Medicine and Health Sciences Commons^™

Purification, Characterization, And Enzymatic Activity Of Human Cytosolic Sulfotransferase 1c4, Amber Lynn Guidry

All ETDs from UAB

Human cytosolic sulfotransferase 1C4 (hSULT1C4) is a dimeric Phase II drug-metabolizing enzyme primarily expressed in the developing fetus. SULTs facilitate the transfer of a hydrophilic sulfonate moiety from 3’-phosphoadenosine-5’-phosphosulfate (PAPS) onto an acceptor substrate altering the substrate’s biological activity and increasing the compound’s water solubility. While several of the hSULTs’ endogenous and xenobiotic substrates have been identified, the physiological function of hSULT1C4 remains unknown. The fetal expression of hSULT1C4 leads to the hypothesis that the function of this enzyme may be to regulate metabolic and hormonal signaling molecules, such as estrogenic compounds, that may be generated or consumed by the …

Immunoregulation During Acute And Chronic Exposure To Aspergillus Fumigatus, Jaleesa M. Garth

All ETDs from UAB

A. fumigatus is one of the most common fungal isolates with clinical disorders ranging from mild to severe. The development of Aspergillus-induced allergic and invasive fungal infections is a major health concern in several patient populations. IL-1 family members have been shown to play critical roles in host defense against A. fumigatus. IL-33, an IL-1 family member widely study in allergic and inflammatory diseases, was induced upon acute exposure to A. fumigatus. IL-33 receptor knockout mice, (Il1rl1-/-), demonstrated lower lung fungal burden in the presence of enhanced IL-1α, IL-1β, IL-6, IL-17A, IL-22, and PGE2 production. Administration of IL-33 to normal …

Identification Of The Microrna Mir-101a And Its Target Ezh2 As Contributors To Rodent Anxiety-Like Behavior, Joshua Cohen

All ETDs from UAB

Anxiety disorders are the most commonly diagnosed mental illness in the United States. Yet current treatment options are of limited efficacy, resulting in chronic disability for many patients. A greater mechanistic understanding of the neural states that cause anxiety behavior is necessary to develop better treatments for anxiety disorders. Since rodent models provide greater opportunity for investigating cellular and molecular under-pinnings of anxiety-like behavior, the present studies utilized rats bred for High Response to novelty (High Responders, HRs) and Low Response to novelty (Low Responders, LRs) which naturally exhibit low and high levels of anxiety respectively. Because the HR/LR anxiety …

Tgf-Β Regulates The Stability Of Sox9 In Cartilage, George Coricor

All ETDs from UAB

One out of two people in the U.S. will experience some form of Osteoarthritis (OA) in their lifetime. Members of the Transforming Growth Factor-β (TGF-β) superfamily are important factors that stimulate chondrocyte matrix biosynthesis. Mice with a dominant-negative mutation of the TGF-βIIR develop a degenerative joint disease resembling OA. Another key chondrogenic factor, SOX9, is important for maintaining chondrocyte function. SOX9 and TGF-β receptors are decreased in OA patients. Our overall hypothesis is that TGF-β regulates SOX9 to maintain articular cartilage. We utilized two cell culture models for these experiments, ATDC5 cells, and primary bovine articular chondrocytes. We showed that …

Attachment Of Streptococcus Pneumoniae Capsular Polysaccharide To The Cell, Thomas Robbin Larson

All ETDs from UAB

Streptococcus pneumoniae is an important human pathogen. The major virulence factor for S. pneumoniae is the capsular polysaccharide (CPS). Proper expression and localization of the CPS is essential for pathogenesis. Despite the importance of the proper transfer to the cell surface of this virulence factor, no studies have shown the exact structure and attachment to either the cell wall or membrane. Using the S. pneumoniae serotype 2 CPS as a model, which is synthesized by the widespread Wzy mechanism, we found that the CPS attaches to the cell wall β-D-N-acetylglucosamine (GlcNAc) of peptidoglycan (PG) via a direct glycosidic linkage. This …

N-Acetyl-D-Glucosamine-Reactive Natural Antibodies: Roles In Suppression Of Autoimmune Diabetes And Environmental Factors Influencing Their Development, James Stewart New

All ETDs from UAB

Type 1 Diabetes suppression in diabetes prone mice following immunization with Group A Streptococcus correlates with the B lymphocyte response to N-acetyl-D-glucosamine (GlcNAc) present in the Group A Carbohydrate cell wall polysaccharide. GlcNAc-specific B cells recognize cryptic GlcNAc-epitopes in beta cells. Following exposure of GlcNAc-modified antigens on beta cells during cellular apoptosis, GlcNAc-specific IgM antibodies opsonize these epitopes and mediate classical complement pathway activation. In vitro, opsonization of apoptotic beta cells with GlcNAc-specific IgM increases their uptake by dendritic cells, while suppressing the subsequent presentation of beta cell-derived antigens to diabetogenic T lymphocytes. Passive administration of Group A Streptococcus antisera …

Elucidating The Physiologic And Prognostic Significance Of N-Myc And Stat Interactor Using Models Of Mammary Development And Metastasis, Hawley Christine Pruitt

