Other Immunology and Infectious Disease Commons^™

Arachidin 3 Modulation Of Lipid Metabolism In Rotavirus Infections, Stormey Wisdom

Electronic Theses and Dissertations

Rotavirus (RV) can cause severe and deadly gastroenteritis in young children, infants, and immunocompromised individuals. Previous studies have shown that arachidin 3 (A3) inhibits RV replication, and that RV replication is dependent on the presence of lipids. This study investigated the alteration of lipid metabolism by A3 in RV infected HT29.f8 cells. A decrease in the RV regulation of lipid biosynthesis genes was observed with the addition of A3 using qRT-PCR. Also, immunofluorescent and histochemical staining for neutral fats, a major component of cellular lipid droplets, revealed an increased accumulation with both RV and RV+A3 when compared to no virus …

Htlv-1 Latency-Maintenance Factor P30ii Modulates Tax-Induced Nf-Kappa B Signaling Through A P53-Regulated Mechanism, Aditi Malu

Biological Sciences Theses and Dissertations

The human T-cell leukemia virus type-1 (HTLV-1) infects CD4+ T-cells and is the etiological agent of adult T-cell leukemia/lymphoma (ATL), an aggressive and often-fatal lymphoproliferative neoplastic disease. The major transactivator protein, Tax, drives proviral gene expression and replication and plays a key role during the early-stage immortalization of T-cells by HTLV-1. Tax has also been shown to regulate many host cellular signaling pathways, including CREB/ATF, SRF, and NFκB. Another accessory viral protein p30_II acts as a latency-maintenance factor and negatively regulates proviral gene expression and replication. The p30^II protein counters Tax-dependent gene expression at the transcriptional and posttranscriptional …

An Examination Of The Potential Threat Of A State-Sponsored Biological Attack Against The United States: A Study Of Policy Implications, Courtney Anne Pfluke

Graduate Theses/Dissertations

In 2002, US Navy Seals found a list of pathogens in an Afghanistan cave that Al Qaeda had planned to use in a series of biological attacks. Unique about the discovery was that the pathogens were not limited to human ones. Six pathogens targeted livestock and four targeted crops. Despite this discovery, limited attention has been given to the possibility of a state-sponsored terrorist attack utilizing biological agents against the US population, food source, or water supply. Throughout history, biological agents have been developed for use as an offensive weapon for both states and terrorist groups. The United States may …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

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 …

Rejuvenation Of The Epigenetic Landscape Of The Aged Brain Through Manipulation Of Circulating Factors, Edward Koellhoffer

Dissertations and Theses (Open Access)

The aging population of the United States is expanding at an alarming rate. The Center for Disease Control and Prevention estimates that the population of those age 65 years and older will reach over 50 million by 2020 and will double to 100 million by 2060. This will not only put a massive strain on national healthcare resources, but will also increase the number of those who are not able to live and function independently. It is becoming increasingly vital to understand how the brain changes with age and mechanisms to possibly protect and rejuvenate the aged brain to a …

The Validity Of Medicare Claims-Based Codes To Identify Nontuberculous Mycobacterial Infection In Patients With Bronchiectasis, Jennifer Ku

OHSU-PSU School of Public Health Annual Conference

Background: Nontuberculous mycobacteria (NTM) is a disease of increasing incidence, causing permanent airway damage leading to destructive pulmonary disease. Medicare claims-based codes have been used to identify NTM infection and to evaluate trends in diagnosis and disease outcomes. However, claims-based codes to identify NTM infection have not been validated.

Methods: We linked patients with a bronchiectasis diagnosis (ICD-9-CM 494.0 or 494.1) excluding cystic fibrosis from the national 2006-2014 Centers for Medicare and Medicaid (Medicare) data to the U.S. Bronchiectasis Research Registry (BRR). The BRR is a national prospective cohort of patients with bronchiectasis, that collects detailed clinical, laboratory, microbiology and …

Non-Invasive Analysis Of The Sputum Transcriptome Discriminates Clinical Phenotypes Of Asthma, Xiting Yan

