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2008

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Regulation Of Tau Functions By Posttranslational Modifications Of Tau And Histone Deacetylase 6, Huiping Ding Jan 2008

Regulation Of Tau Functions By Posttranslational Modifications Of Tau And Histone Deacetylase 6, Huiping Ding

All ETDs from UAB

Alzheimer’s disease (AD), the most common neurodegenerative disease, is pathologically characterized by senile plaques composed of amyloid β peptide and neurofibrillary tangles composed of hyperphosphorylated and aberrantly cleaved microtubule-associated protein tau. Numerous studies have demonstrated the critical importance of tau in AD pathogenesis; however, the mechanisms involved in the regulation of tau functions by posttranslational modifications of tau and by other cellular factors need to be further elucidated. The first part of my study focused on how posttranslational modifications of tau, specifically, site-specific phosphorylation and C-terminal cleavage, regulate its physiological function in associating with cytoskeleton, binding to and stabilizing microtubules …

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High Field Functional Magnetic Resonance Imaging In The Awake, Behaving Primate: Cortical Networks Involved In Vergence Eye Movements, Matthew K. Ward Jan 2008

High Field Functional Magnetic Resonance Imaging In The Awake, Behaving Primate: Cortical Networks Involved In Vergence Eye Movements, Matthew K. Ward

All ETDs from UAB

Animals with eyes positioned towards the front of the head are capable of making saccadic and smooth pursuit eye movements to fixate an object at a given distance. These eye movements are conjugate (i.e. both eyes move the same amount in the same direction). To fixate objects at different distances, such animals are also capable of making vergence eye movements in which both eyes move the same amount in opposite directions i.e. disconjugately. While purely conjugate or vergence eye movements rarely occur in daily life, it is useful to study these types of eye movements separately due to the relative …

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A Dual-Action, Armed Replicating Adenovirus For The Treatment Of Bone Metastases Of Breast Cancer, James Joseph Cody Jan 2008

A Dual-Action, Armed Replicating Adenovirus For The Treatment Of Bone Metastases Of Breast Cancer, James Joseph Cody

All ETDs from UAB

Most patients with advanced breast cancer develop osteolytic bone metastases, which have numerous complications. Because current therapies are not curative, new treatments are needed. Conditionally replicating adenoviruses (CRAds) are anti-cancer agents designed to infect and lyse tumor cells. For increased efficacy, CRAds have been armed with therapeutic transgenes. Osteoprotegerin (OPG), an inhibitor of osteoclastic bone resorption, represents a promising candidate with which to arm a CRAd intended to treat osteolytic bone metastases. We hypothesize that a CRAd armed with OPG will inhibit breast cancer bone metastasis and reduce tumor burden in the bone by directly lysing tumor cells and by …

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Mesenchymal Stem Cell Interaction With Nanostructured Biomaterials For Orthopaedic Applications, William Charles Clem Jan 2008

Mesenchymal Stem Cell Interaction With Nanostructured Biomaterials For Orthopaedic Applications, William Charles Clem

All ETDs from UAB

Orthopaedic implants fail when bone loss around the anchoring region of the prosthesis causes the components to loosen. A revision surgery is needed to replace worn components, and bone grafting is often required to fill the void caused by osteolysis. A solution for the problem of osteolysis may be the improvement of wear resistance at the articulating surfaces by substituting materials with greater hardness. This dissertation describes two strategies for increasing the surface hardness of titanium alloy (Ti-6Al-4V) implants, without increasing surface roughness or compromising osseointegration. The first strategy utilizes microwave plasma to induce titanium nitride formation by nitrogen diffusion. …

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Thrombospondin Type-1 Repeats And Their Potential Role In Inhibiting Glioblastoma Angiogenesis, Joshua C. Anderson Jan 2008

Thrombospondin Type-1 Repeats And Their Potential Role In Inhibiting Glioblastoma Angiogenesis, Joshua C. Anderson

