Life Sciences Commons^™

The Effects Of Maternal Delta-9-Tetrahydrocannabinol And Cannabidiol Exposure On Fetal Heart Development In Mice, Gregory Robinson

Electronic Thesis and Dissertation Repository

Up to 22.6% of pregnant women consume cannabis during pregnancy despite the uncertainty of teratogenicity of the main ingredients in cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). This study tested the hypothesis that gestational THC and CBD exposure leads to heart abnormalities. Daily, oral THC exposure induced heart abnormalities in 68% of offspring with three main phenotypes including thickened semilunar valves, ventricular myocardial hypertrophy and hypoplastic coronary arteries in fetuses, and postnatal cardiac dysfunction. Altered gene expression of key cardiogenic regulators, increased proliferation, and reduced epicardial epithelial-to-mesenchymal-transition were demonstrated implicating potential mechanisms responsible for these abnormalities. Also, maternal CBD exposure resulted …

Perspectives Of Canadian University Coaches On Integrating Sport Psychology And Mental Performance Consultants In Varsity Programs, Federico Cisneros Sánchez

Electronic Thesis and Dissertation Repository

Recently, sport psychology has become a more popular resource for athletes and coaches when looking to increase performance. It is unknown how many Canadian universities utilize sport psychology services in their athletic programs. Semi-structured interviews were conducted with coaches of Canadian university varsity teams to learn about their opinions on sport psychology and mental performance consultants (MPCs). The research was approached from a pragmatic perspective. Results showed that MPCs are important to enhance performance and provide mental health resources. MPCs provide athletes with personal and leadership development, mental skills training, and mental health support. MPCs can also be a resource …

Targeting Cd5 To Enhance Immune T Cell Activation And Function In Treatment Of Solid Tumours, Faizah Alotaibi

Electronic Thesis and Dissertation Repository

CD5 is a member of scavenger receptor cysteine-rich superfamily that is expressed primarily on T cells. It can attenuate T-cell receptor signaling and impair cytotoxic T lymphocyte (CTL) activation and is a therapeutic targetable tumour antigen expressed on leukemic T and B cells. However, the potential therapeutic effect of functionally blocking CD5 to increase T cell anti-tumour activity against tumours (including solid tumours) has not been explored. CD5^- solid tumours in CD5 knockout mice display increased in anti-tumour immunity. Hence, blocking CD5 function may have a potential therapeutic effect by enhancing CTL function. Here, I assessed CD5 levels in …

Understanding Physical Activity Behaviour In Ontario, Canada: A Cross-Sectional Cohort Analysis Of Carrot Rewards App Users, David D. Mchugh

Electronic Thesis and Dissertation Repository

Little device-measured data are available to describe the physical activity (PA) of rural-dwelling individuals living with chronic disease. PURPOSE: From accelerometer data collected using a smartphone app (‘Carrot Rewards’), we sought to provide mean daily step counts for app users in general and by age and gender for those living in rural/urban areas and those self-reporting a chronic disease or not. METHODS: This cross-sectional cohort study used device-assessed data from Ontario app users (i.e., PA data collected over a 7-day period for each user) who completed an in-app chronic disease survey from December 2018 to April 2019. A …

Deciphering The Ck2-Dependent Phosphoproteome And Its Integration With Regulatory Ptm Networks, Teresa Nunez De Villavicencio Diaz

Electronic Thesis and Dissertation Repository

Protein functions are regulated by the post-translational addition of covalent modifications on certain amino acids. Depending on their distance within the 3-dimensional structure, addition/removal of individual post translational modifications (PTMs) can be impacted by others. This PTM interplay constitutes an essential regulatory mechanism that interconnects the molecular networks in the cell. Protein CK2, a clinically relevant acidophilic Ser/Thr kinase, may be responsible for 10-20% of the human phosphoproteome. Such estimates agree with the number of known substrates, which continues to expand. Furthermore, the demonstration that CK2 participates in hierarchical phosphorylation and has similar sequence determinants to caspases suggest extensive PTM …

Pan-Cancer Analysis Of Telomerase Reverse Transcriptase (Tert) Isoforms, Mathushan Subasri

