Medical Sciences Commons^™

The Role Of Complement In The Clearance Of Streptococcus Pneumoniae Through Immune Adherence, Jie Li

All ETDs from UAB

Streptococcus pneumoniae is the most frequently isolated pathogen causing bacteremia in young children and elderly adults. Complement-dependent opsonophagocytosis is thought to be essential to eliminate pneumococci from the circulation. Pneumococci are reported to attach to erythrocytes through immune adherence (IA), a complement and antibody- dependent process that facilitates phagocytosis of pneumococci. In these studies we have determined that protein (chapter 1) and polysaccharide (chapter 2) virulence factors of pneumococci can interfere with this process and that antibody to pneumococci can enhance this process. Using PspA and/or PspC negative strains and complement-deficient mouse sera, we demonstrated that PspA inhibits complement C1q …

Kainate Receptor Modulation Of Synaptic Transmission In Neocortex, Seena S. Mathew

All ETDs from UAB

The actions of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) are tightly regulated to ensure effective information processing as well as prevention of excess excitatory activity, which can lead to seizures and neurological disorders such as epilepsy. Drugs which enhance the effects of GABA are used as anesthetics, sedatives and anticonvulsants. Using whole-cell patch clamp recordings from neocortical neurons, we examined the mechanisms of GABAergic modulation that occur when kainate receptors (KARs) are activated. First, we address a novel signaling mechanism for the KAR-mediated facilitation of GABAergic synaptic transmission. Our first observation involved the presence of presynaptic KARs located on the …

Primer Selection Of E. Coli Trna Lys,3 By Human Immunodeficiency Virus Type-1, Anna Mcculley

All ETDs from UAB

Human immunodeficiency virus (HIV) is the cause of acquired immunodeficiency syndrome (AIDS). HIV replication includes the notable process of reverse transcription, a conversion of RNA to DNA. Reverse transcription is initiated from a primer by a viral enzyme, reverse transcriptase. The primer, tRNALys,3, is selected from the cytoplasm of an infected cell, annealed via the 3’ terminal 18-nucleotides to the viral primer binding site (PBS), and used in a subsequent infection. The mechanism of primer selection has not been determined although numerous studies have been performed. This has been hampered by the challenge of tRNALys,3 manipulation in the cell and …

Directing Akt And Gsk3ss: Molecular Insights Into Cell Signaling And Survival, Gordon P. Meares

All ETDs from UAB

Proper regulation of survival signaling is critical for all organisms. One important signaling cascade involved in the coordinated effort to control signals influencing cell fate is the phosphatidylinositol 3-kinase (PI3K)-Akt-glycogen synthase kinase 3β (GSK3β) signaling cascade. Following activation by growth factors the PI3K-Akt pathway promotes cell survival and, cell death is facilitated following inhibition of Akt. Many factors influence the function of the Akt-GSK3β signaling dyad, including phosphorylation, protein complex formation and subcellular localization. Previous work had demonstrated that the 90kDa heat shock protein, HSP90, directly binds and stabilizes Akt. Furthermore, several heat shock proteins including HSP90 and HSP105 can …

The Function Of Hiv-1 A-Loop On Primer Selection, Na Ni

All ETDs from UAB

Reverse transcription is the hallmark of retroviruses, such as HIV-1. A cellular tRNA bound to the primer binding site region (PBS) is used for initiation of reverse transcription. HIV-1 specially selects tRNALys3 as primer, although changing the PBS can force HIV-1 to use alternative tRNAs as a primer. However, HIV-1 reverts back to use tRNALys3 following in vitro replication. The A-loop, located upstream of PBS, interacts with the anti-codon of primer tRNA. The inclusion of A-loop modification has been shown to stabilize the utilization of some alternative tRNAs. The studies in this dissertation focus on further defining the role of …

Regulation Of Vertebrate Gastrulation By Erbb Signaling, Shuyi Nie

All ETDs from UAB

ErbB receptor tyrosine kinases have long been implicated in cancer formation and progression by regulating cell division, migration, and survival. ErbBs are also essential in multiple processes during invertebrate development; however, their activities during vertebrate embryogenesis are not well understood. For functional characterization of ErbB signaling during vertebrate development, frog model Xenopus laevis was used in our studies. The expression pattern and the general activities of ErbB receptors during early frog development were first analyzed and results shown that ErbBs regulate gastrulation, somite organization and head patterning. As gastrulation is the first major morphogenetic event in vertebrate development, I focused …

Surveying The Chromosomal Supercoiling Levels In Rapidly Growing Wild Type And Gyrase Mutant Strains Of Salmonella Enterica Serovar Typhimurium With Γδ Resolvase-Mediated Recombination Assay, Zhenhua Pang

All ETDs from UAB

A gyrase mutant strain (gyrB652) has severe growth defect at 42°C. The survival at high temperature is dependent on DNA repair proteins. The purified mutant gyrase was assayed for supercoiling acitivity and quinolone-induced DNA cleavage activity. The results suggested that the mutant enzyme is not temperature-sensitive, but has slower kinetics than the wild type gyrase. The DNA supercoiling levels at multiple chromosomal loci in exponential phase cells were monitored with γδ resolvase-mediated recombination assay. The wild type cells showed homogenous supercoiling levels throughout most of the chromosome. But the superhelicity at dif locus was significantly lower than the other loci. …

