Medicine and Health Sciences Commons^™

Elevated Hydrostatic Pressure Selectively Enhances Matricellular Gene Expression In Human Trabecular Meshwork Cells, Jonathan Lautz

Dissertations

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy

characterized by loss of peripheral vision secondarily associated with elevated intraocular pressure (IOP). Transforming growth factor (TGF)-β2 is markedly elevated in the aqueous humor (AH) of patients with POAG. It has been previously shown that TGF-β2 increases IOP, in part, by inducing expression and release of endothelin-1 (ET-1) and connective tissue growth factor (CTGF) within the trabecular meshwork (TM). ET-1 and CTGF may ultimately lead to increases in IOP by enhancing TM cell contractility and extracellular matrix (ECM) deposition. Here we confirm that TGF-β2 enhances mRNA content of ET-1, CTGF, and …

Examining The Effects Of Adolescent Binge Alcohol Exposure On The Negative Feedback Of The Hpa Axis And Adult Responses To Psychological Stress, Audrey Rose Torcaso

Dissertations

Binge drinking during adolescence is a common occurrence which is associated with increased risk of developing alcohol dependence and other mental health disorders. Hypothalamo-pituitary-adrenal (HPA) axis dysfunction is one characteristic commonly observed in many affective disorders, including anxiety and depression. Our laboratory has previously demonstrated that adolescent binge-pattern alcohol exposure results in long-term dysfunction of the HPA axis in a Wistar rat model, characterized by deficient glucocorticoid feedback inhibition. The current study aimed to characterize the behavioral phenotype of these rats in response to psychological stress during adulthood, and furthermore sought to understand the molecular mechanisms by which adolescent binge …

Investigating Novel Methods Of Interaction With Pharmaceutically Relevant Enzymes, Cory T. Reidl

Dissertations

Metalloproteins requiring one or more metal ions for normal function make up 30% of all known proteins, and many critical biological pathways contain at least one metallo-enzyme. Di-nuclear metallo-proteins constitute a large class of these proteins yet we currently lack effective methods of inhibiting these enzymes for the development of new medical therapies, particularly for the discovery of new antibiotics. Our work has focused on developing novel functionalities that selectively interact with di-nuclear catalytic centers, and we are targeting three separate di-zinc-metallo-enzymes that are unique to bacteria and play key roles in their growth and development. These enzymes are DapE, …

The Unconventional Secretion Of Alpha-Synuclein By Autophagic Mechanisms And The Novel Characterization Of Pathological Alpha-Synuclein Associated Extracellular Vesicles, Kevin Burbidge

Master's Theses

Synucleinopathies are a group of neurodegenerative diseases associated with the intracellular accumulation of aggregated α-synuclein, a neurotoxic process resulting in cell death. Research indicates that pathology results from α-synuclein misfolding and self-propagation, as well as, cell-to-cell transmission. Furthermore, pathological α-synuclein transmission may occur through unconventional secretion.

In this thesis, we investigated how autophagy influences unconventional secretion of our novel α-synuclein dual-split protein model that we first verified by reproducing documented results from treatment of known autophagic regulators. Afterwards, we investigated how knocking out autophagic proteins ATG7 and Beclin-1 influenced α-synuclein secretion.

Additionally, we developed a methodology for analyzing extracellular vesicles …