Medicine and Health Sciences Commons^™

Characterizing The Human Vaginal Microbiome Using High-Throughput Sequencing, Jean Megan E. Macklaim

Electronic Thesis and Dissertation Repository

The human vaginal microbiome undoubtedly has a significant role in reproductive health and for protection from infectious organisms. Recent efforts to characterize the bacterial species of the vagina using molecular techniques have uncovered an unexpected diversity. Using high-throughput sequencing I sought to describe the structure and function of the vaginal microbiome under different physiological states including healthy, bacterial vaginosis (BV), post-menopausal vaginal atrophy, and acute vulvovaginal candidiasis (VVC).

Partial 16S rRNA gene sequencing revealed that healthy, asymptomatic women most often have vaginal biotas dominated by Lactobacillus iners or L. crispatus. In contrast, BV is a heterogeneous, highly diversified condition …

Exploring The Structure And Biochemistry Of Oxidation-Mediated Inhibitation Of The Peptidyl-Prolyl Isomerase Pin1, Brendan T. Innes

Electronic Thesis and Dissertation Repository

Pin1 is a phosphorylation-dependent peptidyl-prolyl isomerase that has been shown to be neuroprotective in aging-related neurodegenerative diseases such as Alzheimer's disease (AD). However, it is not active in AD brain, and a recent proteomic screen of Mild Cognitive Impairment (MCI) brain samples revealed that Pin1 is oxidized in the brains of these pre-AD patients. This suggests that this oxidation may be the cause of the loss of the neuroprotective Pin1 function in AD. The Pin1 active site contains a functionally critical cysteine residue (Cys113) with a low predicted pKa, making it highly susceptible to oxidation. We hypothesize that Pin1 is …

Prenatal Programming Of Hepatic Glucose And Cholesterol Regulation In Male Rat Offspring By Chronic Intermittent Hypoxia, Waseem Iqbal

Electronic Thesis and Dissertation Repository

Obstructive sleep apnea (OSA) is a chronic disorder involving repetitive interruptions in breathing during sleep. Sufferers of OSA are exposed to chronic intermittent hypoxia (CIH), characterized by cyclical reductions in oxygen availability. A number of studies have established a link between OSA and various cardiovascular and metabolic comorbidities in adulthood, including hypertension, obesity, and type II diabetes. While the consequences of OSA in adults have been well described, the cross-generational impact of this condition and potential effects on fetal development are not known. Epidemiological and animal studies have demonstrated that physiological insults during pregnancy lead to diminished growth of offspring …

Characterization Of Staphylococcus Aureus Lipase, Vithooshan Vijayakumaran

Electronic Thesis and Dissertation Repository

USA300, a strain of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA), has become prevalent in the community. Colonization of human skin requires mechanisms that allow this bacterium to overcome the innate immune defenses on the skin, including secretion of antimicrobial lipids. Antimicrobial lipids inhibit S. aureus growth and induce the staphylococcal proteolytic cascade, producing aureolysin (Aur) which processes the lipase glycerol ester hydrolase (Geh). Nearly all S. aureus strains secrete Geh, yet little information exists concerning its function. Using purified Aur and Geh we confirm that aureolysin processes proGeh to Geh. We then confirmed that geh was required for lipase activity …

Adjustment Of Pulmonary O2 Uptake, Muscle Deoxygenation And Metabolism During Moderate-Intensity Exercise Transitions Initiated From Low And Elevated Baseline Metabolic Rates, Joshua P. Nederveen

Electronic Thesis and Dissertation Repository

When instantaneous step-wise transitions within the moderate intensity domain are initiated from elevated metabolic rates, the rate of pulmonary oxygen uptake (V̇O_2p) adjustment is slowed, and the V̇O_2p gain (ΔV̇O_2p /ΔWR) is greater. This study sought to determine the relationship between V̇O_2p kinetics and metabolic activity and energy status during step transitions from low and elevated metabolic rates within the moderate intensity domain. Ten young men completed six double-step constant load cycling bouts, consisting of step-wise transitions from 20 W to 45% θ_L and 45% θ_L [lower step (LS)] to 90% θ_{L …}

Investigation Of Auditory Encoding And The Use Of Auditory Feedback During Speech Production, Laura E. Beamish

