Electronic Thesis and Dissertation Repository

Rabies, a viral zoonotic disease, is widespread in Zimbabwe, with human fatalities reported annually in the country. To supplement the Government’s effort on rabies control, the Victoria Falls Wildlife Trust and Veterinarians for Animal Welfare Zimbabwe have joined forces to carry out dog rabies vaccinations in rural communities adjacent to the major tourist attraction of The Victoria Falls. A One Health approach was used to 1) determine the level of protective rabies antibodies among a sample of rural dogs and 2) collect information and describe the knowledge, attitudes, and practices related to rabies among dog owners. In 2020, blood was …

The Effect Of Propionic Acid On The Habituation To Social And Non-Social Odour Cues In Adult Male Rats, Cashmeira-Dove P. Tyson

Electronic Thesis and Dissertation Repository

The enteric bacterial metabolite, propionic acid (PPA), elicits physiological and behavioural changes in rodents reminiscent of autism spectrum disorder (ASD). This includes abnormal sensory processing and social behaviour. ASD may contribute to social deficits through impaired habituation; therefore, the present study examined the effects of intraperitoneal PPA on the habituation to social and non-social odours. Adult male rats were injected daily with PPA or the vehicle control, and for 3 days, habituated to a conspecific odour or vanilla extract for 10 minutes. On day 4, rats were exposed to a novel conspecific odour or almond extract for 10 minutes to …

Role Of The Default-Mode Network During Narrative Integration In Major Depressive Disorder, Darren Ri-Sheng Liang

Electronic Thesis and Dissertation Repository

How brain activity is synchronized across individuals during narrative comprehension has previously been characterized by functional magnetic resonance imaging (fMRI) in healthy and patient populations. To our knowledge, there has been limited investigation as to how it is affected by major depressive disorder (MDD). We addressed this issue with fMRI through examination of inter-subject synchronization in the default mode network (DMN), brain structures which have previously been implicated in MDD pathology. Twenty-two patients with MDD and 20 matched control participants listened to Intact versus Scrambled versions of an auditory narrative; these experimental conditions differed in the degree of temporal integration …

Exploring The Inter-Relationship Between Cognitive And Motor Function In People With Lower Limb Amputations, Humberto Adolfo Omaña Moreno

Electronic Thesis and Dissertation Repository

The main objective of the present dissertation was to expand our understanding of the inter-relationship between cognition and mobility in people with lower limb amputations (PLLA). Study 1 systematically reviewed the literature to assess the effects of dual-task testing on the balance and gait of PLLA. A total of twenty-two studies were included. Overall, PLLA demonstrated a disproportionately greater dual-task effect than controls, characterized by increased sway velocity and reduced pace and rhythm, and increased asymmetry when balance or walking was paired with a secondary task. Additionally, the dual-task effect was not influenced by differences in etiology, level of amputation, …

Myeloarchitectonic Maps Of Cat Auditory Cortex, Austin Robertson

Electronic Thesis and Dissertation Repository

The cerebral cortex contains myriad cortical areas that differ in structure, function, and connectivity. Current methods of delineating cortical structures and their subregions are insufficient for in vivo applications, either being highly invasive or requiring a detailed knowledge of a region’s tuning properties. To address this, we seek to establish a structural biomarker capable of delineating the cortex that possesses a non-invasive correlate. We explore myelin as a potential candidate by evaluating its efficacy in parcellating the feline auditory cortex through the generation of depthwise myelin density profiles for each of the 13 auditory cortical subregions. Our analyses revealed significant …

A Theoretical Perspective On Parasite-Host Coevolution With Alternative Modes Of Infection, George N. Shillcock

Electronic Thesis and Dissertation Repository

We investigate how natural selection shapes the coevolution of parasitism. We discuss the antagonism fuelled by parasites’ necessity to transmit to novel hosts, and host’s desire to minimise virulence. In support, we build a mathematical model which considers the epidemiology and life-history trade-offs faced by an obligate microparasite and its host. Our model allows parasites to be transmitted to new hosts via direct contact (horizontally) or from parent to offspring during birth (vertically). We test the hypothesis that vertical transmission causes virulence to diminish in the long run, and contrary to widely accepted views, find that vertical transmission need not …

Tetr Family Regulator Farr Variation Controls Antimicrobial Fatty Acid Efflux In Staphylococcus Aureus, Camryn M. Bonn

