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Biochemistry, Biophysics, and Structural Biology Commons™
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Articles 1 - 13 of 13
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
The Role Of Stem Cells In Adipose Tissue Remodeling., Candice Reshay Holden 1988-
The Role Of Stem Cells In Adipose Tissue Remodeling., Candice Reshay Holden 1988-
Electronic Theses and Dissertations
The work presented in this dissertation outlines the role of stem cells in the remodeling of adipose tissue under conditions of nutrient excess. Obesity-induced variations in adipose tissue stem cell distribution were uncovered by analysis of the stromal vascular fraction isolated from mice fed a high fat diet for several weeks. Bone marrow cell transplantation was used to determine the derivation of progenitor cells found in adipose tissue; and supplementation of depleted progenitor cell populations achieved via direct cell transplantation, helped to determine the contribution of these progenitor cells to the remodeling process. The dissertation is presented in five chapters …
Troglitazone Suppresses Glutamine Metabolism And Tumor Cell Growth Through A Ppar-Independent Mechanism., Miriam R. Reynolds 1965-
Troglitazone Suppresses Glutamine Metabolism And Tumor Cell Growth Through A Ppar-Independent Mechanism., Miriam R. Reynolds 1965-
Electronic Theses and Dissertations
In tumor cells, glutamine metabolism provides anaplerotic carbon for the TCA cycle, fatty acid synthesis, and precursors for the production of nucleotides and glutathione. This metabolic alteration is primarily driven by disruptions in oncogenic or tumor suppressor function and results in glutamine dependency for tumor cell survival. Troglitazone, a PPARγ agonist, has been reported to alter glutamine metabolism. This thesis project addresses whether troglitazone treatment could disrupt glutamine metabolism in glutamine-dependent tumor cells. Results obtained with troglitazone treatment include: dose-dependent inhibition of cell proliferation, glutamine uptake, glutaminolytic protein expression, steady-state ATP levels, and glutamine carbon flux into the TCA cycle. …
Enzyme Kinetics : 6-Phosphofructo-2-Kinase/2,6-Bisphosphatase., Jennifer Clark
Enzyme Kinetics : 6-Phosphofructo-2-Kinase/2,6-Bisphosphatase., Jennifer Clark
Electronic Theses and Dissertations
Altered energy metabolism is an established hallmark of cancer cells. Fructose-2,6-bisphosphate is an allosteric activator of glycolysis and its concentration in a cell is dictated by the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) family of bifunctional enzymes. The PFKFB family of enzymes are characterized by their different kinase: bisphosphatase activities and were originally determined to be tissue-specific. More recent data however suggest that multiple isoforms are co-expressed in both normal and neoplastic tissues. PFKFB4 is highly expressed in human cancer, strongly induced by hypoxia, and required for the survival of cancer cells. However, it remains unclear whether the kinase or phosphatase activity of human …
Mirna-21 Has Anti-Inflammatory Effects In The Macrophage Response To Peritonitis., Rebecca Elise Barnett
Mirna-21 Has Anti-Inflammatory Effects In The Macrophage Response To Peritonitis., Rebecca Elise Barnett
Electronic Theses and Dissertations
This project investigated the role of miRNA-21 in the macrophage response to peritonitis; with the goal of understanding whether the associated mechanism has potential benefits in the clinical treatment of peritonitis. A novel therapeutic intervention in the treatment of peritonitis could modulate the host immune response to decrease an exaggerated pro-inflammatory innate response and then prevent or ameliorate the development of sepsis and organ failure. We found the following: 1. MiRNA-21 expression increases in peritoneal macrophages after lipopolysaccharide (LPS) stimulation. 2. Over expression of miRNA-21 decreases TNF-a secretion from macrophages after LPS stimulation. Suppression of miRNA-21 expression results in increased …
Biophysical And Computational Investigations Into G-Quadruplex Structural Polymorphism And Interaction With Small Molecules., Huy Tuan Le
Electronic Theses and Dissertations
