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Roles Of Th2 And Th17 Cd4+ T-Helper Cell Cytokines In The Pathogenesis Of Experiemental Cytomegalovirus Retinitis, Emily L. Blalock

Biology Dissertations

Human cytomegalovirus (HCMV) is a betaherpesvirus that infects up to 80% of the population worldwide, and establishes latency in monocytes and bone marrow cells. Reactivated HCMV can become an opportunistic pathogen in individuals who are immunocompromised, such as those with acquired immunodeficiency syndrome (AIDS). HCMV infection of AIDS patients causes a sight-threatening retinitis that leads to vision loss and blindness in up to 46% of this population without antiretroviral treatment. Because untreated HIV-infected individuals exhibit the loss of cell-mediated immunity and alterations in CD4+ T-helper (Th) cell cytokines, including elevation of interleukin-4 (IL-4), IL-10, and IL-17, we sought to test …

Functional Study Of The Threonine Phosphorylation And The Transcriptional Coactivator Role Of P68 Rna Helicase, Heena T. Dey

Biology Dissertations

P68 RNA helicase is a RNA helicase and an ATPase belonging to the DEAD-box family. It is important for the growth of normal cells, and is implicated in diverse functions ranging from pre-mRNA splicing, transcriptional activation to cell proliferation, and early organ development. The protein is documented to be phosphorylated at several amino-acid residues. It was previously demonstrated in several cancer cell-lines that p68 gets phosphorylated at threonine residues during treatments with TNF-α and TRAIL. In this study, the role of threonine phosphorylation of p68 under the treatment of anti-cancer drug, oxaliplatin in the colon cancer cells is characterized. Oxaliplatin …

Structure Based Study Of Ca Spase-3 And D-Arginine Dehydrogenase, Guoxing Fu

Biology Dissertations

Caspases are important players in programmed cell death. Normal activities of caspases are critical for the cell life cycle and dysfunction of caspases may lead to the development of cancer and neurodegenerative diseases. They have become a popular target for drug design against abnormal cell death. In this study, the recognition of P5 position in substrates by caspase-3, -6 and -7 has been investigated by kinetics, modeling and crystallography. Crystal structures of caspase-3 and -7 in complexes with substrate analog inhibitor Ac-LDESD-CHO have been determined at resolutions of 1.61 and 2.45 Å, respectively, while a model of caspase-6/LDESD is constructed. …

Molecular Mechanisms Of Spermine On Its Synergistic Effect With Beta-Lactams Against Staphylococcus Aureus, Xiangyu Yao

Biology Dissertations

Spermine (Spm), a potent bactericidal polyamine, exerts a strong synergistic effect with β-lactams against methicillin-resistant Staphylococcus aureus (MRSA) in a pH-dependent manner. At high pH (>8) Spm is a potent nucleophile, and able to form Spm-β-lactam adduct. At physiological pH (or lower), Spm carries positive charges, and can bind to DNA through charge interactions. The potential of Spm interfering with cell wall was first investigated. A spontaneous mutant of MRSA Mu50 selected for Spm resistance conferred resistance to Spm/β-lactam synergy. This phenotype was due to the presence of a 7-bp deletion in pbpB as identified by genome resequencing and …

A Comparative Analysis Of The Neural Basis For Dorsal-Ventral Swimming In The Nudipleura, Joshua L. Lillvis

Biology Dissertations

Despite having similar brains, related species can display divergent behaviors. Investigating the neural basis of such behavioral divergence can elucidate the neural mechanisms that allow behavioral change and identify neural mechanisms that influence the evolution of behavior.

Fewer than three percent of Nudipleura (Mollusca, Opisthobranchia, Gastropoda) species have been documented to swim. However, Tritonia diomedea and Pleurobranchaea californica express analogous, independently evolved swim behaviors consisting of rhythmic, alternating dorsal and ventral flexions. The Tritonia and Pleurobranchaea swims are produced by central pattern generator (CPG) circuits containing homologous neurons named DSI and C2. Homologues of DSI have been identified throughout the …

Development Of A Novel Method For Biochemical Systems Simulation: Incorporation Of Stochasticity In A Deterministic Framework, Amit Sabnis

Biology Dissertations

Heart disease, cancer, diabetes and other complex diseases account for more than half of human mortality in the United States. Other diseases such as AIDS, asthma, Parkinson’s disease, Alzheimer’s disease and cerebrovascular ailments such as stroke not only augment this mortality but also severely deteriorate the quality of human life experience. In spite of enormous financial support and global scientific effort over an extended period of time to combat the challenges posed by these ailments, we find ourselves short of sighting a cure or vaccine. It is widely believed that a major reason for this failure is the traditional reductionist …

Tyrosine Phosphorylation Of P68 Rna Helicase Promotes Metastasis In Colon Cancer Progression, Chia Yi Liu

