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Development Of An Adenoviral Vector Platform For Selective Gene Delivery To Neurons, Travis Benjamin Lewis Jan 2012

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 …


The Effect Of Environmental Ozone Exposure On The Postnatal Lung, Katherine Leah Tuggle Stringer Jan 2012

The Effect Of Environmental Ozone Exposure On The Postnatal Lung, Katherine Leah Tuggle Stringer

All ETDs from UAB

In the U.S., approximately 37 million children reside in geographic locales that experience unhealthy ozone levels. This population is of great concern as they are undergoing active lung growth and cellular differentiation which may alter their susceptibility to inhaled toxicants. Epidemiological and animal studies indicate that early life ozone exposure results in altered lung development, potentially facilitating predisposition to chronic pulmonary conditions in adulthood. The goal of this dissertation was to evaluate short and long-term effects of ozone exposure in the developing lung. The first study evaluated acute effects of ozone exposure in the postnatal and adult lung. The results …


Three Dimensional Comparison Of Facial Morphology Of A Caucasian American Population And A Native Brazilian Population, William N. Turner Jan 2012

Three Dimensional Comparison Of Facial Morphology Of A Caucasian American Population And A Native Brazilian Population, William N. Turner

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The aim of this study was to assess the use of 3-dimensional facial averages in determining facial morphologic differences in a Caucasian North American population and a native Brazilian population. Methods and Materials: Three-dimensional images were acquired through a commercially available stereo-photogrammetric camera system (The 3dMDfaceTM system). A total of 200 images from two population groups (Caucasian American and Native Brazilian) were taken. Each image was acquired as a facial mesh and orientated along a triangulated axis. All facial images were overlaid and superimposed, using Rapid Form 6 software to create a composite facial average of one man and one …


Evaluation Of The Association Of Low-Level Prenatal Blood Lead Exposure And Auditory Brainstem Response Among Infants, Timothy A. Dignam Jan 2012

Evaluation Of The Association Of Low-Level Prenatal Blood Lead Exposure And Auditory Brainstem Response Among Infants, Timothy A. Dignam

All ETDs from UAB

Hearing loss is one of the most common major abnormalities present among infants. Two to four infants per 1,000 are born in the United States with severe-to-profound newborn hearing loss (Chu 2003). Undetected, hearing loss delays speech, language, and cognitive development. Numerous studies have shown that prenatal lead exposure is associated with a variety of neurobehavioral and electrophysiological abnormalities (Abbate 1995, Bellinger 2004, Koller 2004). Studies focusing on hearing have primarily described pediatric cases or occupationally exposed adults where blood lead levels (BLLs) are much higher than currently seen in the United States (Otto 1985; Bleecker 2003; Schwartz 1987). Hearing …


Influences Of Habitual Diet, Ethnicity, And Age On Circulating Total Ghrelin, Amy Ellis Jan 2012

Influences Of Habitual Diet, Ethnicity, And Age On Circulating Total Ghrelin, Amy Ellis

All ETDs from UAB

Ghrelin is a hormone known to stimulate appetite and food intake. Although certain macronutrients differentially suppress ghrelin on an acute basis, it is unknown whether habitual macronutrient intake affects circulating ghrelin. Thus, the first experimental aim was to determine whether 8-week habituation to diets differing in carbohydrate or fat would affect fasting ghrelin or ghrelin response to a mixed meal. Recent reports also suggest that ghrelin regulation may relate to propensity for obesity. Obesity is more prevalent among AA compared to EA, with the highest rates among AA females. This disparity becomes apparent before puberty, and childhood obesity tends to …


Proteomic Clues To The Pathogenesis Of Alexander Disease, Daniel L. Flint Jan 2012