Trafficking Of Hantaviral Nucleocapsid Proteins, Harish N. Ramanathan

All ETDs from UAB

Hantaviruses are enveloped, negative-sense RNA viruses belonging to genus Hantavirus, within the family Bunyaviridae. Hantaviruses include many serious human pathogens and are classified as Old and New World based on the geographic distribution of rodent reservoirs and their ability to in induce distinct illnesses in humans. Currently there are no reservoirs known for hantaviruses other than the rodents. Human transmission of hantaviruses occurs via inhalation of aerosolized rodent excreta leading to hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). Hantavirus genome consists of small (S), medium (M) and large (L) segments that encode nucleocapsid (N) protein, two …

The Role Of Complement In Experimental Autoimmune Uveitis, Russell W. Read

All ETDs from UAB

The complement system has been increasingly implicated in the pathophysiology of autoimmune disease. Complement expression in the normal human eye had not been previously completely defined. We performed immunohistochemical studies for membrane complement proteins in normal human retina to provide a baseline for future studies. We found expression of the anaphylatoxin receptors, CD55, and CD59 in the inner retina and CD46 in a polarized fashion on the retinal pigment epithelium. Previous studies in uveitis have shown activated fragments of complement in human eyes with uveitis and animal models have shown an effect on disease by complement depletion with cobra venom …

Pathogenesis And Therapeutic Potential Of Plasmacytoid Dendritic Cells In Siv/Shiv-Infected Macaques, R Keith Reeves

All ETDs from UAB

Plasmacytoid dendritic cells (pDCs) are among the first responders during acute viral infections and are the primary producers of IFN-α, a cytokine known to inhibit viral replication and to activate natural killer (NK) cells. In HIV patients pDCs are decreased in number, are dysfunctional, and can harbor HIV-1 proviruses. However, since the time of transmission is usually unknown, pDC-virus interactions immediately after exposure to HIV remain unclear. Using the SIV/SHIV-macaque model, we showed that an acute and sustained loss of blood pDCs occurred during SIVmac239 infections, and when compared to those from naïve controls, pDCs were also significantly reduced in …

In Vivo Imaging Studies In Animal Models Of Myocardial Infarction With And Without Cell Injections, Balazs Ruzsics

All ETDs from UAB

After prolonged myocardial ischemia, myocardial infarction occurs. Several tissue changes are associated with myocardial infarction and iron labeled cell injections. In the present thesis our major aim was to develop methods to monitor these tissue changes with MRI and MDCT. In the first chapter we used transendocardial injection to deliver iron labeled allogen skeletal myoblasts one week after myocardial infarction. Our goal was to identify the cells and/or injection sites in the myocardium. We used our new Tissue Characterization Mapping method to delineate tissue edema and hemorrhage in the myocardium. The T2 weighted signal intensity enhancement, T2w SIE region was …

The Characterization Of The Subcellular Localization Of Bile Acid Coa: N-Acyltransferase, Nathan Allen Styles

All ETDs from UAB

The liver plays a central role in metabolism. It controls protein metabolism through deamination and transamination of amino acids, removal of ammonia through urea synthesis, synthesis of non-essential amino acids and synthesis of the majority of plasma proteins such as albumin. The liver regulates blood glucose levels through glyconeogenesis and glyconeolysis of glycogen, as well as gluconeogenesis from amino acids. It regulates fat metabolism through oxidation of triglycerides and fatty acids, as well as synthesis of cholesterol, lipoproteins, and phospholipids. Furthermore, the liver is the only site of formation of bile acids and their conjugates, physiologically important compounds that solubilize …

Bacillus Anthracis Spore-Host Interactions, Melissa K. Swiecki

All ETDs from UAB

The use of Bacillus anthracis as a bioweapon depends on the dispersal of its spores into the environment, entrance into the body, spore uptake by human host cells, germination of the spores in the host and the pathological consequences of the virulence factors produced by the vegetative cells. Prior to 2001, very little was known about the mechanisms of spore entry into the host, including targeting cell types at airway, digestive and skin surfaces, potential spore receptors on these cells and spore encounters with cellular and humoral elements of the innate and adaptive immune systems. To this end, we have …

Relaxation Rate-Based Magnetic Resonance Imaging Quantification Of Myocardial Infarction, Pal Suranyi

All ETDs from UAB

Ischemic heart disease is the leading cause of mortality in western societies. Treatment needs to be tailored for each individual, which requires accurate assessment of the underlying pathology. Magnetic Resonance Imaging (MRI) is a relatively young modality in the field of cardiovascular imaging, and boasts with the lack of harmful radiation, excellent soft tissue contrast, and high spatial-temporal resolution. The very foundation of the concept of MRI was the finding that pathology causes changes in the relaxation rates of tissues. Measurement of relaxation rates is more time consuming than generating simple signal intensity images weighted by the longitudinal or transverse …

