M.A. (Master of Arts in English), Ohio Dominican University, 2023, English

Through a combination of biographical evidence and literary analysis, this paper argues that Edgar Allan Poe's knowledge of the Catholic Faith demonstrates the writer had an interest in and a sympathy for Catholicism, and that this interest and sympathy profoundly shaped his work.

Committee: Kelsey Squire Dr. (Committee Member); Jeremy Glazier Prof. (Advisor) Subjects: Literature

Doctor of Philosophy, The Ohio State University, 2006, Chemistry

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by the lack of functional dystrophin. Despite research focused on the replacement of the defective gene and the structure and function of dystrophin, there is no effective treatment of cure for this inevitably fatal disease. Rescue of dystrophin deficient, mdx, and utrophin/dystrophin deficient, dko, mouse models by the reintroduction of dystrophin has validated gene therapy as a therapeutic approach for DMD. Unfortunately the gene exceeds the capacity of adeno-associated viral (AAV) vectors. We investigated the expression of required dystrophin domains from two molecules as a means of expanding AAV capacity. Although the dystrophin proteins co-localize at the membrane, no improvement of dystrophic pathology is observed. Therefore, trans introduction of overlapping, truncated dystrophin proteins cannot be used to overcome cloning capacity limitations. The signaling mechanisms that lead from dystrophin deficiency to clinical DMD are largely unknown. We also conducted a proteomic analysis of phosphorylation differences between mdx and dko skeletal muscle and an immunoblot based examination of known signaling pathways. A serine phosphoprotein was observed in dko mitochondrial and microsome fractions but absent from corresponding mdx preparations. Unfortunately protein identification was inhibited by the abundance of actin in muscle. The nuclear factor-κB inhibitor, IκBβ, was observed to exhibit an increase presence in dko muscle hinged upon the additional presence of both a nuclear and cytosolic form of the protein. Finally, we examined the neuromuscular junction (NMJ) protein, Calmodulin-associated serine/threonine kinase (CASK) in the cellular components of the NMJ. CASK exhibits a developmentally regulated localization in the C2C12 myogenic cell line. It is observed in the nuclei of proliferating myoblasts, but is excluded to the cytosol in differentiating myotubes. CASK also exhibits a nucl (open full item for complete abstract)

Committee: Jill Rafael-Fortney (Advisor) Subjects: Chemistry, Biochemistry

Doctor of Philosophy, The Ohio State University, 2005, Molecular, Cellular, and Developmental Biology

In this dissertation, we examine the in vivo functions of two cell junction proteins, CASK and Claudin-5. CASK is a member of the membrane associated guanylate kinase family of proteins, while Claudin-5 is a protein that has been most thoroughly characterized as a component of tight junctions. This dissertation describes investigations of the CASK protein in skeletal muscle at the neuromuscular junction (NMJ) and Claudin-5 in cardiomyocytes We show that the CASK protein is present in skeletal muscle and is predominantly localized to the primary gutter of the NMJ, with a small amount of presynaptic localization. Immunoprecipitations reveal that CASK interacts in vivo with Dlg. We also examined the CASK protein in the C2C12 myogenic cell line and found that CASK localization is developmentally regulated and determined that CASK is recruited to the NMJ by a mechanism with is independent of that which recruits acetylcholine receptors. Finally, we generated two lines of transgenic mice, which overexpress a full-length or truncated version of the CASK protein. Overexpression of either the full-length or truncated CASK protein does not result in any morphological or functional abnormalities of the skeletal muscle or NMJ. However, overexpression of either CASK protein results in a loss of CASK protein presynaptically at the NMJ. Finally, overexpression of either CASK protein did not alter the expression or localization of Dlg. This dissertation also details an examination of the Claudin-5 protein in cardiac muscle from wild-type mice and two mouse models of cardiomyopathy, the mdx and dko mouse. We show that the Claudin-5 protein is present in normal cardiac muscle and is localized to the lateral membranes of cardiomyocytes. We also demonstrate that Claudin-5 protein expression and localization is unaltered in hearts from mdx mice, but is downregulated in dko hearts, as compared to normal hearts. Expression levels of cell junction proteins present at the intercalated disc w (open full item for complete abstract)

Committee: Jill Rafael-Fortney (Advisor) Subjects: