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All ETDs from UAB

Theses/Dissertations

2013

Doctor of Philosophy (PhD) Heersink School of Medicine

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Full-Text Articles in Medicine and Health Sciences

Identification Of Claudin-1 As An Entry Factor In Dengue Infection And Development Of A High Throughput Screening Assay For Antivirals Against Dengue Virus, Pulin Che Jan 2013

Identification Of Claudin-1 As An Entry Factor In Dengue Infection And Development Of A High Throughput Screening Assay For Antivirals Against Dengue Virus, Pulin Che

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Dengue virus (DENV) has become a huge public health concern around the world with no vaccine or antivirals available. More than one-third of the world's population is living in areas at risk of infection. To conquer the dengue disease, a better understanding of virus-host interactions and development of the appropriate therapeutic treatments are required. In this dissertation, we first broadly reviewed the factors involved in dengue viral entry and the role of tight junctions as a pathogen target. Second, we developed, optimized and validated a high throughput screening (HTS) assay for anti-dengue virus drug screening. Taking advantage of using live …


Sulindac Sulfide Amide As A Novel Agent For The Prevention And Treatment Of Lung Cancer, Evrim Gurpinar Jan 2013

Sulindac Sulfide Amide As A Novel Agent For The Prevention And Treatment Of Lung Cancer, Evrim Gurpinar

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Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac sulfide (SS) have shown promising antineoplastic activity in multiple tumor types, but toxicities resulting from cyclooxygenase (COX) inhibition limit their use in cancer prevention. We recently described a N,N-dimethylethyl amine derivative of SS, sulindac sulfide amide (SSA), that does not inhibit COX-1 or -2, yet displays potent tumor cell growth inhibitory activity. Here, we studied the basis for the growth inhibitory effects of SSA on human lung adenocarcinoma cell lines and evaluated its preclinical pharmacology. SSA potently inhibited the growth of lung tumor cells with IC50 values of 2-5 μ compared with 44-52 …


Role Of Endothelial Mannose Residues In Monocyte Adhesion Under Flow, David Wayne Scott Jan 2013

Role Of Endothelial Mannose Residues In Monocyte Adhesion Under Flow, David Wayne Scott

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Atherosclerosis is a chronic inflammatory disease of the vessel wall and underlying cause of most cardiovascular disease. Much is understood about the nature of atherosclerosis development, including contributions from leukocytes that drive the disease process forward. The general process by which leukocytes are trafficked to sites of atherosclerosis development, and sites of inflammation in general, is understood and relies upon endothelial expressed protein adhesion molecules which serve as ligands for cognate leukocyte receptors. While these adhesion molecules share the post-translation modification of N-glycosylation, relatively little is known as to what functional role these modification plays in: i) interactions of leukocytes …


The Genetic Complexity Of The Human Fc-Gamma Receptor 1q23 Locus And Its Relationship To Autoimmunity, Travis Samuel Ptacek Jan 2013

The Genetic Complexity Of The Human Fc-Gamma Receptor 1q23 Locus And Its Relationship To Autoimmunity, Travis Samuel Ptacek

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The human immune system must be able to adapt to a wide spectrum of invading pathogens in order to keep the human body alive. This variation includes directed recombination and mutation at the level of the individual and genetic variation and natural selection at the population level. A direct consequence of the adaptability of the immune system is autoimmunity: as the immune system adapts to a shifting spectrum of antigens, it can shift to self-antigens, and therefore attack the body and cause disease. Since genetic factors are part of this adaptability, they are also connected with autoimmune disease. SLE is …


The Role Of Gadd45b In Hippocampus-Dependent Cognition, Synaptic Plasticity And Activity-Associated Transcriptional Dynamics, Faraz Sultan Jan 2013

The Role Of Gadd45b In Hippocampus-Dependent Cognition, Synaptic Plasticity And Activity-Associated Transcriptional Dynamics, Faraz Sultan

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An expanding body of literature argues for a pivotal role of molecular epigenetic mechanisms in memory. Defined as mechanisms that regulate gene expression in the absence of DNA sequence modifications, these regulate various stages of memory-associated transcription. These phenomena are present at diverse anatomical subregions of the central nervous system (CNS) and regulate corresponding behaviors. Epigenetic mechanisms comprise a unique category of behavioral and physiological modulators because of their potential to modify the cellular phenotype in a stable manner. Hence, epigenetics offers a novel potential solution to a central paradox in memory retention: the finding that most putative molecular substrates …


Neutropenia And Progenitor Cell Mobilization In Ap3-B1 Mutant Pearl Mice, Matthew Vallejo Jan 2013

Neutropenia And Progenitor Cell Mobilization In Ap3-B1 Mutant Pearl Mice, Matthew Vallejo

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Mutations in the AP3-ß1 gene are known to cause Hermansky-Pudlak syndrome type 2 (HPS2) in humans and canine cyclic hematopoiesis (CH) in gray collie dogs. HPS2 patients have severe congenital neutropenia (SCN), and dogs have cyclic neutropenia (CN). The mechanism behind neutropenia is uncertain. Pearl mice have an AP3-ß1 mutation, but whether they actually have neutropenia has not yet been evaluated. This dissertation presents a discussion of the evaluation of neutropenia in pearl mice, hematopoietic progenitor cell mobilization defect in pearl mice and finally an evaluation of methods of dog-to-mouse xenotransplantation to establish a xenotransplant model of the dog hematopoietic …


The Origin, Regulation, And Function Of Tbet In Effector Cd4 T Cells During Chronic Autoimmune Disease, Wen-I Yeh Jan 2013

The Origin, Regulation, And Function Of Tbet In Effector Cd4 T Cells During Chronic Autoimmune Disease, Wen-I Yeh

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Multiple Sclerosis (MS) is an autoimmune disease resulting from aberrant immune cells causing demyelination. We utilize the well-studied mouse model, experimental autoimmune encephalomyelitis (EAE), to decipher the underlying pathogenesis of MS. Effector CD4 T-cells play a critical role during EAE because the disease is induced by adoptively transferring myelin-specific CD4 T-cells into naïve mice. Classically, effector CD4 T-cells have been divided into distinct subsets based on their functional properties: Th1 cells produce IFNγ, Th2 cells secrete IL-4, IL-5, and IL-13, Th17 cells make IL-17A, IL-17F, IL-21, and IL-22, and regulatory T cells produce IL-10. Th1 cells were originally identified as …


An Investigation Of Trem-Like Transcript 2 Expression, Kimberly Anne Thomas Jan 2013

An Investigation Of Trem-Like Transcript 2 Expression, Kimberly Anne Thomas

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Acute inflammation is a necessary component for the clearance of pathogens. Cells at the site of infection utilize highly conserved receptors to both recognize microbes and induce the production of pro-inflammatory stimuli. These stimuli set off a chain reaction that includes localized vasodilation, leukocyte infiltration, and tissue destruction, collectively known as inflammation. Tightly controlled, this process is protective, and can compartmentalize the damage to a defined area, but when dysregulated can be catastrophic, inducing chronic inflammation and even death. Families of innate receptors can modulate inflammatory processes, and in doing so, increase or decrease their severity, as well as tailor …


Potential Roles Of The Immunostimulatory Signals Il-15 And Mica In Oncolytic Hsv-1 Therapy For Malignant Glioma, David Curtis Gaston Jan 2013

Potential Roles Of The Immunostimulatory Signals Il-15 And Mica In Oncolytic Hsv-1 Therapy For Malignant Glioma, David Curtis Gaston

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Malignant gliomas are the most frequently diagnosed and the most fatal primary brain tumors. Innovative therapeutic approaches are necessary to combat these devastating cancers, and oncolytic herpes simplex virus type-1 (oHSV) deleted of the γ134.5 neurovirulence gene is a promising adjunctive therapy. The primary mechanism of tumor clearance by oHSV is lytic replication specifically within malignant cells. oHSV also stimulates tumor infiltration of cytotoxic immune effector cells that can participate in tumor clearance. However, cytotoxic immune cells target oHSV as well as tumor, which may limit therapeutic efficacy. Further knowledge regarding the nature of these interactions and how the interactions …


The Development Of An In Vitro Surrogate Assay For Screening Protective Antibodies Against Pneumococcal Surface Protein A (Pspa), Kristopher Ruben Genschmer Jan 2013

The Development Of An In Vitro Surrogate Assay For Screening Protective Antibodies Against Pneumococcal Surface Protein A (Pspa), Kristopher Ruben Genschmer

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PCV13 is the current pneumococcal protein conjugated vaccine made up of the 13 most clinically relevant capsular polysaccharides. While protective, it is limited to a small portion of the overall serotypes of Streptococcus pneumoniae. The possibility of "serotype replacement" by serotypes not covered by the vaccine and the high cost of producing this conjugated polysaccharide vaccine stress the need for a protein based vaccine, one that is more broad in its protection. Pneumococcal surface protein A (PspA) has been shown to be both immunogenic and protective in mice and is a promising protein vaccine candidate. However, there are no current …


