Medicine and Health Sciences Commons^™

Human Cytosolic Sulfotransferase 2b1b: Structure, Function And Expression In Human Brain, Emily D. Salman

All ETDs from UAB

The human cytosolic sulfotransferases are a family of phase II drug-metabolizing enzymes that conjugate a sulfonate moiety from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to a hydroxyl moeity on a substrate. SULT2B1b catalyzes the sulfation of hydroxysteroids as well as many xenobiotics; and is expressed extra-hepatically. SULT2B1b is a unique SULT because it has amino (N)- and carboxy (C)-terminal peptide extensions, undergoes post-translational modification, and is localized in both the cytosol and nucleus. Analysis of SULT2B1b revealed that the N- and C-terminal extensions of SULT2B1b are predicted to be intrinsically unstructured peptides. Size exclusion chromatography has revealed that SULT2B1b is enzymatically active as …

In Vivo Analysis Of The Natural Diversity Of The Igr Ires Family And Characterization Of The Role Of Ribosomal Protein S25 In Ires-Mediated Translation, Marla Ilene Hertz

All ETDs from UAB

Translation of the majority of eukaryotic mRNAs is initiated upon recognition of its 5' cap structure by translation initiation factors in so-called cap-dependent translation. Cap-dependent translation is repressed during cell stress and translation initiation by internal ribosome entry sites (IRESs) predominates. IRESs, located in the 5' untranslated region of specific mRNAs, recruit the ribosome independent of the 5' cap and are essential regulatory elements in many RNA viruses and cellular messages. The dysregulation of cellular IRESs has been linked to cancer because they regulate the expression of genes involved in growth, development and stress response. In comparison to cap-dependent translation, …

Biological Characterization Of Transmitted Human Immunodeficiency Virus Type-1, Tara Grant Edmonds

All ETDs from UAB

Heterosexual transmission of human immunodeficiency virus type&ndash1 (HIV&ndash1) accounts for the majority of infections worldwide, with women representing the larger percentage of infected individuals. The events leading to the transmission of HIV&ndash1 at mucosal surfaces are not well defined. Based on the observations that transmitted viruses nearly exclusively utilize the CCR5 coreceptor, and that in 80% of heterosexual transmissions a single virus variant establishes infection, there appears to be a selection mechanism that allows only a subset of viruses to be transmitted. This genetic bottleneck suggests that transmitted viruses may possess specific phenotypic and/or genotypic properties that allow for their …

Molecular Mechanisms Regulating Caenorhabditis Elegans Sperm Migration, Johnathan Wesley Edmonds

All ETDs from UAB

Fertilization is the process by which male and female gametes join to give rise to a new organism. Union of sperm and ova requires that sperm be able to successfully locate and migrate towards oocytes in the female reproductive tract. By analyzing the in vitro migration of sperm from diverse species and mapping the complex architecture of their female reproductive tracts, we can infer that sperm must respond to directional cues to seek out the mature oocyte. However, the internal fertilization schemes of most complex animals complicate the analysis of in vivo sperm migration. The transparent epidermis of the nematode …

The Role Of Tgf-Ss Receptors In The Induction Of Mucosal Tolerance, Rebekah Sims Gilbert

All ETDs from UAB

Oral tolerance, defined as the immunologic state of systemic and mucosal unresponsiveness to an antigen, is an essential function of the mucosal immune system. Although antigen presentation has been found to play an important role in oral tolerance, T cells are known to be the effector immune cells that perpetrate this state. Recent studies found that antigen-specific T regulatory (Treg) cells are important in the induction and maintenance of oral tolerance. The extrathymic development of these Tregs depends on the presence of TGF-ß1 during the differentiation process. However, it has also been shown that oral tolerance could be induced in …

The Sodium-Potassium-Chloride Cotransporter In Glioma Biology, Brian R. Haas

All ETDs from UAB

The most common malignant primary brain tumor, gliomas usually derive from glial cells including oligodendrocytes and astrocytes. These tumors are characterized by high rates of proliferation and aberrant migration which make them notoriously difficult to treat using standard treatment paradigms such as chemotherapy and radiation. In order for glioma cells to migrate into the surrounding brain tissue, they must undergo rapid and dynamic volume changes. Previous work published by the Sontheimer laboratory and others indicates glioma utilize the flux of ions across the cell membrane to aid in volume changes associate with cell migration. In this dissertation, I show the …

Qualitative Analysis Of Hiv-1-Specific Cd8 T Cell Responses, Olusimidele Tolulope Akinsiku

