Digital Commons Network^™

Is P53 A Target Of Hpv-18 E6 In The Viral Life Cycle?, Eun-Young Kho

All ETDs from UAB

The large family of human papillomaviruses (HPVs) infects the cutaneous or mucosal epithelia causing benign hyper proliferative diseases. Infections by the high-risk (HR) HPV genotypes in the anogenital tracts can progress to high grade lesions and cancers in men and women. Because the viral productive program requires squamous differentiation of epithelia, HPV encodes oncoproteins that recondition the differentiated cells that have withdrawn from the cell cycle to support viral DNA amplification. The HR HPV E6 and E7 oncogenes are selectively expressed in cervical carcinomas and are necessary to maintain the malignant state. In vitro, constitutive expression of the HR HPV …

Regulation Of Cell Death By Autophagy In Glial Neoplasms, Latika R. Kohli

All ETDs from UAB

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive malignancies of the peripheral nervous system. The majority of MPNSTs arise in patients of the autosomal dominant genetic disorder neurofibromatosis type I (NF1) although they also arise sporadically. In the absence of any effective chemotherapeutic options and with surgery constituting the mainstay of treatment, MPNST patients face an extremely poor prognosis. This underscores the need to develop novel therapeutic strategies against this tumor type. It is well accepted that the crosstalk between autophagy and apoptosis can be exploited to derive maximal therapeutic benefit, especially through combinatorial therapies. However, this interaction is extremely …

The Effects Of Psychological Stress, Depressive Symptoms, And Cortisol On Body Mass And Central Adiposity In 10-To12-Year-Old Children, Hong-Thuy Lam

All ETDs from UAB

The percentage of children with elevated body mass and central adiposity has tripled in the U.S. over the past thirty years. While physical factors, such as decreased physical activity and poor nutrition, have been noted to influence elevated body mass and central adiposity in school-aged children, less is known about psychological factors, such as psychological stress and depressive symptoms, especially in 10-to12-year-old children. Further, it has been suggested that cortisol, a biomarker of psychological stress, plays a role in the underlying mechanism that links psychological stress and depressive symptoms to increased body mass and central adiposity, but this has not …

Mechanism Of Nfi-C Functionin During Tooth Root Formation, Ejvis Lamani

All ETDs from UAB

Currently, very little is known regarding tissue-specific gene regulation during the later stages of tooth development, especially those associated with root formation. Re-cent studies have identified nuclear factor I-C (NFI-C) as a critical factor for root for-mation in mammals. NFI-C functions as a cellular transcription factor and adenovirus DNA replication factor. Its role in root formation first became evident when Nfi-c null mice were shown to lack molar roots. A similar phenotype of incomplete or absent root formation is observed in patients with the autosomal dominant disease Radicular Dentin Dysplasia (RDD; MIM125400) also known as Rootless Teeth or Dentin Dysplasia …

Development Of An Adenoviral Vector Platform For Selective Gene Delivery To Neurons, Travis Benjamin Lewis

All ETDs from UAB

Parkinson disease (PD) is a devastating movement disorder affecting between 500,000 and 1,000,000 individuals in the United States alone, and for which there is currently no cure. Therapies such as dopamine replacement help initially, but with disease progression these lose efficacy and do not alter the underlying degenerative process. Gene therapy is the delivery of exogenous genetic material to correct an underlying disorder. A major advantage of this approach is the ability to distribute potent therapies to specific targets over an extended duration, properties necessary for the treatment of progressive degenerative diseases such as PD. A number of clinical trials …

Design Of An Underground Storage Tank Involving Water Collection For Water Reuse To Irrigate The Campus Green Area Of The Uab Campus, Zhuo Li

All ETDs from UAB

The UAB Campus Recreation Center is located in the Birmingham city block whose boundaries are University Blvd., 10th Avenue South, 14th Street South, and 16th Street South. The water supply of the UAB Campus Recreation Center is based on a natural underground water source, which is use such needs as pool water. The underground water is continuously pumped from its foundation in order to avoid flooding the basement of the Recreation Center. As a result, in addition to the water usage of the Recreation Center, the additional water pumped underground could be utilized to irrigate the campus green area. A …

