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Full-Text Articles in Medicine and Health Sciences
Novel Biomarkers For Parkinson Disease, Kyle Bradley Fraser
Novel Biomarkers For Parkinson Disease, Kyle Bradley Fraser
All ETDs from UAB
Parkinson disease (PD) is the most common neurodegenerative movement disorder for which no treatments exist capable of slowing progression of the disease. One obstacle slowing the development of novel therapies is the lack of molecular biomarkers for PD prognosis, tracking of disease progression, and assessing efficacious target engagement of compounds that do reach clinical trials. Missense mutations in LRRK2 account for between 1-5% of late onset PD and lead to increases in LRRK2 kinase activity and LRRK2 autophosphorylation. This thesis characterizes the secretion of LRRK2 into extracellularly secreted microvesicles called exosomes. We find that kinase-active LRRK2 is secreted within exosomes …
Neurobiological Consequences Of Perinatal Ssri Exposure, Matthew Edward Glover
Neurobiological Consequences Of Perinatal Ssri Exposure, Matthew Edward Glover
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Selective serotonin reuptake inhibitors (SSRIs) have been a mainstay pharmacological treatment for women experiencing depression during pregnancy and postpartum for nearly three decades. Recently, though, growing evidence indicates that early-life SSRI exposure triggers long-lasting behavioral abnormalities. Clinically, children exposed to SSRIs in early life exhibit increased internalizing behavior, reduced social behavior, and increased risk for depression in adolescence. Similarly, in rodents, perinatal SSRI exposure leads to increased traits of anxiety- and depression-like behavior. Interestingly, certain individuals are more susceptible to early-life SSRI exposure than others, suggesting that perinatal SSRI exposure poses greater risks for negative outcome within certain populations; however, …
Genome-Wide Transcription And Dna Methylation Profiling In An App Mouse Model Of Alzheimer’S Disease, Mikael C. Guzman Karlsson
Genome-Wide Transcription And Dna Methylation Profiling In An App Mouse Model Of Alzheimer’S Disease, Mikael C. Guzman Karlsson
All ETDs from UAB
The ability to encode information for long-term behavioral adaptation relies on experience-dependent alterations in neuronal plasticity. Neuronal plasticity encompasses the cellular and molecular changes that modulate synaptic communication between neurons as well as intrinsic electrophysiological properties within neurons. Epigenetic mechanisms, including DNA cytosine methylation and histone post-translational modifications, are powerful regulators of neuronal gene expression, allowing for dynamic, bidirectional regulation of transcriptional signatures necessary for neuronal plasticity. Emerging evidence using candidate-gene and microarray-based approaches suggest that the deficits in neuronal plasticity and cognitive impairment observed in Alzheimer’s disease (AD) is attributable, in part, to aberrant cytosine methylation and transcription of …
The Matricellular Protein Ccn1 Potentiates Fibrogenic Responses To Lung Injury, Ashish Kurundkar
The Matricellular Protein Ccn1 Potentiates Fibrogenic Responses To Lung Injury, Ashish Kurundkar
All ETDs from UAB
Normal wound healing is a well-coordinated reparative response to injury aimed at restoring the normal tissue function. The dynamic interactions between cells and ex-tracellular matrix (ECM) regulate and dictate the fate of tissue repair process. Fibrosis is a dysregulated wound healing with excessive deposition of ECM and loss of tissue func-tion. Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic disease of lung with no cure. Matricellular proteins are non-structural matrix proteins which regulates the cellular functions by directly binding to cell surface integrins and/or indirectly modulating growth factor signaling. Matricellular proteins are emerging as critical mediators of tissue injury …
14-3-3 Proteins Regulate Mutant Lrrk2 Kinase Activity And Neurite Shortening, Nicholas Lavalley