All ETDs from UAB

In the absence of antiretroviral therapy (ART), the majority of individuals infected with human immunodeficiency virus-1 (HIV-1) will develop AIDS. HIV-1-infected controllers are exceptions to the rule; without the use of ART, these individuals spontaneously control virus replication. A better understanding of the immune mechanisms that mediate delayed disease progression, as seen in controllers, will provide valuable insight to the design and development of an effective HIV-1 vaccine. CD8 T cells are important mediators of the antiviral immune response. However, it is unclear which components of the response are critical for long-lasting protection during HIV-1 infection. We first review methods …

The Role Of Protease-Activated Receptor-1 In Synaptic Plasticity And Memory, Antoine Gabriel Almonte

All ETDs from UAB

Protease-activated receptor-1 (PAR1) is an unusual G-protein coupled receptor (GPCR) that is activated through proteolytic cleavage by extracellular serine proteases. While previous work has shown that inhibiting PAR1 activation is neuroprotective in models of ischemia, traumatic injury, and neurotoxicity, surprisingly little is known about PAR1's contribution to normal brain function. In the central nervous system (CNS), PAR1 is expressed in glial cells in the hippocampus, a brain region critical for memory formation. I am particularly interested in PAR1 because its activation enhances the function of N-methyl-D-aspartate receptors (NMDARs), which are required for some forms of behavioral learning and synaptic plasticity. …

Structural Analyses Of Streptococcus Agalactiae Sortases, Baldeep Khare

All ETDs from UAB

Multi-drug resistance in Gram-positive bacteria is a growing and unwavering challenge for twenty-first century medicine. The enzyme sortase, identified just around the turn of the century, has since become a promising target for development of anti-infective drugs. Streptococcus agalactiae or Group B Streptococcus (GBS), encodes multiple sortases, which participate in various processes and whose functions are only beginning to be understood in detail. Sortases are cysteine proteases that are crucial for Gram-positive pili biogenesis. Two classes of sortases, class C and class A, participate in the assembly of structural components (pilins) to form the pili and subsequent anchoring of the …

Broad And Potent Neutralizing Antibody Responses Elicited In Natural Hiv-2 Infection, Rui Kong

All ETDs from UAB

Little is known about the potency, breadth and epitope specificities of neutralizing antibody (Nab) responses elicited in natural HIV-2 infection. Analysis of plasma specimens from 64 HIV-2 chronically-infected subjects in a single round infectivity assay (JC53bl-13/TZM-bl) revealed median reciprocal IC50 Nab titers of 1.7x105, 2.8x104 and 3.3x104 against three primary virus strains, HIV-27312A, HIV-2ST and HIV-2UC1, respectively. A subset of 5 plasma samples was tested on 17 additional HIV-2 strains, and similarly high Nab titers were observed against all but four viruses. These Nab titers were higher, by orders of magnitude, than HIV-1 Nab titers in plasma from chronically infected …

Structural And Functional Studies On Group A Streptococcal Bacteriophage Hyaluronidase, Joo Hyoung Lee

All ETDs from UAB

Aberrant hyaluronan production is frequently associated with tumors where the elevated levels of tumoral hyaluronan are often associated with higher expression levels of cellular hyaluronidases that produce saturated hyaluronan fragments with divergent pro-tumoral activities. In this thesis, we provide evidence that different hyaluronan metabolism of bacteriophage hyaluronidase (HylP) elicits distinct alteration in breast cancer cell behavior. We demonstrate through comparative analysis with bovine testicular hyaluronidase (BTH) that higher enzyme activity, specificity for hyaluronan and production of unsaturated oligosaccharides render HylP to have profound effects on growth, migration and invasion activities of breast carcinoma cells, whereas BTH and its saturated metabolites …

Role Of Ras Proteins In Malignant Peripheral Nerve Sheath Tumors, Nicole Marie Brossier

All ETDs from UAB

Malignant peripheral nerve sheath tumors (MPNSTs) arising in patients with neurofibromatosis type I (NF1) are null for the tumor suppressor neurofibromin, a negative regulator of signaling from both classic Ras (H-Ras, N-Ras and K-Ras) and R-Ras (R-Ras, R-Ras2/TC21, M-Ras/R-Ras3) subfamily members. Treatment of these tumors with Ras-targeted agents such as farnesyltransferase inhibitors has proven unsuccessful, likely due to the inability of these agents to successfully target all of the Ras isoforms regulated by neurofibromin. Thus, determining which Ras isoforms are critical for MPNST pathogenesis would be of therapeutic value. In this dissertation, we first review the clinical manifestations of NF1 …