Biology Dissertations

The initiation of cancer metastasis usually requires Epithelial-Mesenchymal Transition (EMT), by which tumor cells lose cell-cell interactions and gain the ability of migration and invasion. Previous study demonstrated that p68 RNA helicase, a prototypical member of the DEAD-box RNA helicases, functions as a mediator to promote platelet-derived growth factor (PDGF)-induced EMT through facilitating nuclear translocation of β-catenin in colon cancer cells. In this context, p68 RNA helicase was found to be phosphorylated at the tyrosine 593 residue (referred as phosphor-p68) by c-Abl kinase, and this phosphorylation is required for the activation of β-catenin signaling and the consequent EMT. The phosphor-p68 …

The Reorganization Of Primary Auditory Cortex By Invasion Of Ectopic Visual Inputs, Yuting Mao

Biology Dissertations

Brain injury is a serious clinical problem. The success of recovery from brain injury involves functional compensation in the affected brain area. We are interested in general mechanisms that underlie compensatory plasticity after brain damage, particularly when multiple brain areas or multiple modalities are included. In this thesis, I studied the function of auditory cortex after recovery from neonatal midbrain damage as a model system that resembles patients with brain damage or sensory dysfunction. I addressed maladaptive changes of auditory cortex after invasion by ectopic visual inputs. I found that auditory cortex contained auditory, visual, and multisensory neurons after it …

Regulation Of Interferon Stimulated Genes In West Nile Virus Infected Mouse Embryofibroblasts, Joanna A. Pulit-Penaloza

Biology Dissertations

The induction of type I interferon (IFN) and subsequent activation of interferon stimulated genes (ISGs) represent a first line of defense against viral infection. Typically type I IFN signaling leads to the phosphorylation of the STAT1 and STAT2 transcription factors (TFs) which then form a trimetric complex with IRF-9 and translocate to the nucleus to induce ISG expression. However, the results of this study showed that IFN-mediated upregulation of the ISG Oas1b, the product of which confers resistance to flavivirus induced disease, can be induced in a STAT1-independent manner. Since numerous ISGs have antiviral functions, many viruses have evolved strategies …

Immunoglobulin Gamma Subclasses And Corresponding Fc Receptors In Rhesus Macaques: Genetic Characterization And Engineering Of Recombinant Molecules, Doan C. Nguyen

Biology Dissertations

Rhesus macaques represent a valuable model in biomedical research and in development of vaccines and therapeutics. Due to the lack of reagents, the general properties of IgG and corresponding cellular receptors (FcγR) in this species are poorly characterized. We engineered recombinant IgGs containing each of the four rhesus macaque heavy constant region (CH) subclasses. To define FcγRs that mediate IgGs, we identified and characterized three FcγR classes, and generated recombinant cDNA constructs. cDNA IgH constructs were created by fusing – by sequence overlap extension PCRs – a gene segment encoding the murine variable heavy domain specific for the hapten NIP, …

Liv-1 Promotes Prostate Cancer Epithelial-To-Mesenchymal Transition And Metastasis Through Hb-Egf Shedding And Egfr-Mediated Erk Signaling, Hui-Wen Lue

Biology Dissertations

LIV-1, a zinc transporter, is an effector molecule downstream from soluble growth factors. This protein has been shown to promote epithelial-to-mesenchymal transition (EMT) in human pancreatic, breast, and prostate cancer cells. Despite the implication of LIV-1 in cancer growth and metastasis, there has been no study to determine the role of LIV-1 in prostate cancer progression. Moreover, there is no clear delineation of the molecular mechanism underlying LIV-1 function in cancer cells. In this study, we found increased LIV-1 expression in a progresssive manner in benign, PIN, primary and bone metastatic human prostate cancer. We characterized the mechanism by which …

The Influences Of Luxs In Escherichia Coli Biofilm Formation And Improving Teacher Quality Through The Bio-Bus Program, Chandan Morris Robbins

Biology Dissertations

The objectives of this work are: 1) to agarose-stabilize fragile biofilms for quantitative structure analysis; 2) to understand the influences of LuxS on biofilm formation; 3) to improve teacher quality by preparing Georgia’s middle school science teachers to integrate inquiry-based, hands-on research modules in the classroom. Quantitative digital image analysis demonstrated the effectiveness of the agarose stabilization technique for generating reproducible measurements of three dimensional biofilm structure. The described method will also benefit researchers who transport their flow cell-cultivated biofilms to a core facility for imaging. AI-2-dependent and independent effects of LuxS on biofilm-related phenotypes were revealed, suggesting that LuxS …

Analysis Of The Streptococcal Hemoprotein Receptor: A Role In Virulence And Host Defense, Ya-Shu Huang

Biology Dissertations

Group A streptococcus (GAS) is an important pathogen that produces a wide spectrum of suppurative infections and autoimmune sequelae in humans, ranging from less complex pharyngitis, impedigo to more severe manifestations such as necrotizing fasciitis, toxic shock syndrome, rheumatic fever and glomerulonephritis. The worldwide burden of GAS infections and sequelae is considerable, but an immunization program that defends against the hyper-variable GAS is missing. The streptococcal hemoprotein receptor (Shr), is an iron-regulated protein involved in heme acquisition. An unspecified region in the amino terminus of Shr mediates the interactions with hemoglobin and two protein modules named NEAT1 and NEAT2 bind …