14-3-3 Proteins Regulate Mutant Lrrk2 Kinase Activity And Neurite Shortening, Nicholas Lavalley
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Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common known cause of inherited Parkinson’s disease (PD), and LRRK2 is a risk factor for idiopathic PD. How LRRK2 function is regulated is not well understood. Recently, the highly-conserved 14-3-3 proteins, which play a key role in many cellular functions including cell death, have been shown to interact with LRRK2. In this study, we investigated whether 14-3-3s can regulate mutant LRRK2-induced neurite shortening and kinase activity. In the presence of 14-3-3θ overexpression, neurite length of primary neurons from BAC transgenic G2019S-LRRK2 mice returned back to wildtype levels. Similarly, 14-3-3θ overexpression …
Leukemia Stem Cell Markers And Inv(16) In Acute Myeloid Leukemia, Jason Legrand
Leukemia Stem Cell Markers And Inv(16) In Acute Myeloid Leukemia, Jason Legrand
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Although greater than 85% of inv(16) acute myeloid leukemia patients are able to achieve first complete remission after anthracycline- and cytarabine-based therapy, only about 60% of patients survive the disease long-term due to relapsed disease or treatment-related mortality. Multiple studies have shown that acute myeloid leukemia is composed of heterogeneous populations of leukemic clones that can exhibit a wide degree of genetic, epigenetic, and functional diversity, accounting for different outcomes in response to therapy. Genomic analysis of leukemic clones in paired diagnostic and relapse samples of acute myeloid leukemia has shown that all relapses stem from surviving leukemic or ancestral …
Behavioral And Developmental Abnormalities In Sult4a1 Deficient Zebrafish, Francis Crittenden
Behavioral And Developmental Abnormalities In Sult4a1 Deficient Zebrafish, Francis Crittenden
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Since its identification in 2000, sulfotransferase (SULT) 4A1 has presented an enigma to the field of cytosolic SULT biology. SULT4A1 is exclusively expressed in neural tissue, is highly conserved, and has been identified in every vertebrate studied to date. Despite this singular level of conservation, no substrate or function for SULT4A1 has been identified. Previous studies demonstrated that SULT4A1 does not bind the obligate sulfate donor, 3’-phosphoadenosine-5’-phosphosulfate (PAPS), yet SULT4A1 is classified as a SULT superfamily member based on sequence and structural similarities to the other SULTs. In this study, RNA-seq was used to search for alterations in gene ex-pression …
Structural And Biochemical Charactereization Of Lrrk2, Zhiyong Liu
Structural And Biochemical Charactereization Of Lrrk2, Zhiyong Liu
All ETDs from UAB
Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are the most common known genetic cause of Parkinson disease (PD) , with pathogenic mutations located within each of the two catalytic cores of the protein, the GTPase and kinase domains. The most prevalent pathogenic mutation, G2019S increases kinase activity up to 5-fold, causing significant changes in the protein’s biochemical behavior. Other mutations such as R1441G and I2020T have also been demonstrated to increase LRRK2 kinase activity, however, the detailed mechanisms remains unclear. A major limitation in the field is the lack of structural information of LRRK2. This dissertation detailed …
The Role Of Hydrogen Peroxide In The Modulation Of Capsule Biosynthesis In Streptococcus Pneumoniae Serotype 2, Jocelyn Renee Hauser
The Role Of Hydrogen Peroxide In The Modulation Of Capsule Biosynthesis In Streptococcus Pneumoniae Serotype 2, Jocelyn Renee Hauser
All ETDs from UAB
