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Articles 1 - 14 of 14

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Elucidating Functional Roles For Myogenin In Adult Skeletal Muscle Metabolism, Exercise Capacity, And Regeneration, Jesse Flynn Dec 2010

Elucidating Functional Roles For Myogenin In Adult Skeletal Muscle Metabolism, Exercise Capacity, And Regeneration, Jesse Flynn

UT GSBS Dissertations and Theses (Open Access)

The four basic helix-loop-helix myogenic transcription factors, myogenin, Myf5, MRF4, and MyoD are critical for embryonic skeletal muscle development. Myogenin is necessary for the terminal differentiation of myoblasts into myofibers during embryogenesis, but little is known about the roles played by myogenin in adult skeletal muscle function and metabolism. Furthermore, while metabolism is a well-studied physiological process, how it is regulated at the transcriptional level remains poorly understood. In this study, my aim was to determine the function of myogenin in adult skeletal muscle metabolism, exercise capacity, and regeneration. To investigate this, I utilized a mouse strain harboring the Myogflox ...


Agrobacterium Virb10 Contributions To Type Iv Substrate Secretion, T-Pilus Biogenesis, And Outer Membrane Pore Formation, Isaac Garza Dec 2010

Agrobacterium Virb10 Contributions To Type Iv Substrate Secretion, T-Pilus Biogenesis, And Outer Membrane Pore Formation, Isaac Garza

UT GSBS Dissertations and Theses (Open Access)

The VirB/D4 type IV secretion system (T4SS) of Agrobacterium tumefaciens functions to transfer substrates to infected plant cells through assembly of a translocation channel and a surface structure termed a T-pilus. This thesis is focused on identifying contributions of VirB10 to substrate transfer and T-pilus formation through a mutational analysis. VirB10 is a bitopic protein with several domains, including a: (i) cytoplasmic N-terminus, (ii) single transmembrane (TM) α-helix, (iii) proline-rich region (PRR), and (iv) large C-terminal modified β-barrel. I introduced cysteine insertion and substitution mutations throughout the length of VirB10 in order to: (i) test a predicted transmembrane topology ...


Dynamic Remodeling Of The Stressed Heart: Role Of Protein Degradation Pathways, Deborah Vela Dec 2010

Dynamic Remodeling Of The Stressed Heart: Role Of Protein Degradation Pathways, Deborah Vela

UT GSBS Dissertations and Theses (Open Access)

The heart is a remarkable organ. In order to maintain its function, it remodels in response to a variety of environmental stresses, including pressure overload, volume overload, mechanical or pharmacological unloading and hormonal or metabolic disturbances. All these responses are linked to the inherent capacity of the heart to rebuild itself. Particularly, cardiac pressure overload activates signaling pathways of both protein synthesis and degradation. While much is known about regulators of protein synthesis, little is known about regulators of protein degradation in hypertrophy. The ubiquitin-proteasome system (UPS) selectively degrades unused and abnormal intracellular proteins. I speculated that the UPS may ...


Artemis Interacts With The Cul4a Ubiquitin E3 Ligase Complex And Regulates The Cell Cycle Progression, Yiyi Yan Aug 2010

Artemis Interacts With The Cul4a Ubiquitin E3 Ligase Complex And Regulates The Cell Cycle Progression, Yiyi Yan

UT GSBS Dissertations and Theses (Open Access)

Artemis, a member of the SNM1 gene family, is one of the six known components of the non-homologous end joining pathway. It is a multifunctional phospho-protein that has been shown to be modified by the phosphatidylinositol 3-kinases (PIKs) DNA-PKcs, ATM and ATR in response to a variety of cellular stresses. Artemis has important roles in V(D)J recombination, DNA double strand breaks repair and damage-induced cell-cycle checkpoint regulation. The detailed mechanism by which Artemis mediates its functions in these cellular pathways needs to be further elucidated. My work presented here demonstrates a new function for Artemis in cell cycle ...


Role And Regulation Of Epha2 In Pancreatic Cancer, Pavel A. Levin Aug 2010

Role And Regulation Of Epha2 In Pancreatic Cancer, Pavel A. Levin

UT GSBS Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cancer cause of death in the US. Gemcitabine is the first-line therapy for this disease, but unfortunately it shows only very modest benefit. The focus of the current study was to investigate the role and regulation of EphA2, a receptor tyrosine kinase expressed in PDAC, to further understand this disease and identify new therapeutic targets.