Role Of The Cystine/Glutamate Exchanger In Glioma Cell Biology, Toyin Adeyemi Ogunrinu

All ETDs from UAB

Changes in the glioma microenvironment including oxygen (O2) levels, supply of amino acid such as L-glutamate and L-cystine and glutathione (GSH) concentrations play a critical role in glioma biology. Previous data from our laboratory and others have implicated the L-cystine/L-glutamate exchanger, system xc- in the invasion and proliferation of cancers including glioma. The central aim of this dissertation was to characterize the contribution of L-cystine uptake, GSH synthesis and L-glutamate release to migration and proliferation of glioma cells. In my first study, I examined the role of system xc- mediated L-glutamate release on glioma migration. I show that activation of …

Molecular Piracy In The Mobilization Of Staphylococcus Aureus Pathogenicity Island 1, Michael Spilman

All ETDs from UAB

Staphylococcus aureus bacteriophage 80α is a temperate, double-stranded DNA phage that serves as a "helper" phage for the mobilization of several S. aureus pathogenicity islands (SaPIs), including SaPI1. When mobilized by 80α, SaPI1 genomes are packaged into smaller phage-like transducing particles composed of 80α capsid (gp47), scaffolding (gp46) and portal (gp42) proteins. In this dissertation, I utilize electron microscopy and biochemistry to tease apart the structural and genetic controls and consequences of SaPI1 as a molecular pirate. More specifically, I show that two SaPI1 proteins shift assembly from 63-nm, T = 7 icosahedral capsids to 47-nm, T = 4 capsids, …

Calcium Dynamics Of Glial Cells And Genetic Influences On Behavior Of The Nematode Caenorhabditis Elegans, Randy Franklin Stout

All ETDs from UAB

A major challenge in neuroscience is understanding how the different neural cell types work together to process information and produce a behavioral output. Glial cells of the human brain have long been thought to act as support for the fundamental cell to cell communication at the core of cognition: neuronal synaptic communication. Research over the past several decades measuring glial activity and experimentally controlling glial cells in rodent model systems has shown that the two macroglia sub-types of glial cells (astrocytes and oligodendrocytes) have active roles in establishment, maintenance, and modulation of synaptic communication in the mammalian brain. Much of …

Assessment Of Mitochondrial Stressors On Cellular Bioenergetics, Blake Reid Zelickson

All ETDs from UAB

The mitochondrion plays a central role in the maintenance of bioenergetic function through the production of ATP and essential metabolites. The development of mitochondrial bioenergetic defects is a hallmark of important pathologies such as cardiovascular and liver diseases. It is well established that a decrease in mitochondrial function, typically of 20-40%, is associated with the progression of these pathologies. Causal relationships have been more difficult to establish because of the challenge of assessing mitochondrial function in a cellular setting. Specifically, it is known that mitochondria function at less than their maximal respiratory capacity and the remainder, known as reserve or …

In Vivo Interactions Between Virus Genomes And Host Proteins For Members Of The Order Picornavirales, Erik Michael Lenarcic

All ETDs from UAB

A significant number of pathogens of economical and medical importance are positive sense RNA viruses. Their genomes enter host cells and subvert them to support virus growth. These large-scale changes involve the co-opting of cellular proteins through interactions with viral RNA and proteins. Characterizing these interactions leads to a better understanding of viral life cycles and the identification of new antiviral therapies. The order Picornavirales contains viruses that infect a wide array of eukaryotes. Their genomes serve as a messenger RNA (mRNA) that is translated by host ribosomes cap-independently through an internal ribosome entry site (IRES). Most members of the …

The Intestinal Extracellular Matix As An Innate Regulator Of Effector T-Cell Responses, Kayci Renee Huff

All ETDs from UAB

Extracellular matrix (stroma) regulation of mucosal T-cell function is incompletely understood. Here we uncovered a role for intestinal stromal products in the innate regulation of effector T-cells. Stroma-conditioned media (S-CM) derived from normal human intestinal stroma (TGF-&betahi/IL-6lo/IL-1ßlo) significantly down-regulated T-cell proliferation and IFN-&gamma production compared to S-CM derived from inflamed Crohn's mucosa (TGF-&betahi/IL-6hi/IL-1&betahi). Antibody neutralization studies showed that TGF-&beta in normal S-CM inhibited T-cell proliferation and IFN-&gamma production, whereas IL-6 plus IL-1&beta in Crohn's S-CM promoted T-cell proliferation, and the IL-1&beta alone promoted IFN-γ and IL-17 release. Importantly, stromal cells in normal tissue produce TGF-&beta and contribute to mucosal homeostasis …

Faculty Publications 2010, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 844 publications.