Genetic And Epigenetic Regulation Of Dihydropyrimidinase And Beta-Ureidopropionase In Individuals With Altered Uracil Catabolism And Normal Dihydro Pyrimidine Dehydrogenase Enzyme Activity, Holly Reed Thomas

All ETDs from UAB

There remain a number of patients presenting with 5-fluorouracil (5-FU) toxicity despite normal dihydropyrimidine dehydrogenase (DPD) enzyme activity, suggesting possible deficiencies in the two enzymes downstream of DPD in the uracil catabolic pathway: dihydropyrimidinase (DHP), encoded by the DPYS gene, or β-ureidopropionase (BUP-1), encoded by the UPB1 gene. Unlike DPD, which is expressed in peripheral blood mononuclear cells (PBMCs), DHP and BUP-1 enzyme activity is detected in only the liver and kidney, thus requiring an invasive biopsy for determination of activity. This dissertation, therefore, focuses on the role of the genetic and epigenetic regulation of DPYS and UPB1. The genetic …

Effects Of Specific Alterations In Capsule Structure On Streptococcus Pneumoniae Capsule Assembly And Virulence, Bobbi Xayarath

All ETDs from UAB

The polysaccharide capsules of Streptococcus pneumoniae represent the most important virulence determinant produced by this organism. Ninety-one different serotypes have been identified, but only a small number of these serotypes are responsible for most of the infections caused by S. pneumoniae. The reasons why certain serotypes predominate in infections over others are not well understood. One common serotype found in invasive diseases is type 2, however, it is unclear what characteristics of a type 2 capsule makes strains producing it virulent. The type 2 capsule consists of repeat units made of a backbone of Glc-Rha-Rha-Rha, with a side chain Glc-GlcUA …

The Role Of Cd5 In Experimental Autoimmune Encephalitomyelitis, Robert C. Axtell

All ETDs from UAB

The regulation of activation, differentiation and persistence of effector T-cells are critical for the development of Experimental Autoimmune Encephalomyelitis (EAE), the animal model of Multiple Sclerosis. Until now, the function of CD5 was accepted to be a negative regulator of T-cell activation. This dissertation reports that CD5 has an addi-tional role in T-cell responses, which is to promote cell survival. Observations from EAE experiments revealed that mice deficient in CD5 exhibited decreased disease severity which was associated with the inability of activated T-cells to survive. Moreover, block-ing the engagement of CD5 in mice led to enhanced activation induced cell death …

Cd8+ T-Lymphocytes And The Control Of Cytomegalovirus Infection Of The Newborn Central Nervous System, Glenn Robert Burgner Bantug

All ETDs from UAB

Congenital HCMV infection of the developing brain is the leading viral cause of mental retardation and sensorineural hearing loss. To elucidate the pathogenesis of congenital HCMV CNS infections, we developed a small animal model of CMV infection where newborn Balb/c mice are peripherally inoculated with murine cytomegalovirus. In this model we observed transient deficits in cerebellar/hindbrain development as well as the recruitment of peripheral immune effector cells to the CNS parenchyma. CD8+ T-lymphocytes were the predominant mononuclear cellular infiltrates in the brain and immune-depletion of CD8+ cells resulted in increased viral genome copy numbers in the CNS. CD8+ T-lymphocytes exhibited …

A Proteome-Wide Protein Interaction Map For Campylobacter Jejuni, Jodi R. Parrish, Jingkai Yu, Guozhen Liu, Julie A. Hines, Jason E. Chan, Bernie A. Mangiola, Huamei Zhang, Svetlana Pacifico, Farshad Fotouhi, Victor J. Dirita, Trey Ideker, Phillip Andrews, Russell L. Finley Jr

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Data from large-scale protein interaction screens for humans and model eukaryotes have been invaluable for developing systems-level models of biological processes. Despite this value, only a limited amount of interaction data is available for prokaryotes. Here we report the systematic identification of protein interactions for the bacterium Campylobacter jejuni, a food-borne pathogen and a major cause of gastroenteritis worldwide.

Results

Using high-throughput yeast two-hybrid screens we detected and reproduced 11,687 interactions. The resulting interaction map includes 80% of the predicted C. jejuni NCTC11168 proteins and places a large number of poorly characterized proteins into networks that provide initial …

Exploration Of Computational Methods For Classification Of Movement Intention During Human Voluntary Movement From Single Trial Eeg, Ou Bai, Peter Lin, Sherry Vorbach, Jiang Li, Steve Furlani, Mark Hallett

Electrical & Computer Engineering Faculty Publications

Objective: To explore effective combinations of computational methods for the prediction of movement intention preceding the production of self-paced right and left hand movements from single trial scalp electroencephalogram (EEG).

Methods: Twelve naïve subjects performed self-paced movements consisting of three key strokes with either hand. EEG was recorded from 128 channels. The exploration was performed offline on single trial EEG data. We proposed that a successful computational procedure for classification would consist of spatial filtering, temporal filtering, feature selection, and pattern classification. A systematic investigation was performed with combinations of spatial filtering using principal component analysis (PCA), independent component analysis …