Adap1 And Arf6 Mediate Regulated Secretory Trafficing In Neurosecretory Cells And Neurons, Sharday Ewell Jan 2013

Adap1 And Arf6 Mediate Regulated Secretory Trafficing In Neurosecretory Cells And Neurons, Sharday Ewell

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ADP ribosylation factor 6 (Arf6) is a member of the Arf family of small GTPases known to function in vesicular membrane trafficking and cytoskeletal organization. Arf6 cycles between its GTP and GDP bound states, facilitated by GTP exchange factors (GEFs) and GTPase activating proteins (GAPs), respectively. In my dissertation studies I have investigated the neuronal functions of Arf6 and ADAP1, an Arf6 GAP and candidate PI 3-kinase target required for dendritic differentiation in developing neurons. I demonstrated that in neurosecretory PC12 cells and neurons, ADAP1 and Arf6 colocalize with regulated secretory granules (SGs) that traffic chromogranin B and brain-derived neurotrophic …


The Role Of Il-21 And Il-17 In Regulating Follicular T Helper Cells In Germinal Center Response Of Autoimmunity, Yanna Ding Jan 2013

The Role Of Il-21 And Il-17 In Regulating Follicular T Helper Cells In Germinal Center Response Of Autoimmunity, Yanna Ding

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Overreactivity of the germinal center (GC) is a central feature of autoantibody-mediated autoimmune diseases. Follicular T helper (Tfh) cells are the primary T helper subset that migrates to the incipient GC and forms close contacts with GC-B cells to promote GC formation and help GC-B cell differentiation, resulting in high-affinity antibody production. Increased levels of interleukin (IL)-21 and aberrant accumulation or function of Tfh cells have been associated with autoimmune disease severity in humans and lupus-prone mice. Follicular regulatory T (Tfr) cells are the regulatory T cell subset that also localizes in the GC and inhibits GC B cell differentiation. …


The Role Of Nr4a3 And Its Agonists In Skeletal Muscle Glucose Transport And Insulin Sensitivity, Qinglan Liu Jan 2013

The Role Of Nr4a3 And Its Agonists In Skeletal Muscle Glucose Transport And Insulin Sensitivity, Qinglan Liu

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Insulin resistance plays a central role in the pathogenesis of Type 2 Diabetes (T2DM) and involves diminished stimulation of glucose transport in skeletal muscle. Improvements in insulin sensitivity are essential for both prevention and treatment of T2DM. However, the limitation of current medications highlights the need for alternative molecular regulators of insulin action and developing new insulin sensitizers. Our laboratory has initially identified roles for the orphan nuclear receptor NR4A3 in insulin-sensitization and stimulation of glucose transport. However, the cellular effect and downstream mechanisms of NR4A3 and its agonists (e.g. 6-mercaptopurine/6-MP) on insulin effector system in skeletal muscle remain unknown. …


Investigation Of Death Receptor-5 Mediated Apoptosis And Inhibition Of Wnt/Ss-Catenin Signaling In Basal-Like Breast Cancer Stem Cells, Angelina Ix-Ik' Londono-Joshi Jan 2013

Investigation Of Death Receptor-5 Mediated Apoptosis And Inhibition Of Wnt/Ss-Catenin Signaling In Basal-Like Breast Cancer Stem Cells, Angelina Ix-Ik' Londono-Joshi

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Basal-like breast cancers (BLBC) display aggressive clinical behavior attributed to the presence of cancer stem cells (CSCs). TRA-8, a monoclonal antibody that binds specifically to TRAIL death receptor 5, preferentially induces apoptosis in BLBC subtype cells; however it is unknown if TRA-8 is also cytotoxic to the CSC population. Moreover, some BLBC cell lines are resistant to TRA-8, and overcoming resistance is critical for clinical translation of this therapy. One potential approach to overcome TRA- 8 resistance is to target the Wnt/ß-catenin pathway. LRP6 is a cell surface receptor that is an indispensable element of the Wnt/ß-catenin signaling pathway that …


Surveying The Serum Proteome For Biomarkers Of Early-Stage Pancreatic Cancer, Michael Robert Ludwig Jan 2013

Surveying The Serum Proteome For Biomarkers Of Early-Stage Pancreatic Cancer, Michael Robert Ludwig