All ETDs from UAB

Thrombospondin-1 (TSP-1) is a 420 kilodalton homotrimeric protein; it is one of the first identified anti-angiogenic proteins found to be expressed in some normal tissues. Peptides derived from the type-1 repeat (TSR) domains of full length TSP-1 have been shown to have anti-angiogenic activity, and thus anti-tumor activity in some non-glioma tumor models. I hypothesized that peptides derived from the TSRs of TSP-1, such as ABT-510, could inhibit angiogenesis and thus malignant glioma tumor growth in vivo. I found that ABT-510 inhibited angiogenesis of the human brain microvascular endothelial cell (MvEC) in an in vitro tubulomorphogenesis assay. To determine the …

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Human Papillomavirus: Segregation And Replication, Luan D. Dao Jan 2008

Human Papillomavirus: Segregation And Replication, Luan D. Dao

All ETDs from UAB

Human papillomavirus are small DNA tumor viruses. The viral genome is a small circular double stranded DNA that replicates autonomously as an extrachromosomal plasmid. Occasionally infections by the high risk HPV viruses can lead to DNA integration and progression to cancer. How the HPV DNA is maintained and becomes established in the dividing host cells is not well understood. Additionally, as a double-stranded DNA virus it is likely that double-stranded DNA breaks in the viral genome, either from replication or random damage, will trigger a DNA repair response from the host cell. Such responses have been alternatively reported to be …

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Metabolism Of Neutrophil-Deprived Chlorinated Isoflavones, Tracy Lyn D'Alessandro Jan 2008

Metabolism Of Neutrophil-Deprived Chlorinated Isoflavones, Tracy Lyn D'Alessandro

All ETDs from UAB

Despite medical advances in both drug therapy and surgical techniques, Americans mostly die from heart disease. Many belong to the low- and middle-class families who do not have sufficient access to medical care due to its high costs. An alternative is the development of healthier lifestyles such as diet which may play a positive role in chronic disease management. Epidemiological and migratory studies suggest that soy plays a pivotal role in the decreased incidence of heart disease in East Asian countries, such as China, Japan, and Korea. The role of soy in cardiovascular disease progression has been the subject of …

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Perception Of Motion-In-Depth: Induced Motion Effects On Monocular And Binocular Cues, John Eric Gampher Jan 2008

Perception Of Motion-In-Depth: Induced Motion Effects On Monocular And Binocular Cues, John Eric Gampher

All ETDs from UAB

Three cues are available to the visual system to determine motion: image displacement across the retina (retinal slip), eye movements, and configuration changes within a scene (Becklen and Wallach, 1985). Any one may lead to the false perception of motion. Induced motion is the illusory movement of one object (or objects) as a result of other movement in the visual field. A wide variety of displays have been used to study induced motion, leading to apparently different classes of induced motion. Current theories of induced motion can be categorized based on local motion, global motion, eye movement suppression, and cognitive …

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Functionalizing Hydroxyapatite Biomaterials With Biomimetic Peptides Of Integrin Ligands, Kristin Marie Hennessy Jan 2008

Functionalizing Hydroxyapatite Biomaterials With Biomimetic Peptides Of Integrin Ligands, Kristin Marie Hennessy

All ETDs from UAB

Hydroxyapatite (HA) coatings of hard tissue implants have been shown to increase osseointegration, but the mechanisms by which HA improves implant integration are not well understood. Numerous studies have shown that modifying HA with adhesive peptides, including RGD, and the collagen I mimetics, DGEA and P15, stimulates the adhesion of mesenchymal stem cells (MSCs), a cell type that differentiates along the osteoblast lineage. However, HA is a highly adsorptive biomaterial, and therefore it is unlikely that cells at the implant site would ever encounter a peptidemodified HA surface in the absence of an adsorbed protein layer. In fact, our laboratory …

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The Role Of Melanopsin Containing Retinal Ganglion Cells In The Pupillary Responses Of Human And Non-Human Primates, David H. Mcdougal Jan 2008

The Role Of Melanopsin Containing Retinal Ganglion Cells In The Pupillary Responses Of Human And Non-Human Primates, David H. Mcdougal