Streptococcus pneumoniae is a gram-positive bacterial pathogen that causes diseases such as pneumonia, meningitis, bacteremia and middle ear infections. The major virulence factor of S. pneumoniae is its polysaccharide capsule. The capsule enables the organism to evade host defenses by providing protection against complement-mediated opsonophagocytosis in systemic sites and by allowing the organism to successfully colonize the nasopharynx. The nasopharynx is the natural reservoir of S. pneumoniae. In the nasopharynx, S. pneumoniae is in a high oxygen (O2) environment, however when it has the opportunity to bypass host defenses and invade systemic sites, it reaches environments with low O2. Capsule …
Human Cytosolic Sulfotransferase (Sult) 1b1 Half-Site Reactivity And The Identification And Characterization Of A Novel Variant Sult1b1 Isoform (L145v), Zachary Evan Tibbs
Human Cytosolic Sulfotransferase (Sult) 1b1 Half-Site Reactivity And The Identification And Characterization Of A Novel Variant Sult1b1 Isoform (L145v), Zachary Evan Tibbs
All ETDs from UAB
The human cytosolic sulfotransferases (hSULTs) are a fourteen-member family of phase II drug-metabolizing enzymes that catalyze the transfer of a sulfonate moiety from 3’-phosphoadenosine 5’-phosphosulfate (PAPS) to a recipient substrate. SULT-mediated sulfation serves to deactivate physiological hormones and detoxify xenobiotics. SULT1B1 is primarily resident to the gastrointestinal tract, liver, and possibly peripheral white blood cells (WBCs), whereby it performs its supposed physiological role. The iso-form has the capacity to sulfate thyroid hormones, small phenols, and polyaromatic hy-drocarbons resulting in their inactivation, detoxification, and bioactivation/detoxification, respectively. Immunohistochemistry was used to show hSULT1B1 protein is present in periph-eral lymphocytes and neutrophils. Further, …
The Role Of Mammalian Tribbles Homolog 3 (Trb3) In Macrophage Biology; Evidence For Reciprocal Regulation Of Macrophage Function In Foam Cell Formation, Dennis Steverson
The Role Of Mammalian Tribbles Homolog 3 (Trb3) In Macrophage Biology; Evidence For Reciprocal Regulation Of Macrophage Function In Foam Cell Formation, Dennis Steverson
All ETDs from UAB
Atherosclerosis is disease characterized by dysregulated lipid metabolism and chronic inflammation. Macrophages are critical to the progression of the disease and are involved in the pathophysiology at all stages of the disease. In the early stages, macrophages are responsible for fatty streak formation by becoming foam cells through lipid uptake. In the later stages, macrophages contribute to the degradation of the fibrous cap and are largely responsible for chronic inflammation in atherosclerotic plaques. Tribbles homolog 3 (TRB3) is a pseudokinase that inhibits Akt activation by blocking its phosphorylation site. TRB3 is expressed on numerous cell types in the body (pancreatic …
Fcrl5 Counter-Regulates Natural And T Cell-Independent Immunoglobulin Production By Innate-Like B Cells, Eugene John Becker
Fcrl5 Counter-Regulates Natural And T Cell-Independent Immunoglobulin Production By Innate-Like B Cells, Eugene John Becker
All ETDs from UAB
At homeostasis and during the initial phases of primary responses to pathogens, humoral host defense is chiefly coordinated by specialized B cells known as splenic marginal zone (MZ) and body cavity-derived B-1 B cells. These front line immune mediators are termed “innate like” due to their ability to secrete broadly-reactive natural antibodies and respond rapidly to antigens in a T cell-independent manner. The production of natural antibodies possessing specificities for self-antigens allows clearance of cellular debris, maintenance of homeostasis and protection from infections that can also predispose the host to immunological disease. However, how the functions of these specialized cells …
Exploring Bacteriophage P22 As A Selective Molecular Scaffold And Molecular Sensor, Gregory Joseph Bedwell
Exploring Bacteriophage P22 As A Selective Molecular Scaffold And Molecular Sensor, Gregory Joseph Bedwell
All ETDs from UAB