Electronic Thesis and Dissertation Repository

To colonize human skin and survive within abscesses, Staphylococcus aureus has evolved mechanisms to evade host innate defenses. USA300 has become the predominate community-acquired methicillin-resistant S. aureus (CA-MRSA) clone, which can be in part attributed to detoxification of unsaturated free fatty acids (uFFA) found in sebum and the nares. Our lab has previously identified the TetR family regulator FarR responsible for induction of the resistance-nodulation-division (RND) superfamily efflux pump FarE to promote efflux of toxic uFFA. However, RND family efflux pumps remain poorly characterized in Gram-positive species and the mechanism by which FarR regulates FarE has yet to be determined. …

Regulation Of Mhc Ii Trafficking And Expression By Host And Viral Factors, Alex Lac

Electronic Thesis and Dissertation Repository

Antigen presentation by major histocompatibility complex class II (MHC II) to the adaptive immune system is crucial for mounting sterilizing immune responses. This central role has made antigen presentation a target for antagonism by many pathogens. Notably, infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) decrease MHC II expression in several immune cells. The mechanisms responsible for this suppression are unknown but involves either redirecting MHC II molecules away from the cell surface or inhibiting MHC II expression. To understand how pathogens manipulate intracellular MHC II trafficking, we first investigated the role of the Golgi trafficking regulator, ERC1, in …

Examining The Association Between Brain Mri Measures At 7 Tesla And Cognition Following Covid-19 Infection, Helma Heidari

Electronic Thesis and Dissertation Repository

The long-term neuropsychological, cognitive, and neurobiological effects of the severe acute respiratory syndrome (SARS-CoV-2) in survivors with milder symptoms are still poorly understood. In this thesis we evaluated cognitive and psychological changes approximately five weeks after a wide range of symptoms in COVID-19 illness and determined whether advanced diffusion magnetic resonance imaging measures within subcortical brain structures of the limbic system were related to neurological, respiratory, psychiatric, and gastric symptoms experienced during the acute phase of illness. Cognitive and neuropsychological evaluations were performed in 45 participants who experienced neurological symptoms during the acute phase of COVID-19 illness. Participants also underwent …

Extrinsic And Intrinsic Factors Influencing Homeostasis And Repair In Oral Tissues, Georgia Nikoloudaki

Electronic Thesis and Dissertation Repository

The oral tissues, including gingiva and buccal mucosa, heal rapidly with minimal scar formation. Although in the oral cavity, the palatal mucosa is associated with excessive scarring in response to injury. In this thesis, first, I investigated the complex relationship between cells and their microenvironment using wound healing models in which extracellular matrix composition and mechanical stiffness affect cellular responses during acute wound repair. I also determined how intrinsic differences of cells recruited during healing contribute to wound resolution.

In Chapter 2, I first investigated cell-extrinsic factors, specifically the influence of the pro-fibrotic matricellular protein periostin on palatal healing. Using …

The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, Mia P. Sams

Electronic Thesis and Dissertation Repository

B cell acute lymphoblastic leukemia (B-ALL) is the most prevalent type of cancer in young children and is associated with recurrent mutations and high levels of reactive oxygen species (ROS). The antioxidant N-acetylcysteine was tested for its ability to prolong lifespan of a mouse model of B-ALL and reduce frequency of mutations. Mice treated with 1g/L of N-acetylcysteine in drinking water were found to have delayed onset of B-ALL at 11 weeks of age and changes in gene expression relating to B cell development, calcium-apoptosis signaling, and pathways in cancer, although no differences in lifespan were observed. Tumours from treated …

Evaluating The Impact Of A Safe Exercise Training Workshop On Knowledge And Self-Efficacy To Manage Dysfunctional Exercise Among Eating Disorders Clinicians At Alsana Eating Disorders Center, Danika A. Quesnel

Electronic Thesis and Dissertation Repository

Engaging in dysfunctional exercise (DEX) is detrimental to eating disorders (EDs) prognosis, although common amongst clients. Though nutritionally supported exercise can improve ED treatment outcomes, without negatively impacting weight restoration, clinicians remain hesitant to address DEX, perhaps due to a lack of information and training. The current study examined the effects of a Safe Exercise at Every Stage (SEES) training on clinician knowledge and self-efficacy in managing DEX in ED treatment. Eating disorders clinicians completed measures before (n = 96) and after (n = 44) SEES training to assess their knowledge and self-efficacy around treating DEX, with a …

An Implementation Of Integrated Information Theory In Resting-State Fmri, Idan E. Nemirovsky

