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Full-Text Articles in Medicine and Health Sciences
Cell-Specific Pgc-1Α-Dependent Transcription: Implications For Cognitive And Motor Dysfunction, Laura Mcmeekin
Cell-Specific Pgc-1Α-Dependent Transcription: Implications For Cognitive And Motor Dysfunction, Laura Mcmeekin
All ETDs from UAB
Expression and/or function of transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is reduced in a variety of both neurodegenerative and psychiatric disorders. However, it is difficult to determine the significance of decreased PGC-1α expression and/or function in disease without knowing 1) the localization of these changes, 2) what the normal function of PGC-1α is in that specific cell-type, and 3) how its role in one neuronal population is different from its role in another. PGC-1α is highly expressed in GABAergic interneurons, and although it plays a significant role in interneuron function, several reports suggest that it also plays …
Analysis Of The Ciliary Genes Gas8 And Mks6 Reveal Conserved Roles In Cilia Motility And Transition Zone Function, Wesley Robert Lewis
Analysis Of The Ciliary Genes Gas8 And Mks6 Reveal Conserved Roles In Cilia Motility And Transition Zone Function, Wesley Robert Lewis
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Cilia are microtubule based cellular appendages that are present throughout the hierarchy of the animal kingdom. These appendages are utilized for a wide array of functions such as motility in single celled organisms to coordinating complex cellular signaling pathways in more complex organisms. Though these appendages are well conserved, the exact function of cilia in many cell types remains unknown. Recently, cilia are tied to a myriad of developmental diseases and diseases of adult homeostasis collectively referred to as ciliopathies. Dysfunction in cilia results in a wide array of phenotypes ranging from retinal degeneration to polydactyly, cystic kidney disease, and …
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
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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 …
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
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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 …
The Function Of Prmt1 In Normal And Abnormal Megakaryopoiesis, Hairui Su
The Function Of Prmt1 In Normal And Abnormal Megakaryopoiesis, Hairui Su
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Protein arginine methylation is a common type of post-translational modifications. Protein arginine methyltransferase 1 (PRMT1) is the predominant PRMT that is involved in diverse physiological and pathological processes in mammalian cells. Dysregulation of PRMT1 is often positively correlated with cancer development, yet many aspects of PRMT1’s role in cancer, especially in acute megakaryoblastic leukemia (AMKL) remain unclear. We identified two PRMT1-methylated substrates and how they impact normal and abnormal megakaryopoiesis. In this dissertation, we demonstrate that dual-specificity protein phosphatase 4 (DUSP4) and RNA binding motif protein 15 (RBM15), two crucial factors for megakaryocytic (MK) differentiation, are methylated by PRMT1 and …
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 …
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 …
Interplay Between Her2, Parp1, And Nf-Κb In Breast Cancer: Potential Therapeutic Implications, Monicka Ewa Wielgos
Interplay Between Her2, Parp1, And Nf-Κb In Breast Cancer: Potential Therapeutic Implications, Monicka Ewa Wielgos
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We previously reported that HER2+ breast cancers are susceptible to Poly (ADP-Ribose) polymerase inhibitors (PARPi) alone, agents that are efficacious against homologous recombination (HR) deficient tumors. However, this phenomenon was determined to be independent of a HR repair deficiency but rather due to suppression of NF-κB activity and signaling by PARP inhibition. Further, HER2 overexpression itself was necessary and sufficient to confer this susceptibility. Interestingly, PARP1 and phosphorylated RelA/p65 (NF-κB) levels were found to be elevated in human HER2+ breast cancers compared to luminal breast cancers. These data suggest a possible interplay between HER2, PARP1, and NF-κB, and how this …
Development Of A Split Luciferase Complementation Assay To Investigate Growth Hormone Receptor/ Prolactin Receptor Homo-/ Hetero-Association, Ying Liu
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Growth hormone receptor (GHR) and prolactin receptor (PRLR) are transmembrane glycoproteins cytokine receptors that are structurally homologous. Each can pre-homodimerize and ligand binding of each activates JAK2-STAT signaling pathways by inducing conformational change within the receptor homodimer. Human GHR can be activated by growth hormone (GH) while human PRLR can be activated by both GH and prolactin (PRL). We devised a split luciferase complementation assay, in which one receptor is fused to the N-terminal fragment of luciferase and the other receptor is fused to the C-terminal fragment of luciferase. When the two receptors approximate, luciferase activity (complementation) results. Using this …