Proteomic Clues To The Pathogenesis Of Alexander Disease, Daniel L. Flint

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Since the initial report identifying mutations in GFAP as the primary genetic defect in the astrogliopathy Alexander Disease (AxD) much progress has been made in elucidating the molecular details underpinning the pathogenic role of mutant GFAP in astrocytes. In particular, data collected from mouse, fly, and cell culture models of AxD have isolated several prominent cellular changes that are associated with mutant GFAP expression including oxidative stress, proteasome inhibition, reduced expression of the astrocyte glutamate transporter GLT-1, and loss of neurons; these models have also successfully recapitulated the pathological hallmark of AxD--protein aggregates known as Rosenthal fibers (RFs). To date, …


A Histologic And Radiologic Analysis Of Bone Formation Under The Elevated Maxillary Sinus Using Venous Coagulum As The Sole Filling Material, Kathleen Ann Beaudry Jan 2012

A Histologic And Radiologic Analysis Of Bone Formation Under The Elevated Maxillary Sinus Using Venous Coagulum As The Sole Filling Material, Kathleen Ann Beaudry

All ETDs from UAB

Insufficient bone height is a common obstacle to placing dental implants in the posterior maxilla. Sinus lift procedures using various grafting materials have been shown to be a highly predictable way to increase bone height in the posterior maxilla (Jensen 1998). Given the wide range of materials that have proven successful in augmenting the sinus, the argument could be made that the presence of graft is not critical. Instead, the creation and maintenance of space, provided by two implants, along with the osteoinductive properties of the membrane, the periosteum, and growth factors provided by a blood clot are the only …


Full Scale Calcium Bromide Injection With Subsequent Mercury Oxidation And Removal Within Wet Flue Gas Desulphurization System: Experience At A 700 Mw Coal-Fired Power Facility, Mark Simpson Berry Jan 2012

Full Scale Calcium Bromide Injection With Subsequent Mercury Oxidation And Removal Within Wet Flue Gas Desulphurization System: Experience At A 700 Mw Coal-Fired Power Facility, Mark Simpson Berry

All ETDs from UAB

The Environmental Protection Agency promulgated the Mercury and Air Toxics Standards rule, which requires that existing power plants reduce mercury emissions to meet an emission rate of 1.2 lb/TBtu on a 30-day rolling average and that new plants meet a 0.0002 lb/GWHr emission rate. This translates to mercury removals greater than 90% for existing units and greater than 99% for new units. Current state-of-the-art technology for the control of mercury emissions uses activated carbon injected upstream of a fabric filter, a costly proposition. For example, a fabric filter, if not already available, would require a $200M capital investment for a …


The Role Of Cd11c+ Cells In Response To Ozone, Jeffrey David Brand Jan 2012

The Role Of Cd11c+ Cells In Response To Ozone, Jeffrey David Brand

All ETDs from UAB

Environmental ozone exposure remains a major public health concern with over one-third of the United States population experiencing unhealthful levels. Epidemiological studies indicate exposure increases morbidity in those with pre-existing disease such as asthma, though the biological mechanisms underlying this phenomenon remain elusive. CD11c+ cells within the respiratory tract include dendritic cells (DCs), which are the most efficient antigen presenters and play major roles controlling immune responses. In addition, DCs are thought necessary for asthma pathogenesis and exacerbation. Therefore the link between ozone associated asthma morbidity may be DCs. We hypothesize ozone exposure may site specifically alter DC phenotypes, numbers, …


Three-Dimensional Magnetic Resonance Imaging Of The Natural Dentition, Ryan Jeffery Cox Jan 2012

Three-Dimensional Magnetic Resonance Imaging Of The Natural Dentition, Ryan Jeffery Cox

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The purpose of this study was to determine if ultra short echo time magnetic resonance imaging (UTE-MRI) technology could be used to image teeth in orthodontics. The objectives of this study were to determine the accuracy and resolution of UTE-MRI on dental morphology and its application to the field of orthodontics with respect to appliance affect on morphology. Teeth were collected from the Orthodontic clinic at the University of Alabama at Birmingham and the Institutional Review Board of the University of Alabama at Birmingham approved the study. High-resolution 3-Tesla UTE-MRI was preformed on sixty extracted human premolar teeth with fixed …