The virus capsids of many dsDNA bacteriophage are finely tuned macromolecular machines. Their functionality begins at assembly, when their capsids are built under the guidance of a class of proteins referred to as scaffolding proteins. The scaffolding protein of bacteriophage P22 is a flexible, highly elongated protein that binds to the interior surface of the P22 procapsid via its C-terminal domain. The finding that N-terminus is dispensable for procapsid binding prompted the development of chimeric scaffolding protein molecules, wherein N-terminal residues of scaffold are replaced with a variety of different peptide sequences or functional proteins that are then encapsidated within …
Cd4 Regulatory T Cells Augment Hiv-1 Expression Of Polarized M1 And M2 Monocyte Derived Macrophages, Tanya Robinson
Cd4 Regulatory T Cells Augment Hiv-1 Expression Of Polarized M1 And M2 Monocyte Derived Macrophages, Tanya Robinson
All ETDs from UAB
Polarization of macrophages is critical for an effective host immune response against invading pathogens. However, the HIV-1 virus can alter the cytokine/chemokine profile of polarized macrophages which may ultimately lead to their increased susceptibility to viral infection. M1 monocyte-derived macrophages (MDM) have been shown to suppress CCR5-tropic HIV-1 replication, while M2 MDM promote it. We generated M1 (GM-CSF + IFN-γ + LPS) and M2 (M-CSF + IL-4) MDM with predicted phenotypes and exposed them to a CCR5 (R5) “highly macrophage-tropic” viral strain, HIV-1BaL. M2 MDM had notably higher levels of HIV-1 infection than M1 MDM. We also investigated R5 HIV-1 …
Regulation Of Vibrio Cholerae Biofilm Formation By H-Ns Repression And Anti-Repression, Julio Cesar Ayala-Figueredo
Regulation Of Vibrio Cholerae Biofilm Formation By H-Ns Repression And Anti-Repression, Julio Cesar Ayala-Figueredo
All ETDs from UAB
The diarrheal disease cholera is caused by the Gram-negative and motile bacterium Vibrio cholerae of serogroups O1 and O139. V. cholerae can switch between planktonic (motile) and sessile (biofilm) lifestyles. Biofilms are sessile communities encased in a self-produced extracellular matrix mainly composed of exopolysaccharide, proteins and extracellular DNA. Biofilm formation enhances the capacity of V. cholerae to persist in environmental waters and increases its infectivity. The bacterial second messenger cyclic diguanylic acid (c-di-GMP) regulates the transition between motile and biofilm lifestyles in V. cholerae. At low cell density, two c-di-GMP receptors, the LuxR-type regulator VpsT and the NtrC-type regulator VpsR …
Structure-Function Relationships In The Sec7 Guanine Nucleotide Exchange Factor Gbf1, Jay Manoj Bhatt
Structure-Function Relationships In The Sec7 Guanine Nucleotide Exchange Factor Gbf1, Jay Manoj Bhatt
All ETDs from UAB
All eukaryotic cells contain a secretory pathway composed of membrane-bound compartments connected by vesicles that transport cargo from the endoplasmic reticulum (ER) through the Golgi apparatus to various destination within and outside the cell. The Golgi Brefeldin A-resistant Factor 1 (GBF1) is required for protein traffic between ER and Golgi and within the Golgi. GBF1 belongs to a family of Guanine nucleotide Exchange Factors (GEFs) that stimulate the nucleotide exchange of GDP for GTP on small GTPases called ADP-ribosylation factors (ARFs). Once GTP-bound, ARFs become active and initiate a cascade of events that lead to vesicle formation. Thus, GBF1 is …
The Role Of Glutamate In Immune Cell Infiltration And Excitotoxic Mechanisms In Autoimmune Demyelination, Kirsten Scarlett Evonuk
The Role Of Glutamate In Immune Cell Infiltration And Excitotoxic Mechanisms In Autoimmune Demyelination, Kirsten Scarlett Evonuk
All ETDs from UAB
Multiple sclerosis is the most common neurological disorder in young adults. Current treatments modulate the immune system, but no treatments prevent central nervous system damage. Inflammation occurs even during disease remission, contributing to ongoing damage and resulting in disease progression. The lack of neuroprotective treatments despite continued inflammatory onslaught in the central nervous system indicates the need for therapeutic discovery in this area. One potential therapeutic target is glutamate, whose dysregulation in multiple sclerosis has been implicated in excitotoxic cellular death. Herein we describe the roles of glutamate in multiple sclerosis and explore the blockade of a source of excitotoxic …