Novel Biomarkers For Parkinson Disease, Kyle Bradley Fraser
Novel Biomarkers For Parkinson Disease, Kyle Bradley Fraser
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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 …
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
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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
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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 …
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 …
The Matricellular Protein Ccn1 Potentiates Fibrogenic Responses To Lung Injury, Ashish Kurundkar
The Matricellular Protein Ccn1 Potentiates Fibrogenic Responses To Lung Injury, Ashish Kurundkar
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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 …
Early-Life Programming Of Emotional Behaviors And Cardiovascular Function, Samir Rana
Early-Life Programming Of Emotional Behaviors And Cardiovascular Function, Samir Rana
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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 …
Hiv-1 Adaptation To T-Cell Responses During Infection, Victor Yimin Du
Hiv-1 Adaptation To T-Cell Responses During Infection, Victor Yimin Du
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It is well known that CD8 T cells play an important role in viral control. Many viruses, including human immunodeficiency virus-1 (HIV-1), escape from CD8 T-cell mediated immune pressure. Increasing number of studies have suggested that CD4 T cells, usually considered as primary targets of HIV-1 infection, can also play an active antiviral role and hence can drive viral escape like their CD8 counterparts. The works presented in this dissertation examined the impact of transmitted HIV-1 escapes on CD8 T-cell responses and clinical outcomes following infection, the ability of CD8 T cells to cross-recognize viral variants during acute infection, and …
Motor Unit Remodeling During Neuromuscular Degeneration In Aging And Parkinson's Disease, Neil Anthony Kelly
Motor Unit Remodeling During Neuromuscular Degeneration In Aging And Parkinson's Disease, Neil Anthony Kelly
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The human neuromuscular system deteriorates progressively with age and disease. This results in denervation events and ultimately motor unit remodeling, which is revealed by abnormal “groups” of myofibers expressing the same myosin protein isoform – a phenomenon described as myofiber type grouping. Despite the acceptance of myofiber type grouping as a hallmark indicator of motor unit remodeling, traditional techniques of detecting it lack quantitative parameters and therefore comparative data in aging and disease are scarce. The purpose of this dissertation is to establish a statistically-driven, quantitative method for detecting myofiber type grouping and to use it to characterize the effects …
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
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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 …
Glycosyltransferases Involved In The Glycosylation Of Serine-Rich Glycoproteins From Streptococci, Fan Zhu
Glycosyltransferases Involved In The Glycosylation Of Serine-Rich Glycoproteins From Streptococci, Fan Zhu
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Serine - rich repeat glycoproteins (SRRPs) play important roles in mediating bac-terial attachment to a variety of host and microbial surfaces. They have been im-plicated in the development of tissue infections such as pneumonia, infective en-docarditis, meningitis and oral infectious diseases. Streptococcus parasanguinis, one of the commensal streptococci present in the oral cavity, utilizes its fimbriae to mediate the initial attachment to the tooth pellicle. Fap1 (Fimbriae-associated-protein 1), the first identified SRRP, is the subunit of the fimbriae which utilizes proteins encoded by an 11-gene cluster (gly-gtf3-dGT1-galT2 and secY2-gap1-gap2-gap3-secA2-gtf1-gtf2) to mediate its glycosylation and secretion. The key enzymes responsible for …
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, …
Examination Of 4-Hydroxy Tamoxifen- And Bh3 Mimetic-Induced Cell Death Pathways In Glioblastoma And Malignant Peripheral Nerve Sheath Tumor Cells, Christopher Dillon Graham
Examination Of 4-Hydroxy Tamoxifen- And Bh3 Mimetic-Induced Cell Death Pathways In Glioblastoma And Malignant Peripheral Nerve Sheath Tumor Cells, Christopher Dillon Graham
