Life Sciences Commons^™

The Mitochondrial Calcium Uniporter Regulator 1 (Mcur1) Matrix Domain Is A Self-Associated Multimer Sensitive To Divalent Cations, Naveed Siddiqui

Electronic Thesis and Dissertation Repository

Mitochondria are primarily appreciated for the generation of adenosine triphosphate (ATP), a chemical store of energy required by all cells. These organelles, however, also play key roles in apoptosis, autophagy and shaping cytosolic calcium (Ca²⁺) signaling via Ca²⁺ uptake into the mitochondrial matrix. This Ca²⁺ uptake is mediated chiefly via the mitochondrial Ca²⁺ uniporter (MCU), an inner mitochondrial membrane protein that oligomerizes to form a Ca²⁺ selective pore. MCU is regulated by several protein binding partners, including the recently identified MCU regulator-1 (MCUR1). MCUR1 stabilizes a higher order MCU heterocomplex through interactions with MCU …

Head Impact Exposures In Youth Canadian Football Players Aged 12-14 Do Not Significantly Impair Antisaccade Performance, William J. Smith

Electronic Thesis and Dissertation Repository

There is a growing body of research evaluating head impacts in sport, but studies have not evaluated youth football in Canada. It is important to evaluate football in Canada as the rules and field size are different than American football, and this may influence the impact exposures. The purpose of this study was to quantify the head impact exposures in youth Canadian football and determine if a season’s worth of impacts could cause impairments in executive function. Players (n=50) had their head impacts recorded using an impact measuring device (GForceTracker) throughout all contact practices and games. A subset of players …

Investigation Of Flow Disturbances And Multi-Directional Wall Shear Stress In The Stenosed Carotid Artery Bifurcation Using Particle Image Velocimetry, Amanda L. Dicarlo

Electronic Thesis and Dissertation Repository

Hemodynamics and shear forces are associated with pathological changes in the vascular wall and its function, resulting in the focal development of atherosclerosis. Flow complexities that develop in the presence of established plaques create environments favourable to thrombosis formation and potentially plaque rupture leading to stroke. The carotid artery bifurcation is a common site of atherosclerosis development. Recently, the multi-directional nature of shear stress acting on the endothelial layer has been highlighted as a risk factor for atherogenesis, emphasizing the need for accurate measurements of shear stress magnitude as well direction. In the absence of comprehensive patient specific datasets numerical …

Top-Down And Bottom-Up Effects On Collembola Communities In Soil Food Webs, Jordan Kustec

Electronic Thesis and Dissertation Repository

Anthropogenic changes are causing shifts within soil food web communities, which may alter ecosystem processes such as nutrient cycling, carbon storage and decomposition. I quantified ecological stressor effects on the abundance, richness, community composition and body size of a soil-dwelling microarthropod (Collembola: Hexapoda). I quantified the effects of warming and nitrogen deposition in two separate field studies and demonstrated that warming shifts Collembola community structure and decreases community body size. I quantified the interactive effects of top-down and bottom-up forces mediated by warming as ecological stressors in Collembola communities. I found that bottom-up effects of nutrient addition did not affect …

True North Strong Canada 150: Canadian Identity And Its Contribution To Doping Free Sport, Helena A. Hlas

Electronic Thesis and Dissertation Repository

This thesis, a reflective piece inspired by “Canada 150” events, explores the psychosocial and sociocultural factors surrounding the ongoing evolution of the clean sport movement in Canada. A literature review recounts the critical events in the history of doping, viz. the Ben Johnson scandal, which resulted in a call to overhaul sport culture and realign it with fair play values. Theories in sports philosophy and psychology provide a further understanding of the meaning of sport, and psychosocial factors that are inextricably linked to doping behavior, respectively. The autoethnographic method provides insight into current Canadian values to compare with those in …

19f-Mri To Monitor Therapeutic Cell Migration And Distribution, Corby Fink

Electronic Thesis and Dissertation Repository

A major hurdle hindering the advancement of cell-based cancer vaccines is the inability to non-invasively track in vivo therapeutic cell migration. Within cancer immunotherapy, antigen presenting cell-based (APC) immunotherapies can be dendritic cell-based (DC) and elicit de novo anti-tumor immune responses or formulated as mixed APC-based immunotherapy generated from peripheral blood mononuclear cells (PBMC). Mixed APC-based therapies contain monocytes and B cells as APC and can enhance a pre-existing anti-tumor immune response such that objective anti-tumor responses are observed. In either APC-based formulation, the quantity of anti-tumor APC reaching a secondary lymphoid organ post injection is predictive of the magnitude …

