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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 …

Impact Of Extremely Low-Frequency Magnetic And Electric Stimuli On Vestibular-Driven Outcomes, Nicolas Bouisset

Electronic Thesis and Dissertation Repository

The vestibular system is extremely sensitive to electric fields (E-fields). Indeed, vestibular hair cells are graded potential cells and this property makes them very susceptible to small membrane potential modulations. Studies show that extremely low-frequency magnetic fields (ELF-MF) induced E-fields impact postural control in which the vestibular system plays an important role. However, the knowledge of whether this is indeed a vestibular specific effect is still pending.

Considering its crucial role and the specific neurophysiological characteristics of its hair cells, the vestibular system emerges as an ELF-MF likely target

The three studies presented in this thesis aimed to further address …

Investigating The Impact Of Environmentally Relevant Imidazole Concentrations On The Antifungal Susceptibility And Community Composition Of Soil Fungi, Farhaan Kanji

Electronic Thesis and Dissertation Repository

Miconazole and clotrimazole are environmentally-persistent drugs that are entrained into crop soils through the application of biosolids. There is concern that environmental exposure to such azole antifungals, which inhibit fungal growth by disrupting the production of the fungal cell membrane component ergosterol, promotes resistance in clinically or agriculturally relevant fungi. Thus, either environmentally-relevant or excessive levels of these drugs were applied to microplots over ten years and compared with drug-free plots. Overall, ergosterol quantification, plates counts, and identification of >250 fungal isolates showed lower fungal counts and species richness in plots receiving excessive drug amounts. In addition, fungi from treated …

The Genetic Determinants Of Complex Lipid And Lipoprotein Phenotypes, Jacqueline S. Dron

Electronic Thesis and Dissertation Repository

Cardiovascular disease (CVD) is the primary cause of death globally and is estimated to cause one-third of deaths in Canada. Each year, millions of Canadians are affected by CVD despite ongoing efforts to reduce risk through lifestyle modifications and pharmacological therapies. With the expected rise in CVD prevalence due to the obesity epidemic, we need to better understand the genetic basis of heritable, modifiable risk factors, including levels of high-density lipoprotein (HDL) cholesterol and triglyceride, for insights into future therapeutic treatments and risk prediction. Through the use of a targeted next-generation sequencing panel designed specifically to study lipid and metabolic …

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 …

The Subplate And Its Role In The Gaba System In The Prefrontal Cortex, Gaeul Kyla Lee

Electronic Thesis and Dissertation Repository

During early brain development, the subplate relays thalamocortical afferents. Lesions to the subplate have been implicated in developmental abnormalities of cortical GABAergic circuits. This thesis examined the effects of subplate lesions in the prefrontal cortex of rats on the expression of GABA markers (parvalbumin and GAD67) and GABA synapse maturation [potassium-chloride cotransporter (KCC2) and sodium-potassium- chloride cotransporter (NKCC1)] with relevance to the characterization of a rat model for schizophrenia. Lesions were made on postnatal day 1 (P1). Lesioned and control rats were sacrificed between P5 and P90 and immunolabelled for parvalbumin, GAD67, KCC2, and NKCC1. We found decreased parvalbumin expression …

Reconstructing Carbon Dynamics Of Alpine And Temperate Zone Lakes Using Stable Isotopic Analysis, Rebecca M. Doyle

Electronic Thesis and Dissertation Repository

Lake sediments integrate signals from the catchment, atmosphere and water column, offering a unique window through which to view changes in the carbon cycle. Carbon dynamics in lakes are changing due to nitrogen loading and anthropogenic climate warming (ACW), threatening the water quality of lakes. This thesis identifies how the carbon dynamics of lakes have responded to anthropogenically-driven forcings by comparing pre- and post- AD 1850 records preserved in lake sediments. First, the carbon dynamics of Barry Lake (Ontario, Canada), a low-elevation temperate lake, are investigated. Effective moisture (the net of water inputs and evaporation) is reconstructed using the carbon …

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 …

The Impact Of Impacts: Repetitive Head Impact Exposure In Canadian University Football Players, Jeffrey S. Brooks

Electronic Thesis and Dissertation Repository

Due to the physical nature of the game and repeated head impacts between players each play, the sport of football has one of the highest incidence rates of concussion. With nearly two million participants, this incidence rate translates to a reserved estimate of 100,000 concussions per year due to the contact nature of the sport. Injury thresholds have proven difficult to establish, so American football concussion research has shifted focus to measuring the accumulation of repetitive head impacts. As there are numerous rule differences between Canadian and American football, head impact exposure may present differently for Canadian players. Accordingly, the …

