Digital Commons Network^™

Deterministic Model Of The Voltage Dependent Anion Channel (Vdac) Kinetics, Viren Shah

Theses and Dissertations

The voltage-dependent anion channel (VDAC) is a voltage gated channel residing on the outer mitochondrial membrane (OMM) that facilitates the flow of metabolites between the cytosol and mitochondria. The channel is regulated through conformational changes driven by electrostatic effects along with numerous regulatory mechanisms. The aim of this study is to mechanistically model kinetics of substrate flow through VDAC and incorporate them into existing mechanistic computational models of mitochondrial function. The resulting model is used in two ways: 1) to establish mitochondrial bioenergetics (conductance, permeability, and current/flux) under physiological conditions, and 2) to conduct perturbations simulating the effect of altered …

Quantitative Optical Imaging Of Metabolic And Structural Biomarkers In Rodent Injury Models, Shima Mehrvar

Theses and Dissertations

The assessment of organ metabolic function using optical imaging techniques is an overgrowing field of disease diagnosis. The broad research objective of my PhD thesis is to detect quantitative biomarkers by developing and applying optical imaging and image processing tools to animal models of human diseases. To achieve this goal, I have designed and implemented an optical imaging instrument called in vivo fluorescence imager to study wound healing progress. I have also developed a 3-dimensional (3D) vascular segmentation technique that uses intrinsic fluorescence images of whole organs.

Intrinsic fluorophores (autofluorescence signals) provide information about the status of cellular bioenergetics in …

Reconsidering Undergraduate Anatomy And Physiology Curriculum, Eric Michael Walsh

Theses and Dissertations

In the past 50 years several convergent factors have spurred unprecedented change in anatomy and physiology (A&P) instruction. An explosion of biomedical knowledge, an increased demand for students well-versed in A&P, and decreased resources for the course has provoked a vast array of research. However, most studies employ one of three strategies to enact change: testing the effectiveness of new pedagogies, exploring the utility of new technologies, or documenting learning in new contexts. By comparison, a much smaller body of research focuses on changing the A&P curriculum to improve student learning. To address this gap, the musculoskeletal curriculum for an …

An Identification Of Tgf-B'S Role In Ischemic Cholangiopathy, Courtney Chmielewski

Theses and Dissertations

Organ transplants are a necessary intervention for many diseases that result in end stage organ failure. The donation pool cannot match the demands of the transplant list, so expanding the pool to include donation after cardiac death (DCD) is desired. However, there are increased odds of graft failure and ischemic cholangiopathy leading to inferior outcomes when DCD livers are used. Ischemic cholangiopathy consists of multiple diffuse strictures and fibrosis of the bile ducts leading to a loss of epithelialization and fibrosis. The cellular mechanism is proposed to be epithelial-to-mesenchymal transition (EMT). TGF-�� is seen as a key initiator of EMT, …

Focal Augmentation Of Somatostatin Interneuron Function And Subsequent Circuit Effects In Developmentally Malformed, Epileptogenic Cortex, Nicole Ekanem

Theses and Dissertations

Drug-resistant epilepsy (DRE) is a common clinical sequela of developmental cortical malformations such as polymicrogyria. Unfortunately, much remains unknown about the aberrant GABA-mediated circuit alterations that underlie DRE's onset and persistence in this context. To address this knowledge gap, we utilized the transcranial freeze lesion model in optogenetic mice lines (Somatostatin (SST)-Cre or Parvalbumin (PV)-Cre x floxed channelrhodopsin-2) to dissect features of the SST, PV, and pyramidal neuron microcircuit that are potentially associated with DRE. Investigations took place within developmental microgyria’s known pathological substrate, the adjoined and epileptogenic paramicrogyral region (PMR). As well, microcircuit relationships within the previously unexplored range …

Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation, Ria C. Fyffe-Freil

Theses and Dissertations

Of the over 108,000 American awaiting a life-saving organ transplant today, over 12,000 (11%) of those need a new liver (OPTN, 2020). Last year, only 35% of patients on the waiting list for an organ were transplanted. Improving the quality of marginal organs by preventing or reversing preservation injury could vastly increase the number of transplants performed. Washout of circulating blood during liver procurement with cold University of Wisconsin solution flushes out any endogenous pro-survival signaling molecules. We investigated lysophospholipid (LPL) surface receptors (G-protein coupled receptors for lysophosphatidic acid (LPA) and sphingosine- 1-phosphate (S1P)) and their role in protecting hepatocytes …