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Articles 1 - 30 of 59
Full-Text Articles in Medicine and Health Sciences
Novel Insights Into Oligodendrocyte Biology From Developmental Myelination Studies In Autophagy Deficient Mice And Analysis Of Oligodendrocyte Translatome Response To Contusive Spinal Cord Injury., Michael David Forston
Novel Insights Into Oligodendrocyte Biology From Developmental Myelination Studies In Autophagy Deficient Mice And Analysis Of Oligodendrocyte Translatome Response To Contusive Spinal Cord Injury., Michael David Forston
Electronic Theses and Dissertations
Loss of myelin causes severe neurological disorders and functional deficits in white matter injuries (WMI) such as traumatic spinal cord injury (SCI). This dissertation is focused on autophagy in OL development and the OL translatome after SCI. Chapter I describes the history of myelin, OL development, and their involvement in neurodegenerative diseases and SCI. The proteostasis network, in particular autophagy, and its contributions to white matter pathology is discussed. It concludes examining advantages and disadvantages of unbiased omics tools, like RiboTag, to study transcriptional/translational landscapes after SCI. Chapter II focuses on autophagy in OPC/OL differentiation, survival, and proper myelination in …
The Role Of E-Liquid Constituents In E-Cigarette-Induced Cardiac Arrhythmia And Autonomic Imbalance., Cory Kucera
The Role Of E-Liquid Constituents In E-Cigarette-Induced Cardiac Arrhythmia And Autonomic Imbalance., Cory Kucera
Electronic Theses and Dissertations
Introduction. Accumulating evidence indicates that exposure to electronic cigarettes (e-cigs) promotes sympathetic dominance and electrophysiologic instability in the heart, potentially culminating in arrhythmogenesis. E-liquids contain various formulations of nicotine and flavorings, but the effects of specific e-liquid constituents and their concentrations on e-cig-induced autonomic imbalance and electrical dysfunction are unresolved. To that end, we tested the hypothesis that e-cigs modify cardiac autonomic balance and ventricular arrhythmogenesis in mice dependent on e-liquid constituent type and concentration. Methods. Using a crossover design and a serial exposure regimen, ECG-telemetered male C57BL/6J mice underwent whole-body exposure to e-cig aerosols generated from e-liquids containing different …
Supraspinal Reorganization After Pediatric-Onset Spinal Cord Injury., Luis Alvarado
Supraspinal Reorganization After Pediatric-Onset Spinal Cord Injury., Luis Alvarado
Electronic Theses and Dissertations
Pediatric spinal cord injury (SCI) disrupts the efferent and afferent flow of the developing brain, leading to devastating functional impairments below the injury site, yet our understanding of its impact on the brain remains limited. This study examines supraspinal reorganization in children with SCI using electrophysiology and neuroimaging techniques to understand the relationship between residual spinal transmission and supraspinal reorganization. Chapter 2 discusses the development of a child-centric approach using ‘learn, play, and practice’ to foster a trusting relationship with each child and increase compliance with experimental protocols. Chapter 3 evaluates the residual neural transmission of three spinal pathways in …
Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury
Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury
Electronic Theses and Dissertations
Graphical models determine associations between variables through the notion of conditional independence. Gaussian graphical models are a widely used class of such models, where the relationships are formalized by non-null entries of the precision matrix. However, in high-dimensional cases, covariance estimates are typically unstable. Moreover, it is natural to expect only a few significant associations to be present in many realistic applications. This necessitates the injection of sparsity techniques into the estimation method. Classical frequentist methods, like GLASSO, use penalization techniques for this purpose. Fully Bayesian methods, on the contrary, are slow because they require iteratively sampling over a quadratic …
Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum
Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum
Electronic Theses and Dissertations
Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …
Aggregatibacter Actinomycetemcomitans Exploits And Modulates The Immune Response By Human Neutrophils For Survival In The Anaerobic Environment., Hazel Ozuna
Electronic Theses and Dissertations
Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative facultative anaerobe and an opportunistic oral pathogen, strongly associated with localized periodontitis and other inflammatory diseases. Periodontitis is a chronic inflammation of the periodontium resulting from the inflammatory response of the host towards the dysbiotic microbial community present at the gingival crevice. The host immune response creates a hostile environment for microorganisms; therefore, it is important for Aa to be able to regulate the necessary genes to survive and thrive in such an environment. Aaexpresses several virulence factors such as a cytolethal distending toxin (Cdt), lipopolysaccharide (LPS) and leukotoxin A (LtxA), …
Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan
Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan
Electronic Theses and Dissertations
Retinal fibrosis is detrimental to vision. Retinal pigment epithelial (RPE) cells contribute to several retinal fibrotic diseases. Upon exposure to TGF-β, a key fibrotic cytokine, RPE cells trans-differentiate to myofibroblasts marked by the integration of α-SMA fibers into F-actin stress fibers, which confer strong contractility. Myofibroblasts produce and contract the collagen-rich fibrotic scar and disrupt retinal architecture. In this study, we investigated the in vitro effects of the putative endocannabinoid compound N-oleoyl dopamine (OLDA) on TGF-β2 induced porcine RPE cell contraction and α-SMA expression. Using an in vitro collagen matrix contraction assay, we found that OLDA inhibited TGF-β2 induced contraction …
Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge
Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge
Electronic Theses and Dissertations
It is generally believed that the tear film lipid surface film inhibits the rate of evaporation (Revap) of the underlying tear aqueous. It is also generally believed that changes in the composition of the tear film lipid layer is responsible for an increase in Revap in patients with dry eye. Both of these ideas have never been proven. The purpose of the current studies was to test these ideas. Revap was measured in vitro gravimetrically. Lipid spreading was measured using Raman spectroscopy and microscopy. The influence of the following surface films on the Revap of the sub phase of physiologically …
Impact Of Pank1 Deletion On Mitochondrial Acetylation And Cardiac Function During Pressure Overload., Timothy N. Audam
Impact Of Pank1 Deletion On Mitochondrial Acetylation And Cardiac Function During Pressure Overload., Timothy N. Audam
Electronic Theses and Dissertations
Recent studies have associated elevated protein acetylation levels with heart failure in humans. Although mechanisms promoting elevated acetylation levels are not fully known, excess acetyl-CoA may drive enzyme-independent acetylation of cardiac proteins. Accumulation of acetyl-CoA depends on the availability of sufficient CoA, whose production is regulated by pantothenate kinases in the CoA biosynthetic pathway. We show that cardiac proteins are hyperacetylated during heart failure in humans and tested in mice whether limiting CoA abundance would improve ventricular remodeling during pressure overload-induced hypertrophy. We limited cardiac CoA levels by deleting the rate-limiting enzyme in CoA biosynthesis, Pank1 (one of three PANK-encoding …
Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller
Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller
Electronic Theses and Dissertations
Despite the success of immunotherapy in many types of cancer, pancreatic adenocarcinoma (PDAC) has yet to benefit. Innate immune cells are critical to antitumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Though trained innate immunity has mostly been investigated in the context of infection, the induction of trained innate immunity could also protect against tumors, and specifically pancreatic tumors. Here, we demonstrate that yeast-derived particulate β-glucan, a known inducer of trained immunity, traffics to the pancreas following IP administration. This causes …
Identifying The Cardiovascular Effects Of Multiple Pollutants., Katlyn Elizabeth Mcgraw
Identifying The Cardiovascular Effects Of Multiple Pollutants., Katlyn Elizabeth Mcgraw
Electronic Theses and Dissertations