Electronic Thesis and Dissertation Repository

Reactivation of the multi-subunit ribonucleoprotein telomerase is the primary telomere maintenance mechanism in cancer, but it is rate-limited by the enzymatic component, telomerase reverse transcriptase (TERT). While regulatory in nature, TERT alternative splice variant/isoform regulation and functions are not fully elucidated and are further complicated by their highly diverse expression. In this thesis, I characterized TERT expression across normal and neoplastic tissues using TCGA and GTEx RNA-sequencing data. In doing so, I demonstrated the global overexpression and splicing shift towards full-length TERT in neoplastic tissue. Furthermore, my studies identified tumour subtype expression differences possibly regulated by subtype-specific characteristics, detailed heterogeneity …

An Approach For The In-Vivo Characterization Of Brain And Heart Inflammation In Duchenne Muscular Dystrophy, Joanne Tang

Electronic Thesis and Dissertation Repository

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by dystrophin loss—notably within muscles and CNS neurons. DMD presents as cognitive weakness, progressive skeletal and cardiac muscle degeneration until pre-mature death from cardiac or respiratory failure. Innovative therapies improved life expectancy, but this is accompanied by increased late-onset heart failure and emergent cognitive degeneration. Thus, there is an increasing need to both better understand and track disease pathophysiology in the dystrophic heart and brain prior to onset of severe degenerative symptoms. Chronic inflammation is strongly associated with skeletal and cardiac muscle degeneration, however chronic neuroinflammation’s role is largely unknown in …

Optimizing Preprocessing Of Fmri Data To Maximize Correspondence Of Functional Anatomy Across Individuals, Nargess Ghazaleh

Electronic Thesis and Dissertation Repository

In movie-activation fMRI, intersubject correlation (ISC) indicates a functional correspondence across viewers. Brains di↵er in shape; spatial normalization and smoothing enhance inter-subject functional overlap. We compare three normalization methods and six smoothing levels to discover which method yields the best functional overlap, indexed by ISC. This is key to optimizing data analysis in clinical studies using movie-activation fMRI in future. In a 3T scanner, 44 healthy subjects watched an 8-min movie. Both normalization and smoothing a↵ected the strength and extent of the ISC. ISC values were more robust for ANTs and DARTELthanforSPM12andwere(asymptotically)thestrongestat12mmsmoothing. When image data are preprocessed with high-dimensional volumetric …

The Role Of Regulator Of G Protein Signaling 2 In Inflammatory Cytokine Release In Endotoxemia In Mice, Xin Tong Ma

Electronic Thesis and Dissertation Repository

In sepsis, lipopolysaccharide (LPS) activates toll-like receptor 4 to stimulate the release of inflammatory cytokines (e.g. tumor necrosis factor-alpha, TNF-α), leading to cardiac dysfunction. Regulator of G protein signaling 2 (RGS2) limits G protein-coupled receptor signaling by increasing the rate of G protein deactivation or inhibiting G protein-effector interactions. We hypothesized that RGS2 deficiency would enhance proinflammatory responses in endotoxemia. Adult wild-type and RGS2^-/- C57BL/6 mice and neonatal cardiomyocytes were treated with LPS and assessed for inflammatory responses and cardiac function. Myocardial TNF-α expression was higher in RGS2^-/- mice during endotoxemia. Additionally, cardiac function was impaired in …

Evaluating The Implementation Of The Centrally Procured School Food Program (Cpsfp) In Southwestern Ontario Elementary Schools, Mariam R. Ismail

Electronic Thesis and Dissertation Repository

School food programs can improve children’s health and well-being, while also creating economic opportunities for local food systems. Program evaluations of such interventions have always been done, but from the perspectives of their effectiveness. Yet, few have thoroughly examined the process or implementation practices of these interventions. The aim of this dissertation was to evaluate the implementation of the Centrally Procured School Food Program (CPSFP), a procurement and delivery-based school food program in Southwestern Ontario, that aims to improve elementary school-aged children’s intake of fruit and vegetables (FVs). Canada remains one of the few industrialized nations without a national school …

Nutrient Sensing Pathways Mediating Igfbp1 Phosphorylation In Fgr, Shapnil Bhuiyan

Electronic Thesis and Dissertation Repository

Impairment of fetal oxygen levels and nutrient delivery contributes to fetal growth restriction (FGR), which affects 20% of pregnancies. Such cellular stress induces hepatic Insulin-like Growth Factor Binding Protein 1 (IGFBP1) phosphorylation, which sequesters Insulin-like Growth Factor 1 (IGF-I) and markedly reduces fetal growth signaling. IGFBP1 hyperphosphoryaltion in hypoxia is mediated through the mTOR signaling pathway and through the Amino Acid Response (AAR) pathway during amino acid deprivation. Hypoxia stimulates upstream mTORC1 regulators, AMPK and REDD1 which are well-established upstream regulators of one of the two mTOR complexes, mTORC1. The molecular mechanisms by which upstream mTORC1-driven processes regulate IGFBP1 phosphorylation …