Yale Day of Data

Whole transcriptome wide gene expression profiles in the sputum and circulation from 100 asthma patients were measured using the Affymetrix HuGene 1.0ST arrays. Unsupervised clustering analysis based on pathways from KEGG were used to identify TEA clusters of patients from the sputum gene expression profiles. The identified TEA clusters have significantly different pre-bronchodilator FEV1, bronchodilator responsiveness, exhaled nitric oxide levels, history of hospitalization for asthma and history of intubation. Evaluation of TEA clusters in children from Asthma BRIDGE cohort confirmed the identified differences in intubation and hospitalization. Furthermore, evaluation of the TH2 gene signatures suggested a much lower prevalence of …

Enhancement Of Immune Response Against Bordetella Spp. By Disrupting Immunomodulation, Monica C. Gestal, Laura K. Howard, Kalyan Dewan, Hannah M. Johnson, Mariette Barbier, Clare Bryant, Illiassou Hamidou Soumana, Israel Rivera, Bodo Lina, Uriel Blas-Machado, Eric T. Harvill

Faculty & Staff Scholarship

Well-adapted pathogens must evade clearance by the host immune system and the study of how they do this has revealed myriad complex strategies and mechanisms. Classical bordetellae are very closely related subspecies that are known to modulate adaptive immunity in a variety of ways, permitting them to either persist for life or repeatedly infect the same host. Exploring the hypothesis that exposure to immune cells would cause bordetellae to induce expression of important immunomodulatory mechanisms, we identified a putative regulator of an immunomodulatory pathway. The deletion of btrS in B. bronchiseptica did not affect colonization or initial growth in the …

White-Nose Syndrome And Immune Responses In A Resistant Bat Species (Eptesicus Fuscus), Keslie Skye Naffa

Graduate Theses/Dissertations

White-nose syndrome (WNS) has had a large negative impact on bat populations across eastern North America since its arrival in 2006. Bats affected by WNS appear to die of starvation, possibly due to the increased arousals during hibernation when there is no food present to replace the energy used to arouse. During hibernation, the bat’s immune system should be suppressed. However, once a bat of a susceptible species is exposed to the fungus that causes WNS, Psuedogymnoascus destructans (Pd), the immune system seems to respond, potentially causing an elevation in metabolic rate, which may cause the bat to …

Control Efforts And Serologic Survey Of Pseudorabies And Brucellosis In Wild Pigs Of Tennessee, Lisa I. Muller, Neelam C. Poudyal, Roger Applegate, Chuck Yoest

Human–Wildlife Interactions

European wild pigs (Sus scrofa) are an introduced invasive species that now constitute a major threat to agriculture and the natural ecology of the environments they now inhabit. Wild pigs also carry many diseases known to infect wildlife, humans, and livestock. Two of these diseases, pseudorabies (PRV) and brucellosis, constitute major diseases in the United States. Better data are needed regarding the prevalence of these diseases in wild pigs to understand and manage the potential risks to wildlife, humans, and livestock. From July 1, 2011 to June 30, 2017, Tennessee Wildlife Resources Agency personnel trapped and euthanized 4,727 …

Induction Of Cerebral Hyperexcitability By Peripheral Viral Challenge: Role Of Cxcl10 Chemokine, Tiffany J. Petrisko

Graduate Theses, Dissertations, and Problem Reports (ETD)

Peripheral viral infections are po­tent comorbid factors that exacerbate neuro­degene­ration. Although the under­lying mecha­nisms have not been defined, neuronal hyperexcitability has been established as an underlying feature. Our lab has developed a preclinical model in which a viral mimetic, poly­inosinic-poly­cytidylic acid (PIC) is injected in­tra­peritoneally to induce an anti-viral acute phase response (APR). APR in turn elicits robust neuronal hyperexcitability. The present study was undertaken to characterize molecular mechanisms that mediate the development of hyperexcitability in response to PIC challenge. The analysis of brain tissue after PIC challenge revealed a robust elevation of CXCL10 chemokine, indicating its putative role in …

Mastering Mycological Mysteries With Explorations Of Harpellales Associated With Culicidae And Other Dipterans In Idaho, Michael Mccormick