All ETDs from UAB

Historically, the characteristics of the light-evoked neural signals driving the human pupillary light reflex (PLR) have been poorly understood. It was assumed that these light signals originated exclusively from rod and cone photoreceptors, although the measured spectral sensitivity and response dynamics of the PLR were difficult to reconcile with the known properties of rods and cones. Recently, a novel photoreceptive cell class has been discovered in the mammalian retina. These unique retinal ganglion cells not only receive rod and cone inputs, but also express the photopigment melanopsin, and exhibit intrinsic photoresponses independent of rod and cone inputs. These intrinsically photosensitive …

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Function Of Human Retinol Dehydrogenase 12 (Rdh12) In Retinoid Metabolism, Seung-Ah Lee Jan 2008

Function Of Human Retinol Dehydrogenase 12 (Rdh12) In Retinoid Metabolism, Seung-Ah Lee

All ETDs from UAB

Retinol dehydrogenase 12 (RDH12) is a member of the microsomal short-chain dehydrogenase/reductase superfamily of proteins that is highly expressed in photorecep-tor cells. Mutations in RDH12 are associated with severe early-onset autosomal recessive retinal dystrophy, leading to legal blindness. Disease-associated RDH12 variants exhibit lower protein levels when expressed in eukaryotic cells. However, the physiological role of RDH12 remains unclear. As established previously, RDH12 recognizes both retinoids and lipid peroxidation products (medium-chain aldehydes) as substrates and exhibits the highest catalytic efficiency for all-trans-retinaldehyde. As the main goal of this dissertation, we characterized the catalytic properties of RDH12 and its naturally occurring mutants …

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The Role Of Strychnine-Sensitive Nachrs In Rabbit Retinal Off Ganglion Cells, Jordan Michael Renna Jan 2008

The Role Of Strychnine-Sensitive Nachrs In Rabbit Retinal Off Ganglion Cells, Jordan Michael Renna

All ETDs from UAB

that when heteroskedasticity is present, but ignored, there is significant evidence to suggest

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Changes In Hippocampal Excitability During Withdrawal From Chronic Nicotine, Rachel E. Penton Jan 2008

Changes In Hippocampal Excitability During Withdrawal From Chronic Nicotine, Rachel E. Penton

All ETDs from UAB

seeking behavior following chronic drug use lasts for many months or even years. Short-term withdrawal experiments have suggested that the neuroadaptations thought to underlie learning and memory may also contribute to addictive behavior. However, there is little information about the physiological mechanisms that participate in craving and relapse following long-term withdrawal. Here I show in hippocampal slices from rats treated with nicotine for 1 week that there is a change in the excitability of CA1 pyramidal cells that persists for up to 9 months following the cessation of drug treatment. The expression of this enhanced excitability is dependent on different …

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Roles Of Extracellular Atp And Zinc In Pancreatic Ss-Cell Physiology, Clintoria Richards-Williams Jan 2008

Roles Of Extracellular Atp And Zinc In Pancreatic Ss-Cell Physiology, Clintoria Richards-Williams

All ETDs from UAB

Insulin secretory defects within pancreatic beta-cells (β-cells) of islets of Langerhans play a role in the pathogenesis of diabetes mellitus. Furthermore, it is also well established that ATP and zinc are co-secreted with insulin in response to elevated extracellular glucose. Despite this knowledge, the physiological roles of extracellular secreted ATP and zinc within islets are ill-defined. We hypothesized that secreted ATP and zinc are autocrine purinergic signaling molecules that activate P2X purinergic receptor (P2XR) channels expressed by β-cells to enhance glucose-stimulated insulin secretion (GSIS). To test this postulate, ELISA, luciferin/luciferase-based bioluminescence and zinquin-based fluorescence assays were utilized to examine insulin, …

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Characterizing Semantic Memory In Mild Cognitive Impairment, Kelli L. Netson Jan 2008

Characterizing Semantic Memory In Mild Cognitive Impairment, Kelli L. Netson

All ETDs from UAB

Episodic memory is clearly impaired in mild cognitive impairment (MCI), although recent studies have revealed deficits in other cognitive domains such as attention, executive function, and semantic memory. Studies of semantic memory in MCI have been limited by inconsistent use of diagnostic criteria and variability in the measures used. The purpose of this study was to examine semantic memory in a sample of individuals diagnosed with amnestic MCI using Mayo criteria. Performance of individuals with consensus-diagnosed MCI (n=12) was compared to that of normal controls (n=15) on a battery of semantic memory tasks. MANOVA results indicated that the MCI group …