The role of EphA2 was determined in PDAC by siRNA mediated silencing. In combination with gemcitabine, silencing of EphA2 caused a dramatic increase in apoptosis even in highly resistant cells in vitro. Furthermore, EphA2 silencing was found ...


Specific, Reversible Cytostatic Protection Of Normal Cells Against Negative Effects Of Chemotherapy, Benjamin B. Mull Aug 2010

Specific, Reversible Cytostatic Protection Of Normal Cells Against Negative Effects Of Chemotherapy, Benjamin B. Mull

UT GSBS Dissertations and Theses (Open Access)

Chemotherapy is a common and effective method to treat many forms of cancer. However, treatment of cancer with chemotherapy has severe side effects which often limit the doses of therapy administered. Because some cancer chemotherapeutics target proliferating cells and tissues, all dividing cells, whether normal or tumor, are affected. Cell culture studies have demonstrated that UCN-01 is able to reversibly and selectively arrest normal dividing cells; tumor cells lines do not undergo this temporary arrest. Following UCN-01 treatment, normal cells displayed a 50-fold increase in IC50 for camptothecin; tumor cells showed no such increased tolerance.

We have examined the response ...


Preeclampsia, Autoimmunity And The At1 Receptor, Roxanna A. Irani May 2010

Preeclampsia, Autoimmunity And The At1 Receptor, Roxanna A. Irani

UT GSBS Dissertations and Theses (Open Access)

Preeclampsia (PE) is a disease of late pregnancy characterized by maternal hypertension and proteinuria. It is associated with preterm delivery and significant perinatal morbidity and mortality. Despite affecting ~7% of first pregnancies, there is no effective screening method to identify women at risk, nor is there a definitive treatment other than delivery of the baby and placenta. Though the pathogenesis of PE remains unclear, an imbalance in the renin-angiotensin and immune systems are thought to be major contributors. Bridging these two concepts, it has recently been shown that women with PE harbor specific autoantibodies: the angiotensin II type 1 receptor ...


A New Tumor Suppressor Gene Candidate Regulated By The Non-Coding Rna Pca3 In Human Prostate Cancer, Alessandro K. Lee May 2010

A New Tumor Suppressor Gene Candidate Regulated By The Non-Coding Rna Pca3 In Human Prostate Cancer, Alessandro K. Lee

UT GSBS Dissertations and Theses (Open Access)

Prostate cancer is the second leading cause of cancer-related death and the most common non-skin cancer in men in the USA. Considerable advancements in the practice of medicine have allowed a significant improvement in the diagnosis and treatment of this disease and, in recent years, both incidence and mortality rates have been slightly declining. However, it is still estimated that 1 man in 6 will be diagnosed with prostate cancer during his lifetime, and 1 man in 35 will die of the disease.

In order to identify novel strategies and effective therapeutic approaches in the fight against prostate cancer, it ...


Host-Pathogen Interactions Of Secreted And Surface Staphylococcus Aureus Factors, Vanessa Vazquez May 2010

Host-Pathogen Interactions Of Secreted And Surface Staphylococcus Aureus Factors, Vanessa Vazquez

UT GSBS Dissertations and Theses (Open Access)

Staphylococcus aureus is an opportunistic bacterial pathogen that can infect humans and other species. It utilizes an arsenal of virulence factors to cause disease, including secreted and cell wall anchored factors. Secreted toxins attack host cells, and pore-forming toxins destroy target cells by causing cell lysis. S. aureus uses cell-surface adhesins to attach to host molecules thereby facilitating host colonization. The Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs) are a family of cell-wall anchored proteins that target molecules like fibronectin and fibrinogen. The Serine-aspartate repeat (Sdr) proteins are a subset of staphylococcal MSCRAMMs that share similar domain organization. Interestingly ...