Suberin Biosynthesis And Deposition In The Wound-Healing Potato (Solanum Tuberosum L.) Tuber Model, Kathlyn Natalie Woolfson

Electronic Thesis and Dissertation Repository

Suberin is a heteropolymer comprising a cell wall-bound poly(phenolic) domain (SPPD) covalently linked to a poly(aliphatic) domain (SPAD) that is deposited between the cell wall and plasma membrane. Potato tuber skin contains suberin to protect against water loss and microbial infection. Wounding triggers suberin biosynthesis in usually non-suberized tuber parenchyma, providing a model system to study suberin production. Spatial and temporal coordination of SPPD and SPAD-related metabolism are required for suberization, as the former is produced soon after wounding, and the latter is synthesized later into wound-healing. Many steps involved in suberin biosynthesis remain uncharacterized, and the mechanism(s) that regulate …

Investigating The Role Of Brachypodium Distachyon Cellulose Synthase 8 In Gluconacetobacter Diazotrophicus Colonization, Xuan Yang

Electronic Thesis and Dissertation Repository

Nitrogen is an essential nutrient for plant growth. Significant amount of nitrogen fertilizer is applied to crop field to maintain high yield. Alternatives to chemical nitrogen fertilizer are needed to reduce the costs of crop production and offset environmental damage. Gluconacetobacter diazotrophicus is a nitrogen fixing bacterium that was originally isolated from sugarcane and has been proposed as a possible biofertilizer for monocot crop production. However, the colonization of G. diazotrophicus in most monocot crops is limited and deep understanding of the response of the host plants to G. diazotrophicus colonization is still lacking. In this study, research was conducted …

Landscape-Level Effects Of Agricultural Intensification On The Condition And Diet Of Nestling Barn Swallows (Hirundo Rustica), Jackson W. Kusack

Electronic Thesis and Dissertation Repository

Farmland bird populations have experienced declines with increasing agricultural intensification for which the leading hypothesis is a reduction of prey insects. This may be especially relevant for aerial insectivores whose primary diet is aerial insects. For this thesis, I examined nestling body condition and used stable isotopes (δ¹³C, δ¹⁵N) and fecal DNA barcoding to determine the diet of a farmland breeding aerial insectivore, the Barn Swallow (Hirundo rustica), within an agro-ecosystem in Southern Ontario, Canada. Nestling body condition was positively affected by agricultural intensification, but all benefits were lost by the pre-fledging stage and …

Determining The Molecular Mechanisms Of Pacs-1-Mediated Protein Sorting, Brennan S. Dirk

Electronic Thesis and Dissertation Repository

Membrane trafficking events are required to direct proteins to their precise subcellular locations. The cellular Phosphofurin Acidic Cluster Sorting protein – 1 (PACS-1) has emerged as a protein of interest in controlling the localization of a multitude of cellular and viral proteins. Specifically, PACS-1 is hijacked by type-1 Human Immunodeficiency Virus (HIV-1) to contribute to immune evasion in addition to regulating neuroendocrine hormone storage and release. To accomplish this, PACS-1 connects the cytoplasmic tail of cellular receptors to the heterotetrameric adaptor proteins (APs) to form a functional trafficking unit. Throughout this dissertation, I explored the role of PACS-1 and AP-1 …

Expression Of Hepatic Cytochrome P450 Drug Metabolizing Enzymes In Diabetes And Diabetic Nephropathy, Cheng Jay Fang

Electronic Thesis and Dissertation Repository

The prevalence of diabetes worldwide is rapidly increasing. Polypharmacy, along with a high risk of adverse drug reactions, is common in diabetic patients. Cytochrome P450 (CYP) 3A and 2C drug metabolizing enzymes are reduced in chronic kidney disease (CKD), altering drug pharmacokinetics and contributing to adverse drug reactions. A large fraction of commonly prescribed drugs are metabolized by CYP3A and CYP2C. Approximately 40% of all CKD cases are attributed to diabetic nephropathy (DN) and early DN presents as mild kidney disease. This study aims to evaluate the impact of diabetes and DN on levels and activity of hepatic CYP3A and …

The Use Of Current Steering During Subthalamic Deep Brain Stimulation To Alleviate Upper Limb Symptoms Of Parkinson's Disease, Shabna Iftikar Mohideen

Electronic Thesis and Dissertation Repository

Subthalamic (STN) deep brain stimulation (DBS) is an established treatment to alleviate the appendicular motor symptoms of Parkinson's Disease (PD). Current steering during DBS allows the unequal fractionation of current between two electrodes on the lead, resulting in a non-spherical electrical field. It is hypothesized that the way the electrical field is shaped will affect a patient’s upper limb symptom alleviation. Seven PD patients who underwent bilateral STN-DBS were tested over four weeks post-operation. 16 current fractionation settings were tested each week at an amplitude that increased weekly. Optimal setting was defined as the setting that provided the best …

