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Serotonergic System And Gait: Dorsal Raphe Nucleus As A Control System For Gait, Nahal Farhani

Electronic Thesis and Dissertation Repository

In advanced stages of Parkinson Disease (PD), gait and postural abnormalities emerge. These symptoms are not prominent at early stages of PD despite significant dopaminergic neuronal loss. Gait abnormalities are largely not responsive to levodopa. Therefore, other types of neurons might be responsible for gait abnormalities of the PD.

Since the reticulospinal tract (RET) is mainly implicated in the control of axial muscles, the degeneration of this pathway or populations of neurons controlling this pathway might be responsible for axial symptoms. However, there is limited data about the neurons controlling the RET. Our aim in this study is to delineate …

The Role Of Bone Sialoprotein In Periodontal Tissue Development And Bone Repair, Yohannes Soenjaya

Electronic Thesis and Dissertation Repository

Bone development and repair involve complex processes that include interaction between cells and their surrounding matrix. In the body, bone sialoprotein (BSP) expression is up-regulated at the onset of mineralization. BSP is a multifunctional acidic phosphoprotein with collagen-binding, hydroxyapatite nucleating, and integrin recognition (RGD sequence, which is important for cell-attachment and signaling) regions. Mice lacking BSP expression (Bsp^-/-), exhibit a bone phenotype with reductions in bone mineral density, bone length, osteoclast activation, and impaired bone healing. This thesis examined the role of BSP in tooth development and also its potential use as a therapeutic reagent for bone …

The Rational Design And Evaluation Of Ck2alpha Mutants Bearing Inhibitor-Refractory Amino Acid Substitutions, Sam Reid Fess

Electronic Thesis and Dissertation Repository

CK2 is a ubiquitously expressed and constitutively active serine/threonine protein kinase that is implicated in many cellular functions. Previous studies have indicated that the generation of mutants that are less sensitive to inhibition can be advantageous when studying protein kinases. Importantly, studies have demonstrated that mutants of CK2 rendered less sensitive to inhibition are attainable. To extend these observations, mutants of CK2α were designed and evaluated to test their effect on the inhibition of CK2 by CX-4945 using in vitro enzymatic assays followed by the development of inducible cell lines. CX-4945 is a CK2 inhibitor that has demonstrated anti-tumor activity …

The Role Of Thymine Dna Glycosylase (Tdg) And Dna Demethylation In Tgf Beta Signaling, Matthew E.R. Maitland

Electronic Thesis and Dissertation Repository

Prompted by findings that TGFβ stimulates thymine DNA glycosylase (TDG) dependent rapid DNA demethylation and activation of the CDKN2B gene, I investigated the global role of TDG and DNA demethylation in TGFβ signaling in HaCaT cells. Using dot blot analysis, I show that TGFβ treatment increases the global levels of 5-formylcytosine, an intermediate metabolite of active DNA demethylation. Characterization of genomic regions that undergo DNA demethylation and recruitment of TDG indicate that they are both frequent events, but only overlap at 11 genomic locations. I identified 440 TGFβ upregulated genes, 40 of which were bound by TDG and 169 that …

Females In Control: Female Sensitivity To Predation Risk Affects Courtship And Reproductive Behaviours, Tin Nok Natalie Cheng

Electronic Thesis and Dissertation Repository

Even in the absence of direct killing, predators have a pervasive effect on prey populations through costly anti-predator behavioural responses. In high risk environments, animals can reduce conspicuous behaviours such as courtship displays decreasing exposure at the cost of reproduction. Previous studies typically looked at male behaviour immediately following a predator cue, thus, not considering temporal variations in risk or the impact of female receptivity on male courtship. I placed male and female brown-headed cowbirds under chronically elevated predation risk with periods of high and low risk. Under high predation risk, females performed fewer chatter calls and were more likely …

Investigation Of Cell-Penetrating Peptide Transformation In Two Regenerable Tissue Culture Systems, Atiyyah S. Ferouz

Electronic Thesis and Dissertation Repository

The genetic engineering of plants allows for the modification of plant genomes, subsequently improving plant traits. There are, however, plants recalcitrant to established transformation methods, requiring the implementation of novel techniques. This study investigates the viability of cell-penetrating peptide (CPP) transformation using Tat₂, a CPP with demonstrated transformation efficiency in plant and animal systems, in two regenerable tissue culture systems, soybean somatic embryos and Arabidopsis protoplasts. Assessments of complex formation, Tat₂ cellular translocation, complex uptake, and CPP-mediated transformation were carried out. The results show the formation of a Tat₂-plasmid complex and the uptake of Tat …