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Adenovirus As A Platform For Assembly And Targeted Delivery Of Gold Nanoparticles To Tumor Cells, Vaibhav Saini Jan 2008

Adenovirus As A Platform For Assembly And Targeted Delivery Of Gold Nanoparticles To Tumor Cells, Vaibhav Saini

All ETDs from UAB

Novel combinatorial strategies need to be explored to achieve tumor eradication. In this regard, viral vector based gene therapy and nanotechnology offer unique possibilities for cancer therapy. As an example, multifunctional adenoviral (Ad) vectors capable of targeting, imaging, and successful cancer gene therapy have been advanced into multiple clinical trials. Similarly, novel multifunctional gold nanoparticles (AuNPs) have been utilized for drug delivery, targeting, imaging, and hyperthermia tumor therapy. Therefore, to accrue the benefits of both gene therapy and nanotechnology for cancer therapy, we proposed to combine Ad vectors and AuNPs in a single multifunctional nanodevice. Towards this goal, herein, we …

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The Role Of Tgf-Ss And Wnt5a In Mammary Gland Development And Tumurorigenesis, Kevin Patrick Roarty Jan 2008

The Role Of Tgf-Ss And Wnt5a In Mammary Gland Development And Tumurorigenesis, Kevin Patrick Roarty

All ETDs from UAB

cancer is the second most common cancer worldwide behind lung cancer, affecting women of all ages, races, ethnicities, and socioeconomic strata. Concerted efforts have been made to understand this heterogeneous disease from the clinical stage down to the molecular level. Importantly, it has become clear that an understanding of the normal biology of the breast at all stages of development is needed to gain insight into how alterations in normal regulatory networks contribute to the initiation and development of breast cancer. TGF-ß plays a role in growth and patterning of the mammary gland and alterations in its signaling exhibit biphasic …

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Correction Of Sickle Cell Disease By Homologous Recombination, Li-Chen Wu Jan 2008

Correction Of Sickle Cell Disease By Homologous Recombination, Li-Chen Wu

All ETDs from UAB

The hematological disorder sickle cell disease (SCD) is a prevalent human genetic disease. It causes severe tissue damage that can result in strokes, splenic infarction, kidney failure, liver and lung disorders, painful crises, and other complications. Although palliative therapies and allogenic stem cell transplantation therapies have been developed for this disorder, there is still no optimal treatment and SCD patients continue to suffer significant morbidity. Recently, several powerful technologies have been developed that increase the possibility for developing therapeutic treatments for SCD. Previously, our lab group demonstrated that SCD can be corrected in our humanized mouse model by transduction of …

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Physiological Charactterization Of The Light Response Of Rod Photoreceptors In The Light Damaged Rat, Yuquan Wen Jan 2008

Physiological Charactterization Of The Light Response Of Rod Photoreceptors In The Light Damaged Rat, Yuquan Wen

All ETDs from UAB

Constant light exposure has long been known to induce photoreceptor degeneration. However, it is not known whether photoreceptors alter their physiology to adapt to the environmental stress caused by constant light exposure. In this study, we have developed a slow light damage model in rats to study changes in single rod physiology and retinal morphology after light damage. Rod physiology was documented by single rod recording using a suction electrode at 3 days (R3), 5 days (R5), 15 days (R15), and 30 days (R30) after 10 days of light damage, or sham light damage for controls. In addition, we used …

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The Use Of Molecular Imaging To Evaluate Te Efficacy Of Treatments For Metastatic Breast Cancer, April Adams Szafran Jan 2008

The Use Of Molecular Imaging To Evaluate Te Efficacy Of Treatments For Metastatic Breast Cancer, April Adams Szafran

All ETDs from UAB

The development of molecular imaging technologies has allowed biomedical researchers to study the process of cancer metastasis in animal models of disease. Bioluminescence imaging has been a crucial tool for non-invasive monitoring of tumor growth, dissemination, and response to therapies. In this report, we have applied bioluminescence imaging to evaluate the efficacy of Death Receptor 5 agonist therapy for the treatment of breast cancer metastasis, predominately to the skeleton, in an athymic nude mouse model. Initially, we determined that bioluminescence imaging was the most ideal technology for studying secondary bone lesions in vivo when compared to both x-ray Computed Tomography …