Hitchhiker's Guide To Migration: Effects Of Experimental Parasitic Infection And Other Immune Challenges On Migratory Traits Of Sparrows, Tosha R. Kelly

Electronic Thesis and Dissertation Repository

Seasonal migration exposes animals to a variety of habitats and parasites, and if infected migratory birds migrate successfully there is great potential for birds to transport infectious diseases long distances. Our current understanding of whether birds contribute to the spread of disease relies upon observational field studies that are limited in their ability to discern cause from effect. Using captive and field-based experiments for my doctoral research, I answered three research questions: (1) are nocturnal migratory restlessness (Zugunruhe) and body condition affected by mounting an acute phase immune response during migration; (2) what are the impacts of parasitic …

Interferon-Induced Herc5 Is A Novel And Potent Inhibitor Of Ebola Virus-Like Particle Production, Nina Hunt

Electronic Thesis and Dissertation Repository

Ebola’s severe pathogenesis can be attributed to its suppression of the Type I interferon (IFN) response, suggesting this pathway plays a role in restricting viral replication. One IFN-induced protein, HERC5, warrants further investigation as it inhibits the replication of evolutionarily diverse viruses. We showed that HERC5 drastically reduces the expression of structural protein VP40 at the protein and mRNA level. Mutagenesis of HERC5 demonstrated that the RCC-1-like domain is necessary and sufficient for restriction. This domain is also responsible for HERC5’s interaction with ZAP, a protein required for VP40 mRNA degradation. Finally, we showed that Ebola GP antagonizes HERC5 activity. …

White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment, Alexander Levit

Electronic Thesis and Dissertation Repository

White matter integrity is crucial to healthy executive function, the cognitive domain that enables functional independence. However, in the ageing brain, white matter is highly vulnerable. White matter inflammation increases with age and Alzheimer disease (AD), which disrupts the normal function of white matter. This may contribute to executive dysfunction, but the relationship between white matter inflammation and executive function has not been directly evaluated in ageing nor AD. White matter is also particularly vulnerable to cerebrovascular disease, corresponding with the common presentation of executive dysfunction in vascular cognitive impairment (VCI). Thus, white matter may be an important substrate by …

The Effect Of Multiple Environmental Stressors On The Growth And Toxicity Of The Red Tide Alga Heterosigma Akashiwo, Malihe Mehdizadeh Allaf

Electronic Thesis and Dissertation Repository

Heterosigma akashiwo (Y.Hada) Y.Hada ex Y.Hara & M.Chihara is a golden-brown phytoflagellate with high potential to kill fish. These cells create large, nearly mono-specific blooms that persist from weeks to months. Although bloom persistence and frequency remain a mystery, environmental factors such as light, temperature, salinity and CO₂ level are proposed as drivers for both bloom initiation and toxicity. As timing and locations of nature blooms are difficult to predict, most of the information on this species comes from laboratory experiments on isolated cells. In this age, when multiple stressors occur simultaneously the traditional “One-factor-at-a-time” (OFAT) approach limits our …

Spatial And Temporal Patterns Of Neutral And Adaptive Genetic Variation In The Alpine Butterfly, Parnassius Smintheus, Maryam Jangjoo

Electronic Thesis and Dissertation Repository

Understanding how much genetic diversity exists in populations, and the processes that maintain that diversity, has been a central focus of population genetics. The evolutionary processes that determine patterns of genetic diversity depend on underlying ecological processes such as dispersal and changes in population size. In this thesis, I examine the influence of dispersal and population dynamics on neutral and adaptive genetic variation in a naturally occurring network of populations of the alpine butterfly, Parnassius smintheus.

My first objective was to determine the combined consequences of demographic bottlenecks and dispersal on neutral genetic variation within and among populations. Using …

Magnetic Field Frequency-Response For Human Magnetophosphene Perception And Associated Eeg Modulations, Cadence M. Baker

Electronic Thesis and Dissertation Repository

Background: Magnetophosphenes are among the most reliably reported effects resulting from magnetic induction. The frequency dependence of the perception threshold is crucial, as guideline agencies use this information to set exposure limits whose purpose is to protect public and workers.

Objective:Establish the magnetophosphene perception thresholds throughout the extremely low frequency range (0-300 Hz) and evaluate the use of EEG as a biomarker.

