Digital Commons Network^™

Characterization Of Pg1604 (Porz) As An Essential Component Of Type 9 Secretion System In Porphyromonas Gingivalis., Apurva Tadimari Prabhakar

Electronic Theses and Dissertations

Background: The numerous virulence factors of Porphyromonas gingivalis are essential for the organism to invade host tissues while escaping immune responses [1, 2]. Some of these factors, like major proteases referred to as gingipains, are secreted by a unique secretion system called PerioGate or Type IX Secretion System (T9SS). T9SS consists of a number of membrane and periplasmic proteins, which provide transportation only for proteins that possess a conserved C-terminal domain (CTD). The CTD functions as a specific recognition signal for the T9SS. PG1604 of P. gingivalis W83 is a CTD-containing protein, which has been shown in our initial studies …

Endothelial Hspa12b Is A Novel Protein For The Preservation Of Cardiovascular Function In Polymicrobial Sepsis Via Exosome Mir-126, Xia Zhang

Electronic Theses and Dissertations

Sepsis is the most frequent cause of mortality in most intensive care units. Cardiovascular dysfunction is a major complication associated with sepsis, with high mortality rates up to 70%. Currently, there is no effective treatment approach for sepsis.

The integrity of the endothelium is fundamental for the homeostasis of the cardiovascular system. Sepsis induces endothelial cell injury which is the key factor for multiple organ failure. The increased expression of adhesion molecules and chemokines in endothelial cell promotes leukocytes infiltration into the tissue. The loss of tight junction proteins and increased permeability of the endothelial cells will provoke tissue hypoxia …

Extraction, Purification And Characterization Of An Antibiotic-Like Compound Produced By Rhodococcus Sp. Mtm3w5.2, Pushpavathi Reddyvari Manikindi

Electronic Theses and Dissertations

The bacterium Rhodococcus is a potential source for novel antimicrobial metabolites. Recently, the Rhodococcus strain MTM3W5.2 was isolated from a soil sample collected from Morristown, East Tennessee and was found to produce an inhibitor molecule that is active against similar Rhodococcus species. The aim of this research is to extract, purify, and characterize the active compound. The compound was obtained from both agar and broth cultures of strain MTM3W5.2 and purified by primary fractionation of crude extract on a Sephadex LH-20 column, followed by semi-preparative reversed phase column chromatography. Final purification was achieved using multiple rounds of an analytical C …

Development And Evaluation Of Custom Prosthetic Devices For A Companion Animal Utilizing Additive Manufacturing., Benjamin Joseph Cahill

Electronic Theses and Dissertations

BACKGROUND AND SIGINIFICANCE: Few options exist for companion animals in need of prosthetic devices. With the rise of rapid prototyping technology, the availability and customization of prosthetic devices for individual companion animals is now a viable and cost effective alternative to the current options of a peg leg prosthetic, or wheel-assisted prosthetic device. The goals of this study were to describe the (1) specific needs and (2) biomechanics of a feline with bilateral thoracic limb amputation, (3) develop custom prosthetic devices utilizing rapid prototyping technology, and (4) describe the biomechanics of a feline with bilateral thoracic limb amputation using the …

Environmental Vegetation : A Possible Association With Cardiovascular Disease Risk., Ray Anthony Yeager Ii

Electronic Theses and Dissertations

The built environment affects numerous aspects of human health and wellbeing, including risk of cardiovascular disease (CVD), the leading cause of morbidity and mortality in both the U.S. and worldwide. The amount and quality of environmental vegetation, is an important aspect of the built environment that affects known CVD risk factors, including psychosocial stress, health behaviors, and exposure to air pollutants. Nevertheless, little evidence on the role of potential mechanisms and geographic scale in these relationships exists. Of previous studies that describe associations between vegetation and CVD outcomes, limited investigation has been performed to assess these observed relationships in differing …