Boise State University Theses and Dissertations

Presented is the first field survey and laboratory-based study focused on Harpellales gut fungi found in Culicidae (mosquito) larvae collected from various parts of Idaho. Overall, 34 sites were sampled ranging from urban storm drains and irrigation puddles to pristine stream-side puddles. These sites yielded 17 different species of mosquitoes and three previously described species of gut fungi. Three species of mosquitoes were the first recorded observations as hosts of the following gut fungi: Culiseta alaskaensis was infested with Zancudomyces culisetae (from Renwyck Creek), Culex tarsalis with Smittium culicis (from Cottonwood Creek), and Ochleratus sp. with Smittium minutisporum (from Bear …

Modeling The Transmission Of Wolbachia In Mosquitoes For Controlling Mosquito-Borne Diseases, Zhuolin Qu

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Biomathematics And Social Justice: Reinventing Models Of Disease Spread To Study Efficacy Of Bystander Violence Prevention, Hannah Callender Highlander

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Proposed Interventions For The Containment Of Influenza In Boarding Schools And Small Colleges, Alexis Vittengl

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

The Rational Design, Synthesis, Characterization, And Biological Evaluation Of Cancer-Targeting Immunostimulatory Peptide-Protein Conjugates And Tripeptides, Keith Smith

Seton Hall University Dissertations and Theses (ETDs)

With the advent of cancer immunotherapy and the rise in applications of synthetic biologics, there has been a steady decline in the incidence of cancer. Despite this trend, there is an anticipated 1.7 million new cancer cases with an estimated 610,000 deaths expected by the end of 2018.2 Therefore, the call for continued efforts in creating more effective treatment options are still in high demand. In this thesis, the rational design of a semi-synthetic cancer-targeting immunostimulatory peptide-protein bioconjugate—using N-succinimidyl carbamate chemistry is described. This bio-orthogonal chemistry approach was used to conjugate the synthetic Pep42, cancer-targeting peptide (CTP) and the immunostimulatory …

The Role Of Outcome Preferences In Optimizing Heterogenous Disease Control Strategies., Evan Milliken

Biology and Medicine Through Mathematics Conference

No abstract provided.

Changes In The Microbial Community Of Lubomirskia Baicalensis Affected By Red Sponge Disease, Colin Rorex

Electronic Theses and Dissertations

Lake Baikal is the oldest known lake and a unique ecosystem, home to several species of fresh water sponge. A disease outbreak affecting the dominant species, Lubormirskia baialensis, was recently reported. The cause of the disease has not been determined but one of the current hypothesis is that the increase in methane concentration is correlated to the disease outbreak. This pilot study characterized the microbiomes of sick and healthy sponges through the use of 16S rRNA sequencing. Sick sponge microbiomes shared a conserved group of taxa while the healthy sponge microbiomes had greater diversity. Indicator species analysis identified two significant …

Enhanced Production Of Pro-Il-1Βeta Contributes To Immunopathology During The Coinfection Of Influenza A Virus And Streptococcus Pneumoniae, Angeline E. Rodriguez

Graduate Theses/Dissertations

Viral bacterial coinfections are known to cause severe pneumonia, especially in the elderly and in pediatric patients. Antibiotics like β-Lactams kill the bacteria but fail to improve symptoms suggesting a faulty immune system may play an important role in the disease. Interleukin-1β (IL-1β) is an important immune signaling cytokine responsible for inflammation. It exists as an inactive precursor that can be activated by caspase-1 containing inflammasomes (multi-protein complex). Influenza A virus (IAV) and Streptococcus pneumoniae (S. pneumoniae) activate the inflammasome through the NOD-like receptor protein NLRP3 and/or AIM2. Previous reports in mice indicate that IL-1β levels are dramatically …

Autoimmune Disorders And Hypersensitivities In The Developed World, Margaret S. Bohm

Conspectus Borealis

No abstract provided.

