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Articles 1 - 30 of 72
Full-Text Articles in Medicine and Health Sciences
High Resolution Analysis Of Clonal Pluripotent Stem Cell Lentiviral Gene Therapy In A Mouse Model Of Beta-Thalassemia, Rui Yang
All ETDs from UAB
Gene therapy for hematopoietic disorders using viral vectors has achieved significant clinical benefit. However this approach has been held back by adverse genotoxic events due to random viral integration into the genome. A better understanding of viral transgene chromosomal position effects is critical for the design of safer viral vectors and clinical protocols. However, detailed analysis of viral transgenes is hampered by the heterogeneity of the viral-transduced bone marrow cell populations. I hypothesized that viral transduction of pluripotent stem cells would enable the clonal analysis of viral transgene expression, safety, and efficacy both in vitro and in vivo. Here I …
Human Cytosolic Sulfotransferase 2b1b: Structure, Function And Expression In Human Brain, Emily D. Salman
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 …
Mechanisms And Consequences Of Thy-1 Shedding, John Edwin Bradley
Mechanisms And Consequences Of Thy-1 Shedding, John Edwin Bradley
All ETDs from UAB
Idiopathic Pulmonary Fibrosis (IPF) is characterized by chronic fibrosis in the lung interstitium of unknown etiology, and causes death within 2 to 4 years after diagnosis. There are no clinical interventions save for lung transplantation that give any survival benefit. Aberrant collagen deposition and aggregates of proliferating fibroblasts and myofibroblasts called fibroblastic foci (FF) are the classic features of IPF. Therefore, the cell type most often implicated as pathogenic in IPF is the fibroblast, especially its differentiated phenotype, the myofibroblast. Fibroblasts are a remarkably heterogeneous cell type. Expression of the cell surface glycoprotein Thy-1 (Thymocyte differentiation antigen 1) delineates a …
Differential Contributions Of C-Kit Activating Mutations To Promotion Of Aml1-Eto Associated Neoplasia, Heidi Coppersmith
Differential Contributions Of C-Kit Activating Mutations To Promotion Of Aml1-Eto Associated Neoplasia, Heidi Coppersmith
All ETDs from UAB
The t(8;21) translocation, which generates an AML1-ETO fusion protein (also known as RUNX1-ETO), is one of the most frequent cytogenetic abnormalities in acute myeloid leukemia (AML). Murine studies have demonstrated that AML1-ETO promotes the accumulation of myeloid progenitor cells with self-renewal capability and impaired differentiation capacity. However, AML1-ETO+ mice do not progress to AML in the absence of additional mutations, suggesting that expression of the translocation is insufficient for leukemogenesis. This hypothesis is supported by studies demonstrating the persistence of AML1-ETO-expressing hematopoietic progenitors obtained from patients in long-term clinical remission. Mutations affecting receptor tyrosine kinases, particularly c-KIT, are commonly detected …
Role Of The Cardiomyocyte Circadian Clock In Modulating Myocardial Physiology And Pathophysiology, David Joseph Durgan
Role Of The Cardiomyocyte Circadian Clock In Modulating Myocardial Physiology And Pathophysiology, David Joseph Durgan
All ETDs from UAB
It is well established that multiple parameters of cardiovascular physiology and pathophysiology exhibit diurnal variations. For example, human heart rate and blood pressure peak during the morning and trough in the evening. Similarly, there is a morning prevalence for the onset of multiple adverse cardiovascular events, including myocardial ischemia, arrhythmias, and sudden cardiac death. Traditionally these rhythms have been attributed to rhythms in neurohumoral stimulation. However recent identification of the circadian clock mechanism in cardiovascular relevant cell types, including the cardiomyocyte, has prompted investigation into its role in modulating myocardial physiology and pathophysiology over the course of the day. Preliminary …
The Study Of Intracellular Signaling Pathways In Schizophrenia, Adam Funk
The Study Of Intracellular Signaling Pathways In Schizophrenia, Adam Funk
All ETDs from UAB
INTRACELLULAR SIGNALING AND INTEGRATION ABNORMALITIES IN SCHIZOPHRENIA Adam J. Funk DEPARTMENT OF NEUROBIOLOGY ABSTRACT The pathophysiology of schizophrenia is complex and diverse, with many classes of receptors, neurotransmitters, and brain regions implicated in this illness. The many hypotheses proposed have yet to fully explain the heterogeneity of the genetic, postmor-tem, and clinical evidence. It is the goal of this dissertation to integrate the current hy-potheses of schizophrenia into a unified hypothesis of abnormal intracellular signaling and signal integration. Inconsistencies in genetic and postmortem findings suggest that the development of schizophrenia is multifaceted, and the heterogeneity of symptoms supports the hypothesis …
The Role Of Protease-Activated Receptor-1 In Synaptic Plasticity And Memory, Antoine Gabriel Almonte