Ampa Receptor Allosterism: Measurement Of The Conformational Changes In The Ligand Binding Domain Of A Functional Receptor, Jennifer Gonzalez-Mcgehee May 2010

Ampa Receptor Allosterism: Measurement Of The Conformational Changes In The Ligand Binding Domain Of A Functional Receptor, Jennifer Gonzalez-Mcgehee

UT GSBS Dissertations and Theses (Open Access)

Ionotropic glutamate receptors are important excitatory neurotransmitter receptors in the mammalian central nervous system that have been implicated in a number of neuropathologies such as epilepsy, ischemia, and amyotrophic lateral sclerosis. Glutamate binding to an extracellular ligand binding domain initiates a series of structural changes that leads to the formation of a cation selective transmembrane channel, which consequently closes due to desensitization of the receptor. The crystal structures of the AMPA subtype of the glutamate receptor have been particularly useful in providing initial insight into the conformational changes in the ligand binding domain; however, these structures are limited by crystallographic ...


Developmental Changes In The Structure And Composition Of The Postsynaptic Density, Matthew T. Swulius May 2010

Developmental Changes In The Structure And Composition Of The Postsynaptic Density, Matthew T. Swulius

UT GSBS Dissertations and Theses (Open Access)

The development of the brain and its underlying circuitry is dependent on the formation of trillions of chemical synapses, which are highly specialized contacts that regulate the flow of information from one neuron to the next. It is through these synaptic connections that neurons wire together into networks capable of performing specific tasks, and activity-dependent changes in their structural and physiological state is one way that the brain is thought to adapt and store information. At the ultrastructural level, developmental and activity-dependent changes in the size and shape of dendritic spines have been well documented, and it is widely believed ...


The Ubiquitin Ligase Ube4b Is Required For Efficient Epidermal Growth Factor Receptor Degradation, Natalie Sirisaengtaksin May 2010

The Ubiquitin Ligase Ube4b Is Required For Efficient Epidermal Growth Factor Receptor Degradation, Natalie Sirisaengtaksin

UT GSBS Dissertations and Theses (Open Access)

The length of time that integral membrane proteins reside on the plasma membrane is regulated by endocytosis, a process that can inactivate these proteins by removing them from the membrane and may ultimately result in their degradation. Proteins are internalized and pass through multiple distinct intracellular compartments where targeting decisions determine their fate. Membrane proteins initially enter early endosomes, and subsequently late endosomes/multivesicular bodies (MVBs), before being degraded in the lysosome. The MVB is a subset of late endosomes characterized by the appearance of small vesicles in its luminal compartment. These vesicles contain cargo proteins sorted from the limiting ...


Xenoestrogen-Specific Mechanisms Of Developmental Reprogramming Correlate With Gene Expression And Tumor Development, Kristen L. Greathouse May 2010

Xenoestrogen-Specific Mechanisms Of Developmental Reprogramming Correlate With Gene Expression And Tumor Development, Kristen L. Greathouse

UT GSBS Dissertations and Theses (Open Access)

Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental reprogramming. We have shown that neonatal exposure to the xenoestrogen diethylstilbestrol (DES) can developmentally reprogram the reproductive tract in genetically susceptible Eker rats giving rise to complete penetrance of uterine leiomyoma. Based on this, we hypothesized that xenoestrogens, including genistein (GEN) and bisphenol A (BPA), reprogram estrogen-responsive gene expression in the myometrium and promote the development of uterine leiomyoma. We proposed the mechanism that is responsible for the developmental reprogramming of gene expression was through ...


The Role Of A2b Adenosine Receptor Signaling In Adenosine Dependent Lung Disease, Yang Zhou May 2010

The Role Of A2b Adenosine Receptor Signaling In Adenosine Dependent Lung Disease, Yang Zhou

UT GSBS Dissertations and Theses (Open Access)

Chronic lung diseases and acute lung injuries are two distinctive pulmonary disorders that result in significant morbidity and mortality. Adenosine is a signaling nucleoside generated in response to injury and can serve both protective and destructive functions in tissues and cells through interaction with four G-protein coupled adenosine receptors: A1R, A2AR, A2BR, and A3R. However, the relationship between these factors is poorly understood. Recent findings suggest the A2BR has been implicated in the regulation of both chronic lung disease and acute lung injury. The work presented in this dissertation utilized the adenosine deaminase-deficient mouse model and the bleomycin-induced pulmonary injury ...