Epigenetics A Decolonizing Science, Wade Paul

Electronic Thesis and Dissertation Repository

Epigenetics is the study of gene expression that does not entail alterations to the actual DNA. Decolonization is a theoretical and political movement that seeks to deconstruct colonial institutions and ideologies and reconstruct new and balanced approaches that accept and respect Indigenous worldviews. This project studies the decolonizing potential of epigenetics. Using genealogy as the method, the study establishes a long history of reductionist and deterministic thought that shaped the study of genetic science. Particular instances like thrift gene theory are explored to highlight how genetic explanations have been detrimental to the health and wellbeing of Indigenous people and illustrate …

Investigating Elementary School Food Programs: Impacts On Child Knowledge And Dietary Behaviours, Paige Colley

Electronic Thesis and Dissertation Repository

Good nutrition is an important part of maintaining a healthy lifestyle. A balanced diet can promote positive health outcomes, protecting against health problems caused by nutritional deficiencies. Canada has reported poor diet quality and high rates of overweight and obesity among children. Obesity has been linked to several non-communicable diseases including type 2 diabetes, heart disease, and some forms of cancer. Efforts to improve lifelong, healthy eating behaviours must be implemented.

This dissertation investigated the impacts of school food programming on child nutrition. A Centrally Procured School Food Program (CPSFP) was implemented at 30 elementary schools in Southwestern Ontario, Canada. …

Effects Of A Pregnancy Lifestyle Intervention On Emotion Regulation In Infants Responding To A Toy Removal Task At One-Year Of Age, Mollie Manley

Electronic Thesis and Dissertation Repository

Poor infant emotion regulation (ER) has been linked with increased psychopathological risk in infancy and childhood. The Developmental Origins of Health and Disease Hypothesis suggests the prenatal period as the earliest point of intervention, where fetal exposure to healthy lifestyle changes can promote optimal ER in infancy. Infant electroencephalography (EEG; n=13) and heart rate variability (HRV; n=18) were measured at rest and in response to a toy removal task, to determine the ER of infants whose mothers participated in a nutrition and exercise intervention during pregnancy. Results demonstrated positive left frontal alpha asymmetry at rest (0.08± 0.66) and in response …

Assessment Of Intrinsic Hand Neuromuscular Physiology, Philemon Tsang

Electronic Thesis and Dissertation Repository

Alterations to the peripheral nervous system and neuromuscular physiology may impact hand function in a typical or clinical population, such as individuals with ulnar neuropathy. The mechanisms that influence these positive and negative changes are still not well understood. The three studies within my thesis aim to validate the reliability of decomposition-based quantitative electromyography (DQEMG) measurements and explore the changes in intrinsic hand neuromuscular physiology in a typical aging population and individuals recovering from a surgical intervention for severe ulnar neuropathy.

The purpose of the first study was to determine the test-retest reliability of near-fibre (NF) jiggle, a measure of …

Advanced Phenotyping Of Otosclerosis In An Ontario Population And Two Large Newfoundland Families, Matthew B. Lucas

Electronic Thesis and Dissertation Repository

Otosclerosis is a relatively common hearing loss disorder characterized by abnormal bone growth in the otic capsule leading to stapes fixation. In approximately half of cases, otosclerosis is inherited as an autosomal dominant trait. Typically, gene discovery efforts rely on surgical confirmation, audiometry and occasionally acoustic reflexes to identify affected cases of otosclerosis within families, requiring that the otosclerosis was at an advanced stage to be detected. This makes it difficult to identify individuals with early otosclerosis. The use of advanced phenotyping to identify cases of otosclerosis was tested in an Ontario otosclerotic population as well as in two large …

Effects Of Increased Sulfatide In Schwann And Mesenchymal Stromal Cells In Metachromatic Leukodystrophy, Srinitya Gannavarapu