Modification Of T9ss Cargo Proteins Of Porphyromonas Gingivalis For Their Secretion In Soluble Form And Purification By Affinity Chromatography., Apoorv Goel

Electronic Theses and Dissertations

Background: Porphyromonas gingivalis, a keystone-pathogen associated with periodontitis, utilizes the Type IX Secretion System (T9SS) to secrete proteins bearing the conserved C-terminal domain (CTD), many of which are essential virulence factors. These include, besides gingipains and PPAD, 29 other proteins. During or after the outer membrane translocation the CTD is cleaved off and a glycan moiety is covalently attached anchoring the secreted proteins at the bacterial cell surface. Objective: Most of the CTD bearing proteins have only hypothetical functions assigned. It is plausible that these CTD bearing proteins may also play a crucial role in P. gingivalis pathogenesis. Therefore, …

Tobacco-Gene Activity Profile In Porphyromonas Gingivalis, Filifactor Alocis And Treponema Denticola., Neelima Chowdary Cherukumalli

Electronic Theses and Dissertations

Smoking is an established risk factor for periodontitis. Prior studies have shown that cigarette smoke extract (CSE) can induce profound phenotypic changes in Porphyromonas gingivalis and alters the virulence of this important periodontal pathogen. We hypothesized that CSE might also alter gene expression in established periodontal pathogens, Porphyromonas gingivalis and Treponema denticola, as well as in the emerging pathogen, Filifactor alocis. Oral bacteria were grown in CSE-conditioned medium (1000 ng/ml nicotine equivalents) or in unconditioned control medium. Total RNA was extracted and CSE-regulated genes were identified by comparison of the mRNA profiles of CSE with control cultures using RNA-Seq …

Microbiota Activated Cd103+ Dcs Stemming From Oral Microbiota Adaptation Specifically Drive Γδt17 Proliferation And Activation., Christopher Jay Fleming

Electronic Theses and Dissertations

IL-17 producing γδ T cells (γδT17) promote numerous autoimmune diseases such as psoriasis and arthritis, as well as, cancers of the colon, lung and breasts. Yet γδT17 peripheral regulation has yet to be thoroughly explored. In mice deficient in IL-17 signaling, we observed expansion of γδT17 in all major tissues. However, γδT17 expansion was not uniformly distributed systemically and was most prominent in oral draining cervical lymph nodes (LNs) with monoclonal expansion of Vγ6 γδT17. In vitro proliferation assays of these cervical LNs showed endogenous proliferation by γδT17 dependent on cell-to-cell contact with CD103⁺ DCs. CD86⁺ and CD80 …

Porphyromonas Gingivalis Gingipains Induce A Pro-Inflammatory Extracellular Microenvironment : The Role Of Par-2 And Fibronectin., Jeffrey S. Marschall

Electronic Theses and Dissertations

Periodontitis is a chronic inflammatory disease that is characterized by severe tissue destruction of the gingiva and other tooth supporting structures; if left untreated, tooth loss and disintegration of the alveolar bone occurs. This chronic inflammatory state has been linked to other systemic diseases such as cardiovascular disease, diabetes, rheumatoid arthritis, and Alzheimer’s disease. Porphyromonas gingivalis is the major pathogenic microbe in periodontitis. The main virulence factors of P. gingivalis are the Arg-aa and Lys-aa gingipains, which are proteolytic enzymes implicated in a plethora of activities that allow P. gingivalis to subvert the human immune system in the oral cavity …

Characterization Of The Role Of The Burkholderia Pseudomallei Type 3 Secretion System Using In Vivo Imaging., Maria Gabriela Gutierrez

Electronic Theses and Dissertations

Melioidosis is a fatal infectious disease caused by the Tier 1 Select Agent Burkholderia pseudomallei. Hallmarks of melioidosis include pneumonic disease and prominent septicaemic spread. Both forms of disease are contingent upon the bacterium’s intracellular life cycle and particularly on its ability to escape from host cell phagosomes. Upon encountering a host cell, B. pseudomallei is internalized into membrane-bound vacuoles from which the bacterium must rapidly escape to the cytoplasm in order to replicate and promote its survival. In the host cytoplasm, B. pseudomallei is capable of polymerizing actin for intracellular and intercellular motility and spread, lysing the host …