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SURVEYING THE SERUM PROTEOME FOR BIOMARKERS OF EARLY STAGE PANCREATIC CANCER MICHAEL ROBERT LUDWIG MICROBIOLOGY ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is a uniformly fatal disease due to its refractory nature to conventional therapies at the time of initial diagnosis. In order to in-crease the curative potential of surgical resection, early detection of organ-confined neoplasia is needed. Currently, no effective diagnostic tools are available to detect early-stage pancreatic ductal lesions termed pancreatic intraepithelial neoplasia (PanIN) or lo-cally invasive, organ-confined disease. One way to identify biomarkers that may be use-ful for the early detection of PDAC is through the study of the …


The Phenotypic Expression Of Usp14 Deficiency Is Dependent Upon Genetic Background, Andrea Gail Marshall Jan 2013

The Phenotypic Expression Of Usp14 Deficiency Is Dependent Upon Genetic Background, Andrea Gail Marshall

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The ubiquitin proteasome system (UPS) plays a critical role in regulating a diversity of cellular processes that are essential to neuronal function, such as synaptic transmission, axon guidance, and neurite outgrowth. Dysfunctions of the UPS are linked with many neurodegenerative disorders, including motor neuron diseases like spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), although it is not known how UPS dysfunction contributes to disease pathology. The proteasome, an approximate 2.5 megadalton protein complex comprised of a 20S core particle and 19S regulatory particle, is the site of ubiquitin-mediated proteolysis in the cell. Recent studies have linked ubiquitin specific …


The Role Of Palmitoylation And Other Post-Translational Modifications In Cftr Biogenesis, Michelle Mcclure Jan 2013

The Role Of Palmitoylation And Other Post-Translational Modifications In Cftr Biogenesis, Michelle Mcclure

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Post-translational modifications (PTMs) are important contributors to protein bio-genesis and function. CFTR in particular is known to be regulated by multiple PTMs, in-cluding glycosylation, phosphorylation, and ubiquitination. The functional significance and specific CFTR residues responsible for the majority of PTMs within CFTR are not known. The goal of this dissertation was to identify and characterize novel PTMs that influence wild-type and F508del CFTR. The study employed a combination of tandem and multiple reaction ion monitoring mass spectrometry to identify covalent side chain attachments. Analysis revealed the specific locations of numerous phosphorylated resi-dues, several sites of methylation, and more than twenty-five …


Characterizing The Roles Of Il-11 And Cd68 In Breast Cancer Bone Metastasis, Erin Mills Mccoy Jan 2013

Characterizing The Roles Of Il-11 And Cd68 In Breast Cancer Bone Metastasis, Erin Mills Mccoy

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The molecular mechanisms regulating the preferential metastasis of breast cancer to bone have not been fully elucidated, but it is hypothesized that local conditions in the bone create an environment conducive to colonization by breast cancer cells and that the breast cancer cells interact directly with cells in the bone. In this dissertation, two goals were pursued: (1) to explore breast cancer secreted interleukin (IL)-11's role on osteoclast function and (2) investigate the expression and potential role of CD68 in breast cancer adhesion to bone. Higher rates of bone metastasis occur in human breast cancer tumors expressing IL-11, a cytokine …


Intrinsic And Extrinsic Factors Required For Cd4 T Memory Cell Formation And Function, Sarah B. Mollo Jan 2013

Intrinsic And Extrinsic Factors Required For Cd4 T Memory Cell Formation And Function, Sarah B. Mollo

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CD4 T cells are central to the organization of the immune response through the secretion of cytokines that recruit and activate other immune cells. Following infection and pathogen control, the majority of the effector CD4 T cells undergo apoptosis, leaving a subset that persists and gives rise to the memory T cell pool. Upon encountering the same pathogen, memory CD4 T cells respond rapidly, providing enhanced protection from re-infection. What determines which effector CD4 T cells will survive is unclear; however, there are a number of factors both intrinsic to the cell as well as external signals from the environment …


Neuropathological Alterations In Alzheimer's Disease: An Up Close Look At Sympathetic Sprouting, Amy Renee Nelson Jan 2013

Neuropathological Alterations In Alzheimer's Disease: An Up Close Look At Sympathetic Sprouting, Amy Renee Nelson