Fear Of Predators Compromises Parental Care And Juvenile Survival In A Songbird, Philip Blair Dudeck

Electronic Thesis and Dissertation Repository

Predators kill, but the risk of being killed is also a powerful force affecting survival because scared prey eat less, thereby increasing the likelihood of starvation. Young of most animals are extremely vulnerable to predators and may alter their behaviour to limit detection. I investigated the previously unexplored effects that predation risk has on the behaviour of newly fledged offspring and their parents, and the impact this has on offspring survival. I manipulated predation risk using sound and found that parent song sparrows reduced their feedings, providing 60% less food overall. Critically, not only did this parental response estimate survival …

Hd2d Is A Regulator Of Abscisic Acid Responses In Arabidopsis, Joshua A. Farhi

Electronic Thesis and Dissertation Repository

Histone deacetylases have important roles in development and stress response in plants. To further investigate their function, the HD2D gene, of the plant specific HD2 family, was studied. An hd2d-1 mutant and two HD2D overexpression lines were used in this study. Germination was delayed in hd2d-1 and HD2D overexpression seeds only in the presence of ABA. HD2D was found to positively regulate the expression of members of the ABA-response pathway (ABI1, ABI5, and RD29A) leading to increased resistance to drought and salinity treatments. Furthermore, HD2D expression delayed flowering by positively regulating FLC expression. Using bimolecular fluorescence complementation, the HD2D protein …

Genes And Gene Networks Related To Age-Associated Learning Impairments, Raihan Uddin

Electronic Thesis and Dissertation Repository

The incidence of cognitive impairments, including age-associated spatial learning impairment (ASLI), has risen dramatically in past decades due to increasing human longevity. To better understand the genes and gene networks involved in ASLI, data from a number of past gene expression microarray studies in rats are integrated and used to perform a meta- and network analysis. Results from the data selection and preprocessing steps show that for effective downstream analysis to take place both batch effects and outlier samples must be properly removed. The meta-analysis undertaken in this research has identified significant differentially expressed genes across both age and ASLI …

Evidence For Using Immunosuppressive Treatments When Treating Idiopathic Non-Infectious Uveitis: A Systematic Review And Meta-Analysis, Hargurinder Singh

Electronic Thesis and Dissertation Repository

Idiopathic non-infectious uveitis is the spontaneous inflammation of the eye, which can lead to blindness if not treated correctly. Due to long-term side effects of corticosteroids, 4 classes of off-label immunosuppressive treatments are sometimes used (alkylating agents, inhibitors of T-lymphocyte signalling, antimetabolites and biological modifiers). We conducted a systematic review and meta-analysis to assess the effectiveness of different treatment classes on uveitis patients with similar characteristics. Results of the systematic review concurred with the conclusions from the meta-analysis, which found that all immunosuppressive treatments improved patient vision, with a statistically significant change in logMAR of -0.11 (95% CI of -0.152 …

The Evolution Of Kin Recognition, Timothy Ja Hain

Electronic Thesis and Dissertation Repository

The discovery that many animals are promiscuous has challenged the importance of Hamilton’s Rule because it reduces the net benefits of helping nestmates. To resolve this challenge, biologists have investigated animals’ abilities to determine degrees of relatedness among individuals using kin recognition mechanisms. I conducted a literature review and found that most animals use one of two mechanisms: “familiarity” whereby kin are remembered from interactions early in life, such as in a nest, or “phenotype matching” whereby putative kin are compared to a template of what kin should look, smell, or sound like based on relatives encountered during early life …

Avery Brundage, Pan-American Games, And Entrenchment Of The Olympic Movement In Latin America, Doiara Silva Dos Santos

Electronic Thesis and Dissertation Repository

To become firmly established, the Pan-American Games depended on the efforts of particular individuals. With Avery Brundage's attention to the Pan-American Games as the center of this analysis, this study documented the main events leading up to the inauguration of the Pan-American Games as well as their development and significance to Latin American countries in the mid-twentieth century. The research material was mainly drawn from primary sources, most importantly, those found in the Avery Brundage Collection at Western University. The study demonstrated that Brundage saw in the Pan-American Games not only a challenge, but an opportunity to promote the Modern …

Seasonal And Long-Term (1995-2009) Changes In The Distribution And Abundance Of Submerged Aquatic Vegetation And Dreissenid Mussels In Inner Long Point Bay, Lake Erie, Robin Tj Churchill