Cardiovascular disease (CVD) is the leading cause of death from environmental exposures. Although exposure to PM2.5 is an established risk factor for CVD, the contribution of other hazardous pollutant exposure to CVD is less clear. Overall, this work aimed to examine the effect of pollutants with lesser documented effects on cardiovascular disease using a multi-pronged approach to exposure assessment. The three aims were to examine the relationship between county-level toxic chemical releases and CVD mortality in the contiguous United States between 2002 and 2012, to assess the relationship between individual-level VOC metabolites and vascular function, and to build multipollutant …
Characterization Of Adiposity And Inflammation Genetic Pleiotropy Underlying Cardiovascular Risk Factors In Hispanics., Mohammad Yaser (Anwar)
Characterization Of Adiposity And Inflammation Genetic Pleiotropy Underlying Cardiovascular Risk Factors In Hispanics., Mohammad Yaser (Anwar)
Electronic Theses and Dissertations
The observed overlap between genetic variants associated with both adiposity and inflammatory markers suggests that changes in both adiposity and inflammation could be partially mediated by common pathways. The pervasive but sparsely characterized “pleiotropic” genetic variants associated with both adiposity and inflammation have been hypothesized to provide insight into the shared biology. This study explored and characterized the genetic pleiotropy underpinning adiposity and inflammation using genetic and phenotypic observations from the Cameron County Hispanic Cohort (CCHC). A total of 3,313 samples and >9 million single nucleotide polymorphisms (SNPs) were examined in this study. Mixed model genome-wide association studies (GWAS) were …
Tissue-Resident Myeloid-Derived Suppressor Cells Modulate Immune Homeostasis In Healthy Adipose., Katlin Brooke Stivers
Tissue-Resident Myeloid-Derived Suppressor Cells Modulate Immune Homeostasis In Healthy Adipose., Katlin Brooke Stivers
Electronic Theses and Dissertations
Our goal with this study was to gain insight into the homeostatic immune cell network in healthy adipose tissue. Specifically, we sought to determine if the immature myeloid cells found in healthy and inflamed adipose were, in fact, tissue-resident myeloid-derived suppressor cells (MDSCs). Using various in vitro and in vivo methods, we have uncovered a population of CD11bHi Ly6CHi Ly6G- MDSCs resident in healthy adipose tissue. To the best of our knowledge this is the first time that these cells have been investigated and described in healthy adipose tissue. Systemic MDSC depletion lead to the accumulation of …
Identification And Structural Characterization Functional Motifs In The Porphyromonas Gingivalis Mfa1 Short Fimbria., Mohammad K. Roky
Identification And Structural Characterization Functional Motifs In The Porphyromonas Gingivalis Mfa1 Short Fimbria., Mohammad K. Roky
Electronic Theses and Dissertations
Porphyromonas gingivalis is a causative agent of periodontal disease, initially colonizes the oral cavity by adhering to commensal streptococci. Adherence requires the interaction of the minor fimbrial protein (Mfa1) of P. gingivalis with streptococcal antigen I/II (Ag I/II). A peptide derived from Ag I/II peptide has been well characterized and shown to significantly reduce P. gingivalis colonization and bone loss in vivo, suggesting that this interaction represents a potential target for therapeutic intervention. However, the functional motifs of Mfa1 involved in the interaction with Ag I/II remain uncharacterized. A series of N- and C-terminal peptide fragments of Mfa1 were …
N-Acetyltranserase 2 (Nat2) Genotype Polymorphism In Cryopreserved Human Hepatocytes And Chinese Hamster Ovary (Cho) Cells., Mariam Refaat Zaky Habil
N-Acetyltranserase 2 (Nat2) Genotype Polymorphism In Cryopreserved Human Hepatocytes And Chinese Hamster Ovary (Cho) Cells., Mariam Refaat Zaky Habil
Electronic Theses and Dissertations
Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of drugs and aromatic amine carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT2 genotypes thus dividing the population into rapid, intermediate, and slow acetylators. We hypothesize allelic variants of NAT2 genotype will decrease levels of N-acetylation, cytotoxicity, oxidative stress, DNA adduct formation, and mutagenesis compared to the reference allele NAT2*4. Cryopreserved human hepatocytes expressing different NAT2 genotypes and NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and human NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of different xenobiotics. In …
Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding
Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding
Electronic Theses and Dissertations
Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …
Volatile Organic Compound Exposure And Cardiometabolic Syndrome Risk In A Nationally Representative Cohort., Stacey Lane Konkle
Volatile Organic Compound Exposure And Cardiometabolic Syndrome Risk In A Nationally Representative Cohort., Stacey Lane Konkle
Electronic Theses and Dissertations
BACKGROUND: The relative importance of environmental exposures such as volatile organic compounds (VOCs) is one of the paramount public health priorities of our time, yet is presently unstudied. VOCs are ubiquitous in the environment and have been associated with numerous adverse health effects, including a number of cardiovascular and metabolic effects that are components of Cardiometabolic Syndrome (CMS). OBJECTIVES: To examine the relationship between CMS and individual-level exposures to VOCs, measured as urinary metabolites of VOCs (UM-VOCs), in a nationally representative sample. METHODS: Associations between urinary biomarkers of exposure to 19 parent VOCs and CMS were assessed using the National …
Tobacco-Derived Aldehydes: Platelet Activation, Thrombosis, And The Role Of Trpa1., Andre Dwayne Richardson
Tobacco-Derived Aldehydes: Platelet Activation, Thrombosis, And The Role Of Trpa1., Andre Dwayne Richardson
Electronic Theses and Dissertations
Cigarette smoking is the single largest risk factor for cardiovascular disease (CVD) pathophysiology. Numerous researchers have shown potential associations between aldehydes in tobacco-derived aerosols from mainstream cigarette smoke (MCS) or electronic cigarettes (e-cigs) and their cardiotoxicity by damaging blood vessel endothelium. The severity of exposure to these toxicants can furthermore lead to adverse cardiovascular outcomes such as myocardial infarctions, stroke, coronary and peripheral artery disease, or atherosclerosis due to blood clots, a pro-thrombotic event. However, the mechanisms by which levels of harmful and potentially harmful constituents (HPHCs) such as aldehydes induce thrombosis are not well-known. Of specific interest, evidence has …
Tobacco Product-Derived Aldehydes: Effects On Circulating Angiogenic Cells & Implications For Cardiovascular Disease., Jordan B. Lynch
Tobacco Product-Derived Aldehydes: Effects On Circulating Angiogenic Cells & Implications For Cardiovascular Disease., Jordan B. Lynch
Electronic Theses and Dissertations
Cardiovascular disease (CVD) is the leading cause of death worldwide. Tobacco smoke is the most significant modifiable risk factor in CVD development and contains numerous toxic compounds, including aldehydes, which have been linked to CVD. Formaldehyde, acetaldehyde, acrolein, and crotonaldehyde have been identified as significant contributors to cigarette-induced health effects, but the mechanism of these effects is not well understood. These aldehydes are also found in aerosols produced by e-cigarettes (e-cigs). The goal of this dissertation was to explore the systemic, hematological, and endothelium-related effects of exposure to tobacco products and constituent aldehydes and to identify potential mechanisms of injury. …
Tobacco Enhances Bacterial-Induced Periodontal Bone Loss In Mice., Mina Iskander
Tobacco Enhances Bacterial-Induced Periodontal Bone Loss In Mice., Mina Iskander
Electronic Theses and Dissertations
Background: Tobacco smoking is the leading environmental risk factor for periodontal diseases. Delineation of the mechanisms underlying tobacco-induced or exacerbated periodontitis is hampered by the lack of an appropriate and reliable animal model. Hypothesis: We hypothesized that Porphyromonas-gingivalis-infected, cigarette smoke-exposed mice would represent reproducible models of acute (ligature model) and chronic (oral gavage model) tobacco-enhanced periodontitis that reflect multiple aspects of the disease noted in human smokers. Methods: In a chronic oral gavage disease model, Balb/c mice (6-8 weeks, 4 groups of n = 6 per group) were exposed to smoke produced by a Teague-10 smoking machine from 1R6F research …
Dual Role Of Antimicrobial Peptide Cathelicidin In Alcohol-Associated Liver Disease., Fengyuan Li
Dual Role Of Antimicrobial Peptide Cathelicidin In Alcohol-Associated Liver Disease., Fengyuan Li