Ecological Niche Modeling Of The North American Giant Salamander: Predicting Current And Future Potential Distributions And Examining Environmental Influences, Selena S. Roark

Electronic Theses and Dissertations

North American Giant Salamanders (Cryptobranchus alleganiensis), commonly known as hellbenders, have been experiencing a population decline for decades due to human influences, such as pollution and habitat destruction. Many efforts are underway to save the hellbender but their entire potential geographical range has not been well-studied. Currently, hellbender populations are delineated by county boundaries and are on the International Union for Conservation of Nature Red List. The Genetic Algorithm for Rule-set Production, an Ecological Niche Model, was used to model the current hellbender potential distribution at a macro-scale under two different environmental scenarios. Additionally, future potential distributions were …

Sa-4-1bbl As A Modulator Of Innate, Adaptive, And Regulatory Immunity : Implications For Cancer Prevention And Treatment., Hampartsoum Barsoumian

Electronic Theses and Dissertations

SA-4-1BBL is a recombinant costimulatory molecule that is active in its soluble form and has pleiotropic effects on the functions of innate, adaptive, and regulatory immune cells. We have previously shown that SA-4-1BBL makes CD4+ T conventional cells (Tconvs) resistant to suppression by CD4+CD25+Foxp3+ T regulatory cells (Tregs). The mechanistic basis of this observation is the subject of this study. We demonstrate that Tconvs, but not Tregs, are the direct targets of SA-4-1BBL-mediated evasion of Treg suppression without contribution from antigen presenting cells (APCs). SA-4-1BBL engagement with its receptor, 4-1BB, on Tconvs resulted in the production of high levels of …

Comparison Of Anti-Pneumococcal Functions Of Native And Modified Forms Of C-Reactive Protein, Donald Neba Ngwa

Electronic Theses and Dissertations

The anti-pneumococcal function of native C-reactive protein (CRP) involves its binding to phosphocholine molecules present on Streptococcus pneumoniae and subsequent activation of the complement system. However, when pneumococci recruit complement inhibitory protein factor H on their surface, they escape complement attack. Non-native forms of CRP have been shown to bind immobilized factor H. Accordingly, we hypothesized that modified CRP would bind to factor H on pneumococci, masking its complement inhibitory activity, allowing native CRP to exert its anti-pneumococcal function. As reported previously, native CRP protected mice from lethal pneumococcal infection when injected 30 minutes before infection but not when injected …

Quinolines: Novel Synthesis And Derivatives Of Heterocyclic Bioactive Agents, Ginelle A. Ramann

Electronic Theses and Dissertations

Tuberculosis is a pulmonary disease that has ravaged the world throughout history. Even today, many developed and developing countries are experiencing this plight, made worse by the scourge of antibiotic-resistant bacteria.

Mycobacterium tuberculosis's class II fructose-1,6-bisphosphate aldolase presents an interesting target in the design of new therapies against this disease. Previous attempts to construct an inhibitor to this enzyme fell short due to poor selectivity or poor cellular uptake. However a new class of noncompetitive inhibitor based on 8-hydoxyquinoline-2-carboxylic acid presents a fresh approach. Preliminary studies indicate various modifications to this scaffold could be beneficial to its inhibitory efficacy.