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Glioblastoma (GBM) is the most common and aggressive human primary malignant brain tumor with a 5-year survival rate of less than 5%. GBM is highly invasive, rendering complete surgical resection impossible. Additionally, this tumor type is relatively insensitive to radiotherapy. Thus, effective chemotherapeutic options present the last line of defense for GBM patients. Unfortunately, nearly 50% of all GBM tumors are resistant to the current chemotherapeutic standard, temozolomide (TMZ). TMZ is a DNA alkylating agent that promotes apoptosis via DNA damage. Resistance to TMZ-induced cell death is attributed to expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) resultant from …
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
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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 …
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 …
Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough
Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough
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Cerebral blood flow is regulated by vasoactive molecules released by astroglial cell processes that ensheath the entire cerebrovasculature. This regulation of blood flow in response to neuronal activity is a process known as functional hyperemia. Astrocytes, along with their associated neurons and microvessels, are organized into a functional system called the gliovascular unit (GVU). The astroglial component of the GVU is integral in both regulation of blood flow and maintenance of the blood-brain barrier (BBB). In disease, this system can be disrupted. We found that glioma cells displace astrocytic processes, called endfeet, and prevent their communication with associated vessels, leading …
Regulation Of Breast Cancer Metastasis By Sin3 Chromatin Remodeling Complexes, Monica Jeanene Lewis
Regulation Of Breast Cancer Metastasis By Sin3 Chromatin Remodeling Complexes, Monica Jeanene Lewis
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Metastasis continues to be the most difficult clinical challenge for breast cancer. Survival rates for patients with metastatic breast cancer have not significantly changed in the past 20 years. Therefore, we need a better understanding of the molecular mechanisms that regulate breast cancer metastasis to develop effective therapies. SIN3 chromatin remodeling complexes have been implicated in breast cancer progression. Mammalian cells have two paralogs of SIN3 (SIN3A and SIN3B) that are encoded by distinct genes and have unique functions during development. However, specific roles for SIN3A and SIN3B in breast cancer progression have not been characterized. To better understand how …
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
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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 …
Neonatal Microbial Exposure And Its Effects On The B Cell Repertoire And Development Of Respiratory Allergies, Preeyam Patel
Neonatal Microbial Exposure And Its Effects On The B Cell Repertoire And Development Of Respiratory Allergies, Preeyam Patel
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The incidence of asthma has increased dramatically among children living in developed countries, and the hygiene hypothesis suggests that this is the result of decreased neonatal exposure to microbes. Microbes and allergens can bear similar antibody-reactive epitopes, and exposure to microbes bearing these epitopes during early life can permanently alter the frequency and clonality of the antigen-specific B cell repertoire. The objective of this dissertation was to determine if B cells stimulated by microbes during early life could suppress the development of respiratory allergies during adult life. Both Streptococcus pneumoniae (pneumococcus) and house dust mite (HDM) express antibody-reactive phosphorylcholine (PC) …
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
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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 …
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
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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, …
Germline Restriction Of B Cell Receptor Repertoire Influences Antigenic Epitope Recognition And Primary Antibody Deficiency Pathogenesis, Yuge Wang
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Part I. Mouse Studies Complementarity determining region 3 of the immunoglobulin (Ig) H chain (CDR-H3) lies at the center of the antigen binding site where it often plays a decisive role in antigen recognition and binding. Amino acids encoded by the diversity (DH) gene segment are the main component of CDR-H3. Each DH has the potential to rearrange into one of six DH reading frames (RFs), each of which exhibits a characteristic amino acid hydrophobicity signature that has been conserved among jawed vertebrates by natural selection. A preference for use of RF1 promotes the incorporation of tyrosine into CDR-H3 while …