Electronic Theses and Dissertations
Patients with alcohol-associated liver disease (ALD) have high morbidity and mortality in its severe forms. One of the major features in different forms of ALD is the altered gut microbiota. Antimicrobial peptides (AMPs) play a crucial role in maintaining gut microbiota homeostasis. LL-37 (known as CRAMP in mouse) is the sole member of the human cathelicidin family and has piqued great research interest for its dual role in modulating microbiota and the immune response in metabolic diseases. Inflammasome activation is an important component of the liver pathophysiology in ALD and requires two signals for its full activation to induce the …
The Role Of Inter-Enlargement Propriospinal Neurons In Locomotion Following Spinal Cord Injury., Courtney Therese Shepard
The Role Of Inter-Enlargement Propriospinal Neurons In Locomotion Following Spinal Cord Injury., Courtney Therese Shepard
Electronic Theses and Dissertations
The focus of this dissertation is to explore the functional role of two anatomically-defined pathways in the adult rat spinal cord before and after spinal cord injury (SCI). To do this, a TetOn dual virus system was used to selectively and reversibly silence neurons with cell bodies at spinal segment L2 and projections to spinal segment C6 (long ascending propriospinal neurons, LAPNs) and neurons that originate in the C6 spinal segment and terminate at L2 spinal segment (long descending propriospinal neurons, LDPNs). This dissertation is divided into five chapters. Chapter One provides background information regarding spinal cord injury, locomotion, …
The Role Of Slc7a11 In Controlling Extracellular And Intracellular Redox Environments Of Lung Fibroblasts - Potential Targets For Intervention In Aging And Idiopathic Pulmonary Fibrosis., Yuxuan Zheng
Electronic Theses and Dissertations
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by extracellular matrix deposition by fibroblasts. Aging and oxidative stress increase the susceptibility to IPF. Redox couples, cysteine/cystine (Cys/CySS) and glutathione/glutathione disulfide (GSH/GSSG), and their redox potentials (Eh) quantify oxidative stress. Fibroblasts from old mice maintain more oxidized extracellular Eh(Cys/CySS) than young mice. Microarray shows down-regulation of Slc7a11 potentially mediates this age-related oxidation. Slc7a11 is the key component of system Xc-, an antiporter that imports CySS and exports glutamate. The first aim of this dissertation is to investigate the mechanistic link between Slc7a11 …
The Identification Of Long Non-Coding Rna Zfas1 Through An Exploratory Rna-Sequencing Analysis And Its Association With Epithelial-To-Mesenchymal Transition In Colon Cancer Adenocarcinoma., Stephen J. O'Brien
Electronic Theses and Dissertations
Colorectal adenocarcinoma is the fourth most common cancer diagnosed worldwide and is a significant cause of morbidity and mortality. This dissertation performed an exploratory RNA-sequencing analysis comparing gene expression between colon adenocarcinoma tissue and paired normal colon epithelium. After identification of a number of lncRNAs that were increased in expression in colon adenocarcinoma compared to normal colon epithelium, we aimed to validate the expression and investigate their function in vitro. Specifically, we focused on the lncRNA ZFAS1 and its association with epithelial-to-mesenchymal transition. These studies found the following: 1. Seven candidate lncRNAs were identified from the exploratory RNA-sequencing analysis to …
Defects In Fetal Mouth Movement And Pharyngeal Patterning Underlie Cleft Palate Caused By Retinoid Deficiency., Regina Friedl
Defects In Fetal Mouth Movement And Pharyngeal Patterning Underlie Cleft Palate Caused By Retinoid Deficiency., Regina Friedl
Electronic Theses and Dissertations
Cleft palate is a common birth defect. Etiologic mechanisms of palate cleft include defects in palate morphogenesis, mandibular growth, or spontaneous fetal mouth movement. Cleft palate linked to deficient fetal mouth movement has been demonstrated directly only in a single experimental model of loss of neurotransmission. Here, using retinoid deficient mouse embryos, we demonstrate directly for the first time that deficient fetal mouth movement and cleft palate occurs as a result of mis-patterned development of pharyngeal peripheral nerves and cartilages. Retinoid deficient embryos were generated by inactivation of retinol dehydrogenase 10 (Rdh10), which is critical for production of …