Examining The Structure Of Symbolic Number Representations In The Parietal Cortex: An Rsa Study, Aymee Alvarez Rivero

Electronic Thesis and Dissertation Repository

Previous studies using fMRI adaptation to investigate the neural substrate of symbolic number processing have found ratio-dependent responses in regions of the parietal cortex, suggesting that number symbols are coded by overlapping neuronal populations: the larger the ratio between two numerals, the more their representation overlap. The current study analyzed the distributed patterns of activation associated with numerals presented during this task. I could not find substantial evidence supporting the ratio-dependent structure of the similarity space predicted by the univariate adaptation analyses. I also failed to find evidence in favor of the alternative model that similarities were driven by lexical …

Development Of A Thermosensitive Endonuclease To Act As A Plasmid Kill-Switch, Christopher D. Leichthammer

Electronic Thesis and Dissertation Repository

Biocontainment is an integral part of biomedical research that aims to protect the environment and human health by containing hazardous or invasive organisms in the laboratory. Containment systems often rely on elaborate genetic circuits; however, cells may escape containment by developing mutations that render the genetic circuits inviable or resistant to killing mechanisms. The aim of this thesis was to create a site-specific nuclease for biocontainment of plasmids in the mammalian gastrointestinal tract. LAGLIDADG homing endonucleases would be good candidate nucleases for a biocontainment system as they are resistant to mutations in their coding sequence and their target sequence 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 …

Functional Characterization Of Vesicular Trafficking Genes In The Midgut Of Tetranychus Urticae Via Rna Interference, Sean Pham

Electronic Thesis and Dissertation Repository

The two-spotted spider mite Tetranychus urticae is a polyphagous agricultural pest of economic importance. Previous studies have established that reduced gene expression of COPB2, SNAP-α, and V-ATPase genes with RNAi and lowers both the survivorship and fecundity of T. urticae. A visible phenotype was also associated with changes to the digestive cells of the midgut after treatment. Serial sections of paraffin embedded RNAi treated mites to determine the changes caused by the transcriptional silencing of the three focal genes. COPB2 silencing leads to a significant increase in the number of juvenile digestive cells, while SNAP-α and V-ATPase …

Quantifying The Inter-Relationships Amongst Muscle Blood Flow, O2 Uptake And Muscle Deoxygenation Kinetics From Elevated Baseline Metabolic Rates And Increasing Work Rate Amplitudes, Lorenzo Love

Electronic Thesis and Dissertation Repository

Upon an instantaneous increase in work rate (WR), pulmonary O₂ uptake (V̇O_2p) increases in an exponential-like manner towards a new steady-state. To support this increase in V̇O_2p there is an increase in blood flow (BF; O₂ delivery) to the muscle. Previous research has shown that the rate of this increase in V̇O_2p (which defines V̇O_2p kinetics) becomes progressively slower with increasing baseline WR (WR_bl). Given the paucity of research on blood flow dynamics and underlying muscle metabolic rate, this thesis examined the effect of metabolic rate on the dynamics and relationships …

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 …

Hpv Mediated Antagonism Of The Il-18 Proinflammatory Pathway In Head And Neck Cancer, Wyatt W. Anderson

Electronic Thesis and Dissertation Repository

In this thesis, I examined the effect of human papillomavirus (HPV) on the proinflammatory IL-18 cytokine pathway in head and neck cancers. I investigated the expression and methylation of genes associated with this pathway using The Cancer Genome Atlas (TCGA) data. In HPV+ cancers, IL18, CASP1, and AIM2 were downregulated, while IL18BP was upregulated compared to HPV- cancers and adjacent non-cancerous tissues, and IL18’s promoter was significantly more methylated. I compared HPV+ and HPV- head and neck cancer cell lines for expression of RNA and protein levels of IL-18 and IL-18BP by qPCR, western blot, and ELISA. IL-18 …

Molecular Mechanisms Regulating The Platelet Thrombin Receptor Par4, Pierre E. Thibeault

Electronic Thesis and Dissertation Repository

Proteinase activated receptor 4 (PAR4) is a G-protein-coupled receptor with an important role in the platelet response to vascular injury. In platelets, PAR4 activation, by thrombin-cleavage of its N-terminus and unmasking of a tethered ligand, leads to G-protein- and beta-arrestin-mediated intracellular signalling pathways which result in platelet activation, shape change, and ultimately, platelet aggregation. As an important platelet thrombin receptor, PAR4 is an interesting target for the development of anti-platelet therapeutics. However, molecular determinants of PAR4 activation, signalling, and signal regulation remain poorly understood. In this thesis, mechanisms of PAR4 activation and signalling were studied through determination of the molecular …