In the cell, guanine-rich nucleic acids can self-assemble into unique four stranded tertiary structures known as G-quadruplexes. G-quadruplex formation in the telomere leads inhibits telomerase, an enzyme activated in cancer cells to maintain the telomere and allowing for cancer cells to achieve immortality. G-quadruplex formation in the promoters and 5’-untranslated regions regulates the expression of many oncogenes. Furthermore, G-quadruplex formation during cellular replication promotes genomic instability, a characteristic which enables tumor development. Because of their implication in cancer, G-quadruplex structures have emerged as attractive drug targets for anti-tumor therapeutics. In the current dissertation work, we present three experimental approaches to …
Genetic And Mechanistic Analysis Of Rat Mammary Cancer Susceptibility., Jennifer Sanders
Genetic And Mechanistic Analysis Of Rat Mammary Cancer Susceptibility., Jennifer Sanders
Electronic Theses and Dissertations
Breast cancer is a complex disease, which is influenced by genetic, epigenetic and environmental components. Genetic susceptibility to breast cancer is made up of high, moderate and low penetrance alleles. High and moderate penetrance alleles are rare and constitute only a small percentage of the genetic susceptibility. Most variation in genetic susceptibility is controlled by low- penetrance, common polymorphisms. Comparative genetics uses model organisms to study human disease. Rat strains exhibit different susceptibility phenotypes to chemical induced carcinogenesis. The Wistar-Furth (WF) rat strain is susceptible to chemically induced mammary carcinogenesis, while the Wistar-Kyoto (WKy) and Copenhagen (COP) rat strains are …
Augmentation Of Ras-Induced Cell Transformation : A New Role For Mir-200a In Malignancy., Lindsey Erin Becker
Augmentation Of Ras-Induced Cell Transformation : A New Role For Mir-200a In Malignancy., Lindsey Erin Becker
Electronic Theses and Dissertations
Cancer is a multistep disease that begins with malignant cell transformation and frequently culminates in metastasis and death. MicroRNAs (miRNAs) are small regulatory 21-25-nt RNA molecules and are frequently deregulated in cancer. The majority of miRNAs are estimated to be co-expressed with neighboring miRNAs as clusters. Many miRNA clusters coordinately regulate multiple members of cellular signaling pathways or protein interaction networks. miR-200a is a member of the miR-200 family, which are known to be strong inhibitors of the epithelial to mesenchymal transition. As such, the tumor suppressive role of miR-200a in oncogenesis has been well studied; however, recent studies have …
Microgenomic Approaches To Identify Clinically Relevant Gene Signatures That Discriminate Histologic Types Of Breast Carcinomas., Sean Thomas Butterbaugh
Microgenomic Approaches To Identify Clinically Relevant Gene Signatures That Discriminate Histologic Types Of Breast Carcinomas., Sean Thomas Butterbaugh
College of Arts & Sciences Senior Honors Theses
Background: Breast cancer presents itself in a variety of histologic types, and the two most common types are invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). Based on comparative genomic hybridization (CGH) analyses, ILC is more closely related to low grade IDC than it is to intermediate and high grade IDC. Results from the BIG 1-98 trial demonstrate that post-menopausal women who are affected with estrogen receptor positive (ER+) ILC or luminal B (high grade) IDC experience a greater magnitude of benefit when they are treated with the aromatase inhibitor (AI) letrozole compared to treatment with the antiestrogen tamoxifen. …
Mechanisms Of Action And Co-Optive Evolution For Hypervariable Courtship Pheromones In Plethodontid Salamanders., Wilburn Beau Wilburn
Mechanisms Of Action And Co-Optive Evolution For Hypervariable Courtship Pheromones In Plethodontid Salamanders., Wilburn Beau Wilburn
Electronic Theses and Dissertations
Pheromones are an important type of chemical cue used by most animals to convey information between individuals. For more than 100 million years, male plethodontid salamanders have utilized a system of non-volatile, proteinaceous pheromones to regulate female mating behavior and receptivity. One of these pheromone components, Plethodontid Modulating Factor (PMF), is a hypervariable protein related to the three-finger protein (TFP) superfamily. Previous studies revealed that PMF persists as a rapidly evolving multi-isoform mixture. However, many characteristics of PMF as a pheromone remained undetermined, including gene structure and transcriptional regulation, translational regulation, protein structure, evolutionary mechanisms, and the isoform effects on …