Epigenetic Dysregulation In Levodopa-Induced Dyskinesia, David Anthony Figge
Epigenetic Dysregulation In Levodopa-Induced Dyskinesia, David Anthony Figge
All ETDs from UAB
Levodopa-induced dyskinesia (LID) is a persistent behavioral sensitization that develops after repeated levodopa (L-DOPA) exposure in Parkinson disease (PD) patients. LID is characterized by a “priming effect”, whereby initial administrations of L-DOPA trigger a sensitized biochemical and transcriptional response upon subsequent administrations of L-DOPA. In neurons, transcriptional regulation through dynamic changes to epigenetic modifications, including DNA methylation and histone acetylation, have been shown pivotal to many long-term behavioral modifications; however, their role in LID has been minimally explored. Using a rodent model, we show LID development leads to the aberrant expression of DNA demethylating enzymes and locus-specific changes to DNA …
Ribosomal Protein L12 (Rpl12) As A Novel Target In Cystic Fibrosis, Kathryn E. Oliver
Ribosomal Protein L12 (Rpl12) As A Novel Target In Cystic Fibrosis, Kathryn E. Oliver
All ETDs from UAB
Approximately 1,000 new cases of cystic fibrosis (CF) are diagnosed in the United States every year. The disease is caused by over 1,700 naturally occurring variants in the CF transmembrane conductance regulator (CFTR). Defects in the CFTR coding sequence contribute to variable disease severity in the patient population. The majority of individuals born with CF harbor at least one specific mutation in CFTR termed F508del. Clinical manifestations of CF include severe damage of multiple exocrine tissues, including the lungs, intestine, pancreas, reproductive and other organ systems. An overarching goal of our work is to identify cellular targets that contribute to …
Targeting The Tumor-Promoting Microenvironment With Inhibitors Of Pro-Hgf Activation, Benjamin Yaw Owusu
Targeting The Tumor-Promoting Microenvironment With Inhibitors Of Pro-Hgf Activation, Benjamin Yaw Owusu
All ETDs from UAB
The tumor microenvironment plays a key role in tumor progression and therapeutic resistance. Hepatocyte growth factor (HGF), commonly expressed by cancer-associated fibroblasts, mediates signaling via its receptor, MET, and promotes survival, proliferation, migration and invasion of cancer cells. In addition, HGF dependence has emerged as a hallmark of therapeutic resistance. HGF is secreted as an inactive precursor, pro-HGF, which requires proteolytic cleavage and processing to form the mature, active HGF. This is the rate-limiting step in the HGF/MET signaling pathway and it is achieved by one of the serine proteases, matriptase, hepsin and HGF activator (HGFA). At Southern Research, we …
Early-Life Programming Of Emotional Behaviors And Cardiovascular Function, Samir Rana
Early-Life Programming Of Emotional Behaviors And Cardiovascular Function, Samir Rana
All ETDs from UAB
Extensive evidence implicates bi-directional relationship between mood disorders and cardiovascular disorders. Early-life experience can have strong effects both on emotional development and cardiovascular function throughout life. Studies in humans are limited to correlational analyses, which are necessarily limited in terms of revealing mechanistic underpinnings of these associations. Thus, various pre-clinical models are utilized to investigate the effects of early-life experience in various domains, such as behavior and cardiovascular function, which are likely mediated by epigenetic mechanisms. Previous studies have used maternal separation and neonatal handling in developing rodents as a way to model differences in early-life experience. The effect of …
Reorganization Of The Golgi Apparatus During Human Cytomegalovirus Infection, George Michael Rebmann
Reorganization Of The Golgi Apparatus During Human Cytomegalovirus Infection, George Michael Rebmann