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Expression And Function Of Nicotinic Acetylcholine Receptors In Human Vascular Endothelial Cells, Ryan C. Splittgerber Jan 2008

Expression And Function Of Nicotinic Acetylcholine Receptors In Human Vascular Endothelial Cells, Ryan C. Splittgerber

All ETDs from UAB

Neuronal nicotinic acetylcholine receptors (nAChRs) are widely expressed in neural and non-neural tissues and have been reported to play a role in neovascularization and vascular diseases of the eye, specifically age-related macular degeneration (ARMD). However, the subunit composition of functional nAChRs, their mechanisms of action, and the downstream signaling pathways in non-neuronal tissues are not well understood. Since some nAChR subtypes have high Ca2+ permeability, we investigated the possible role of Ca2+ in activating signaling cascades that underlie the affects of nAChR activation in Human Dermal Microvascular Endothelial Cells (HDMECs). RT-PCR experiments revealed message for nearly all of the known …

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The Barbary Wars: Ideology And Politics In Post-Revolutionary America, Christopher R. Null Jan 2008

The Barbary Wars: Ideology And Politics In Post-Revolutionary America, Christopher R. Null

All ETDs from UAB

This thesis examines the build-up to and the events of the First Barbary War (1801-1805) with the purpose of demonstrating that ideological factors significantly influenced the decision to go to war – specifically the republican ideology of Thomas Jefferson and his belief that this ideology represented the essence of the United States and its Revolutionary heritage. As such, Jefferson will be the main focus of this analysis. This focus is justified because it is Jefferson who broke with the policies set by his predecessors and directly engaged the Barbary States with military force. Therefore, to understand why the United States …

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Bone Formation Around Implants In Adult Transgenic Mice With Selective Runx2-Ii Deficiency, Jaime Rodrigo Rivera Jan 2008

Bone Formation Around Implants In Adult Transgenic Mice With Selective Runx2-Ii Deficiency, Jaime Rodrigo Rivera

All ETDs from UAB

Titanium-aluminum-vanadium (Ti-6Al-4V) tacks were placed in the tibiae of 10 female wild type (Runx2 flox/+ or Runx2 flox/flox) and heterozygous (Runx2+/-, ColII Cre) mice littermates to examine healing and bone response. Animals were divided into control and test groups of 5 each. A novel generation of Runx2 knock-out mice where the gene is only deleted in chondrocytes was used. Ten days after implant surgery, specimens were recovered and prepared for histological, histomorphometric, and micro-CT morphometric analysis. Histological examination revealed that wild type animals presented larger regions of bone formation and endochondral ossification when compared to heterozygous mice. Micro-CT morphometric analysis …

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Conservational Implications Of Temperature-Dependent Sex Determination, Corie L. Therrien Jan 2008

Conservational Implications Of Temperature-Dependent Sex Determination, Corie L. Therrien

All ETDs from UAB

A variety of reptiles have temperature-dependent sex determination (TSD), where incubation temperature determines gender. This form of sex determination has significant conservational implications because it has the potential of producing highly biased sex ratios which can affect the reproductive output of a population. TSD is of particular interest to conservation programs that use hatcheries to artificially incubate the eggs of endangered sea turtles because such programs need to select specific incubation temperatures in an effort to produce a desired sex ratio. This type of sex determination also has evolutionary implications as it may be advantageous for an animal to produce …

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Trp-Ing Down A Trk: A New Role For Transient Receptor Potential Channels As Novel Mediators Of Brain-Derived Neurotrophic Factor Actions At Both Sides Of The Excitatory Synapse, Michelle Dawn Amaral Jan 2008

Trp-Ing Down A Trk: A New Role For Transient Receptor Potential Channels As Novel Mediators Of Brain-Derived Neurotrophic Factor Actions At Both Sides Of The Excitatory Synapse, Michelle Dawn Amaral