Mitochondrial Morphology And Function In Neuronal Cells Under Stress, Lonnie Schneider Jan 2012

Mitochondrial Morphology And Function In Neuronal Cells Under Stress, Lonnie Schneider

All ETDs from UAB

Neurodegenerative disease encompasses a wide range of conditions and pathologies that can manifest at any age depending on the etiology. A major factor in both early onset and age-related neurodegeneration is mitochondrial dysfunction. To investigate how mitochondrial bioenergetics is affected by cellular stress, we used an in vitro culture system to examine mitochondrial function in response to oxidative stress. We also studied an in vivo model of neuronal ceroid lipofuscinosis to determine the impact of deficient autophagy-lysosomal activity on mitochondrial morphology, composition and function. In vitro we found that retinoic acid-induced differentiation of dopaminergic neuroblastoma SH-SY5Y cells exhibited increased mitochondrial …


C-C-Motif Chemokine Receptor/Ligand Gene Variants And Their Associations With Hiv-1 Transmission And Pathogenesis, Liangyuan Hu Jan 2012

C-C-Motif Chemokine Receptor/Ligand Gene Variants And Their Associations With Hiv-1 Transmission And Pathogenesis, Liangyuan Hu

All ETDs from UAB

Host factors including genes and their variants are important to HIV-1 acquisition, transmission and disease progression. In particular, chemokine (C-C motif) receptors 2 and 5 genes (CCR2 and CCR5) have multiple variants of interest. We first investigated the impact of CCR2-CCR5 haplotypes on several outcomes among 567 HIV-1 discordant Zambian couples. HHF*2 homozygosity was associated with significantly lower VL in seroconverters (mean beta=-0.58 log10 P=0.027) and the HHD/HHE diplotype was associated with significantly higher VL in the seroconverters (mean beta=0.54, log10 P=0.014) adjusted for age and gender in multivariable model. HHD/HHE was associated with more rapid acquisition of infection by …


Is P53 A Target Of Hpv-18 E6 In The Viral Life Cycle?, Eun-Young Kho Jan 2012

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 …


Apolipoprotein E Mimetic Peptide Improves Hdl Functionality And Inhibits Atherosclerosis Progression In Mouse Models Of Atherosclerosis, Gaurav Nayyar Jan 2012

Apolipoprotein E Mimetic Peptide Improves Hdl Functionality And Inhibits Atherosclerosis Progression In Mouse Models Of Atherosclerosis, Gaurav Nayyar

All ETDs from UAB

Despite major advances in diagnosis and treatment, coronary artery disease (CAD) is still the number one cause of morbidity and mortality in United States. An ideal treatment for lipid-mediated inflammatory disorders would not only reduce plasma cholesterol dramatically but also improve high density lipoproteins (HDL) function. Apolipoprotein E (apo E), a protein component of HDL and very low density lipoprotein (VLDL), is necessary for the receptor mediated hepatic uptake of apolipoprotein-B (apo B) containing remnant lipoproteins and also possesses strong anti-inflammatory properties. We hypothesized that a synthetic dual domain apo E mimetic peptide, Ac-hE18A-NH2 (a 28-residue peptide) containing receptor binding …


Glutamate Release And Uptake At Cerebellar Synapses, Ming-Chi Tsai Jan 2012

Glutamate Release And Uptake At Cerebellar Synapses, Ming-Chi Tsai

All ETDs from UAB

Glutamate mediates excitatory synaptic transmission in the central nervous system (CNS). Regulation of glutamate release and uptake shapes the spatiotemporal dynamics of glutamate at and around synapses to influence information transfer between neural cells. This dissertation focuses on the modulation of glutamate release and uptake at excitatory synapses of cerebellar Purkinje cells (PC). In the first project we show that differential expression of PC glutamate transporters controls the amount of glutamate entering the extrasynaptic space, thereby influencing the excitatory responses in surrounding Bergmann glia. This work provides the first evidence that neuronal glutamate uptake affects glial glutamatergic signaling. In the …