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Human cytomegalovirus (HCMV) is the largest and most structurally complex of all the herpesviruses. HCMV is an important human pathogen that results in significant morbidity and disease in immunocompromised individuals. The assembly of herpesviruses is complex and involves a nuclear and cytoplasmic phase. The nuclear events of capsid assembly and genome incorporation as well as nuclear egress are believed to be similar in all herpesviruses and as such, are more clearly defined then the cytoplasmic phase; including the process of tegument and envelope acquisition. Human Cytomegalovirus induces the reorganization of the cellular secretory pathway including the Golgi apparatus and membranes …
Altering Metabolism In The Tumor Microenvironment To Enhance Anti-Tumor Immunity For Lung Cancer, Cara Schafer
Altering Metabolism In The Tumor Microenvironment To Enhance Anti-Tumor Immunity For Lung Cancer, Cara Schafer
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Overcoming cancer cell immune escape represents a fundamental obstacle in the treatment of cancer. Indoleamine 2,3-dioxygenase (IDO)-expressing myeloid-derived suppressor cells (MDSCs) are known to induce oxidative stress and alter amino acid metabolism within the tumor microenvironment (TME). The tryptophan (Trp)-catabolizing action of IDO not only promotes T cell tolerance and evasion but is also associated with impaired quality of life in cancer patients. We have previously demonstrated that a novel combination therapy, consisting of MDSC-depleting gemcitabine and a superoxide dismutase mimetic, prolonged survival of tumor-bearing mice by enhancing CD8+ memory T cell metabolism. We identify that combination therapy inhibits IDO …
Regulation Of The Mitochondrial Thiol Network With Targeted Electrohpiles, Matthew Ryan Smith
Regulation Of The Mitochondrial Thiol Network With Targeted Electrohpiles, Matthew Ryan Smith
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Cells possess a remarkable plasticity to alter their metabolism and change their function based on stimuli within their resident microenvironment. The mitochondria within these cells utilize a variety of sources such as pyruvate, glutamine, or fatty acids in order to generate metabolites, amino acids, and reducing equivalents needed for cellular proliferation.Many mitochondrial enzymes possess contain a cysteine which possesses a thiol group, a unique redox-signaling moiety that can be activated under specific circumstances by bio-reactive compounds forming a network of mitochondrial proteins which are responsible for mitochondrial respiration. However, it is unknown whether targeting these reactive thiol groups present a …
Microglia Orchestrate The Inflammatory Response To Alpha-Synuclein In Parkinson Disease Models, Aaron Thome
Microglia Orchestrate The Inflammatory Response To Alpha-Synuclein In Parkinson Disease Models, Aaron Thome
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Parkinson disease (PD) is the most common neurodegenerative movement disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and widespread aggregates of the protein alpha-synuclein (α-syn). Increasing evidence points to inflammation as a chief mediator of PD with many of the inflammatory manifestations of human PD cases recapitulated in animal models of PD. We began by examining the inflammatory potential of α-syn fibrils, a newly characterized α-syn conformation that is neurotoxic and prion-like in its endogenous α-syn recruitment and cellular transmission. Our studies provide evidence that the α-syn fibrils evoke a pro-inflammatory response …
The Roles Of Il-21 And Il-10 In Cellular And Humoral Immune Responses, Yuan Tian
The Roles Of Il-21 And Il-10 In Cellular And Humoral Immune Responses, Yuan Tian
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Protective immunity mediated by cellular and humoral immune responses relies on the ability of T cells and B cells to generate both effector cells that cooperate to eliminate antigens and memory cells that can survive for long periods with enhanced abilities to control recurring antigens. Thus, understanding the factors that regulate the development of T cell and B cell responses can improve the development of vaccines and immunotherapies against infectious diseases and cancers. Cytokines play important roles in regulating T cell and B cell responses, and in this thesis I have investigated the functions of two cytokines, interleukin (IL)-21 and …