Modifications …

Protein-Protein Interactions Of Human Mitochondrial Amidoxime-Reducing Component In Mammalian Cells, John Thomas

Electronic Theses and Dissertations

Newly discovered pterin-molybdoenzymes mammalian proteins, mARC1, and mARC2, are though to activate pro-drug, metabolize mutated base pairs, and producing nitric oxide from nitrite. However, the physiological function of the mARC proteins remain unclear. It is hypothesized that identifying partner proteins through protein-protein interactions can provide evidence to their physiological function. This study aimed to further investigate the potential function of mARC proteins through the identification of protein-protein interaction in human cell lysate, utilizing co-immunoprecipitation, crosslinking reagent, and pull-down assays. Several proteins (e.g. mitogen-activated protein kinase 5, phosphatidylinositol 4-phospahte 3-kinase C2 domain-containing subunit beta, ADP/ATP translocase 1, and myotubularin) were identified …

Malondialdehyde (Mda) And Glutathione Peroxidase (Gpx) Are Elevated In Crohns Disease-Associated With Mycobacterium Avium Subspecies Paratuberculosis (Map), Ahmad Qasem

Electronic Theses and Dissertations

Inflamed tissue in Crohn’s disease (CD) are continuously producing toxic oxygen metabolites leading to cellular injury and apoptosis. Here, we are evaluating the role of Mycobacterium avium subspecies paratuberculosis (MAP) in oxidative stress in CD by evaluation of lipid peroxidation and antioxidant defense activity. Specifically, we measured malondialdehyde (MDA) level and selenium-dependent glutathione peroxidase (GPx) activity in the plasma from patients and cattle infected with MAP. The level of MAP antibodies in bovine sera was determined by IDEXX kit whereas detection of MAP DNA was performed by IS900-based nPCR. A total of 42 cattle (21 infected with MAP and 21 …

Role Of Microglial Α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator In Neuroinflammatory Pain Models In Mice, Muzaffar Abbas

Electronic Theses and Dissertations

Neuroinflammatory pain affects about 1.5% of the United States population. Around 20-40% patients having neurological disorders are affected with neuroinflammatory pain. As a part of the limbic system, hippocampus is known to play a critical role in pain perception and processing, and is densely populated with microglial cells and α7 nicotinic acetylcholine receptors (nAChRs). Given the role of microglial α7 nAChRs in neuroinflammation, the α7 nAChRs have emerged as potential target for neuroinflammatory pain treatment. We hypothesized that microglial α7 nAChRs positive allosteric modulation in the hippocampus will decrease neuroinflammatory pain at behavioral, cellular, biochemical, and molecular level. The primary …

The Effect Of Copper And Zinc Source On Pre-Weaning Performance Of Cows, Health And Performance Of Suckling Calves, And Post-Weaning Feedlot Performance, Carcass Composition, And Meat Quality Of Calves, Jesse Fulton

Electronic Theses and Dissertations

During gestation an elevated level of nutrient intake is required by the cow in order to meet the requirements of the maturing fetus and if these requirements are not met, changes in fetal development can occur. However, little is understood about the effects of gestational manipulation of specific nutrients, such as minerals, on progeny growth, performance and carcass traits. Previous research supports the hypothesis that minerals provided in an organic form should be more soluble and readily available to the body for absorption. Therefore the objectives of this study were to determine if source of gestational and post-natal Cu and …

Decolonizing Revelation: A Spatial Reading Of The Blues, Rufus Burnett Jr.

Electronic Theses and Dissertations

Decolonizing Revelation: A Spatial Reading of the Blues demonstrates that the cultural phenomenon of the blues is an indigenous way of knowing that offsets the hidden logic of racialized dominance within modern Christian understandings of revelation. In distinction from the Christian, Religious, and racialized understandings of the blues, this dissertation focuses on the space in which the blues emerges, the Delta Region of the United States. By attending to space, this dissertation shows how critical consideration of geography and region can reveal nuances that are often veiled behind racialized and theologized ways of understanding the people of the Delta Region. …