The Role Of The Mirror Neuron System In Mental State Attribution In Autism: An Fmri Study, Lauren E. Libero

All ETDs from UAB

The ability to interpret others' intentions based on their actions is a vital skill that helps us infer and understand their thoughts and plans. However, individuals with autism have been found to have difficulty in attributing intentions to others (Baron-Cohen et al., 1985; Baron-Cohen, 1995; Happe & Frith, 1996; Williams et al., 2001). The present study investigated the neural mechanisms of inferring intentions from actions in high-functioning adults with autism spectrum disorders (ASD) and typically developing control participants. fMRI data were acquired while participants made judgments about the means (how an action is performed) and intentions (why an action is …

Regulation Of P27kip1 By Trip6 And Its Implications In Cancer Progression, Victor T G Lin

All ETDs from UAB

TRIP6 is a focal adhesion molecule that functions as an adaptor protein to mediate diverse cellular functions, including motility and antiapoptotic signaling, through a wide variety of protein-protein interactions. We were able to characterize a novel interaction between TRIP6 and p27KIP1, a CDK inhibitor which can both suppress and promote tumorigenesis, depending on its regulation. TRIP6 expression specifically promotes the AKT-mediated phosphorylation of p27KIP1 at T157, which leads to its cytosolic retention, and accelerates the protein turnover rate of p27KIP1. We also found that phosphorylation of T157 by itself promotes cell motility and can be linked to the formation of …

Multiscale Modeling Of The Mouse Femur, Shannon Lisenbee

All ETDs from UAB

This paper seeks to advance the knowledge base for bones and how they respond to mechanical stimuli through the use of multiscale modeling. First, a simple but effective approach for segmenting bone from computed tomography images using MATLAB is presented. Using edge detection and gradient operators to identify areas of bone within an image allows for much more accurate and consistent bone segmentation than simpler techniques like thresholding. This technique is applied to the femur of a female mouse for use in further modeling and testing. Next a representative volume element (RVE) for lamellar cortical bone is created based on …

Regulation Of Membrane Traffic By The Big2 Member Of Guanine Nucleotide Exchange Factors, Jason Lowery

All ETDs from UAB

Vesicular transport is an essential cellular process that facilitates the movement of molecules within a cell. The importance of vesicular transport is highlighted by numerous human diseases that result from mutations affecting protein trafficking. The Brefeldin A-inhibited guanine nucleotide exchange factor 2 (BIG2) has emerged as a key regulator of protein trafficking within the late secretory pathway, between the trans-Golgi Network (TGN) and endosomal compartments and within the recycling endosomal pathway. Mutations in BIG2 lead to Autosomal Recessive Periventricular Heterotopia with Microcephly (ARPHM), a disorder characterized by severe brain malformations. BIG2 stimulates nucleotide exchange of GDP for GTP on ADP-ribosylation …

Regulation Of Alpha-Synuclein Accumulation By The Autophagy-Lysosome Pathway In A Preclinical Model Of Parkinson Disease, Leandra Rosa Mangieri

All ETDs from UAB

Finding novel therapeutics that delay or halt the progression of Parkinson Disease (PD) is key to providing symptomatic relief of debilitating symptoms. A defining pathological feature of PD is characterized by the formation of Lewy bodies, intraneuronal inclusions comprised mainly of α-synuclein (ASYN) (4). Vacuolar ATPase (V-ATPase), an enzyme complex comprised of two multi-subunit-containing domains, critically regulates the acidification of vesicles such as lysosomes and thus proper function of the autophagy-lysosome pathway (ALP), which is critical for the degradation of ASYN. Compromises to V-ATPase have been shown to negatively affect lysosome function and its ability to clear toxic forms of …

The Effects Of Venlafaxine On Functional Recovery Following Spinal Cord Injury, Don E. Mccormick

All ETDs from UAB

Spinal cord injury (SCI) can significantly alter a person's physical and psychological health over their lifetime. Depression in persons with SCI is often treated with antidepressants which alter serotonergic and adrenergic signaling, both regulators of plasticity. However, the effects of antidepressants functional recovery after SCI have never been evaluated. Therefore, we hypothesize that antidepressant therapy would alter functional recovery and neuropathic pain behaviors in a SCI rodent model. The aim of this study was to evaluate the effects of venlafaxine (VEN) administration on functional recovery in the rehabilitation setting using a SCI rodent model. Adult male Sprague-Dawley rats received a …