Polycomb Repressive Complex 2 And Heterochromatin Protein 1 Beta Regulate Neural And Neural Crest Development, Chih-Liang Tien
Polycomb Repressive Complex 2 And Heterochromatin Protein 1 Beta Regulate Neural And Neural Crest Development, Chih-Liang Tien
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Epigenetic factors control gene expression via modulating chromatin conformation. Current studies on epigenetics mainly focus on biochemical mechanisms or functions of epigenetic factors in cancer or neurobiology. The underlying mechanism for epigenetic regulation in early embryonic development, particularly neural and neural crest development, is not well understood. In this thesis, the model organism, Xenopus laevis, is used to study epigenetic factors – polycomb repressive complex 2 (PRC2) and heterochromatin protein 1 beta (HP1β) in neural and neural crest development. In chapter one, the processes of neural and neural crest development are described, and the concepts of epigenetic mechanisms, such as …
Genetic Enhancer Screen With Transition Zone Mutant Nphp-4 Reveals Novel Interactions With Mutation Affecting Intraflagellar Transport And Endocytic Pathways, Scott Henke
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Cilia are hair-like microtubule based protrusions from the cell membrane. The Transition Zone (TZ) is a vital sub-domain of cilia and is located at the base of the cilium above the basal body at the entry point into the cilium. While multiple proteins associated with Nephronophthisis (NPHP), Bardet-Biedl Syndrome (BBS) and Meckel Gruber Syndrome (MKS) have been found to specifically localize to this region, little is known about their function. However, because non-ciliary proteins ectopically localize to the cilium in TZ mutants, it is hypothesized that TZ proteins control the trafficking of signaling proteins into and out of the cilium. …
What's Up, Dut? Help, Help I'M Being Derepressed; The Great Derepression Of Sapis Or How I Learned To Stop Worrying And Love Mobilization, Rosanne Lorin Lee Hill
What's Up, Dut? Help, Help I'M Being Derepressed; The Great Derepression Of Sapis Or How I Learned To Stop Worrying And Love Mobilization, Rosanne Lorin Lee Hill
All ETDs from UAB
Staphylococcus aureus is known to cause disease in both human and animal populations. Many of the virulence factors important for S. aureus pathogenesis are found on mobile genetic elements known as S. aureus pathogenicity islands (SaPIs). SaPIs can transduce into surrounding cells, giving those cells the ability to produce virulence factors. Derepression allows SaPIs to be excised from S. aureus genome to initiate mobilization. Derepressors have been identified for multiple SaPIs, but it remains unknown if the same SaPI can be derepressed by multiple derepressors. It has been shown that SaPIbov1 can be derepressed by the type 1 dUTPase from …
The Effect Of Proinflammatory Cytokines On Thioredoxin-Interacting Protein In Pancreatic Beta-Cells, Kyunghee Hong
The Effect Of Proinflammatory Cytokines On Thioredoxin-Interacting Protein In Pancreatic Beta-Cells, Kyunghee Hong
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Pro-inflammatory cytokines, such as Interleukin (IL)-1β, Tumor necrosis factors (TNF) α, and Interferon (IFN)γ, have been implicated as critical mediators of β-cell destruction in diabetes. In addition, although a combination of these three cytokines has been used to mimic the inflammatory conditions of type 1 diabetes in vitro, the mechanisms underlying the effect are not fully understood. Previously, we discovered Thioredoxin-interacting protein (TXNIP) as a key regulator of glucotoxicity-induced β-cell apoptosis and β-cell dysfunction, while deletion of TXNIP prevented type 1 (T1D) and type 2 diabetes (T2D). However, the effects of proinflammatory cytokines on the regulation of TXNIP have not …