Medicine and Health Sciences Commons^™

Characterizing The Function Of B Cells That Accumulate In The Inflamed Central Nervous System In Anti-Myelin Autoimmunity, Lika Chowdhury

Electronic Thesis and Dissertation Repository

While the role of autoimmune T cells has been extensively studied in anti-myelin

autoimmunity, little is known about the function of B cells in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS). B cells form clusters with T cells in the meninges directly adjacent to demyelinating lesions. Previous studies have shown that disease progression is dependent on the depletion of specific populations of B cells, but it is not clear which contributes to pathology or how. The purpose of this thesis is to characterize the population of meningeal B cells to determine how they differ …

Translational Control Of Stress Induced Breast Cancer Plasticity, Michael Jewer

Electronic Thesis and Dissertation Repository

Cancer cell plasticity, whereby stem-cell-like properties are acquired in response to stress, represents a major challenge in cancer treatment. Using cell line and patient-derived xenograft (PDX) models, we demonstrate that translational reprogramming occurs in response to stresses such as hypoxia and chemotherapy which elicits stem cell properties in breast cancer. Other stresses like chemotherapy demonstrate the translational inhibition that has been well characterized as an integral hypoxic cellular response. The inhibition of translation is primarily regulated at initiation by mTOR/4E-BP1 and PERK/eIF2α signalling. We identify previously undescribed 5’ untranslated regions (5’UTRs) of plasticity-associated genes like NANOG, SNAIL and NODAL. …

Exploiting Fission Yeast Genetic Interaction Data To Identify Disease-Specific Drug Targets For Tuberous Sclerosis Complex, Ashyad Rayhan

Electronic Thesis and Dissertation Repository

Tuberous sclerosis complex (TSC) is an inherited genetic disorder caused by loss-of-function mutations in either TSC1 or TSC2. Their respective gene products regulate the mechanistic target of rapamycin (mTOR) signaling pathway, which serves as an activator of cellular proliferation, metabolism, and cell survival. Orthologs of the TSC1 and TSC2 genes exist in a wide range of organisms, including the commonly used and genetically tractable model eukaryote, Schizosaccharomyces pombe. To better understand the functional roles of S. pombe tsc1 and tsc2, I exploited recent advances in genetic interaction biology to identify and characterize genes that modulate the phenotypic …

Effect Of Gamma Radiation On Growth And Mycotoxins Production Of Alternaria Alternata, Danny Karlet

Anatomy and Cell Biology Publications

The ubiquitous genus Alternaria contains many species that are able to invade cereals, oleaginous plants and other crops. Alternaria alternata is considered one of the most important species and can produce several mycotoxins under favourable conditions of temperature and humidity, including the economically important toxins: alternariol (AOH) and alternariol monomethyl ether (AME). The aim of this study was to evaluate the radio-sensitivity of Alternaria alternata spores through different gamma radiation doses. A. alternata growth and the production of AOH and AME were then analyzed. After fungal irradiation with 2 kGy, 5 kGy and 7 kGy, the spores were suspended with …

Olanzapine-Induced Methylation Alters Cadherin Gene Families And Associated Pathways Implicated In Psychosis, Melkaye G. Melka, Christina A Castellani, Nagalingam Rajakumar, Richard O'Reilly, Shiva M Singh

Biology Publications

BACKGROUND: The complex aetiology of most mental disorders involves gene-environment interactions that may operate using epigenetic mechanisms particularly DNA methylation. It may explain many of the features seen in mental disorders including transmission, expression and antipsychotic treatment responses. This report deals with the assessment of DNA methylation in response to an antipsychotic drug (olanzapine) on brain (cerebellum and hippocampus), and liver as a non-neural reference in a rat model. The study focuses on the Cadherin/protocadherins encoded by a multi-gene family that serve as adhesion molecules and are involved in cell-cell communication in the mammalian brain. A number of these molecules …

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 …

Nrf2 Activation By Dimercaptopropanol Attenuates Mutant Huntingtin Toxicity, Kyle M. Dailey

Electronic Thesis and Dissertation Repository

Huntington’s disease (HD) is a fatal neurodegenerative disorder resulting from the expansion of a trinucleotide repeat within the HD gene. At the cellular level mutant HTT (mHTT) aggregates perturb cellular metabolism, intracellular trafficking and mitochondrial function, resulting in the increased production of reactive oxygen species (ROS) an event closely linked with nerve cell death. Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-sensitive transcription factor responsible for transcribing neuroprotective genes under the control of the antioxidant response element (ARE), which work to counteract high intracellular ROS levels. I have identified significant increases in cell viability, NRF2 nuclear localization, and …