Electronic Thesis and Dissertation Repository

Invasion by mussels can cause rapid increases in the abundance of submerged aquatic vegetation (SAV) by increasing water clarity and altering nutrient cycling, but rapid expansion of the mussel population is often followed by a decline until a new regional carrying capacity is reached. I sampled Long Point Bay (LPB), Lake Erie, in 2009 to quantify changes in SAV communities and densities of zebra mussels (Dreissena polymorpha) since the peak of the latter in the early 1990s, and modeled influences of year, water depth, and substrate type on the probability of SAV detection. I detected a 96% decrease …

Cardioprotective Role Of The Cholinergic System, Mouhamed Dakroub

Electronic Thesis and Dissertation Repository

The process of aging is an irreversible continuum experienced by all individuals. A large number of physiological transformations occur to the cardiovascular system as one ages. These changes result in increased risk of developing cardiovascular diseases, many of which are frequently seen in geriatric populations. While the exact mechanisms of age-related cardiac dysfunction have not been established, abnormal cholinergic dysfunction has been implicated in the pathology of other age related diseases; therefore, we have hypothesized that age induced cholinergic dysfunction is detrimental to cardiac function and health. This study seeks to identify whether increased cholinergic signaling, either by transgenic overexpression …

Exploring And Training Spatial Reasoning Via Eye Movements: Implications On Performance, Victoria A. Roach

Electronic Thesis and Dissertation Repository

This dissertation sought to determine if eye movements could serve as an indicator of success in spatial reasoning, and if eye movements associated with successful completion could be applied to strategically improve spatial reasoning.

Using the line images of Shepard and Metzler, an electronic test of mental rotations ability (EMRT) was designed. Two versions of the test were created, allowing for both a timed (6 seconds per question) and untimed testing environment. Four experiments were designed and completed to relate mental rotation ability (MRA) scores from the EMRT, to patterns in chrononumeric and visual salience data. In each experiment, participants …

Functional Analysis Of The Mir156 Regulatory Network In Arabidopsis Siliques, Zhishuo Wang

Electronic Thesis and Dissertation Repository

Siliques are photosynthetically active seed capsules and their development is strongly influenced by embryo development. MicroRNA156 (miR156)-SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) network is involved in regulating plant growth and development, but the downstream genes of this network are still not fully elucidated. Here, I show that the miR156/SPL2 pathway controls the development of floral organs, regulates pollen production, and thus affects male fertility in Arabidopsis thaliana. I present evidence that SPL2 binds to the 5’UTR of the ASYMMETRIC LEAVES 2 (AS2) gene in vivo, indicating that AS2 acts downstream of SPL2. When compared to wild-type plants, AS2 loss-of-function mutants …

The Effects Of Perceived Predation Risk On The Avian Brain, Emma C. Hobbs

Electronic Thesis and Dissertation Repository

Predators do not affect prey solely through direct killing. The fear (i.e. the prospect of imminent, violent death) of predators shapes prey ecology– the mere presence of a predator leaves lasting effects. Current models of fear are based on post-traumatic stress disorder (PTSD) in humans. The scientific community has identified brain regions involved in mammalian fear processing. The neurobiological effects of predator fear on wild animals are unknown. I exposed wild black-capped chickadees (Poecile atricapillus) to auditory playbacks simulating acute and chronic predation risk and quantified the expression of short- and long-term immediate-early genes in brain regions implicated in the …

Brain Injury And Inflammation And Placental Inflammation In Response To Repetitive Umbilical Cord Occlusions In The Near Term Ovine Fetus, Alex Xu

Electronic Thesis and Dissertation Repository

We hypothesized that repetitive umbilical cord occlusions (UCOs) leading to severe acidemia will stimulate a placental and fetal inflammatory response associated with brain injury, which will be exacerbated by chronic hypoxemia and low-grade infection. Chronically instrumented fetal sheep served as controls or underwent repetitive UCOs for up to 4 hours or until fetal arterial pH was2saturation pre-UCOs of >55% and

Regulation Of Hepatic Drug Metabolizing Enzymes In Chronic Kidney Disease, Thomas J. Velenosi

Electronic Thesis and Dissertation Repository

Chronic kidney disease (CKD) occurs as a result of declining renal function for 3 or more months. CKD effects 1 in 10 Canadians and is associated with a number of co-morbidities including diabetes and cardiovascular disease. To manage CKD and associated co-morbidities, patients take an average of 12 medications with a median pill burden of 19. Indeed, renal drug elimination is compromised in CKD, as declining glomerular filtration reduces drug excretion into urine. More recently, studies have provided evidence of altered non-renal drug clearance in CKD. The majority of drug clearance occurs in the liver by CYP2C and CYP3A drug …