The Effects Of Direct To Consumer Advertising On Healthcare Utilization Among Medicaid Children With Asthma, Luceta C. Mcroy

All ETDs from UAB

National guidelines recommend treatment of asthma with preventive long term medication, but adherence remains low, resulting in high healthcare utilization among those affected by the chronic disease. The increase in DTCA since the easing of restrictions by the FDA in 1997 has prompted much debate on the effects of the DTCA, with critics arguing that it is harmful while proponents see many benefits such as increased medication adherence. This study examines the impact of DTCA on healthcare utilization and asthma medication use by combining Medicaid administrative data and a national advertising data set on asthma medication from 1999 to 2002. …

Genome-Wide Dna Methylation Changes During Breast Tumorigenesis, Natalie E. Mitchell

All ETDs from UAB

Neoplastic reprogramming generates cancerous cells from normal derivatives, enabling researchers to create a model of the early stages of oncogenesis and analyze molecular changes in real-time. Aberrations in DNA methylation are considered a major mechanism contributing to the acquisition and maintenance of a cancerous phenotype; however, little research exists regarding gene-specific changes in DNA methylation during the transition from a normal to neoplastic cell. Human mammary epithelial cells (HMECs) underwent neoplastic transformation through the addition of three defined genetic elements to generate one line of semi-transformed, pre-malignant cells (SHMECs) and two separate lines of fully transformed, malignant cells (THMECs). We …

Socioeconomic Patterning Of Obesity Among African American Women In The Jackson Heart Study, Tonya Moore

All ETDs from UAB

Objectives: The purpose of this study was to expand upon what has been observed in literature about obesity and its ties to socioeconomic status (SES) among African American Women (AAW) participants of the Jackson Heart Study (JHS). Methods: This secondary analysis was a sub-study of the JHS and focused on four SES variables: education, income, occupation and wealth; and five outcome variables: body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Two analytic samples were created in order to examine data collected during Exam 1 (2000-2004) and Exam 2 (2005-2008). …

An Information Theoretical Modeling And Analysis Of Systems, Bunyamin Ozaydin

All ETDs from UAB

The growth of the service industry also comes with problems and complications because of its inherent error proneness. As the complexity of systems increases, whether the system of interest is a service product or a natural phenomenon, it only proves that there is always a need for improved modeling approaches. In this study, we approach systems from an information theoretical perspective. More specifically, we model systems by noisy communication channels and analyze them by a structure of relationships whose elements are commonly used analysis tools in science and engineering. We call this modeling approach and the structure of relationships it …

Using Mouse Models To Investigate Ciliopathies, Raymond Carl Pasek

All ETDs from UAB

Cilia and flagella are microtubule based organelles found on nearly every cell type in the mammalian body. Flagella have an essential role in sperm locomotion and reproduction, while motile cilia have a known role in fluid movement in the brain, lungs, and portions of the female reproductive tract. While the role of most primary cilia remained unknown for decades, they are now recognized as being essential to mammalian development, renal homeostasis, and satiety, just to name a few. Because of their widespread presence and importance, dysfunction of cilia and flagella can lead to a variety of human diseases, collectively referred …

Aga Khan University, Report 2012, Aga Khan University

The Aga Khan University Reports Archives

• Chancellor’s Message
• Chairman’s Message
• From the President
• Reflections of a Trustee
• The AKU World
• Overview: Shaping the Future
• Innovative Solutions in Unlikely Places
• Strong Mothers + Healthy Children = A Better World
• Education for Impact
• Acting on Our Values, Leading the Way
• In the Spotlight
• Executive Team
• University Governance
• University Numbers
• Financial Highlights
• Contact Us
• AKDN