Role Of Membrane Lipids In Modulating Protein Structure & Function, Ray Supriyo

Electronic Theses and Dissertations

A-B family of toxins consists of plant toxins such as ricin and bacterial toxins such as cholera. The A subunit is the enzymatic domain and the B subunit is the receptor binding domain. Commonly, these toxins bind to the target cell plasma membrane receptors through their B subunit followed by endocytosis and a transport to the endoplasmic reticulum (ER). Inside the ER, the A subunit dissociates from the rest of the toxin, unfolds and triggers the ER quality control mechanism of ER-associated degradation (ERAD). Most ERAD substrates are purged out of the ER into the cytosol for proteasomal degradation. However, …

Hybrid Adult Neuron Culture Systems For Use In Pharmacological Testing, Darin Keay Edwards

Electronic Theses and Dissertations

Neuronal culture systems have many applications, such as basic research into neuronal structure, function, and connectivity as well as research into diseases, conditions, and injuries affecting the brain and its components. In vitro dissociated neuronal systems have typically been derived from embryonic brain tissue, most commonly from the hippocampus of E18 rats. This practice has been motivated by difficulties in supporting regeneration, functional recovery and long-term survival of adult neurons in vitro. The overall focus of this dissertation research was to develop a dissociated neuronal culture system from human and animal adult brain tissue, one more functionally and developmentally correlative …

Discovery And Optimization Of Novel Small-Molecular Inhibitors Suppressing Stat3-Dependent Tumor Process, Xiaolei Zhang

Electronic Theses and Dissertations

With the critical role of aberrantly active Signal Transducer and Activator of Transcription (Stat) 3 protein in many human cancers, selective small-molecule inhibitors targeting the dimerization event which is required for stat3 activation, would be valuable as therapeutic agents. And the inhibitors will be useful chemical probes to clarify the complex biological functions of Stat3. By computational and structural analyses of the interaction between Stat3 and the lead dimerization disruptor, S3I-201, we have designed a diverse set of analogs. One of the most active analogs, S3I-201.1066 is derived to contain a cyclo-hexyl benzyl moiety on the amide nitrogen, which increases …

Genetic And Physiological Contribution Of Adrenergic Cells In Heart Development, Kingsley Osuala

Electronic Theses and Dissertations

The adrenergic hormones norepinephrine (NE) and epinephrine (EPI) are essential for cardiovascular development as embryos lacking NE/EPI begin to die abruptly between embryonic days 10.5 and 11.5 due to apparent cardiac failure. The objective of this research aims to elucidate the mechanism of the embryonic fatality observed in the NE/EPI deficient mouse model. Here we utilized the dopamine β- hydroxylase knockout (Dbh-/-) mouse model, which lacks the gene and subsequent enzyme necessary for the conversion of dopamine to norepinephrine. Embryonic mouse hearts were extracted from Dbh+/+ (control) and Dbh-/- (experimental model) mice for mRNA transcript expression profiling. These studies were …

Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass

Electronic Theses and Dissertations

Transplanted embryonic stem (ES) cells following myocardial infarction (MI) contribute to limited cardiac repair and regeneration with improved function. Therefore novel strategies are still needed to enhance the efficacy by which ES cells differentiate into cardiac cell types and inhibit adverse remodeling in the infarcted myocardium. Our studies evaluate whether genetic manipulation of transplanted ES cells employing miR- 1, a pro-cardiac microRNA, and TIMP-1, an anti-apoptotic and anti-fibrotic protein, will enhance cardiac myocyte differentiation, inhibit native cardiac apoptosis, and reduce fibrosis in the infarcted myocardium. Furthermore, we assess levels of associated pro- (caspase-3, PTEN) and anti-(Akt) apoptotic proteins as well …

Translocation Of The Cholera Toxin A1 Subunit From The Endoplasmic Reticulum To The Cytosol, Michael Prentice Taylor

Electronic Theses and Dissertations

AB-type protein toxins such as cholera toxin (CT) consist of a catalytic A subunit and a cell-binding B subunit. CT proceeds through the secretory pathway in reverse, termed retrograde trafficking, and is delivered to the endoplasmic reticulum (ER). In order for the catalytic A1 subunit to become active it must separate from the rest of the holotoxin, and this dissociation event occurs in the ER lumen. CTA1 assumes an unfolded conformation upon dissociation from the holotoxin and is recognized by ERassociated degradation (ERAD), a quality control system that recognizes and exports misfolded proteins to the cytosol for degradation by the …

