Medicine and Health Sciences Commons^™

Type Ix Secretion System : Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru

Electronic Theses and Dissertations

Porphyromonas gingivalis and Tannerella forsythia are two of the primary pathogens that are associated in the etiology and progression of chronic periodontitis. In T. forsythia, KLIKK proteases are the recently identified group of proteolytic enzymes that are secreted through Type IX secretion system (T9SS). Among, these KLIKK proteases a synergistic relationship was observed between karilysin and mirolysin in invading the host complement system for the survival of the bacteria. Since, karilysin has been already characterized, in this study we propose to study about mirolysin through structural, biochemical and biological characterization. The obtained results from the experiments has shown the …

Expression Profiling Of Non-Coding Rna By Environmental Interactions In Innate Immunity, Jacob R. Longfellow

Electronic Theses and Dissertations

Cystic fibrosis (CF) is a genetic disorder that affects 30,000 people in the United States and currently has no cure. Although CF affects all of the body’s systems, it is largely characterized as a lung disease. CF is caused by a mutation in both copies of the gene for cystic fibrosis transmembrane conductance regulator (CFTR). A mutation in the CFTR gene leads to improper movement of chloride ions and water into the airways, which dysregulates the airway surface liquid volume and composition. Individuals with CF are prone to lung infections due to inefficient bacterial clearance and by the age of …

Range-Wide Prevalence And Impacts Of Pseudocercosporella Inconspicua On Lilium Grayi And An Assessment Of L. Superbum And L. Michauxii As Reservoirs, Cindy L. Barrett

Electronic Theses and Dissertations

Lilium grayi (Gray’s Lily), a southern Appalachian endemic species, is threatened by a Lilium-specific fungal pathogen, Pseudocercosporella inconspicua. The disease is characterized by tan lesions that can cause early senescence, while also lowering seed production and viability. This project tested for P. inconspicua conidia and accessed health at nine locations. The disease was present and ubiquitous across the range of L. grayi. Through identification of P. inconspicua conidia in the field, L. superbum (Turk’s Cap Lily) was identified as an additional host, while L. michauxii (Michaux’s Lily) was disease-free. However, infection was inducible in both species. With …

Senecavirus A: Epidemiology, Pathogenesis And Infection Dynamics, Lok Raj Joshi

Electronic Theses and Dissertations

Senecavirus A (SVA) is a positive sense single-stranded virus that belongs to the genus Senecavirus within the family Picornaviridae. Senecavirus has been present in US swine population since 1988. However, there have been only a few reports of SVA associated with disease in last two decades. In late 2014 early 2015, a sudden increase in the number of cases of Senecavirus A associated with vesicular disease was observed in Brazil, the US and China. Affected pigs presented vesicles on snout, coronary band, and dewclaw. Additionaly, increased neonatal mortality has been reported in the field. Many aspects of SVA epidemiology, …

Surveillance Of Emerging Livestock Viruses, Faten A. Okda

Electronic Theses and Dissertations

Accurate and rapid diagnostic tests are essential for the management and control of emerging infectious diseases. Therefore, the overall goals of studies presented in this dissertation were to provide improved diagnostic and surveillance capabilities for several emerging viral diseases impacting the livestock industry and to provide insight into appropriate control strategies. Recent, severe outbreaks of porcine epidemic diarrhea virus (PEDV) in Asia and North America highlighted the need for well-validated diagnostic tests for identification of PEDV infected animals and evaluation of their immune status. PEDV was first detected in the U.S. in May 2013 and another swine coronavirus, porcine deltacoronavirus …

Intranasal Immunization Of Pigs With Porcine Reproductive And Respiratory Syndrome Virus Like Particles Plus 2’, 3’ –Cgamp Vaccigrade™ Adjuvant Exacerbates Viremia After Virus Challenge, Alexandria Marie Van Noort

Electronic Theses and Dissertations

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically devastating virus that causes a persistent infection and spreads quickly. The virus causes abortions in sows and respiratory diseases in young piglets. Current PRRSV vaccines appear to provide limited cross-protection. A virus-like particles (VLPs) vaccine is made up of key PRRSV structural proteins, which could be cross protective among the different strains. We tested PRRSV VLPs as a vaccine candidate with a 2’, 3’-cGAMP VacciGradeTM adjuvant against pigs infected with PRRSV after intranasal immunization to evaluate the immune response and protective efficacy by the VLPs and adjuvant. The VLPs contain …