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. …
Molecular Mechanisms Regulating Caenorhabditis Elegans Sperm Migration, Johnathan Wesley Edmonds
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 The Classical Nf-Kb Pathway In Hsc Self-Renewal And Acute Myeloid Leukemia, Robert Jason Flynn
The Role Of The Classical Nf-Kb Pathway In Hsc Self-Renewal And Acute Myeloid Leukemia, Robert Jason Flynn
All ETDs from UAB
Acute myeloid leukemia (AML) comprises approximately 25% of newly diagnosed cases of leukemia each year. The constitutive activation of the classical NF-κB signaling pathway has been observed in up to 70% of AML cases, and could be due to mutations upstream involving the PI3K-Akt cascade, which is also constitutively active in a majority of cases. In mice, constitutive activation of Akt either through deletion of the negative regulator of PI3K-Akt, PTEN, or by expression of Myr-Akt induces rapid stem cell loss along with a lethal, transplantable myeloproliferative disorder and AML. These studies show that constitutive Akt and NF-κB signaling distinguish …
Ampa Receptor Trafficking In Schizophrenia, John Hammond
Ampa Receptor Trafficking In Schizophrenia, John Hammond
All ETDs from UAB
The glutamate hypothesis of schizophrenia is based primarily on NMDA receptor dysfunction. Recent studies have led to an expansion of this hypothesis to include AMPA receptors which are essential for neurotransmission through NMDA receptors. Examination of total AMPA receptor protein expression in schizophrenia has been inconsistent and led to examination of AMPA receptor interacting proteins and trafficking and subcellular localization of the receptors. AMPA receptors are highly trafficked from the endoplasmic reticulum to the synapse and in a complex system of endosomes. Alterations in the subcellular localization of these receptors may be a part of the underlying pathophysiology of schizophrenia. …
Human Cytomegalovirus Ul97 Kinase Activity Modifies Cell Cycle Checkpoint Regulators, Rachel Brooke Gill
Human Cytomegalovirus Ul97 Kinase Activity Modifies Cell Cycle Checkpoint Regulators, Rachel Brooke Gill
All ETDs from UAB
Human cytomegalovirus (CMV) infection results in destructive infections in neonates and immunocompromised individuals. Being the primary congenital infection in the United States, it can often result in permanent neurological deficits in infants. The current therapies for CMV infections all target the viral DNA polymerase and also have dose-limiting toxicities. Isolates resistant to ganciclovir (GCV), the therapy of choice, can sometimes overwhelm immunocompromised hosts. Better therapies for this infection are required. The CMV UL97 kinase is a key enzyme in the treatment of CMV infection because it phosphorylates GCV. Additionally, maribavir (MBV) specifically inhibits UL97 kinase activity and inhibits viral replication. …
The Role Of Tgf-Ss Receptors In The Induction Of Mucosal Tolerance, Rebekah Sims Gilbert
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 …
Qualitative Analysis Of Hiv-1-Specific Cd8 T Cell Responses, Olusimidele Tolulope Akinsiku
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 …
Significance And Regulation Of Cd68 Expression In The Osteoclast, Jason Waid Ashley
Significance And Regulation Of Cd68 Expression In The Osteoclast, Jason Waid Ashley
All ETDs from UAB
The mucin-like Lysosome Associated Membrane Protein (LAMP) family member CD68 is a primarily myeloid lineage restricted transmembrane protein that is expressed in macrophages and osteoclasts. While the existence and expression pattern of human CD68 and mouse CD68 (sometimes called macrosialin) are well-known, and these molecules are routinely used as histological markers of tissue macrophages, the functional signific-ance of CD68 expression remains an unanswered question. Our overall goal is to deter-mine the significance and characterize the function of CD68 in osteoclasts and explore the effects of Receptor Activator of Nuclear Factor κB (RANK) signaling on CD68 post-translational modification. To achieve this …
The Effect Of Sulfasalazine On Functional Recovery And Neuropathic Pain Following Spinal Cord Injury, Kelly Dunham Atkins
The Effect Of Sulfasalazine On Functional Recovery And Neuropathic Pain Following Spinal Cord Injury, Kelly Dunham Atkins
All ETDs from UAB
Spinal cord injury (SCI) is a devastating condition resulting in loss of motor function as well as sensory abnormalities. Insight into the pathophysiology of SCI progression has been gained through use of pre-clinical animal models, however these have not been successful in yielding pharmacological interventions for clinical management of SCI. One proposed reason for this discrepancy may be the use of SCI models which are not fully clinically relevant and do not assess the contribution of gray matter pathology to SCI functional outcomes. Post-SCI inflammation is well-documented and may lead to downstream loss of motor function. Additionally, inflammation is thought …