Glial Differentiation Of Human Umbilical Stem Cells In 2d And 3d Environments, Hedvika Davis

Electronic Theses and Dissertations

During differentiation stem cells are exposed to a range of microenvironmental chemical and physical cues. In this study, human multipotent progenitor cells (hMLPCs) were differentiated from umbilical cord into oligodendrocytes and astrocytes. Chemical cues were represented by a novel defined differentiation medium containing the neurotransmitter norepinephrine (NE). In traditional 2 dimensional (2D) conditions, the hMLPCs differentiated into oligodendrocyte precursors, but did not progress further. However, in a constructed 3 dimensional (3D) environment, the hMLPCs differentiated into committed oligodendrocytes that expressed MBP. When co-cultured with rat embryonic hippocampal neurons (EHNs), hMLPCs developed in astrocytes or oligodendrocytes, based on presence of growth …

Getting To Know You: Key Clinical Concepts In Relationship-Based Interventions And Neurobehavioral Observations With Young Infants, Yvette Blanchard

All PTHMS Faculty Publications

The newborn infant is a social organism, pre-disposed to interact with his caregiver and able to elicit the kind of caregiving necessary for successful adaptation. The earliest developmental task of the newborn is to organize behavior to be able to play an active role in influencing the caregiving environment and eliciting the kind of support needed for development. This task is accomplished through the attainment of self-regulation or balanced neurobehavioral functioning of the infant's autonomic, motor, state, and responsivity behavioral dimensions as described by Als.

Development Of Fetal Movement Between 26 And 36 Weeks’ Gestation In Response To Vibroacoustic Stimulation, Marybeth Grant-Beuttler, Laura M. Glynn, Amy L. Salisbury, Elyssia Poggi Davis, Carol Holliday, Curt A. Sandman

Psychology Faculty Articles and Research

BACKGROUND: Ultrasound observation of fetal movement has documented general trends in motor development and fetal age when motor response to stimulation is observed. Evaluation of fetal movement quality, in addition to specific motor activity, may improve documentation of motor development and highlight specific motor responses to stimulation.

AIM: The aim of this investigation was to assess fetal movement at 26 and 36-weeks gestation during three conditions (baseline, immediate response to vibro-acoustic stimulation (VAS), and post-response).

DESIGN: A prospective, longitudinal design was utilized.

SUBJECTS: Twelve normally developing fetuses, eight females and four males, were examined with continuous ultrasound imaging.

OUTCOME MEASURES: …

The Effect Of High Dose Total Body Irradiation On Acth, Corticosterone, And Catecholamines In The Rat, Eric P. Cohen, Eric D. Bruder, William E. Cullinan, Dana R. Ziegler, Hershel Raff

Biomedical Sciences Faculty Research and Publications

Total body irradiation (TBI) or partial body irradiation is a distinct risk of accidental, wartime, or terrorist events. Total body irradiation is also used as conditioning therapy before hematopoietic stem cell transplantation. This therapy can result in injury to multiple tissues and might result in death as a result of multiorgan failure. The hypothalamic–pituitary–adrenal (HPA) axis could play a causative role in those injuries, in addition to being activated under conditions of stress. In a rat model of TBI, we have established that radiation nephropathy is a significant lethal complication, which is caused by hypertension and uremia. The current study …

An Investigation Of The Subtype Diversity Of Clinical Isolates Of Irish Clostridium Difficile Ribotypes 027 And 078 By Repetitive-Extragenic Palindromic Pcr, Denise Drudy, K. Solomon, S. Murray, L. Scott, S. Mcdermott,, A. Martin, C. O’Donoghue, M. Skally, K. Burns, L. Fenelon, F. Fitzpatrick,, L. Kyne, S. Fanning

Articles

A repetitive-extragenic palindromic PCR (rep-PCR) subtyping method (DiversiLab) in conjunction with ribotyping, toxinotyping and antimicrobial-susceptibility testing was used to detect subtypes within Clostridium difficile ribotypes 027 and 078. Clinical isolates of ribotypes 027 (toxinotype III) (n530) and 078 (toxinotype V) (n523) were provided by health-care facilities across the Republic of Ireland over 2 months in 2006 and 1 month in 2009. Ribotype 027 isolates were significantly more related to each other (9 different subtype profiles) when compared to ribotype 078 isolates (14 different profiles) (P50.001; cut-off .90 % similarity). Almost half of ribotype 078 isolates (45.5 %) showed no relationship …