Dynamic Host-Pathogen Interactions Result In Fungal Epitope Unmasking, Alex Hopke

Electronic Theses and Dissertations

Molecular camouflage is used by a diverse set of pathogens to disguise their identity and avoid recognition by protective host receptors. The opportunistic fungal pathogen Candida albicans is a good example, as it masks the inflammatory component β-glucan in its cell wall to evade detection by the immune receptor Dectin-1. Interestingly, it has been seen that β-glucan becomes unmasked during infection in vivo, though the underlying mechanisms remained unclear. Exposure levels of this epitope may be important, as Dectin-1 mediates protection from some strains of C. albicans and alterations in the organization and composition of the Candida cell wall …

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 …

Development And Characterization Of A Recombinant Orf Virus Vector Expressing The Spike Protein Of Porcine Epidemic Diarrhea Virus, Kyle Hain

Electronic Theses and Dissertations

Orf virus (ORFV), the type member of the genus Parapoxvirus of the family Poxviridae, causes orf or cutaneous pustular dermatitis in sheep and goats. ORFV is a ubiquitous virus capable of re-infecting its hosts multiple times over time. ORFV causes a non-systemic, self-limiting disease which is usually restricted to the skin surrounding the virus entry sites. ORFV has evolved several immunomodulatory proteins (IMPs) that evade and/or modulate host immune responses to infection and contribute to virus virulence and disease pathogenesis. Given biological properties and unique immunomodula tor y properties, ORFV has gained significant attention in recent years for its …

Modulation Of The Ovarian Cancer Humoral Response By Tumor-Derived Exosomes., Carolyn Denise Roberson

Electronic Theses and Dissertations

The pathogenesis of epithelial ovarian cancer is complicated by its diagnosis during the latter stages of the disease resulting from lack of symptoms or from presence of symptoms that mimic other conditions. Because of the often fatal prognosis by the time of actual detection, efforts are being made to better understand the host immune response to ovarian cancer. In this study, the contributions of the humoral immune response were investigated by focusing on the role of tumor-derived exosomes and their ability to modulate humoral immune responses. First, ovarian cancer patient-derived free circulating antibodies were investigated for immunoreactivity to patient antigen. …

A Mathematical Model For Antibiotic Resistance In A Hospital Setting With A Varying Population, Edward H. Snyder

Electronic Theses and Dissertations

Antibiotic-resistant bacteria(ARB) is causing increased health risk and cost to society. Mathematical models have been developed to study the transmission of resistant bacteria and the efficacy of preventive measures to slow its spread within a hospital setting. The majority of these models have assumed a constant total hospital population with the admission and discharge rates being equal throughout the duration. But a typical hospital population varies from day to day and season to season. In this thesis, we apply variable admission and discharge daily rates to existing deterministic and stochastic models which examine the transmission of single and dual resistant …

Microscopic Analysis Of Sympathetic And Parasympathetic Distribution, Terminal Morphology, And Interaction In Whole-Mount Atria, Scott Harden

Electronic Theses and Dissertations

The sympathetic (SNS) and parasympathetic (PSNS) branches of the autonomic nervous system (ANS) innervate the heart, exerting excitatory and inhibitory influences (respectively) over cardiac functions (heart rate, AV conduction velocity, and contractility). However, the distribution and structure of SNS and PSNS innervation has not yet been well studied. Detailed characterization of the distributional organization and structural morphology of the SNS and PSNS in normal states is essential to the study of pathological autonomic remodeling. The present study utilized double immunohistochemical labeling techniques to examine tyrosine hydroxylase (TH) immunoreactive (IR) SNS and vesicular acetylcholine transporter (VAChT) IR PSNS axons and terminal …

Role Of Transient Receptor Potential Canonical-6 (Trpc6) Channel In Metastasis Of Glioblastoma Multiforme, Rajarajeshwari Venkataraman

Electronic Theses and Dissertations

Glioblastoma multiforme (GBM) is one of the extremely fatal brain tumors. The main reason that makes it so lethal is its capability to invade and spread to other parts of CNS producing secondary tumors. Among other factors hypoxia, reduced oxygen availability, is linked to higher metastatic potential of cancers. Hypoxia causes numerous changes in genome and proteome of the cell. These changes help a normal cell to adapt to nutritional deficiency, but the same changes can increase the malignancy and metastasis in tumor cells. Extensive research by a number of curious scientists reveal that various pathways involving numerous proteins cross-talk …