Development Of Bar-Peptide Nanoparticles And Electrospun Fibers For The Prevention And Treatment Of Oral Biofilms., Mohamed Yehia Mahmoud
Development Of Bar-Peptide Nanoparticles And Electrospun Fibers For The Prevention And Treatment Of Oral Biofilms., Mohamed Yehia Mahmoud
Electronic Theses and Dissertations
Background: Periodontal diseases are globally prevalent inflammatory disorders that affect ~47% of U.S adults. Porphyromonas gingivalis (Pg) has been identified as a “keystone” pathogen that disrupts host-microbe homeostasis and contributes to the initiation and progression of periodontitis. Pg associates with oral streptococci in supragingival plaque and this interaction represents a potential target for therapeutic intervention. Previously our group developed a peptide (designated BAR), that potently inhibits Pg/Streptococcus gordonii (Sg) adherence in vitro and Pg virulence in a murine model of periodontitis. While efficacious, BAR (SspB Adherence Region) provided transient inhibition and required higher concentrations of BAR to disrupt established …
Glycine Receptor Expression Across Identified Retinal Ganglion Cell Types., Ian Scot Pyle
Glycine Receptor Expression Across Identified Retinal Ganglion Cell Types., Ian Scot Pyle
Electronic Theses and Dissertations
Retinal ganglion cells (RGCs) represent the culmination of all retinal signaling and their output forms the substrate for vision throughout the rest of the brain. About 40 different RGC types have been defined by differences in their visually evoked responses, morphology, and genetic makeup. These responses arise from interactions between inhibition and excitation throughout the retinal circuit (Franke et al., 2017; Masland, 2012; Sanes & Masland, 2015; Werblin, 2011). Unlike most other areas of the central nervous system (CNS), the retina utilizes both GABA and glycine inhibitory neurotransmitters to refine glutamatergic excitatory signals (Franke & Baden, 2017; Werblin, 2011; C. …
The Q Rule In Bacteriodetes And The Identification And Characterization Of Porphyromonas Gingivalis Glutaminyl Cyclase., John Andrew Houston
The Q Rule In Bacteriodetes And The Identification And Characterization Of Porphyromonas Gingivalis Glutaminyl Cyclase., John Andrew Houston
Electronic Theses and Dissertations
Background: Porphyromonas gingivalis, a major pathogen associated with chronic periodontitis, secretes variety of proteins, majority of which begins with glutamine. Several of these proteins were found with pyroglutamate (pGlu) at N-terminus suggesting the presence of this posttranslational modification pathway in P.gingivalis. The observation that N-terminal glutamine is over-represented as the first amino acid after signal peptide cleavage, and subsequent confirmation of pGlu formation on the nascent protein via mass spectrometry, led us to conclude that an enzyme must be present as the executor of this reaction. Hypothesis: PG2157 is a glutaminyl cyclase and is responsible for the cyclization of …
Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent
Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent
Electronic Theses and Dissertations
This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC50 values. Furthermore, AvFc recognizes a number of cell …
Synthesis And Characterization Of Targeted Bar Encapsulated Polylactic-Co-Glycolic Acid Nanoparticles To Inhibit Porphyromonas Gingivalis Biofilm Formation., Ranjith Radha Krishnan
Synthesis And Characterization Of Targeted Bar Encapsulated Polylactic-Co-Glycolic Acid Nanoparticles To Inhibit Porphyromonas Gingivalis Biofilm Formation., Ranjith Radha Krishnan
Electronic Theses and Dissertations
Periodontal disease is one of the most prevalent infectious diseases worldwide. Between 30-50% of the global adult population suffers from periodontal disease. Some form of periodontitis is present in 46% of American adults, corresponding to annual expenditures in excess of 14 billion dollars for treatment and prevention. Current treatments for periodontal diseases involve mechanical removal of plaque, correction of risk factors, gingival surgery and/or antibiotic therapy. To our knowledge there is no effective therapeutic approach that aims to limit pathogen colonization of the oral biofilm or re-colonization after treatment. Interaction of the pathogen Porphyromonas gingivalis with oral streptococci is critical …