Hypothesis:Perception thresholds will be lowest at ~30 Hz. EEG occipital alpha power will decrease upon perception.

Methods:60 participants were exposed to homogenous magnetic fields up to 300 Hz, and 70 mT. EEG alpha power …

Characterization Of The Coat Protein Of Turnip Mosaic Virus And Its Arabidopsis Interactors In The Virus Infection Process, Zhaoji Dai

Electronic Thesis and Dissertation Repository

Viruses are infectious and obligate intracellular parasites. Turnip mosaic virus (TuMV) is a member of the genus Potyvirus which comprises many agriculturally important viral pathogens that threaten crop production. Potyviruses are fully dependent on the host cellular machinery to fulfil their infection cycle in plant hosts. It is well accepted that viral coat protein (CP) is a multifunctional protein that plays key roles in virus propagation and host-virus interactions. This dissertation project aimed to investigate the role of CP in TuMV cell-to-cell movement, to identify the host interactors of TuMV CP, and further to characterize their roles in TuMV infection. …

Growth And Toxicity Of Geographically-Distinct Isolates Of The Fish-Killing Phytoflagellate, Heterosigma Akashiwo, Veerta Singh

Electronic Thesis and Dissertation Repository

Harmful Algal Blooms (HABs)—an accumulation of toxic phytoplankton—often result from environmental changes reflecting the increasing global human footprint and climate change. One HAB species drawing attention is Heterosigma akashiwo, a fish-killing flagellate that can cause extensive fish loss or be benign, depending on location or environmental conditions. Here, I investigate if this difference in toxicity is regulated by environmental conditions or differences in cellular physiology. Six strains were examined. Three originate from the Salish Sea, where fish-kills are common, and three from Japan, where blooms of Heterosigma are common but fish-kills are rare. By measuring growth and toxicity of cells …

Patterns And Drivers Of Stream Benthic Macroinvertebrate Community Taxonomy And Function In Agroecosystems, Edward M. Krynak

Electronic Thesis and Dissertation Repository

Anthropogenic activities continue to expand and intensify resulting in vast areas of the globe being dominated by human land uses. Effective land management and conservation decisions depend on our ability to understand and predict biological response to further disturbance in already stressed ecosystems. Moreover, insight into biological response to ecological stressors may be advanced by using trait and functional community measures in combination with taxonomy. My dissertation goal was to describe patterns and drivers of variation in benthic macroinvertebrate communities (BMIC) taxonomic composition and function in streams in an agriculturally dominated landscape. I achieved my goal by conducting three related …

Learning Expands The Preplanning Horizon In Finger Sequence Tasks, Neda Kordjazi

Electronic Thesis and Dissertation Repository

Many everyday skills involve the production of complex sequences of movements. However, the dynamics of the interplay between action selection and execution processes in sequential movements is poorly understood.Here, we set out to investigate the extent to which information regarding upcoming actions is utilized by the motor system to preplan into the future and furthermore, how this ability is influenced by learning. We designed a finger sequence taskwhere participants were shown only a fixed number of upcoming cues regarding future presses in every trial (viewing window, W). W varied between 1 (next digit revealed with pressing the current digit – …

Immunization With Recombinant Myelin Oligodendrocyte Glycoprotein Identifies Autoreactive T Cells As A Limiting Factor In Autoreactive Germinal Center Maintenance, Rajiv William Jain

Electronic Thesis and Dissertation Repository

Germinal center (GC) responses are responsible for the protection provided by immunizations but can also drive autoimmunity. B and T cells collaborate in the GC to target the same antigen (Ag) to inform B cell differentiation; however, the properties of Ags differ substantially in autoimmunity and foreign-Ag driven immunity. Currently, it is not well understood how properties of the Ag itself influence the initiation or progression of GC responses, limiting our ability to develop effective vaccinations and predict the progression of autoimmune responses. The purpose of this thesis is to assess how GC responses initiate and progress when immunizing with …

Cardiodynamic Associations With Resilience In Undergraduate Students And The Effect Of A Mentorship Intervention, Rachel J. Knetsch

Electronic Thesis and Dissertation Repository

The National College Health Assessment (NCHA) indicates that a majority of Canadian university students report feeling overwhelmed, stressed, and anxious during their undergraduate studies. Resilience refers to positive adaptation, or the ability to maintain or regain mental health, despite experiencing adversity (Herrman et al., 2011). While autonomic indices have been used to describe chronic physiological stress, the role of heart rate variability (HRV) as an index of resilience remains unclear. This research tested the hypotheses that (1) there is a relationship between HRV and resilience scoresand (2) a mentorship intervention will improve HRV and resilience outcomes. Fifty-seven first year students …