Evaluation Of The Efficacy Of Chloroplast-Derived Antigensagainst Malaria, Melissa Schreiber

Electronic Theses and Dissertations

Malaria is the most prevalent vector-borne parasitic disease worldwide and a major cause of death from infections. There is a great need to develop a low cost vaccine for malaria to control transmission of infection and impact of disease, due to the emergence of anti-malarial resistance. Two leading blood stage malarial vaccine candidates are the apical membrane antigen-1 (AMA-1) and the merozoite surface protein-1 (MSP-1). The aim of this project is to express malarial antigens in tobacco plants via plastid transformation and deliver them by subcutaneous or oral gavage of minimally processed transplastomic tissue to evaluate their efficacy to elicit …

Generation Of Recombinant Mouse Embryonic Stem Cell Lines And Theirapplication For In Vivo Bioluminiscence Imaging In The Heart, Ramana Kammili

Electronic Theses and Dissertations

Cardiovascular disease is the major cause of death in the United States, with 80 million people suffering from some form of heart disease each year. One major limitation is the inability of the heart to repair the damaged tissue. Stem cell therapy holds enormous promise to repair and regenerate the damaged myocardium, but there are many technical difficulties that must first be overcome. One such difficulty is the present lack of ability to track and assess transplanted stem cells over time in vivo. The central hypothesis of this thesis is that in vivo bioluminescence imaging is a safe and useful …

Physical Characteristics Of An Individual: The Identification Of Biomarkers For Biological Age Determination, Michelle Alvarez

Electronic Theses and Dissertations

It is now a matter of routine for the forensic scientist to obtain the genetic profile of an individual from DNA recovered from a biological stain deposited at a crime scene. Potential contributors of the stain must either be known to investigators (i.e. a developed suspect) or the questioned profile must be searched against a database of DNA profiles such as those maintained in the CODIS National DNA database. However, in those instances where there is no developed suspect and no match is obtained after interrogation of appropriate DNA databases, the DNA profile per se presently provides no meaningful information …

A Member Of The Novel Fikk Family Of Plasmodium Falciparum Putative Protein Kinases Exhibits Diacylglycerol Kinase Activity And Is Exported To The Host Erythrocyte, David Floyd Curtis

Electronic Theses and Dissertations

Plasmodium falciparum is one of four species known to cause malaria in humans and is the species that is associated with the most virulent form of the disease. Malaria causes nearly two million deaths each year, many of these occurring among children in under-developed countries of the world. One reason for this is the prevalence of drug resistant strains of malaria that mitigate the efficacy of existing drugs. Hence, the identification of a new generation of pharmacological agents for malaria is extremely urgent. The recent identification of a group of novel protein kinases within the Plasmodium falciparum genome has provided …

Retrocyclin Rc-101 Overcomes Cationic Mutations On The Heptad Repeat 2 Of Hiv-1 Gp41, Christopher Fuhrman

Electronic Theses and Dissertations

Retrocyclin RC-101, a θ-defensin with lectin-like properties, potently inhibits infection by many HIV-1 subtypes by binding to the heptad repeat (HR)-2 region of gp41 and preventing six-helix bundle formation. In the present study, we used in silico computational exploration to identify residues of HR2 that interacted with RC-101 and then analyzed the HIV-1 Sequence Database at LANL for residue variations in the HR1 and HR2 segments that could plausibly impart in vivo resistance. Docking RC-101 to gp41 peptides in silico confirmed its strong preference for HR2 over HR1, and implicated residues crucial for its ability to bind HR2. We mutagenized …

Expression Of Hepatitis C Viral Non-Structural 3 Antigen In Transgenic Chloroplasts, Anubhuti Bhati

Electronic Theses and Dissertations

Hepatitis C viral infection is the major cause of acute hepatitis and chronic liver disease and remains the leading cause of liver transplants (NIH). An estimated 180 million people are infected globally (WHO). There is no vaccine available to prevent hepatitis C. The treatment with antiviral drugs is expensive, accompanied with various side effects and is limited only to those at risk of developing advanced liver disease. The treatment is also effective in only about 30% to 50% of treated patients and still a high percentage of patients are resistant to therapy. Therefore, there is an urgent need for the …

Expression Of Cholera Toxin B Subunit-Rotavirus Nsp4 Enterotoxin Fusion Protein In Transgenic Chloroplasts, Anila Kalluri