Bluesman, Guitar, And Migration, Yaeko Takada

Electronic Theses and Dissertations

This project examines how the bluesman, guitar, and migration have interacted with each other and brought about transformations to American popular music, based upon scholarly works, magazine articles, and the sound recordings of the prewar blues performers. In popular theory, the blues sprang out of the cotton fields and articulated the life experiences of the oppressed people in isolated areas, particularly the Jim Crow south. These are certainly truths of the blues. Also true is that the blues was a product of modernization in every way and a representation of the African American bluesman's aspiring life. The bluesman's mobile lifestyle …

Assessment Of Staphylococcus Aureus Genetics: Clinical Versus Community Epidemiology, Matthew Lawrance

Electronic Theses and Dissertations

Staphylococcus aureus has an historical relationship with anthropogenic environments, particularly hospitals, where infection characteristics differ from community-acquired disease. This has promoted a designation of strains as healthcare or community associated. Despite this affiliation, genetic approaches have failed to support these groupings. In order to establish the genetic relationship between S. aureus from differing anthropogenic environments, I have analyzed the relatedness between three cohorts of S. aureus: nasal carriage isolates from community participants, infectious isolates from hospitals, and a cohort from an uninvestigated environment, an ambulatory clinic. Multilocus Sequence Typing (MLST) and Staphylococcus aureus protein a (spa) repeat regions were analyzed …

Mathematical Modeling Of Infectious Diseases With Latency: Homogeneous Mixing And Contact Network, Keith Carlson

Electronic Theses and Dissertations

In mathematical epidemiology, the standard compartmental models assume homogeneous mixing in the host population, in contrast to the disease spread process over a real host contact network. One approach to incorporating heterogeneous mixing is to consider the population to be a network of individuals whose contacts follow a given probability distribution. In this thesis we investigate in analogy both homogeneous mixing and contact network models for infectious diseases that admit latency periods, such as dengue fever, Ebola, and HIV. We consider the mathematics of the compartmental model as well as the network model, including the dynamics of their equations from …

Exploring New Chemical Entities From Traditional Medicine: Docking, Synthesis And Specific Bioactivities, Chinni Yalamanchili

Electronic Theses and Dissertations

Traditional medical systems contributed significantly to medicine with a number of their phytochemicals found to possess good biological properties. Recently, Dr. Youyou Tu was awarded the Nobel Prize (2015) for her discovery/isolation of Artemisinin from the TCM plant Artemisia annua. Our first aim is to identify active phytochemicals against botulinum neurotoxin A (BoNT/A), and diabetes from Ayurveda and TCM, respectively, by using in silico, in vitro and in vivo approaches. In our second aim, we wanted to enantioselectively synthesize scalable quantities of phytoestrogenic isoflavans such as equol and sativan. The following three chapters summarize results of the three research goals. …

Take The Mountain: The International Order Of Twelve Knights And Daughters Of Tabor And The Black Health Care Initiative In The Mississippi Delta, 1938 – 1983, Katrina Rochelle Sims

Electronic Theses and Dissertations

The dissertation explores the intersection of black racial uplift strategies, black women’s entry and marginalization within distinctly male-dominated spaces such as fraternal orders, and institutional racism, specifically the implementation of regulatory policies to hinder predominately black communities from accessing state programs and funding resources. It demonstrates how African Americans in the Mississippi Delta circumvented Jim Crow practices that restricted black Mississippians access to facilities and funding. It acknowledges the comprehensive health care initiative that provided African Americans with autonomous medical care. It complicates the narrative that defined civil rights strictly within the framework of the franchise and integration of public …

The Owl Sensor: A Smart Nanostructure For Single Nucleotide Variation Analysis, Rebekah Karadeema

Electronic Theses and Dissertations

Analysis of single nucleotide variations (SNVs) in DNA and RNA sequences is extensively used in healthcare for detection of genetic mutations and analysis of drug resistant pathogens. Here we developed a nucleic acid sensor able to differentiate between a fully matched analyte and one with a SNV in a wide temperature range of 5°C-32°C. The sensor, dubbed here the 'Owl Sensor' due to the complex's resemblance to owl eyes, utilizes recent developments in DNA nanotechnology and synthetic biology to self-assemble a fluorescent DNA nanostructure called a Double Crossover, or DX Tile, capable of differentiating SNVs in a large temperature range, …