Identification And Characterization Of Novel Adenosine Cleavage Enzymes In Mycobacteria, Kajal Buckoreelall
Identification And Characterization Of Novel Adenosine Cleavage Enzymes In Mycobacteria, Kajal Buckoreelall
All ETDs from UAB
Tuberculosis (TB) is one of the leading infectious diseases in the world. An estimated one third of the world's population is infected with Mycobacterium tuberculosis, the causative pathogen of TB. With the emergence of drug resistant strains of the mycobacterium, and the HIV-TB coinfection epidemic, TB remains a global health emergency. Purine metabolism is an essential cellular component to all living cells. Previous studies have shown that differences exist between mycobacterial and human purine metabolism. One of the differences was in the metabolism of adenosine (Ado), whose cleavage was observed in mycobacterial cells whereas Ado cleavage is inefficient in human …
Characterization Of Tbx20 Isoforms And Protein Interactions In Heart Development, Paige Debenedittis
Characterization Of Tbx20 Isoforms And Protein Interactions In Heart Development, Paige Debenedittis
All ETDs from UAB
Proper cardiogenesis is critical for the development of vertebrates. Abnormalities in cardiogenesis can lead to congenital heart defects (CHDs), which occur in approximately 1% of live births. The cardiac transcription factor network contains different transcription factor families which direct the expression of critical cardiac genes. Determining how the cardiac transcription factors are regulated will provide insight in the mechanisms of cardiogenesis and CHDs. The T-box (TBX) transcription factor family is an ancient gene family important for development. Several TBX genes are expressed within the developing heart and play critical roles in differentiation, proliferation, and morphogenesis. One important TBX protein is …
Molecular Piracy In The Mobilization Of Staphylococcus Aureus Pathogenicity Island 1, Michael Spilman
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
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 …
The Role Of Protein Folding And Protein Trafficking In Human Disease, Cristy Davette Tower-Gilchrist
The Role Of Protein Folding And Protein Trafficking In Human Disease, Cristy Davette Tower-Gilchrist
All ETDs from UAB
This dissertation documents my findings in two unrelated projects. Project 1: Expansion of CAG repeats encoding glutamine in huntingtin and ataxin 3 causes the neurodegenerative diseases Huntington's disease (HD) and spinocerebellar ataxia 3 (SCA3), respectively. Both poly-glutamine (polyQ) expanded proteins misfold and ag-gregate within the cell. Preventing aggregation of polyQ proteins through molecular or pharmacological approaches provide therapeutic advantage in animal models of HD and SCA3. I hypothesized that the UL97 kinase encoded by the human cytomegalovirus (HCMV) may be able to prevent the aggregation of polyQ proteins. Initially, I showed that the UL97 kinase prevents the deposition of aggregates …
Strategies For Combined Screening And Imaging Of Breast Cancer, Jason Morgan Warram
Strategies For Combined Screening And Imaging Of Breast Cancer, Jason Morgan Warram
All ETDs from UAB
Successful treatment of breast cancer directly correlates with tumor stage and grade at diagnosis. Early diagnosis leads to a five-year relative survival rate of 96.8% as opposed to only a 22.5% five-year survival rate when diagnosed at late stage. Cancer-specific mechanisms need to be extended to enable cancer detection in an individual patient, in particular, the metastatic burden that currently cannot be assessed by conventional imaging. This approach for cancer detection would remove the biases of patient characteristics, permit immediate diagnostic feedback, improve sensitivity for early detection of small metastatic lesions, and be cost effective. Toward this goal, the cancer-specific …
Oxidative Stress And Xanthine Oxidase In Acute And Chronic Cardiac Volume Overload In Rats, James Douglas Gladden
Oxidative Stress And Xanthine Oxidase In Acute And Chronic Cardiac Volume Overload In Rats, James Douglas Gladden
All ETDs from UAB
Mechanisms of left ventricular dysfunction in cardiac volume overload (VO) are not well understood and there is no medical therapy. Cardiac VO is marked by eccentric remodeling and contractile dysfunction ultimately resulting in cardiac failure. Oxidative stress is implicated in the pathophysiology of heart failure and recent evidence suggests xanthine oxidase (XO) plays a role in VO. To study VO, we used a rat model of aortocaval fistula (ACF). ACF results in early diastolic stress on the left ventricle (LV) and recapitulates the progressive nature of heart failure with contractile function being initially maintained and then depressed by 6 weeks. …
Bone Morphogenetic Protein Signaling Pathways During Mouse Heart Development: Roles For Chd7 And Mycn, Cristina Harmelink
Bone Morphogenetic Protein Signaling Pathways During Mouse Heart Development: Roles For Chd7 And Mycn, Cristina Harmelink