Recombinase-Based In Vivo Expression Technology Identifies A Streptococcus Pyogenes Bacteriocin Important For Niche Adaptation In The Nasopharynx, Brent D. Armstrong

Electronic Thesis and Dissertation Repository

Streptococcus pyogenes is a Gram-positive, human-specific bacterial pathogen with the ability to cause a wide range of diseases from strep throat to necrotizing fasciitis and toxic shock syndrome. In addition, S. pyogenes may also induce post-streptococcal sequelae including rheumatic fever, acute glomerulonephritis, and reactive arthritis. Although primarily recognized as a pathogen, S. pyogenes also colonizes the skin and throat often without causing disease, and while numerous surface adhesions are important to attach to these surfaces, additional factors important for colonization and persistence by S. pyogenes are poorly understood. In addition to host defence mechanisms, the upper respiratory tract also contains …

Seasonality Of The Stress Response In House Sparrows (Passer Domesticus)., Michael R. Hasstedt

Electronic Thesis and Dissertation Repository

Seasonal changes in plasma corticosterone (CORT) levels indicate that birds modify their stress response through the year. Although this has been well documented, the method by which birds achieve this seasonality is not well understood. In this study I used house sparrows to determine if changes in glucocorticoid receptor (GR) immunoreactivity in several stress-related brain nuclei showed seasonal variation. The house sparrowsshowed seasonal variation in their stress response with baseline CORT levels being highest during the breeding season and lowest during winter. There was also significant change in plasma CORT post-dexamethasone during breeding, but not during other times of the …

Dexamethasone Regulates Gene Expression Induced By The Mechanosensitive P2x7 Receptor In Osteoblasts, Meena Na

Electronic Thesis and Dissertation Repository

Orthodontic tooth movement involves activation of osteoblasts and osteoclasts in response to mechanical forces. Extracellular nucleotides, released in response to mechanical stimuli, signal through P2 receptors in osteoblasts. P2X7 receptors are ATP-gated cation channels implicated in mechanotransduction in bone. Corticosteroids such as dexamethasone exhibit anti-inflammatory effects and their chronic use has been linked to serious side-effects such as osteoporosis. We investigated gene expression following P2X7 receptor activation with benzoylbenzoyl-ATP (P2X7 receptor agonist) in osteoblast precursor cells in the presence or absence of dexamethasone. We hypothesized that dexamethasone inhibits the ability of ATP to stimulate the expression of anabolic (bone forming) …

Ethanol Exposure During Synaptogenesis In A Mouse Model Of Fetal Alcohol Spectrum Disorders: Acute And Long-Term Effects On Gene Expression And Behaviour, Morgan L. Kleiber

Electronic Thesis and Dissertation Repository

Alcohol is a neuroactive molecule that is able to exert variable and often detrimental effects on the developing brain, resulting in a broad range of physiological, behavioural, and cognitive phenotypes that characterize ‘fetal alcohol spectrum disorders’ (FASD). Factors affecting the manifestation of these phenotypes include alcohol dosage, timing of exposure, and pattern of maternal alcohol consumption; however, the biological processes that are vulnerable to ethanol at any given neurodevelopmental stage are unclear, as is how their disruption results in the emergence of specific pathological phenotypes later in life.

The research included in this thesis utilizes a C57BL/6J (B6) mouse model …

Energetics And Digestive Physiology Of Age Classes Of Songbirds During Fall Migration, Brendan J. Mccabe

Electronic Thesis and Dissertation Repository

Among vertebrates, performance of juveniles is typically poor compared to adults. During fall, North American passerine birds migrate south ahead of deteriorating conditions on northern breeding areas. During this migration, juvenile passerines are typically three or four months old and have predictably poor performances. Differential performance could be due to lack of experience, selection against poor-performing cohort members, or physiological constraints of juveniles. Limited evidence suggests that physiology of juveniles may differ from adults during fall migration. I investigated how body composition, metabolic rate, and digestive physiology of juvenile and adult passerines differ during fall migration. In Chapter Two, I …

Cytochrome P450 3a4 Expression And Regulation In Non-Alcoholic Fatty Liver Disease, Sarah J. Woolsey