Multiple Roles Of Nup1 In Arabidopsis Growth And Development, Raj K. Thapa

Electronic Thesis and Dissertation Repository

The nuclear pore complex (NPC) is the gateway between the nucleus and cytoplasm, which provides the passage for transport of RNA, protein, and other molecules into and out of the nucleus. NPC is conserved across all eukaryotes and plays a vital role in various cellular processes. However, compared to other organisms, the study of NPC in plants is limited. Although more than 30 different types of nucleoporin proteins in the model plant Arabidopsis thaliana have been identified, none of those proteins has been studied in detail. In this thesis, I focused on one such protein named NUCLEOPORIN1 (NUP1) and investigated …

Elucidating The Consequence And Cause Of Microrna Dysregulation In Amyotrophic Lateral Sclerosis (Als), Zachary C. E. Hawley

Electronic Thesis and Dissertation Repository

Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neurodegenerative disorder with an average life expectancy of 2-5 years post-diagnosis. Common pathological features associated with ALS are the formation of cytoplasmic inclusions of intermediate filaments and RNA-binding proteins within motor neurons. The formation of intermediate filament cytoplasmic inclusions is believed to be driven by a loss of stochiometric expression between five neuronal intermediate filament proteins—NFL, NFM, NFH, INA and PRPH—where there is a selective suppression of the steady-state levels of NEFL, INA and PRPH mRNA. Further, three RNA-binding proteins—TDP-43, FUS and RGNEF—have been shown to co-aggregate with each other in …

Inducing Dna-Mismatch Repair Deficiency In Tumours: A Strategy To Enhance Anti-Tumour Immunity, Mikal El-Hajjar

Electronic Thesis and Dissertation Repository

Immunotherapy has improved patient outcomes in advanced or metastatic settings across a number of cancers. Patients with tumours deficient in the DNA mismatch repair (DNA-MMR) pathway often show high response rates to immune checkpoint inhibitors (ICIs) with a rise in immune surveillance. However, little is known about the immune sensitization effects of inducing DNA- MMR-deficiency in low tumour mutational burden (TMB) cancers, such as ICI refractory neuroblastoma. In addition, the dynamic T-cell profile that results from such a DNA-MMR inactivation, and whether this may confer a therapeutic benefit, is poorly understood. Here we used CRISPR/CAS9 genome editing technology to knock …

Genetic Basis Of Hybrid Sterility Between Drosophila Pseudoobscura And D. Persimilis, Alannah J.P. Mattice

Electronic Thesis and Dissertation Repository

Speciation is the underlying process that leads to formation of new species, and therefore is the basis of biodiversity. Genes involved in each stage of speciation, such as those involved in interspecies sterility, remain elusive. Male hybrid sterility and postzygotic isolation between Drosophila pseudoobscura and D. persimilis was examined in this study through backcrossing of female hybrids into each parental line (introgression), selecting for a sterile sperm phenotype, needle-eye sperm. Sperm phenotypes did not separate through backcrossing; instead, males presented with multiple sperm phenotypes. A relationship between the phenotypes observed and the potential genes involved was examined through whole genome …

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 …

Computational Unfolding Of The Human Hippocampus, Jordan M. K. Dekraker

Electronic Thesis and Dissertation Repository

The hippocampal subfields are defined by their unique cytoarchitectures, which many recent studies have tried to map to human in-vivo MRI because of their promise to further our understanding of hippocampal function, or its dysfunction in disease. However, recent anatomical literature has highlighted broad inter-individual variability in hippocampal morphology and subfield locations, much of which can be attributed to different folding configurations within hippocampal (or archicortical) tissue. Inspired in part by analogous surface-based neocortical analysis methods, the current thesis aimed to develop a standardized coordinate framework, or surface-based method, that respects the topology of all hippocampal folding configurations. I developed …

Characterizing The Diversity Of The Eukaryotic Microbiome In Marine Crustacean Zooplankton., Rose-Lynne Savage

Electronic Thesis and Dissertation Repository

Understanding zooplankton productivity is critical for modeling marine food web function, of which one poorly known factor is the influence of zooplankton symbionts. Zooplankton protist symbiont diversity is underestimated due to the limited surveys and techniques previously used. Using 18S V4 metabarcoding, I characterized the eukaryotic microbiomes associated with crustacean zooplankton from the northern Strait of Georgia, BC. Apostome ciliates were most abundant in all hosts except for cyclopoid copepods, which were dominated by Syndiniales. Most symbiont lineages were more abundant in one or two hosts, suggesting some degree of host preference. Microbiome data also provided information on diet, confirming …

Cognitive Resources Are Recruited Consistently Across People During Story Listening, Matthew T. Bain

