Biomedical Engineering and Bioengineering Commons^™

Regulation Of The Transcription And Subcellular Localization Of The Tumor Suppressor Pten By Δnp63Α, Mary Kathryn Leonard

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Non-melanoma skin cancers (NMSCs) are the most common form of cancer in the United States with an estimated 3.5 million new cases each year. Surgical excision is the main treatment for NMSC, but leaves the potential for disfiguring scars and does not fully reduce the risk of recurrence since the surrounding tissue is also sun damaged and may contain tumor-promoting mutations. By understanding the molecular etiology of NMSC we may be able to expand treatment options to more than just resection. Normal epidermal development is dependent upon the expression of the transcription factor p63. Amplification of the ΔNp63α isoform is …

'Omic' Evaluation Of The Region Specific Changes Induced By Non-Cholinergic Diisopropylfluorophosphate (Dfp) Exposure In Fischer 344 Rat Brain, Deirdre A. Mahle

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Organophosphorous compounds (OPs) are a class of serine esterase inhibitors that have widespread application as pesticides, veterinary pharmaceuticals and chemical warfare agents. Environmental contamination is ubiquitous. The threat of exposure is a concern for both military and civilian populations. Acute inhibition of acetylcholinesterase by OPs triggers a cholinergic crisis that results in muscle flaccidity, paralysis, convulsions and death. At low doses OPs can alter neuronal differentiation, cell signaling, behavior and cognition through unknown mechanisms. An imbalance of reactive oxygen species may be implicated in the adverse effects of OPs. An integrated approach using both metabolomic and transcriptomic techniques was used …

The Role Of Amp-Activated Protein Kinase (Ampk) In Hypoxic Chemotransduction By The Carotid Body, Heidi Lynn Jordan

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The carotid bodies are small sensory organs located along the bifurcation of the carotid arteries. They detect changes in blood gases and relay this information to the brain to allow for initiation of appropriate respiratory and cardiovascular responses. A decrease in oxygen (hypoxia) sensed by the carotid body results in an increase in firing of the carotid sinus nerve and ultimately a change in one's breathing pattern. An inability to respond to an acute hypoxic (low oxygen) episode via increased ventilation may result in death or lead to pathological or chronic conditions such as stroke and hypertension (Prabhakar et.al., 2005). …

The Role Of Angiotensin Converting Enzyme (Ace) 2 In A Murine Model Of Insulin Resistance And Albuminuria, Nathan Michael Weir

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Insulin resistance and kidney disease are intimately linked and both independently tied to dysregulation of the renin angiotensin system (RAS). The purpose of this research was to better investigate Angiotensin Converting Enzyme (ACE) 2 as a possible motif in the pathophysiology of these two disease processes. The project was divided into two parts. Part 1 investigated ACE2 KO mice as a model of albuminuria. Part 2 investigated how the lack of ACE2 enzyme affected glucose homeostasis and subsequent albuminuria.

Part 1: The Role of ACE2 in the Progression of Albuminuria. To determine if global loss of ACE2 leads to spontaneous …

The Role Of Ca2+ In Central Respiratory Control Neurons Of The Locus Coeruleus: Development Of The Chemosensitive Brake, Ann Nicole Imber

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Chemosensitive LC neurons increase their firing rate in response to increased CO₂ (hypercapnia) in part via inhibition of K⁺ channels. This increase gets smaller during the first two postnatal weeks (neonatal rats aged P3-P16). Alterations of this "accelerating" pathway may account for the developmental changes in the magnitude of the chemosensitive response in LC neurons. Alternatively, Ca²⁺ and Ca²⁺ channels may play a role in the response to hypercapnia, but little is known about the role of Ca²⁺ in central chemosensitivity. Whole cell patch clamp and fluorescence imaging microscopy were used to study a different …

A Mechanism-Based Model To Describe Gabaa Receptor Trafficking And Benzodiazepine Pharmacoresistance During Status Epilepticus, Elaine Alice Merrill

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Status epilepticus (SE) is a perplexing pathology involving a sudden and long disruption of the brain's normal electrical activity. The study of relevant cellular processes has been useful in identifying therapeutic targets. As a result, many novel drugs are being studied which target receptor systems involved in neuronal membrane excitability. Yet, the standard treatment for SE remains benzodiazepines (BZs), a class of GABAA agonist drugs. Unfortunately, the targeted receptors undergo a desensitization mechanism via enhanced endocytosis (receptor trafficking), leading to rapidly reduced BZ efficacy (pharmacoresistance) within minutes of seizure onset. A comprehensive understanding of the complex interplay between the anticonvulsant's …

Regulation Of The Dna Unwinding Element Binding Protein Due-B In The Cell, Yanzhe Gao

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Eukaryotic cells have evolved tightly controlled processes that make sure the entire genome gets replicated accurately, once per cell cycle. This tight control is fulfilled by degrading replication proteins after their function is carried out, changing their cellular location or by post-translational modification of replication factors to regulate their function. Phosphorylation events carried out by CDKs (cyclin dependent kinases) and DDKs (Dbf4 dependent kinases) play crucial roles in this regulation.

The DNA unwinding element binding protein (DUE-B) is an essential replication protein that binds to the human c-myc DNA replication origin. In this study, I find that DUE-B is also …

Applications Of Capillary Electrophoresis For Studying Serum Albumin Enantioselection Of D,L-Tryptophan Analogs, Jelynn A. Stinson

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The pharmacokinetic difference between drug enantiomers is the impetus for developing analytical techniques to assess enantiomeric purity. Capillary electrophoresis (CE) is an analytical technique that is used for characterizing drug-protein binding. The pitfall to using CE for drug-protein binding studies is protein chiral selectors tend to adsorb onto capillary walls and cause changes in electroosmotic flow that lead to decreased enantioselection and migration time irreproducibility between consecutive injections. The experimental parameters for minimizing the adverse effects of protein adsorption are not clear from the literature.

Rinsing protocols to improve enantioselection and migration time repeatability were developed using the tryptophan-bovine serum …

Limitations Of Functional Recovery Of Stretch Reflex Circuitry After Peripheral Nerve Regeneration, Gabrielle Marie Horstman

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Peripheral nerve regeneration fails to restore complete normal function after surgical repair of severed nerves, and this failure has primarily been attributed to errors in connecting with peripheral targets. However, recent evidence suggests that central deficits remain even after peripheral target reinnervation is largely successful. It has long been established that regeneration fails to restore the stretch reflex despite observation that many of the neural components are intact. Regenerated Ia afferents are largely successful in reinnervating muscle spindles, are capable of encoding stretch, and elicit EPSPs in homonymous motoneurons, while regenerated motor pools are capable of responding to uninjured sources …