Electronic Theses and Dissertations

Rotavirus, the major cause of life-threatening infantile gastroenteritis, is a member of the Reoviridae family and is considered to be the single most important cause of virus-based severe diarrheal illness in infants and young children particularly 6 months to 2 years of age in industrialized and developing countries. Infection in infants and young children is often accompanied by severe life threatening diarrhea, most commonly following primary infection. Diarrhea is the major cause of death among children around the world. Responsible for 4 to 6 million deaths per year according to the World Health Organization (WHO), diarrhea is especially dangerous for …

Evaluation Of Immunogenicity Of Transgenic Chloroplast Derived Protect, Vijay Koya

Electronic Theses and Dissertations

Anthrax, a fatal bacterial infection is caused by Bacillus anthracis, a gram-positive, spore forming, capsulated, rod shaped organism. Centers for Disease Control (CDC) lists anthrax as Category A biological agent due to its severity of impact on human health, high mortality rate, acuteness of the disease and potential for delivery as a biological weapon. The currently available human vaccine in the United States (AVA anthrax vaccine adsorbed) is prepared from Alum adsorbed formalin treated supernatant culture of toxigenic, non-encapsulated strain of Bacillus anthracis with the principle component being protective antigen (PA83). Evaluation of anthrax vaccine given to nearly 400,000 US …

Polycyclic Aromatic Hydrocarbon Degradation By Novel Bacteria Isolated From Burrow Sediments Of Marine Benthic Macrofauna, Wai Ki Chung

Electronic Theses and Dissertations

Polycyclic aromatic hydrocarbons (PAH) are significant environmental pollutants and represent a severe health threat. Many cosmopolitan areas including coastal environments are heavily impacted by PAH. This research investigates the isolation of PAH-degrading bacteria from burrow sediment of marine benthic macrofauna and their potential in bioremediation. Macrofaunal burrow sediment is biogeochemically distinct from bulk sediment and has high microbial activities. Samples were collected from a local uncontaminated cove and PAH degradation potential was measured by incubating sediment slurries with exogenous PAH. Burrow sediments from two polychaetes and a mollusc showed significantly higher PAH degradation potential than the bulk sediment. The degradation …

Characterization Of 50s Ribosomal Subunit Assembly Inhibition In Erythromycin Treated Escherichia Coli Cells., Jerry Edward Usary

Electronic Theses and Dissertations

Erythromycin has long been recognized for its ability to inhibit protein synthesis by interfering with mRNA translation on the bacterial ribosome. We have recently shown that erythromycin also inhibits the assembly of the 50S ribosomal subunit in growing bacterial cells. The nature of this assembly inhibition has been investigated using ³H-uridine pulse-chase labeling of control and erythromycin treated E. coli cells.

Subunit assembly was examined by sucrose gradient centrifugation of labeled cell lysates. Normal assembly kinetics of subunit assembly were observed in control cells at 37°C. Formation of the 30S subunit was completed by 7.5 minutes and assembly of …

Moraxella (Branhamella) Catarrhalis: A Molecular Epidemiology Study, Lyndell R. Gill

Electronic Theses and Dissertations

Moraxella (Branhamella) catarrhalis is the third-most-frequently isolated microorganism associated with acute exacerbations of chronic bronchitis in patients during their stay at the Mountain Home VA Medical Center (MHVAMC). In order to develop a practical, epidemiologically-meaningful typing method for M. (B.) catarrhalis, we tested two methods based on analysis of chromosomal DNA for typeability, reproducibility, and ability to differentiate between unrelated strains (discriminatory power, D). M. (B.) catarrhalis isolants from MHVAMC from 7/1/87-6/30/88 were grown overnight in broth and embedded in agarose. DNA was isolated by standard methods. The DNA was subjected to: (1) restriction endonuclease digestion (with either Bgl II …

Molecular And Cellular Analysis Of Chlamydia Trachomatis: Persistence And Reactivation, Kimberly R. Tau

Electronic Theses and Dissertations

Chlamydia trachomatis (CT) is the most prevalent sexually-transmitted infection in the United States. It has been suggested that CT infections can become latent. This has not been substantiated. CT persistence was examined at the molecular and cellular level in vitro and in vivo. Penicillin treatment of CT in vitro results in abnormal inclusions and reduced recovery of infectious CT. Penicillin did not inhibit initial stages of infection, but did downregulate CT rRNA levels after 25 hours post-inoculation (p.i.). DNA amplification was employed to differentiate between a resolved infection and a persistent one. Utilizing a primer pair that amplified a 144 …