Electronic Thesis and Dissertation Repository

Integrated Information Theory (IIT) is a framework developed to explain consciousness, arguing that conscious systems consist of interacting elements that are integrated through their causal properties. In this study, we present the first application of IIT to functional magnetic resonance imaging (fMRI) data and investigate whether its principal metric, Phi, can meaningfully quantify resting-state cortical activity patterns. Data was acquired from 17 healthy subjects who underwent sedation with propofol, a short acting anesthetic. Using PyPhi, a software package developed for IIT, we thoroughly analyze how Phi varies across different networks and throughout sedation. Our findings indicate that variations in Phi …

The Role Of Coagulase-Negative Staphylococcal Secreted Products On Staphylococcus Aureus And Staphylococcus Lugdunensis Infections, Denny Chin

Electronic Thesis and Dissertation Repository

The Staphylococcus genus is comprised of over 40 bacterial species. The most well-studied species in this genus is the notorious human pathogen Staphylococcus aureus, a bacterium that produces coagulase among many other virulence factors. Since S. aureus is a major health burden and causes a plethora of diseases in humans, it has received significant attention and much research has been done to understand its biology to treat diseases caused by this pathogen. However, the coagulase-negative staphylococci (CoNS) make up most of the staphylococcal species and have received less attention since they are thought to have a lesser impact on …

Identification Of Dna Methylation Episignatures For Classification And Phenotype/Genotype Correlation In Mendelian Neurodevelopmental Disorders, John Reilly

Electronic Thesis and Dissertation Repository

ABSTRACT: Diagnosis for neurodevelopmental disorders poses numerous challenges, related to the lack of specific findings and limited understanding of clinical impact of the majority of genetic variation. Epigenomics mechanisms involve chemical modifications in DNA that involve a range of cellular mechanisms. DNA methylation is an epigenetic mechanism involving addition and removal of methyl groups to cytosine residues. These methylation signals form episignatures; patterns of methylation that can be used as biomarkers capable of differentiating neurodevelopmental disorders. EpiSigns have enabled molecular diagnosis of a number of genetic conditions, classification of variants of unknown significance, and provided insights into the pathophysiology of …

Examining The Impact Of Financial Incentive Removal On Physical Activity: A Quasi-Experimental Study Of 584,760 Mobile Health Application Users, Sean Kevin Spilsbury

Electronic Thesis and Dissertation Repository

BACKGROUND: Government interest in using financial incentives (FIs) to stimulate physical activity (PA) is increasing. The cost of longer-term incentive interventions may be prohibitive, however. PURPOSE: To examine the impact of FI withdrawal on PA. METHODS: A 25-week retrospective pre-post quasi-experimental study was conducted with users of a FI-based mHealth app. Users from three Canadian provinces were included. Daily FI were removed in Ontario (ON; intervention) but not British Columbia (BC) and Newfoundland and Labrador (NL; control). Simple linear regression models were used to examine weekly mean daily step count after FI withdrawal. RESULTS: The total sample included 584,760 users …

Connexin 43 Contributes To Phenotypic Variability Of The Mouse Skull, Elizabeth Jewlal

Electronic Thesis and Dissertation Repository

The purpose of this study was to determine whether connexin 43 (Cx43) contributes to craniofacial phenotypic variability. Skull shape and variation were compared within and among two heterozygous mutant mouse models (G60S/+ and I130T/+) that exhibit different levels of Cx43 channel function when compared to their wildtype counterparts (~80% and ~50% reduction in function, respectively). Results indicated mutants have significant differences in skull shape compared to wildtype littermates. Similar patterns of shape difference were found in both mutants. Increased skull shape variation and a disruption in the covariation of skull structures were observed in G60S/+ mutants only. These results show …

The Genetics Of Pain: An Exploration Of Gene-By-Environment Interactions And Their Effects On Pain, Mohamad F. Fakhereddin

Electronic Thesis and Dissertation Repository

The findings presented in this dissertation are part of the bigger SYMBIOME project which aims to use the biopsychosocial model of pain to develop a prognostic clinical phenotype for people that experience musculoskeletal (MSK) trauma. Chapter 2 presents an exploratory analysis to assess the relationships between genetic polymorphisms and pain severity and interference. Early childhood trauma was also explored as a moderator between genetic polymorphisms and pain outcomes. For pain severity, major allele carriers (A/A and G/A) of FKBP5 rs9394314 reported significantly higher scores than minor allele carriers (G/G). Further, major allele carriers who had at least one adverse childhood …