Electronic Thesis and Dissertation Repository

Responses to altered auditory feedback during speech production are highly variable. The extent to which auditory encoding influences this varied use is not well understood. Thirty-nine normal hearing adults completed a first formant (F1) manipulation paradigm where F1 of the vowel /ε/ was shifted upwards in frequency towards an /æ/–like vowel in real-time. Frequency following responses (FFRs) and envelope following responses (EFRs) were used to measure neuronal activity to the same vowels produced by the participant and a prototypical talker. Cochlear tuning, measured by SFOAEs and a psychophysical method, was also recorded. Results showed that average F1 production changed to …

Imaging Breast Cancer Progression And Lymph Node Metastases In Murine Models Using Mri And Magnetic Nanoparticles, Vasiliki Economopoulos

Electronic Thesis and Dissertation Repository

Most breast cancer related deaths are caused by the spread or metastasis of the primary tumor to distant sites in the body. The lymph nodes are one of the first places where metastases can be detected and are frequently examined for macroscopic metastases to help determine course of treatment for patients. However, little is known about the significance of microscopic metastases and disseminated individual cancer cells within the nodes. The goal of this work was to use MRI to monitor the development of primary tumors and lymphatic metastases in models of breast cancer.

In this thesis, we examined the MRI …

Human Adenovirus E1a Binds And Retasks Cellular Hbre1, Blocking Interferon Signalling And Activating Virus Early Gene Transcription, Gregory J. Fonseca

Electronic Thesis and Dissertation Repository

Upon infection, human adenovirus (HAdV) must block interferon signaling and activate the expression of its early genes to reprogram the cellular environment to support virus replication. During the initial phase of infection, these processes are orchestrated by the first HAdV gene expressed during infection, early region 1A (E1A). E1A binds and appropriates components of the cellular transcriptional machinery to modulate cellular gene transcription and activate viral early genes transcription. We have identified hBre1/RNF20 as a novel target of E1A. hBre1 is an E3 ubiquitin ligase which acts with the Ube2b E2 conjugase and accessory factors RNF40 and WAC1 to monoubiquitinate …

Regulation Of Lipid Homeostasis, Inflammatory Signalling And Atherosclerosis By The Peroxisome Proliferator-Activated Receptor Delta, Lazar A. Bojic

Electronic Thesis and Dissertation Repository

The peroxisome proliferator-activated receptor (PPAR) δ is a ligand-dependent transcription factor that has been implicated in metabolic and inflammatory regulation. The molecular and physiological mechanisms by which PPARδ activation regulates lipid metabolism, inflammatory signaling and protection from atherosclerosis in states of metabolic disturbance such as insulin resistance and dyslipidemia, were investigated in a series of in vitro and in vivo studies. In vitro experiments demonstrated that PPARδ activation inhibits atherogenic lipoprotein-induced lipid accumulation and the associated proinflammatory responses. The primary mechanisms for these effects were increased fatty acid β-oxidation, decreased lipoprotein lipase (LPL) activity, reduced MAPK signaling and improved insulin …

Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is characterized by deposition of the amyloid beta (Ab) peptide in the brain, an event which frequently but not universally correlates with nerve cell death. Although most nerve cells die in response to Ab, small populations of cells are able to survive by becoming resistant to Ab toxicity. Understanding the mechanisms by which cells become resistant to Ab may reveal novel treatments for AD. Interestingly, nerve cell lines selected for resistance against Ab exhibit increased glucose uptake and glycolytic flux. Here I show that these metabolic changes are mediated through an upregulation of pyruvate dehydrogenase kinase 1 …

Genetic Approaches To Studying Complex Human Disease, Joseph B. Dube

Electronic Thesis and Dissertation Repository

Common, complex diseases such as cardiovascular disease (CVD) represent an intricate interaction between environmental and genetic factors and now account for the leading causes of mortality in western society. By investigating the genetic component of complex disease etiology, we have gained a better understanding of the biological pathways underlying complex disease and the heterogeneity of complex disease risk. However, the development of high throughput genomic technologies and large well-phenotyped multi-ethnic cohorts has opened the door towards more in-depth and trans-disciplinary approaches to studying the genetics of complex disease pathogenesis. Accordingly, we sought to investigate select complex traits and diseases using …

Exploring Parental Experiences And Decision-Making Processes Following A Fetal Anomaly Diagnosis, Ramona L. Fernandez