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Pathological hallmarks of AD include neurofibrillary tau tangles, amyloid beta (Abeta) accumulation and cholinergic degeneration. Cholinergic degeneration can be mimicked in rats by lesioning cholinergic neurons in medial septum. Hippocampal cholinergic denervation disrupts retrograde transport of nerve growth factor (NGF), leading to its accumulation, which subsequently triggers sprouting of noradrenergic sympathetic fibers from the superior cervical ganglia into hippocampus. Dr. McMahon's lab previously reported that coincident with this sprouting, there is an increase in cholinergic innervation that correlates with a recovery of M1 muscarinic receptor dependent plasticity at CA3-CA1 synapses and visual cortex. These findings suggest that noradrenergic sympathetic sprouting …


Epigenetic Regulation Of Kir4.1 In Normal And Pathological States: A Focus On Spinal Cord Injury, Sinifunanya Elvee Nwaobi Jan 2013

Epigenetic Regulation Of Kir4.1 In Normal And Pathological States: A Focus On Spinal Cord Injury, Sinifunanya Elvee Nwaobi

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Astrocytes are the most numerous cells in the brain and play a critical role in maintaining homeostatic extracellular potassium ([K+]e). This process is mediated, in part, by a glial-specific, inwardly rectifying potassium channel, Kir4.1. Pharmacological inhibition, knock down, or complete knock out of this channel results in astrocytes with increased membrane resistance, depolarized resting membrane potential, and altered extracellular potassium dynamics. Subsequent to the dysregulation of [K+]e, Kir4.1 knockout (KO) animals suffer from ataxia, seizures, and early postnatal death. Interestingly, Kir4.1 has long been characterized as a seizure susceptibility gene. The importance of Kir4.1 is further underscored by recent studies …


New Mouse Models To Aid Studies Of The Role Of Primary Cilia In Limb Patterning And Bone Development, Amber Kathleen O'Connor Jan 2013

New Mouse Models To Aid Studies Of The Role Of Primary Cilia In Limb Patterning And Bone Development, Amber Kathleen O'Connor

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Hedgehog (Hh) signaling is required for many developmental processes, and causes several diseases and cancers. Described in chapter one below, vertebrate Hh sig-naling is dependent on the primary cilium (PC), a small organelle that extends from the surface of most mammalian cell types. A better understanding of how the PC modulates Hh signaling is important, as defects in the structure or function of PC result in severe human disorders termed the ciliopathies. For example, patients with Meckel-Gruber Syndrome have extra digits and neural tube defects, which are Hh both related pheno-types. In chapter two we sought to further understand the …


Microevolution Of Capsule Synthesis Genes Contributes To Pneumococcal Capsule Diversity, Melissa Beth Oliver Jan 2013

Microevolution Of Capsule Synthesis Genes Contributes To Pneumococcal Capsule Diversity, Melissa Beth Oliver

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Streptococcus pneumoniae (pneumococcus) is an important human pathogen that expresses a capsular polysaccharide (PS) to shield underlying antigenic structures from complement-mediated opsonophagocytosis. Thus, capsular PS is the major virulence factor, the target of primary immune responses to pneumococcal infections, and the antigenic component of pneumococcal vaccines. Pneumococci have diverse capsular PS synthesis (cps) loci and express over 90 different capsule types. Such diversity helps pneumococci escape immune detection and adapt to changing environments. Recombination of cps genes has been recognized as the main driver of capsule diversity. However, we show point mutations in cps genes encoding glycosyltransferases can broaden enzymes' …


Phospho-Erk And Amyloid Beta: Targets Of Estrogen In The Brain, Thomas Reed Peavy Jan 2013

Phospho-Erk And Amyloid Beta: Targets Of Estrogen In The Brain, Thomas Reed Peavy

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Estrogen replacement therapy (ERT) has been shown to improve memory function in menopausal women, but increases hormone sensitive cancers, prompting a more targeted investigation of estrogen's action in learning and memory to develop more targeted therapeutics. Estrogen improves performance on the novel object recognition task by increasing phosphorylation of extracellular signal-regulated kinase (pERK) within minutes in the hippocampus. Dr. Lori McMahon's lab showed that the improvement in novel object recognition can be seen 24 hours after subcutaneous injection of proestrous levels of estrogen (referred to as E24). Whether a corresponding increase in pERK occurs at the E24 time point had …


Clinical Consequences Of Micrornas In Colorectal Cancer, Liselle C. Bovell Jan 2013

Clinical Consequences Of Micrornas In Colorectal Cancer, Liselle C. Bovell

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Colorectal cancer (CRC) is a heterogeneous disease, and factors such as tumor location, the environment, genetics, and ethnic differences, can influence its development and progression. Over the last few decades, overall CRC mortality rates have declined; however, racial disparities in mortality rates have increased. The discovery of biomarkers that focus on identifying individual differences based on confounders such as tumor stage and patient race/ethnicity is needed, for such biomarkers can lead to development of personalized therapeutic approaches to target these molecules. MicroRNAs (miRNAs) are a class of small molecules that regulate genes at the post-transcriptional level. Altered miRNA expression levels …