Epigenetic Modifications Associated With Aortic Remodeling In Hyperhomocysteinemia., Nithya Narayanan
Epigenetic Modifications Associated With Aortic Remodeling In Hyperhomocysteinemia., Nithya Narayanan
Electronic Theses and Dissertations
Background: Hyperhomocysteinemia (HHcy) is prevalent in hypertensive patients and is an independent risk factor for aortic pathologies. HHcy is known to cause an imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) leading to accumulation of collagen in the aorta resulting in stiffness and development of hypertension. Although the exact mechanism of extracellular matrix remodeling (ECM) is unclear, emerging evidence implicates epigenetic regulation involving DNA methylation. The purpose of the study was to investigate whether inhibition of DNA methylation reduces high blood pressure by regulating aortic ECM remodeling in HHcy. Methods: In the first set of experiments, we …
Myocyte-Specific Overexpression Of Stromal Cell-Derived Factor 1 Facilitates Cardiac Regeneration And Improves Myocardial Function After Infarction In Mice., Detlef Ernst-Rudolf Obal
Myocyte-Specific Overexpression Of Stromal Cell-Derived Factor 1 Facilitates Cardiac Regeneration And Improves Myocardial Function After Infarction In Mice., Detlef Ernst-Rudolf Obal
Electronic Theses and Dissertations
Background: Interruption of cardiac stromal cell-derived factor 1 (SDF1)-CXCR4 axis by chronic AMD3100 administration increased myocardial injury after permanent coronary artery ligation, demonstrating the important role of this chemokine in cardiac regeneration. Hypothesis: Cardiomyocyte-specific conditional overexpression of SDF prevents heart failure after permanent coronary ligation and facilitates cardiac regeneration. Methods and Results: Tetracycline-controlled, a-myosine heavy chain promoter directed overexpression of cardiac SDF resulted in a significant increase of SDF expression (SDF: 8.1 ng / g protein) compared with littermate WT mice (0.02 ng / g protein) four weeks after doxycycline withdrawal. SDF overexpression increased AKT and casein kinase 1 levels …
The Anti-Obesogenic Effects Of Nitric Oxide., Brian Edward Sansbury 1985-
The Anti-Obesogenic Effects Of Nitric Oxide., Brian Edward Sansbury 1985-
Electronic Theses and Dissertations
Obesity is a strong risk factor for developing type 2 diabetes and cardiovascular disease and has quickly reached epidemic proportions with few tangible and safe treatment options. While it is generally accepted that the primary cause of obesity is energy imbalance, i.e., more calories are consumed than are utilized, understanding how caloric balance is regulated has proven a challenge. Molecular processes and pathways that directly regulate energy metabolism represent promising targets for therapy. In particular, nitric oxide (NO) is emerging as a central regulator of energy metabolism and body composition. NO bioavailability is decreased in animal models of obesity and …
Inflammation-Resolving Lipid Mediators Promote Revascularization To Enhance Wound Healing., Michael Jingyuan Zhang
Inflammation-Resolving Lipid Mediators Promote Revascularization To Enhance Wound Healing., Michael Jingyuan Zhang
Electronic Theses and Dissertations
Wound healing is a highly concerted cellular process that begins with inflammation and proceeds to resolution to revascularize the site of injury. Although inflammation is essential to revascularization during wound healing, it is now recognized that resolution is an active process that is equally important. Other investigations have implicated a beneficial effect of resolving inflammation and promoting resolution in the remission of inflammatory pathologies. Recently investigations have yielded a novel class of ?-3 fatty acid derived lipid mediators, biosynthesized by leukocytes, which are capable of resolving inflammation and promoting resolution. We therefore hypothesized that these leukocyte-derived pro-resolving lipid mediators can …