A Comprehensive Catalog Of Post-Translational Modifications Of Drosophila Melanogaster Hox Protein, Sex Combs Reduced, Anirban Banerjee

Electronic Thesis and Dissertation Repository

During formation of the anterior-posterior axis, Homeotic selector (HOX) proteins determine the identity of Drosophila body segments. HOX proteins are transcription factors that regulate gene expression during development. Besides a highly conserved DNA-binding homeodomain (HD), HOX proteins also contain functionally important, evolutionarily conserved small motifs. These short motifs found in HOX proteins may be Short Linear Motifs (SLiMs). SLiMs are proposed to be sites of phosphorylation and this may regulate the activity of HOX proteins. The primary aim of this work was to develop a comprehensive catalogue of the sites of phosphorylation and other post-translational modifications (PTMs) for Fushi tarazu …

The 2Β Insert Perturbs Folding, Stability And Hydrophobic Exposure Of Stromal Interaction Molecules, Steve Chung

Electronic Thesis and Dissertation Repository

Stromal interaction molecule (STIM)1 and 2 regulate agonist-induced and basal cytosolic calcium (Ca2+) levels through oligomerization and translocation to endoplasmic reticulum (ER)-plasma membrane (PM) junctions. At these junctions, the STIM cytosolic coiled-coil domains couple to PM Orai1 protein subunits to form Ca2+ released activated Ca2+ (CRAC) channels that facilitate store-operated Ca2+ entry (SOCE). One splice variant of STIM2, STIM2β, contains an extra 8-residue (2β insert) located within the coiled-coils and inhibits SOCE through an unresolved mechanism, adding another layer of complexity to Ca2+ regulation in mammals. I hypothesize that the 2β insert perturbs the coiled-coil conformation and dynamics commensurate with …

The Role Of Hand1 In The Development Of The Lateral Plate Mesoderm In Xenopus, Victoria A. Deveau

Electronic Thesis and Dissertation Repository

The transcription factor hand1 is expressed in the heart, lateral plate mesoderm (LPM) and neural crest cells during development. As Hand1-null mice die early in embryogenesis, identification of the precise role of Hand1 in development is difficult. In Xenopus, we observed that hand1 expression patterns correlates very closely with development of LPM derivatives, leading us to hypothesize that hand1 is required for normal LPM development. Using hand1 knockdown and overexpression models in Xenopus, development of LPM derivatives were assessed by whole mount in situ hybridization. I found that hand1 is required for proper heart morphogenesis. Furthermore, hand1 …

The Effects Of Perceived Predation Threat On Stress Response And Memory In Birds, Chlöe S. N. Carter

Electronic Thesis and Dissertation Repository

This study examined how perception of predator cues, across three sensory modalities, affects physiology and behaviour of songbirds. I hypothesized that the perception of predator threat would elicit physiological and behavioural responses in both acute and chronic exposure conditions. My first study examined the responses of wild-caught black-capped chickadees (Poecile atricapillus) and house sparrows (Passer domesticus), as well as lab-bred zebra finches (Taeniopygia guttata), to acute predation cue exposure by coding video recorded behaviour and corticosterone analysis. My second study examined changes in black-capped chickadees’ foraging behaviour and memory retention after chronic exposure to …

Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee

Electronic Thesis and Dissertation Repository

Fetal growth restriction (FGR) is defined by low birth weight and contributes to a variety of adult-onset diseases with different severities between males and females. However, the effects of FGR on the pulmonary surfactant are not fully elucidated. In this thesis, first, we investigated the FGR effects on the lung function and the surfactant system at the early postnatal life. It was hypothesized that FGR contributes to alterations of lung mechanics and the surfactant system during the neonatal period. Second, we assessed the FGR effects on the surfactant system in response to sepsis in adulthood. It was hypothesized that FGR …

Adaptation Mechanisms Of Two-Spotted Spider Mite, Tetranychus Urticae, To Arabidopsis Indole Glucosinolates, Golnaz Salehipourshirazi

Electronic Thesis and Dissertation Repository

The two-spotted spider mite Tetranychus urticae Koch is a key agricultural pest that causes significant yield losses in a wide range of economically important crops. Rapid development of resistance to several classes of pesticides in T. urticae necessitates introduction of alternative management strategies to control this pest. Indole glucosinolates (IGs) are secondary metabolites found in Brassicaceae plants (including Arabidopsis thaliana) that have been shown to be effective against T. urticae and could be potential candidates to control spider mites. However, a laboratory population selected on IG-containing Arabidopsis was able to evolve adaptation to this plant. The overall objective of …