Electronic Thesis and Dissertation Repository

Often the first indication that something may be wrong in a seemingly normal pregnancy occurs during the first detailed ultrasound appointment between 16 and 20 weeks gestation. Even the most tentative suspicions of fetal anomalies is jarring. Parent’s default reality of a normal pregnancy and a ‘perfect child’ changes to one of risk factors and the possibility of an ‘unhealthy child’. This study begins with the realization of this first loss in a series of losses that follow for parents as they grapple with diagnostic information to be able to make informed medical decisions regarding their fetus and pregnancy. The …

Governing Occupation Through Constructions Of Risk: The Case Of The Aging Driver, Silke Dennhardt

Electronic Thesis and Dissertation Repository

Risk and risk-management have become increasingly pervasive features of modern society and governmentality scholars have highlighted various ways risk discourses are taken up to govern citizens and their everyday conduct. Thus, attending to risk is imperative to advance an understanding of how everyday occupation is shaped and governed within contemporary society. Within this study, the example of driving in later life is drawn upon to address two objectives: 1. to advance the understanding of how risk is taken up to govern everyday occupation, and 2. to explicate how risk is taken up in discourses to constitute particular subjectivities and their …

Elongation Factor 1a-1 And Hepatocyte Response To Fatty Acid Excess, Alexandra M. Stoianov

Electronic Thesis and Dissertation Repository

Obesity is associated with elevated levels of serum fatty acids, which accumulate in nonadipose tissues including the liver. Elongation factor 1A-1 (EF1A-1) has previously been shown to participate in the cell stress and death response of cardiomyocytes to excess saturated fatty exposure, and in steatotic mouse myocardium. In this thesis, the hypothesis that the hepatocyte response to fatty acid overload involves EF1A-1 was tested. EF1A-1 expression was induced in the livers of obese mice in association with severe hepatic steatosis, and in HepG2 human hepatoma cells in response to excess palmitate. Partial translocation of EF1A-1 from the ER to polymerized …

Magnetic Resonance Imaging Of Brain Tissue Abnormalities: Transverse Relaxation Time In Autism And Tourette Syndrome And Development Of A Novel Whole-Brain Myelin Mapping Technique, Yann Gagnon

Electronic Thesis and Dissertation Repository

The transverse relaxation time (T2) is a fundamental parameter of magnetic resonance imaging sensitive to tissue microstructure and water content, thus offering a non-invasive approach to evaluate abnormalities of brain tissue in-vivo. Prevailing hypotheses of two childhood psychiatric disorders were tested using quantitative T2 imaging and automated region of interest (ROI) analyses. In autism, the under-connectivity theory, which proposes aberrant connectivity within white matter (WM) was assessed, finding T2 to be eleveted in the frontal and parietal lobes, while dividing whole brain data into neurodevelopmentally relevant WM ROIs found increased T2 in bridging and radiate WM. In Tourette syndrome, tissue …

Awareness Of Physical Activity Levels And Sedentary Behaviour: An Assessment Of Awareness Of Physical Activity Levels And Sedentary Behaviour Among Parents And Children, Tripat Simran Kaur Grewal

Electronic Thesis and Dissertation Repository

The purpose of this study was to assess awareness of physical activity and sedentary behaviour among parents and children aged 10-13 years. Associations between awareness and factors including age, BMI, gender, and obesity status were also examined. A total of 53 parent-child dyads participated in the study. Agreement between parent and child subjective measures (self-report) and objectively measured physical activity was examined to determine awareness. Most parents (87%) and children (83%) overestimated child moderate-vigorous physical activity (MVPA) beyond 30 minutes/day. The majority of parents (87%) and children (85%) also underestimated child sedentary behaviour by at least 3 hours/day. Older children …

Exploring The Neural Basis Of Top-Down Guided Action In Macaque Monkeys, Jessica M. Phillips

Electronic Thesis and Dissertation Repository

To thoroughly characterize any brain mechanism requires an appropriate animal model for invasive studies. An invaluable model system used toward a comprehension of cognitive neurophysiology is the macaque monkey. It is important to delineate similarities and limitations for this model in relation to the human brain and cognition. In this thesis, we have thus conducted three experiments to investigate putative generalizations between monkeys and humans regarding the neural processes associated with top-down action control in monkeys.

Our daily behaviour is largely comprised of automatic routine actions. The frequent repetition of certain behaviours in response to particular contexts can give rise …