Electronic Thesis and Dissertation Repository

Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disease caused by deficient arylsulfatase A (ARSA) activity, resulting in intra-lysosomal accumulation of sulfatide. Sulfatide is integral for proper maintenance of myelin in the central and peripheral nervous systems. This study characterized mitochondrial morphology, cytokine secretion and phagocytic activity in Schwann and mesenchymal cells isolated from ARSA^-/- mice. Cells were treated with different, increasing concentrations of sulfatide for a period of 24 hours. ARSA^-/- cells presented with persistent, increased fragmented mitochondrial structures suggestive of prolonged mitochondrial fission. Sulfatide treatments increased secretion of pro-inflammatory cytokines TNF-α and IL-1β in ARSA^{-/- …}

The Now Trial: A Pragmatic Randomized Controlled Trial Of Personalized, Genetic-Based Lifestyle Advice, Justine Rochelle Horne

Electronic Thesis and Dissertation Repository

Background: The impact of nutrigenomics and lifestyle genomics interventions on health outcomes and behaviours remains controversial and under-explored.

Objectives: To determine the short-term (3-month), moderate-term (6-month) and long-term (12-month) impact of providing personalized, genetic-based lifestyle information and advice on anthropometric measures, as well as dietary intake and adherence.

Methods: The nutrigenomics, overweight/obesity and weight management trial (NOW Trial) is a pragmatic randomized controlled trial that was incorporated into the Group Lifestyle Balance™ (GLB) program (N=140). Inclusion criteria: overweight or obesity (BMI ≥ 25 kg/m²), ≥ 18 years of age, English-speaking, having access to internet at least …

The Effects Of Chronic Inflammatory Demyelinating Polyneuropathy On The Neuromuscular System In Humans, Kevin J. Gilmore

Electronic Thesis and Dissertation Repository

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is an inflammatory autoimmune peripheral nerve disorder. CIDP is associated with demyelination, slow motor nerve-conduction velocity, and distal muscle weakness. CIDP is under-recognized due to its heterogeneous presentation and the limitations of clinical diagnostic criteria. Using a combination of electrophysiology and muscle imaging techniques the four studies outlined in this thesis systemically investigate the impacts of this demyelinating disease on motor nerves and their innervated muscles.

The first two studies examine the neuronal consequences of demyelination caused by CIDP and the following two studies investigate how skeletal muscle is affected by these neuronal complications. Specifically, …

Investigating The Role Of Nuclear Receptor Peroxisome Proliferator-Activated Receptor Δ In Obesity-Associated Osteoarthritis, Bethia C. To

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a heterogeneous disease, differentiated based by risk factors that drive joint damage. Peroxisome proliferator-activated receptor delta (PPARd) is a nuclear receptor previously implicated in cartilage damage in OA. Given its deleterious role in post-traumatic OA and in regulating metabolism, we hypothesized that PPARd inhibition will protect against obesity-associated OA. Diet-induced obesity was used to induce OA in mice. Mice fed the western diet for 40 weeks exhibited mild OA, with subchondral bone remodelling occurring alongside cartilage damage. Cartilage-specific Ppard knockout (KO) mice were generated to study its role in metabolic OA. Both wildtype and PPARd KO mice …

Cell-Free Dna Release During Programmed Cell Death In Kidney Ischemia Reperfusion Injury, Alexander Dionne

Electronic Thesis and Dissertation Repository

Transplantation is invariably associated with ischemia reperfusion injury (IRI) which causes organ dysfunction. IRI is also directly linked to several forms of programmed cell death including apoptosis and necroptosis, which increase kidney dysfunction, promote inflammation and may contribute to premature graft failure. The contribution of necroptosis and apoptosis following kidney IRI to cell-free DNA (cfDNA) generation and the potential of cfDNA to activate effectors such as NK cells involved in kidney IRI have not been defined. Our data indicate that necroptotic microvascular endothelial cells (MVECs) release considerably more cfDNA than apoptotic MVECs or untreated controls (p

Behavioural And Molecular Consequences Of Postnatal Stress In A Mouse Model Of Fetal Alcohol Spectrum Disorder, Bonnie Alberry

Electronic Thesis and Dissertation Repository

Fetal alcohol spectrum disorders (FASD) are caused by prenatal alcohol exposure (PAE) and affect 1‑5% of the North American population. Children born with FASD often face maternal separation throughout childhood. How this early life stress (ELS) affects the severity of FASD-related deficits is poorly understood. Using a mouse model, this dissertation establishes that behavioural deficits accumulate following prenatal alcohol exposure and early life stress, assessed using tests for activity, anxiety-like behaviour as well as learning and memory. Hippocampal gene expression was evaluated using RNA-seq followed by clustering of expression profiles through weighted gene co-expression network analysis (WGCNA). A set of …