All ETDs from UAB

Over the years, various roles for neurotrophins have been revealed, being initially described as survival signals for neurons making their initial synaptic contacts in the developing brain. Eventually, it was discovered that these molecules also play important modulatory roles in the adult brain. The work encompassed in this dissertation serves to characterize one particular neurotrophin, brain-derived neurotrophic factor (BDNF), which has been implicated in long-term potentiation (LTP), and its effects at CA3-CA1 synapses in the hippocampus following acute application in vitro. To this end, we have demonstrated the presence of a novel, non-selective cationic current that is initiated by BDNF …

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Characterization Of Sortase And Its Effect On The Virulence Of Streptococcus Pneumoniae, Allison E. Bennett Jan 2008

Characterization Of Sortase And Its Effect On The Virulence Of Streptococcus Pneumoniae, Allison E. Bennett

All ETDs from UAB

Sortases are transpeptidases that covalently link surface proteins to the stempeptide on the cell wall peptidoglycan of Gram-positive bacteria. This work endeavored to characterize the various sortase enzymes and their effect on the virulence of Streptococcus pneumoniae. The genome of S. pneumoniae may encode up to four sortase enzymes. We found that 38 of 54 strains of serotype 6B clonal complex 14 (CC14) carry the genes for the secondary sortases srtB, srtC, and srtD. The presence of these sortases did not seem to influence the ability of strains within CC14 to infect the nasopharynx, lungs, or blood of strains within …

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Bach's Oratorios: The Parallel German-English Texts, With Annotations, J. S. Bach, Michael Marissen Jan 2008

Bach's Oratorios: The Parallel German-English Texts, With Annotations, J. S. Bach, Michael Marissen

Music Faculty Works

No abstract provided.

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The Public Domain: Enclosing The Commons Of The Mind, James Boyle Jan 2008

The Public Domain: Enclosing The Commons Of The Mind, James Boyle

Faculty Scholarship

Our music, our culture, our science and our economic welfare all depend on a delicate balance between those ideas that are controlled and those that are free, between intellectual property and the public domain. In his award-winning book, The Public Domain: Enclosing the Commons of the Mind (Yale University Press) James Boyle introduces readers to the idea of the public domain and describes how it is being tragically eroded by our current copyright, patent, and trademark laws. In a series of fascinating case studies, Boyle explains why gene sequences, basic business ideas and pairs of musical notes are now owned, …

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A Construct With Fluorescent Indicators For Conditional Expression Of Mirna., Linghua Qiu, Hongyan Wang, Xugang Xia, Hongxia Zhou, Zuoshang Xu Jan 2008

A Construct With Fluorescent Indicators For Conditional Expression Of Mirna., Linghua Qiu, Hongyan Wang, Xugang Xia, Hongxia Zhou, Zuoshang Xu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Transgenic RNAi holds promise as a simple, low-cost, and fast method for reverse genetics in mammals. It may be particularly useful for producing animal models for hypomorphic gene function. Inducible RNAi that permits spatially and temporally controllable gene silencing in vivo will enhance the power of transgenic RNAi approach. Furthermore, because microRNA (miRNA) targeting specific genes can be expressed simultaneously with protein coding genes, incorporation of fluorescent marker proteins can simplify the screening and analysis of transgenic RNAi animals. RESULTS: We sought to optimally express a miRNA simultaneously with a fluorescent marker. We compared two construct designs. One expressed …

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New Strategy For The Search Of Natural Biologically Active Substances., Vyacheslav Dushenkov, Ilya Raskin Jan 2008

New Strategy For The Search Of Natural Biologically Active Substances., Vyacheslav Dushenkov, Ilya Raskin

Publications and Research

The modern pharmaceutics actively screens an immense diversity of substances occurring in plants and other natural resources in the search for new effective medicinal agents. The Global Institute for Bioexploration (GIBEX) established by joint efforts of Rutgers University and the University of Illinois (United States) represents the organizational core of international scientific community whose activity is directed towards the search and development of new medicinal preparations from natural raw materials. The basis of GIBEX activity is the transfer of modern screening technologies to countries and geographical regions characterized by remarkable biodiversity. The GIBEX goals are to encourage the search for …

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