Molecular Biology Commons^™

The Role Of Heat Shock Protein 90 In The Keap1/Nrf2 Mediated Oxidative-Stress Response, Zheng Song

Electronic Thesis and Dissertation Repository

Oxidative and proteotoxic stress are common hallmarks of Neurodegenerative diseases (NDs). Cellular proteostasis is maintained through Heat shock protein (Hsp) 90 and Stress-inducible protein 1 (STIP1) modulating the stability of their substrates (clients). Hsp90/heat shock factor (HSF)1 pathway activation attenuates proteotoxicity. Meanwhile, activating the Kelch-like ECH associated protein 1 (Keap1)/ nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway combats oxidative stress. Numerous studies attempted to individually manipulate the expression of Hsp90 or Nrf2 to treat NDs.

Novel interactions of Hsp90 with Nrf2 and Keap1 were discovered via yeast-2-hybrid screening (unpublished data). We analyzed their interactions through NMR spectroscopy, ITC, protein-binding assay, …

Excess No Stabilizes The Luminal Domain Of Stim2 In A Cys-Specific Manner Thereby Regulating Basal Calcium Homeostasis And Store-Operated Calcium Entry, Matthew Novello

Electronic Thesis and Dissertation Repository

Stromal-interaction molecule 2 (STIM2) is an endoplasmic reticulum (ER) membrane-inserted Ca²⁺-sensing protein which, together with the plasma membrane Ca²⁺ channel Orai1, regulates basal Ca²⁺ homeostasis and store-operated Ca²⁺ entry (SOCE). Recent evidence suggests that S-nitrosylation, which is the covalent attachment of a nitric oxide (NO) moiety to a cysteine thiol, can attenuate the function of the paralog STIM1 protein. Compared to STIM1, STIM2 also functions as a basal Ca²⁺ homeostatic feedback regulator. Therefore, the objective of my study was to evaluate the susceptibility of STIM2 to S-nitrosylation and the effects that this …

Microvascular Stenosis In Critical Limb Ischemia: Role Of Partial Endothelial To Mesenchymal Transition, Jacqueline M. Chevalier

Electronic Thesis and Dissertation Repository

Critical limb ischemia (CLI) is a widespread and debilitating manifestation of atherosclerosis. Unfortunately, revascularization strategies are often precluded or unsuccessful, resulting in amputation. A major reason for treatment failure is likely co-existing abnormalities in ­­the microvasculature. However, the specific microvascular defects present in end-stage PAD in humans remain unknown.

The purpose of this study was to delineate abnormalities in the microvascular wall in the critically ischemic skeletal muscle of patients with CLI.

To elucidate the microvascular landscape in CLI, we studied human tibialis anterior and gastrocnemius muscles harvested from below-knee amputations of 10 individuals with CLI. Control muscles are from …

Fabricating Cost-Effective Nanostructures For Biomedical Applications, Erden Ertorer

Electronic Thesis and Dissertation Repository

In this thesis we described inexpensive alternatives to fabricate nanostructures on planar substrates and provided example applications to discuss the efficiency of fabricated nanostructures.

The first method we described is forming large area systematically changing multi-shape nanoscale structures on a chip by laser interference lithography. We analyzed the fabricated structures at different substrate positions with respect to exposure time, exposure angle and associated light intensity profile. We presented experimental details related to the fabrication of symmetric and biaxial periodic nanostructures on photoresist, silicon surfaces, and ion-milled glass substrates. Behavior of osteoblasts and osteoclasts on the nanostructures was investigated. These results …

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 …