Genetic Structures Commons^™

Using Genetically Diverse Mice To Examine The Effects Of Environmental Enrichment Of The Transcriptome, Michael Richard Leonardo

Theses, Dissertations and Capstones

Environmental impoverishment is a model of early life stress with direct consequences across a wide range of neurological and physiological conditions. Neuron morphology and density as well as anxiety disorders and addiction have shown to have significant relationships with environmental impoverishment models. Conversely, environmental enrichment confers therapeutic benefits that are protective across these conditions. There is an observed spectrum of resistance or vulnerability to the effects of housing conditions across populations, indicating genetics as an influential factor. Understanding this interaction is critical for deepening our knowledge of how genes and environment interact in ways that confer resistance or vulnerability, and …

Employing The Enzyme Cofactor Function Of Ascorbic Acid To Affect Oncogenic Pathways In Human Melanoma: Modulating Hypoxia Inducible Factor-1Α And Dna Demethylation To Reduce Malignant Potential, Adam Patrick Fischer

Theses, Dissertations and Capstones

Dioxygenase enzymes such as the HIF hydroxylases (PHD1-3, FIH) and the Ten-eleven translocation (TET1-3) enzymes regulate the activity of the hypoxia inducible factor-1_a (HIF1_a) transcription factor and the DNA methylation status of cells, respectively. Aberrant accumulation and activation of HIF-1_a can allow malignant cells to acquire attributes that promote progression, chemotherapy resistance, and survival, while aberrant hypermethylation of gene promoters can silence the expression of tumor suppressor genes essential to preventing tumorigenesis. Inadequate levels of intracellular ascorbic acid (AA), a necessary cofactor for optimal dioxygenase enzyme function, could potentiate these tumorigenic conditions. In fact, plasma levels …

Investigation Of Ultrasound Targeted Microbubbles As A Therapeutic Gene Delivery System For Prostate Cancer, Rounak Paramjeet Nande

Theses, Dissertations and Capstones

A major challenge for effective gene therapy is systemic delivery of viruses carrying therapeutic genes into affected tissue. The immunogenic nature of human adenoviruses (Ads) limits their use for intratumoral (IT) injection in gene therapy. Ads transfection is further hampered by the fluctuating presence of Coxsackie and Adenovirus Receptor (CAR) and integrins on the cells’ surface. To circumvent these limitations we developed a novel approach wherein Ads are encapsulated inside the shell of lyophilized, lipid-encapsulated, perfluorocarbon microbubbles (MBs)/ultrasound (US) contrast agents, which act as delivery vehicles for a sitespecific gene transfer system.

We performed infection studies with Ad.GFP (Green Fluorescent …

Role Of Iron In Ethanol Derived Hepatic Stress, Jesse A. Thornton

Theses, Dissertations and Capstones

Chronic alcohol abuse is the third leading cause of preventable death in the United States. Ethanol metabolism causes liver injury through alterations in hepatic metabolic state, redox status, and acetaldehyde adduct formations. Increased iron absorption is associated with chronic ethanol consumption and may play a role in ethanol induced oxidative stress. We tested the hypothesis that normal labile iron in the liver plays a role in ethanol related pathological stress, using C57/Bl6 mice pair-fed Lieber-DeCarli liquid ethanol diets for 11 and 22 weeks. Normal iron group mice received 55mg/kg iron as ferric citrate, whereas the low iron groups received 5mg/kg. …

Pitx2 Is Overexpressed In Follicular Cell-Derived Thyroid Cancer And Promotes Thyroid Cancer Proliferation By Regulating Cell Cycle, Yue Huang

Theses, Dissertations and Capstones

Thyroid cancer is the most prevailing malignancy of the endocrine system. Its incidence is rapidly rising at the second fastest rate of all malignancies in the United States, making it a significant health problem. Although the majority of thyroid cancer is slowly-growing and well-differentiated, available treatment options are very limited, and most of them require complete removal of the thyroid gland and surrounding tissues. Patients who have undergone thyroid removal have to take life-long hormone replacement therapy, which is very inconvenient and costly. Therefore, there is an urgent need to develop new treatments for this disease. As a prerequisite for …

Identification And Characterization Of Novel Sir3/Mecp2-Chromatin Interactions, Nicholas L. Adkins

Theses, Dissertations and Capstones

The eukaryotic genome is packaged into chromosomes that are made up of a highly organized and heavily regulated structure called chromatin. The proteins involved in the compaction of DNA into this condensed state are mostly understood at the level of the structure of the nucleosome. The higher order arrangement of chromatin and how it effects gene regulation is only partially understood and characterized. The compaction of nucleosomal arrays into 30-nm and higher structures are partially the responsibility of architectural, or structural, chromatin associated proteins. The following dissertation analyzes the individual chromatin contributions of two well studied architectural proteins, the yeast …

Regulation Of Biofilm Formation Of Pseudomonas Aeruginosa, Nathaniel Edwards Head

Theses, Dissertations and Capstones

Cystic fibrosis (CF) is the most common, autosomal recessive lethal genetic disease in the Caucasian population, resulting from a malfunctioned cystic fibrosis transmembrane conductance regulator (CFTR) and leading to bacterial lung infections. P. aeruginosa, an opportunistic pathogen, establishes a chronic infection in CF with a phenotype of overproduction of an exopolysaccharide (alginate) due to host-directed mutagenesis. While free-floating planktonic bacteria can be properly cleared from the CF lung, P. aeruginosa, along with alginate production, establishes an infection in the form of a biofilm which supports its survival in nature and in vivo. As a result, genomic structure, …

Cytoanalysis Of Pancreatic B-Cells: Using An Avian Model, Mammalian Tissue Culture And Implications Of Antisense Oligonucleotides Transfection, Ayman Salah-El-Deen Amer

Theses, Dissertations and Capstones

Calbindin-D_28k (CaBP_28K) is a vitamin D-dependent calcium-binding protein that may alter intracellular calcium ion levels, [Ca²⁺]i. This dissertation describes experiments done to gain an understanding of the potential role of CaBP_28k in pancreatic B-cells in control of insulin secretion. The localization of CaBP_28k and insulin in chicken pancreas are shown in Chapter 1. CaBP_28k expression was found to be highest in ventral and dorsal lobes and lowest in splenic lobe. Insulin concentrations were distributed similarly among these lobes. Confocal microscopic studies demonstrated colocalization of insulin and CaBP_28k in Bcells. These findings …