Electronic Thesis and Dissertation Repository

Degraded speech encoding as a result of hearing loss increases cognitive load and makes listening effortful. Standard hearing assessment does not capture this cognitive impact of hearing impairment. Speech-in-noise testing measures intelligibility for isolated sentences that are typically not engaging and lack meaningful context. These materials may not capture the processes involved in everyday listening situations, in which people are often intrinsically motivated to comprehend the speech they are hearing. The current study explored a novel approach using natural, spoken stories. We first characterized time courses of executive load during story listening in young individuals with normal hearing using a …

Investigating Cognitive Impairment In Tdp-43 Mouse Models Of Ftd-Als Using Automated Touchscreens, Keon Coleman

Electronic Thesis and Dissertation Repository

TAR-DNA-binding protein 43 (TDP-43) misfolding and aggregation is a major pathological hallmark of frontotemporal dementia-amyotrophic lateral sclerosis (FTD/ALS). FTD/ALS is characterized by motor and cognitive impairment, with cognitive impairment frequently reported before the onset of classical motor symptoms. Yet, treatment for cognitive decline in FTD/ALS is lacking, and robust cognitive phenotypes related to TDP-43 proteinopathy have not been established for most mouse models of FTD/ALS. Herein, we used automated touchscreen technology to assess executive function (affected in FTD/ALS) in male TDP-43^Q331Klow and ^-G348C FTD/ALS transgenic mice. The touchscreen pairwise visual discrimination task revealed impairments in 4-5-month-old TDP-43^Q331Klow and …

The Influence Of Estrogen And Glucocorticoid On Th2 Cell Survival And Transcriptional Activation Of Crth2, Jenna H. Fortunato

Electronic Thesis and Dissertation Repository

Women are more likely to have severe asthma than men. Recent data suggest this could be due to women having more circulating CD4⁺CRTh2⁺ T cells (Th2 cells). Glucocorticosteroids (GC)s are the main therapy for asthma as they inhibit cytokine production and eliminate inflammatory cells by apoptosis. The current study examined whether the female sex hormone estrogen influences the anti-inflammatory action of GC. Experiments show that ER⍺ agonist reduced GC-induced apoptosis of primary Th2 cells and enhanced GC-mediated transcriptional activation of the proximal CRTh2 promoter. Genetic variation within CRTh2 is associated with asthma and allergic phenotypes. Using constructs …

Development Of The Model Marine Diatom Phaeodactylum Tricornutum For Synthetic Biology Applications, Samuel S. Slattery

Electronic Thesis and Dissertation Repository

Harnessing organisms for protein and chemical production is useful to the scientific community and has applications in the fuel, food, and pharmaceutical industries. Biological systems commonly used for industrial chemical production include yeast and bacteria due to their fast growth rates and potential for high product yields. However, biologically active proteins, such as for human therapeutics, usually require production in mammalian and insect systems that are prohibitively expensive to grow at scale. Recently, photoautotrophic microalgae have emerged as promising platforms, as some species can be grown quickly and inexpensively at large scales and have the potential to produce biologically active …

Molecular Identification And Characterization Of Viral Pathogens Infecting Sweet Cherry, Aaron J. Simkovich

Electronic Thesis and Dissertation Repository

Stone fruits are a valuable crop grown worldwide, however pathogens such as viruses threaten fruit production by reducing tree health and fruit yield. In an orchard within the Niagara region of Ontario, symptoms typical of viral infection such as chlorosis and leaf deformation were seen on sweet cherry (Prunus avium L.) trees. Next generation sequencing was performed on symptomatic and asymptomatic leaves and four viruses were identified. On the tree displaying the most severe symptoms, Prune dwarf virus (PDV), was the only virus detected. A survey conducted during this work showed 42% of cherry trees on a single …

Reactive Oxygen Species Damage And Consequences For Mitochondrial Function In The Hibernating Thirteen-Lined Ground Squirrel, Ictidomys Tridecemlineatus, Brynne Duffy

Electronic Thesis and Dissertation Repository

Hibernators experience changes in blood flow, similar to ischemia-reperfusion injury, which may lead to oxidative damage. I hypothesized that suppression of mitochondrial metabolism during hibernation protects against such damage. I compared oxidative damage and antioxidant capacity in tissues and isolated liver mitochondria among summer, torpid, and interbout euthermic thirteen-lined ground squirrels (TLGS). I found less oxidative tissue damage during summer than hibernation, but no mitochondrial differences. I also compared metabolic activity of isolated mitochondria before and after five minutes of anoxia, followed by reoxygenation, among hibernation states and rats. Anoxia-reoxygenation decreased state-three respiration (ST3) in all groups, with rat mitochondria …