All ETDs from UAB
Bone Morphogenetic Protein (BMP) signaling pathways are imperative for proper heart development. BMP ligands bind serine threonine kinase receptors, which activate intracellular receptor-regulated SMAD proteins. SMAD1, SMAD5, and SMAD8 transduce BMP signals from the cytoplasm to the nucleus, where they regulate transcription. We have investigated two aspects of BMP signaling during mouse cardiogenesis: identifying SMAD1-interacting proteins and exploring the roles of a known BMP target, Mycn, in the developing myocardium. Chromodomain helicase DNA binding protein 7 (CHD7) is a highly conserved transcription factor that promotes protein synthesis, proliferation, and differentiation. Haploinsufficiency for CHD7 causes CHARGE syndrome, a developmental disorder characterized …
The Role Of Mitochondrial Oxidative Stress In Cardiovascular Disease Development, Corey Michael Harrison
The Role Of Mitochondrial Oxidative Stress In Cardiovascular Disease Development, Corey Michael Harrison
All ETDs from UAB
An estimated 70 million Americans have one or more types of cardiovascular disease (CVD). Although the sequence of events leading to CVD are still controversial, there is a general consensus that atherosclerotic lesions result from oxidative stress associated with risk factor. For this study, it was hypothesized that endogenous mitochondrial oxidative stress would influence susceptibility to atherogenesis and mitochondrial damage mediated by CVD risk factor exposure. To test this hypothesis, atherosclerotic lesion formation, oxidant stress, and mitochondrial DNA damage were assessed in hypercholestoremic mice (apolipoprotein E null - apoE -/- SOD2 +/+) and mice with significantly decreased levels of the …
Regulation Of Neuronal Death By The Autophagy Lysosomal Pathway: Implications For Parkinson Disease, Violetta N. Pivtoraiko
Regulation Of Neuronal Death By The Autophagy Lysosomal Pathway: Implications For Parkinson Disease, Violetta N. Pivtoraiko
All ETDs from UAB
Parkinson Disease (PD) is the second most common age-related neurodegenerative disorder and is characterized pathologically by the loss of dopaminergic (DA) neurons in the stubstantia nigra pars compacta (SNpc). Mitochondrial dysfunction, increased oxidative stress, and accumulation of aggregated α-synuclein (α-syn), an intracellular protein involved in synaptic function, are all pathological hallmarks of PD have been implicated in PD pathogenesis. However, it is debated whether α-syn aggregates themselves are responsible for neurodegeneration in PD, cellular pathways involved in degradation of α-syn aggregates are believed to promote neuron survival. The autophagy lysosomal pathway (ALP), a physiological mechanism for recycling of intracellular components, …
Role Of Ras Proteins In Malignant Peripheral Nerve Sheath Tumors, Nicole Marie Brossier
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 …
Pax5 Controls B Lineage Specific Gene Expression Program Through Association With The Nuclear Matrix, Sang Yong Hong
Pax5 Controls B Lineage Specific Gene Expression Program Through Association With The Nuclear Matrix, Sang Yong Hong
All ETDs from UAB
Pax5 is an essential regulator for B lineage cell development and controls hundreds of positive and negative target genes. The nuclear matrix (NM) has long been proposed to provide a dynamic structural support for biological reactions inside of the nucleus, including DNA replication, RNA transcription, and RNA splicing. Although Pax5 binding sites have been identified in numerous Pax5 target genes, it is not clear how Pax5 controls so many target genes. In this dissertation, I demonstrate that Pax5 association with the NM is essential for regulation of the B lineage specific gene expression program. In part I, I found that …
The Intestinal Extracellular Matix As An Innate Regulator Of Effector T-Cell Responses, Kayci Renee Huff
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 …
Structural Analyses Of Streptococcus Agalactiae Sortases, Baldeep Khare
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 …
Elucidation Of The Elongated Fibrillar Structure Of Streptococcus Mutans Antigen I/Ii, Matt Rodney Larson
Elucidation Of The Elongated Fibrillar Structure Of Streptococcus Mutans Antigen I/Ii, Matt Rodney Larson
All ETDs from UAB
Streptococcus mutans (S. mutans) is the causative agent behind dental caries, an infectious disease also known as tooth decay or dental cavities. S. mutans has a cell wall-attached protein known as Antigen I/II (AgI/II) utilized for bacterial adhesion to the tooth surface. Here we have solved the structures of both amino- and carboxy-terminal regions of the AgI/II molecule using X-ray crystallography. Using this structural information we have now built a tertiary model for AgI/II as a fibrillar protein. Further, we have functionally characterized AgI/II and determined minimal regions of AgI/II that are implicated in its adherence to the salivary agglutinin …