Targeting Mitochondrial Function In Diabetic Nephropathy, Colin Reily

All ETDs from UAB

TARGETING MITOCHONDRIAL FUNCTION IN DIABETIC NEPHROPATHY The incidence of diabetes has increased to epidemic proportions over the last 50 years, due to a complex interaction of lifestyle and dietary factors. Changes in physical activity, caloric intake, and the composition of foods consumed over the last century are thought to interact with metabolic syndrome prone subpopulations leading ultimately to diabetes. It is widely accepted that chronic hyperglycemia in the blood characterizes the diabetic condition. Since the discovery of insulin therapy in the first half of the 20th century, diabetics have extended their lifespan considerably, but at the cost of increased morbitity …

Cystine/Glutamate Transporters As Prognostic & Therapeutic Markers Of Primary Brain Tumors, Stephanie Marie Robert

All ETDs from UAB

Glioblastoma multiforme (GBM) are the most prevalent and aggressive malignant brain tumors. Current treatment - a combination of radiation, chemotherapy and resection - has limited effectiveness and offers poor prognosis. In this study, we examined the roles of system xc- (SXC) and excitatory amino acid transporters (EAATs), which transport the amino acids cystine and glutamate, on tumor growth, neurotoxicity, and peritumoral seizure activity. Tissue micro-arrays from 45 patients were examined by immuno-histochemistry, comparing tumor-bearing tissue and adjacent normal brain. Using a novel flank tumor propagation technique, we chose 3 glioma samples with varying SXC and EAAT expression levels to study …

Connexin 43 Remodeling Contribute To Slowed Conduction Velocity In An Irreversible Arrhythmogenic Canine Model Of Non-Ischemic Heart Failure, Jiajie Yan

All ETDs from UAB

Heart failure is associated with a high mortality due to ventricular tachycardia leading to ventricular fibrillation that could arise from impaired conduction velocity. Myocardial conduction relies on intercellular coupling maintained primarily by the gap junction protein connexin43. The objective of this research is to assess the correlation between connexin43 remodeling and altered conduction in our novel irreversible and arrhythmogenic HF large animal model that mimics human heart failure. A novel heart failure canine model was established with combined strategy of creating aortic insufficiency and aortic constriction. We measured conduction velocity in heart failure and control left ventricular epicardium (n=5, 5) …

Fcrl5 Exerts Binary And Compartment-Specific Influence On Innate-Like B Cell Receptor Signaling, Zilu Zhu

All ETDs from UAB

Innate-like splenic marginal zone (MZ) and peritoneal cavity (PEC)-derived B1 B lymphocytes are the major contributors to primary humoral responses and play an important role in connecting innate and adaptive immunity, but are known to significantly differ in their B cell receptor (BCR) signaling characteristics. In mice, FCRL5 is discretely expressed by innate-like MZ and B1 B cells and is furthermore equipped with cytoplasmic ITAM-like and ITIM elements, suggesting diverse signaling potential for it. Our results showed that FCRL5 markedly inhibited BCR-mediated activation in MZ B cells, but not in PEC B1 B cells. To characterize its signaling function, a …

Clinical Evaluation Of Treatment Of White Spot Lesions With Icon, Candace A. Cronan

All ETDs from UAB

Introduction: Despite an increased awareness by clinicians and their attempt to aid patients in the prevention of white spot lesions, enamel demineralization continues to be a problem associated with orthodontic treatment. Current treatment options for these unaesthetic scars on the teeth range from conservative options for remineralization such as the use of fluoride and CPP-ACP to more aggressive treatment involving loss of tooth structure with microabrasion or restorations. An innovative option for treatment has recently been introduced in the form of the infiltrant resin, Icon. Icon infiltration is a minimally invasive procedure performed by a dentist that is claimed to …

Analysis Of Ergothioneine Production In Mycobacterium Tuberculosis, Loni Ann Guidry

All ETDs from UAB

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, currently infects more than two billion people worldwide. Mtb is a highly adaptable pathogen, capable of modifying its metabolism in response to its environment. We previously showed that Mtb WhiB3 is a redox-responsive regulator of core intermediary metabolism and lipid anabolism through which it maintains redox homeostasis. In this work, through the use of metabolomic analysis and a novel radioactive thin layer chromatography assay, we discovered that WhiB3 regulates the production of the intracellular thiol ergothioneine (ergo) when using immunomodulatory lipid precursors as the major carbon source. Our results suggest that this …

