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Full-Text Articles in Life Sciences

Human Adenovirus E1a Binds And Retasks Cellular Hbre1, Blocking Interferon Signalling And Activating Virus Early Gene Transcription, Gregory J. Fonseca Jun 2013

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 …


Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington Jun 2013

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 …


Regulation Of Lipid Homeostasis, Inflammatory Signalling And Atherosclerosis By The Peroxisome Proliferator-Activated Receptor Delta, Lazar A. Bojic Jun 2013

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 …


Genetic Approaches To Studying Complex Human Disease, Joseph B. Dube Jun 2013

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 …


Elongation Factor 1a-1 And Hepatocyte Response To Fatty Acid Excess, Alexandra M. Stoianov Apr 2013

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 …


Involvement Of Interleukin-33/St2 In Myocardial Dysfunction In Murine Model Of Sepsis, Yoonmi Choe Dec 2012

Involvement Of Interleukin-33/St2 In Myocardial Dysfunction In Murine Model Of Sepsis, Yoonmi Choe

Electronic Thesis and Dissertation Repository

The disruption of myocardial extracellular matrix (ECM) has been implicated in myocardial dysfunction during sepsis. However, the underlying mechanism(s) are not clear. Interleukin-33 (IL-33) is a cytokine which regulates collagen synthesis in various cardiac pathologies. The purpose of the present study is to test whether IL-33 contributes to sepsis-induced myocardial dysfunction through regulation of matrix metalloproteinase-9 (MMP-9). The in vivo, feces-induced peritonitis (FIP) in mice and in vitro lipopolysaccharide (LPS) treatments to isolated cardiomyocytes were used. In FIP mice, myocardial IL-33 and MMP-9 expression were increased and myocardial contractility was decreased. Myocardial function in FIP mice was improved when treated …


Evaluating The Impact Of Two Different Methods Of Diabetes Self-Management Education On Knowledge, Attitude, And Behaviours Of Patients With Type 2 Diabetes Mellitus, Laura B. Briden Nov 2012

Evaluating The Impact Of Two Different Methods Of Diabetes Self-Management Education On Knowledge, Attitude, And Behaviours Of Patients With Type 2 Diabetes Mellitus, Laura B. Briden

Electronic Thesis and Dissertation Repository

This study compared the effectiveness of diabetes self-management education (DSME) methods by examining changes in knowledge, attitude, and behaviour (KAB) after receiving education. Participants from a convenience sample were randomized into two groups, one receiving education through conversation maps and the other through traditional group education. Participants’ knowledge and attitude changes were measured by using a repeated measures pre-test/post-test design and changes in Hb A1c were observed. Focus groups were conducted after education was received to obtain perceptions and self-reported behaviour changes. Significant knowledge and attitude score changes were observed in the conversation map group after education. When comparing the …


Characterization Of Cardiomyopathy In A Mouse Model Of Duchenne Muscular Dystrophy (Dmd) Using Echocardiography, Dce-Ct, And Pet-Fdg, Seyed Hamed Moazami Nov 2012

Characterization Of Cardiomyopathy In A Mouse Model Of Duchenne Muscular Dystrophy (Dmd) Using Echocardiography, Dce-Ct, And Pet-Fdg, Seyed Hamed Moazami

Electronic Thesis and Dissertation Repository

Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disease that is the result of a loss of functional dystrophin, which causes cardiomyocyte fibrosis and death, leading to cardiomyopathy. In this thesis, I have utilized dynamic contrast-enhanced computed tomography (DCE-CT), positron emission tomography-fluorodeoxyglucose (PET-FDG), echocardiography, and traditional histology to longitudinally assess disease progression and degree of cardiomyopathy in a murine model of DMD (mdx:utrn-/-). No significant changes were observed in the blood flow, blood volume, or cardiac volume measured via DCE-CT, nor in standard uptake value (SUV) of glucose as measured by PET-FDG in the left myocardium between and within …


An Investigation Into The Combined Effects Of Β-Amyloid Toxicity And Cerebral Ischemia On The Pathological Expression Of Gangliosides., Jeffrey D. Hepburn Oct 2012

An Investigation Into The Combined Effects Of Β-Amyloid Toxicity And Cerebral Ischemia On The Pathological Expression Of Gangliosides., Jeffrey D. Hepburn

Electronic Thesis and Dissertation Repository

Identifying mechanisms underlying the synergistic pathological interaction between stroke and Alzheimer’s disease (AD) can effectively guide future therapeutic strategies for these highly co-morbid conditions. Aberrant ganglioside expression marked by the pathological accumulation of ganglioside GM3 is common to stroke and AD, yet it is unclear whether GM3 is synergistically enhanced in a comorbid model, or if GM3 is a viable therapeutic target. Adult male Wistar rats received a unilateral ischemic striatal infarct via endothelin-1 (ET-1) injection alone or in combination with bilateral intracerebroventricular injection of the β-Amyloid 25-35 peptide (Aβ) to induce generalized Aβ toxicity (Aβ/ET-1). Animals were sacrificed after …


Restriction Of Hiv-1 Replication By Unique Trim22 Isoforms., Clayton Hattlmann Mar 2012

Restriction Of Hiv-1 Replication By Unique Trim22 Isoforms., Clayton Hattlmann

Electronic Thesis and Dissertation Repository

Understanding how the immune system reacts to HIV infection and why normal antiviral defenses are insufficient to fight infection is a key step towards creating better therapies. Several interferon-induced proteins, such as the tripartite motif protein TRIM22, are capable of restricting HIV-1 replication; however single nucleotide polymorphisms (SNPs) can dramatically impact the actions of these proteins. While the trim22 gene contains numerous SNPs, no study has addressed how these may affect TRIM22 functions. Here we provide the first direct comparison of two TRIM22 unique isoforms. Through confocal microscopy we observed these isoforms exhibit different patterns of localization. In vitro studies …


The Role Of Granulocyte Colony-Stimulating Factor In The Intestinal Immune System And The Response To Probiotics, Andrew J. Martins Mar 2011

The Role Of Granulocyte Colony-Stimulating Factor In The Intestinal Immune System And The Response To Probiotics, Andrew J. Martins

Electronic Thesis and Dissertation Repository

Loss of immunoregulation in the intestine results in inflammation, such as is observed in the chronic, relapsing, inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. However, our understanding of this process remains incomplete. The cytokine granulocyte-colony stimulating factor (G-CSF) is an important stimulator of granulopoiesis in steady-state and during inflammation, but has also been shown to have anti-inflammatory effects and is a potential therapeutic for IBD. In addition, certain strains of bacteria, termed probiotics, have been postulated to have anti-inflammatory effects in the intestine. The mechanisms by which these strains of bacteria elicit anti-inflammatory effects are not fully understood. …