Electronic Thesis and Dissertation Repository

Non-alcoholic fatty liver disease (NAFLD) is defined as lipid accumulation within hepatocytes (steatosis) in the absence of excess alcohol consumption. It is the most common liver disease in the western world, affecting one third of the general adult population with particularly high prevalence in obesity and type 2 diabetes. NAFLD is a disease continuum originating with simple hepatic steatosis that can progress to non-alcoholic steatohepatitis (NASH) with fibrosis and potentially cirrhosis, which places patients at risk for hepatocellular carcinoma. Unfortunately, there are not yet specific pharmacologic agents to treat NAFLD and so its management involves treatment of comorbidities, but there …

Developmental Stress And The Effects On Physiological And Cognitive-Behavioural Traits In European Starlings, Tara M. Farrell

Electronic Thesis and Dissertation Repository

Birdsong is a complex, learned vocalization that is a phenotypic expression of male quality. The developmental stress hypothesis describes how the cost to possessing a high quality song is paid in early development. Stressful early-life experiences have adverse effects on the development of the neural circuitry that regulates song learning and production, which results in a male advertising with a low quality song in adulthood. The purpose of this thesis was to test the developmental stress hypothesis in several respects in European starlings (Sturnus vulgaris). My objectives were to assess the long-term effects of developmental stress on (1) …

A Comparative Analysis Of Softball Gloves: Catcher's Glove Yields Highest Peak Hand Pressure, Brittany M. Hicks

Electronic Thesis and Dissertation Repository

Catchers commonly develop abnormal blood flow in the ulnar artery, digital ischemia in the index finger, and index finger hypertrophy as a result of continual trauma to the hand. The hand sustains peak pressures that are much greater than the recommended thresholds for repetitive tasks. The objective of this study was to measure the peak pressure on the hand when catching a softball and to determine which glove type (catcher’s glove, first baseman’s glove or fielder’s glove) is most effective at reducing the peak pressure on the hand. Pressure data was collected using Tekscan pressure sensors. Results indicate the hand …

Non-Canonical Activation Of Nrf2 By Dimercaptopropanol As A Treatment For Huntington's Disease, Margaret Lauren Tindale

Electronic Thesis and Dissertation Repository

Mitochondrial dysfunction and elevated reactive oxygen species (ROS) levels are strongly implicated in various neurodegenerative disorders, including Huntington’s disease (HD). Expression of the mutant Huntingtin protein (mHTT) containing an expanded polyglutamine repeat is associated with oxidative stress and toxicity in striatal neurons. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor responsible for regulating expression of a diverse array of antioxidant and cytoprotective genes. Most known Nrf2-activating compounds act through the canonical pathway by mimicking a transient oxidative insult, and treatment effects are short-lived. This study reveals an increase in striatal cell viability, and a reduction in …

The Effect Of A Combined Multiple-Modality Exercise Intervention On Sensorimotor Function In Community Dwelling Older Adults, With A Subjective Cognitive Complaint: The M4 Study (Multi-Modal; Mind Motor), Sam Titheridge

Electronic Thesis and Dissertation Repository

Aging is associated with the increased onset of diseases such as cognitive impairment, and ultimately dementia. Participants, 55+ years, with a self-reported cognitive complaint completed a 6-month exercise intervention. They were randomized to either a multiple modality exercise program (M2), consisting of aerobic, stretching and balancing exercises or a multiple modality plus mind motor program (M4), whereby a square stepping exercise was incorporated. Participants were assessed for reaction time (RT), movement time (MT) and % errors at baseline and at 6-months using an eye tracking 1000 system. Participants performed prosaccades and antisaccades (AS). AS RT was significantly quicker from baseline …

Mechanisms Of Neuroprotection Against Ischemic Insult By Stress-Inducible Phosphoprotein-1, Jason Xu

Electronic Thesis and Dissertation Repository

Stress-inducible phosphoprotein-1 (STI1) levels are increased in the brain following ischemia. STI1 is a co-chaperone for Hsp70/Hsp90 modulating protein folding. STI1 can also be secreted by a number of cells and function to activate extracellular signalling by the prion protein (PrP^C) and type-I bone morphogenetic protein receptor ALK2. However, the mechanisms by which STI1 can protect neurons against ischemia are currently unknown. A caspase-3 reporter mouse line was used to evaluate the consequences of increased extracellular STI1 levels. Neurons were treated with recombinant STI1 and specific agonists/antagonists for PrP^C, α7nAChR, and ALK2 prior to oxygen-glucose deprivation …