The Role Of Histone Methylation In The Medial Temporal Lobe During Long-Term Memory Formation, Swati Gupta

All ETDs from UAB

Several studies have established the importance of epigenetic regulation of gene transcription in the brain during memory consolidation. Epigenetic mechanisms involve modifying the DNA or the associated histone proteins to determine the transcriptional outcome of a gene. The work encompassed in this dissertation serves as an initial investigation for the role of histone lysine methylation mechanisms in regulating gene activation and suppression in the medial temporal lobe that includes entorhinal cortex (EC), hippocampus, and amygdala during memory consolidation. To this end, we found that di-methylation of histone H3 at lysine 9 (H3K9me2) which promotes gene suppression was specific to associative …

The Role Of Vpr-1 Msp Signaling In C. Elegans, Sung Min Han

All ETDs from UAB

In C. elegans, the major sperm protein (MSP) is the most abundant protein in sperm and functions as an intracellular cytoskeleton protein and a secreted extracellular signal that induces oocyte maturation and sheath contraction. Evolutionarily, MSP domain-containing proteins originate from the VAPs (VAMP/synaptobrevin-associated proteins), which comprise a highly conserved protein family with an MSP domain at the N-terminus and a transmembrane domain at the C-terminus. I have been studying the signaling role of VAP MSP domains using the C. elegans model system. In collaboration with Hugo Bellen's lab at Baylor College of Medicine, we have shown that C. elegans, Drosophila, …

Effect Of Childhood Obesity On Risk Of Pelvic Bone Fracture In Simulated Sideways Fall, Min-Heng Hsieh

All ETDs from UAB

Since the number of obese children in the U.S. has been increasing, the question arises whether obese children could be at higher or lower risk compared to nonobese children. The objective of this research was to investigate the risk of pediatric pelvic bone fracture in sideways falls using computational modeling and simulation considering various levels of obesity. Two sets of models were developed and tested. The first set was body component models. Several 10-year-old pelvis-femur complex models were developed. The models included biological soft tissue layers to reflect various levels of obesity, and they were validated against published experimental data. …

Model System Using Controlled Receptor Expression For Molecular Ultrasound Imaging Applications, Reshu Saini

All ETDs from UAB

Ultrasound is a noninvasive, inexpensive imaging modality used to characterize biological tissues. Targeted contrast-enhanced ultrasound imaging is an emerging preclinical strategy which uses contrast agents for characterization of biological processes on a molecular level. These microbubble agents are lipid shelled micron-sized particles that have the capability to be coated with ligands such as antibodies or small peptides in order to bind to their target receptors. Molecular ultrasound imaging, using these targeted contrast agents, allows for a quantitative assessment of molecular targets with a high sensitivity. Although this technique is in preclinical research, further advances in contrast agent design and potential …

Innate Immune Mechanisms Against The Atypical Fungal Pathogen Pneumocystis Murina, Michael Paul Nelson

All ETDs from UAB

Pneumonia caused by the fungal pathogen Pneumocystis continues to be the leading cause of morbidity and mortality in AIDS patients. In addition, there are a number of other non-HIV-associated diseases that render an individual susceptible to Pneumocystis infection, including chronic obstructive pulmonary disease. Innate immune mechanisms are important for controlling Pneumocystis lung infection. As alveolar macrophages serve the front lines of lung host defense, our goal was to elucidate their responses during lung Pneumocystis infection. Here, we established a role for Src family kinases in the lung immune response to Pneumocystis, which uncovered a role for alternatively activated alveolar macrophages. …

Electrophysiological Investigation Of Rabbit Retinal Ganglion Cells, Przemyslaw Nowak

All ETDs from UAB

The retina is the first stage of the visual system, responsible for transducing light into the neural signal and for subsequent processing of this signal before sending it to the higher visual centers in the brain. The output to the higher visual centers is mediated by retinal ganglion cells, which not only relay the signal, but also substantially contribute to its processing. Depending on what computations they perform, they are subdivided into different types. These cells have been extensively studied in various spices, one prominent example being the rabbit. In rabbits, one characteristic type comprises On-Off directionally selective retinal ganglion …