Regulation Of Capsule By Cpsa And Global Regulatory Networks In Streptococcus Pneumoniae Type 2, Kanupriya Gupta Jan 2013

Regulation Of Capsule By Cpsa And Global Regulatory Networks In Streptococcus Pneumoniae Type 2, Kanupriya Gupta

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Streptococcus pneumoniae is a major human pathogen that can reside asymptomatically in the nasopharynx before causing invasive disease by entering systemic sites. This involves regulation of colonization and virulence factors including capsule. cps2A, the first gene of the capsule (cps) locus has been proposed to regulate capsule, however its exact role and mechanism is not well understood. A complete deletion of cps2A resulted in enhanced capsule levels, with no alteration in the transcription levels of cps genes. Complementation of Cps2A restored wild type levels of capsule. Expression of the C-terminal tail alone was able to partially complement the deletion strain, …


Therapeutic Potential Of Genetically-Engineered Mesenchymal Stem Cells In Multiple Myeloma, Jerome T. Higgs Jan 2013

Therapeutic Potential Of Genetically-Engineered Mesenchymal Stem Cells In Multiple Myeloma, Jerome T. Higgs

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ABSTRACT Multiple Myeloma (MM) remains the second most common hematologic malig-nancy occurring in adults, which primarily affects the skeletal system causing severe bone destruction, spinal cord compression and hypercalcemia. Current therapies, which include chemotherapy, radiotherapy, autologouos stem cell transplantation and in some cases surgery, have extended the median survival between 3 and 10 years. However, MM is still incurable and therefore improving current therapies or developing newer ones to reduce the burden of osteolytic damage and extend survival rate will be highly beneficial for patient management. The long-term goal of this study is to develop a novel therapeutic approach to …


The Role Of Histone Deacetylase Inhibitors In Ameliorating Memory Dysfunction Of An Alzheimer's Disease Mouse Model, Mark Kilgore Jan 2013

The Role Of Histone Deacetylase Inhibitors In Ameliorating Memory Dysfunction Of An Alzheimer's Disease Mouse Model, Mark Kilgore

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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid beta plaques and neurofibrillary tangles, along with cognitive impairments that progress to dementia and eventually death. The development of drug treatments that rescue memory deficits could be a promising therapy given in the early stages of AD. In the following studies, we tested the potential for systemic treatment with histone deacetylase (HDAC) inhibitors to ameliorate cognitive deficits in a mouse model of AD. Using the APPSwe/PS1dE9 mouse model of AD, we showed that giving HDAC inhibitors systemically for 3 weeks reversed contextual memory deficits, stably maintained memories over a 2-week …


Virus-Induced Inflammation And Central Nervous System Development, Kate Kosmac Jan 2013

Virus-Induced Inflammation And Central Nervous System Development, Kate Kosmac

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Congenital human cytomegalovirus (HCMV) infection is a complex cause of central nervous system (CNS) disease. Infection with HCMV during pregnancy results in virus transmission across the placenta and infection of the fetus. With a seroconversion rate in pregnant women between 1% and 4%, HCMV is the most frequently transmitted virus from mother to developing child. Each year between 2,000 and 4,000 infants will suffer from long-term neurologic deficits as a result of congenital infection. The well documented CNS sequelae resulting from congenital HCMV infection have described a wide range of damage without a specific set of pathologic markers for disease. …


Genetic And Biochemical Characterizations Of The Capsular Glycosyltransferases In Streptococcus Pneumoniae Serotype 2, David Boyd Anthony James Jan 2013

Genetic And Biochemical Characterizations Of The Capsular Glycosyltransferases In Streptococcus Pneumoniae Serotype 2, David Boyd Anthony James

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The principle objective of this dissertation is to develop a thorough understanding of the genetics and biochemistry of capsule synthesis. Specifically, it involves the identification and characterization of the capsular glycosyltransferases in Streptococcus pneumoniae serotype 2, with investigations into their regulation. S. pneumoniae (the pneumococcus) is a significant human pathogen that has the ability to persist as a commensal and then transition to a virulent state, the latter of which is a major contributor to global morbidity and mortality. The capsular polysaccharide (CPS) of S. pneumoniae is a protective surface structure that plays an integral role in this disease process. …