All ETDs from UAB

Distant metastasis of breast carcinoma reduces the five year survival rate of patients from 90% to a dismal 25%. Although the metastatic cascade has been extensively studied for decades, players that influence the progression of metastatic disease remain elusive. N-MYC and STAT Interactor (NMI) is a gene previously demonstrated by Devine et. al. to be downregulated with metastatic progression of breast cancer. However, due to the lack of a relevant genetic model, details of biological consequence of the loss of expression of this gene were unknown. We have constructed and characterized a mammary specific Nmi knock out mouse to elucidate …

Uncovering The Role Of Common Gamma-Chain Cytokines In Aspergillus Fumigatus Associated Diseases, Kristen Marie Reeder

All ETDs from UAB

Fungal pathogens contribute to a wide range of diseases that are largely dependent on the host’s immune state. In the case of immune suppression, Aspergillus fumigatus is the causative agent of invasive aspergillosis. Furthermore, asthmatics sensitized to fungi such as Aspergillus fumigatus are reported to have more severe asthma. We have previously described a role for IL-22 in mouse models of invasive aspergillosis and fungal asthma. IL-22 was found to play a protective role in invasive aspergillosis, while it was found to play an immunopathogenic role in asthma. Here we describe the cell sources of IL-22 in both models. We …

Relationship Between Walking Speed And Kinematic Trajectory Complexity In People With Poststroke Hemiparesis, Deanna Delayne Rumble

All ETDs from UAB

Individuals with chronic poststroke hemiparesis (PS) exhibit increased variability in spatiotemporal kinematic variables related to endpoint control during walking. For nonimpaired individuals, walking faster or slower than a preferred walking speed, results in less consistent stepping behavior. In three studies I investigated variability in swing phase foot trajectory area on a step-by-step basis (SBS-FTA) in nonimpaired individuals and people with PS. The primary aims of these studies were to 1) validate SBS-FTA in nonimpaired individuals, 2) observe if there was a difference in SBS-FTA variability between nonimpaired individual’s limb, the PS paretic, and nonparetic limbs, and across a wide range …

The Role Of Hur In Astrocytes In Spinal Cord Injury, Thaddaeus Kwan

All ETDs from UAB

Neuroinflammation is a defining event during the acute phase of spinal cord injury (SCI). The inflammatory cascade is initiated by activated glial cells such as astrocytes and microglia in the milieu of the injured tissue through release of pro-inflammatory cytokines, matrix metalloproteinases, and reactive oxygen species. These soluble factors produce cytotoxicity to neurons and other cells either directly or indirectly by promoting permeabilization of the blood-spinal cord barrier, edema and subsequent ischemia. These factors also serve to recruit and activate additional glia and peripheral immune cells. The mRNAs of many of these soluble factors such as TNFα, IL-1β, CXCL1, and …

Post-Transcriptional Regulation Of Autophagy By The 5’-3’ Mrna Decay Pathway In Saccharomyces Cerevisiae, Matthew Weaver

All ETDs from UAB

The process of bulk degradation of cytoplasmic contents, called macroautophagy or simply autophagy, is a heavily conserved cellular process from yeast to humans. In yeast, it involves more than 30 different autophagy related genes (ATG) that coordinate the process of building a double membrane vesicle, called the autophagosome, that fuses with the vacuole to allow degradation and recycling of its contents. This process can also be selective, involving the recruitment of the autophagic machinery to specific organelles. In this work, we used RNA sequencing (RNA-seq) to identify a subset of ATG genes that are heavily upregulated in response to nitrogen …

The Role Of Adipocytes And Osteocytes In Multiple Myeloma Progression, Timothy Nathan Trotter

All ETDs from UAB

Multiple myeloma (MM) is a hematological malignancy of plasma cells that is intrinsically tied to the bone marrow (BM). Many cells in the BM microenvironment have been studied in MM, yet there is still much progress to be made. Recent work has revealed two new potential cellular targets in MM: adipocytes and osteocytes. Both are endocrine cells and secrete many molecules that regulate other cells proximally and systemically. Our lab previously showed that MM cells shift osteoblast precursor cells towards adipogenesis through soluble molecules alone. Recent findings also revealed that osteocyte apoptosis is enhanced in MM patients compared to healthy …

Characterization Of Molecular Pathways Involved In The Production Of Class-Switched Antibodies, Arthur James Vanvalkenburg

All ETDs from UAB

This dissertation research describes two independent characterizations of molecular pathways involved in the manufacture of class-switched antibodies and differentiation of B cells involving the adaptor protein Hematopoietic SRC Homology 2 Domain-containing protein (HSH2) and the surface molecule CD19. HSH2 is dynamically expressed in different subsets of B cells, showing high expression in B1 and MZ B cells and low expression in GC B cells. Experiments involving HSH2 transgenic mice have determined that HSH2 may act as a rheostat regulating the production of class-switched antibodies. Various factors that stimulate B cell activation and differentiation induce HSH2 expression, although regulation of HSH2 …

GabaA Receptors As Targets For The Management Of Pain-Related Disorders: Historical Perspective And Update., Bradford D. Fischer

Bradford Fischer

Neurobiology Of The Premonitory Urge In Tourette's Syndrome: Pathophysiology And Treatment Implications, Andrea E. Cavanna, Kevin J. Black, Mark Hallett, Valerie Voon

Kevin J. Black, MD