Political, Economic, And Health Determinants Of Tuberculosis Incidence, Ashley Rutherford

Electronic Theses and Dissertations

The epidemiologic transition has shifted major causes of mortality from infectious disease to chronic disease; however, infectious diseases are again re-emerging as a major global concern (Diamond, 1997; Karlen, 1995; McNeil, 1976). This research aimed to identify potential areas of infectious disease influence that are not health-related in order to help governments and policymakers establish new policies, correct current policies, or further address these issues in order to effectively prevent and combat infectious disease. This study employed a retrospective, cross-sectional, non-experimental design via structural equation modeling (SEM) and examined tuberculosis incidence rates at the country-level. Secondary data from open-source, international …

Preschool Attendance: A Parental And Teacher Perspective Of Barriers And Behaviors Using Grounded Theory Research, Anne Meoli

Electronic Theses and Dissertations

Background: Preschool children from single-parent households with lower socioeconomic status (SES) are absent from preschool at rates higher than any other group. Some children are chronically absent, missing more than 10% of the school year. The phenomenon of preschool attendance related to behaviors, practices, and parental decision making associated with health and illness in lower SES households has not been previously studied using grounded theory methodology. Aim: The purpose of this study was to explore decision making related to supporting attendance in a preschool of 67 children (aged 3 to 4 years) with primarily low-income, single parents and preschool teachers …

Chemoattractant Receptors Blt1 And Cxcr3 Regulate Anti-Tumor Immunity By Facilitating Cd8+ T Cell Migration To Tumors., Zinal S. Chheda

Electronic Theses and Dissertations

Presence of increased numbers of CD8⁺ T cells in the tumors correspond to better overall survival in the patients. Variety of immuno-therapies have shown considerable efficacy in the clinic, however, a multitude of patients remain unresponsive. Most of these immunotherapies rely on effector T cell responses in the tumor. A major obstacle in the success of these immunotherapies is poor recruitment of CD8⁺ T cells into tumors despite intact effector responses in the periphery. Therefore understanding the mechanisms that regulate CTL infiltration into tumors becomes essential. Previous studies in our laboratory suggested an important role for BLT1 in …

Synthesis And Functional Evaluation Of Peptide Modified Poly (Lactic-Co-Glycolic Acid) Nanoparticles To Inhibit Porphyromonas Gingivalis Biofilm Formation., Paridhi Kalia

Electronic Theses and Dissertations

Periodontal disease is an oral inflammatory disorder that afflicts roughly 46% of the adults in the U.S. Currently, treatment of periodontal disease involves the removal of plaque from the gingival pocket (with possible antibiotic treatment) and if necessary, gingival surgery. To our knowledge, no therapeutic approach exists that promotes host-biofilm homeostasis by limiting pathogen recolonization of the oral cavity after prophylaxis or treatment. The interaction of the pathogen Porphyromonas gingivalis with commensal streptococci is critical for initiation of periodontitis and represents a target for limiting P. gingivalis colonization of the oral cavity. Previous studies showed that a synthetic peptide …

The Effect Of The Patient Protection And Affordable Care Act On The Medicare Part D Coverage Gap As Reflected In Diabetes Medication Adherence., Jennifer A. Forristal

Electronic Theses and Dissertations

This dissertation involves an evaluation of the effect of the Patient Protection and Affordable Care Act (ACA) on diabetic medication adherence for mail order utilizers over 6 years as the Medicare Part D coverage gap begins to close. The study had 3 objectives: 1) to evaluate diabetes medication adherence of health plan members before they reach the coverage gap and then while they are in the coverage gap, 2) to compare diabetes medication adherence between two similar groups with differing benefit structures, one group with a gap in coverage as opposed to a group with no benefit changes within the …