Paclitaxel Enhances Oncolytic Potential Of Herpes Simplex Virus Type-1 In Cancer Cells, Misagh Naderi

LSU Master's Theses

Taxanes are spindle poisons that bind to and stabilize microtubules resulting in mitotic arrest. Herpes simplex Typ-1 (HSV-1) virions utilize the microtubular network for intracellular transport during both virus entry and virus egress from infected cells. It has been reported previously that taxanes may synergize with oncolytic herpes simplex viruses in the treatment of experimental prostate and breast tumors in mice. Other reports have indicated that taxanes may inhibit viral replication in infected cells. In this study the previously characterized Oncolytic Herpes Simplex Virus type 1 (OSVP), which was constructed in Kousoulas lab was used in conjugation with paclitaxel (taxol) …

Do Paraben Derivatives Alter T Cell Immunity?, Hailey Kintz

Spring Presentation of Undergraduate Research

T cells immunity is linked to a complex system of cytokines that determine differentiation of naïve T cells into Th1, Th2, Th17, and Treg cells. Estrogen production or periods of elevated production have been correlated with an anti-inflammatory state in which Th2 and Treg cells are up-regulated. Such responses in the immune system are capable of supporting pre-cancerous activity. We are investigating the tie between the xenoestrogen compounds found in cosmetics, parabens, and their ability to regulate T cell immunity. Testing parabens and paraben derivatives with weaker estrogen receptor association will allow for a better understanding of the interplay between …

Bone Marrow Derived Progenitor Cells And Their Contributions To The Thymic Stroma, Mohammed Hoque

Dissertations and Theses

The thymus serves as the primary lymphoid organ responsible for the development and selection of a self-tolerant T cell repertoire. In paradox to its critical functions for the adaptive immune response, the thymus undergoes a profound age associated decline beginning in early adult life resulting in significant decline in T-cell function.Thymic epithelial cells (TECs) are the most critical component of the thymic microenvironment and undergo rapid turn-over, so understanding the cellular mechanisms responsible for the maintenance of TEC number and organization will be critical in counteracting age associated involution, particularly in cancer patients, due to enhanced degeneration in response to …

Establishing Relationships Among Environmental Stressors, Host Immune Status, And Wasting Disease Susceptibility In The Dominant Seagrass Species Thalassia Testudinum, Paige Joy Duffin

UNF Graduate Theses and Dissertations

A growing body of evidence supports the observation that marine disease outbreaks, especially those caused by opportunistic pathogens, are increasing in frequency and severity. One genus of such pathogens, Labyrinthula, has been identified as the causative agent of seagrass wasting disease, an epidemic that has historically plagued seagrass beds around the world. It is suspected that pathogenicity is intimately linked to the ability of the host to initiate defense responses, but a lack of compelling evidence prevents any meaningful application of preliminary observations. This body of work investigated the roles of host genotype, host immune status, and environmental stressors …

Prevention Of Childhood Obesity And Diabetes, Karen Carig

Master's Projects and Capstones

One of the public health concerns that have been on the rise is childhood obesity and diabetes. The National Health and Nutrition Examination Survey indicate that approximately one-third of children in the United States are overweight or obese with 17% meeting criteria for obesity (Pulgaron and Delamater, 2014). This crisis exists nationally and internationally which can effect children in the following ways: physically, socially, psychologically and mentally. Although, genetics also play a role in these diseases, environmental factors, lifestyle preferences and cultural environmental play have a major influence. My internship with the Food Education Project covers a better understanding to …

Improving Hpv Vaccination Series Initiation Rates And Compliance Among Indigent Women In South Texas, Ages 19-26, Through Provider Recommendation And Additional Clinic Funding: A Quality Improvement Project, Lacey Cudd

Doctor of Nursing Practice

The purpose of this quality improvement project was to increase human papillomavirus vaccination series initiation rates among indigent women, ages 19-26, at a clinic in South Texas. The human papillomavirus is a sexually transmitted infection that has been associated with multiple types of cancers. Each year, approximately 6.2 million cases of the human papillomavirus infection are diagnosed; as many as 75% of all new infections occur among females 18-26 years of age. The human papillomavirus vaccination has a high efficacy in regards to cancer prevention, preventing as many as 76% of cancers with only one dose. The project included educating …

A License To Kill: Understanding Natural Killer Cell Licensing To Fight Cancer, Jolie Schafer

Dissertations and Theses (Open Access)

Natural killer (NK) cell education is an essential developmental process for NK cell effector function, that renders some NK cells “licensed” and others “unlicensed” (with heightened or lowered effector function potential, respectively) against tumor and targets lacking self-molecules. However, the underlying mechanisms responsible for the heightened effector responses of licensed cells remain unknown. Using NK cells derived from humans and expanded ex vivo we performed high-throughput protein expression analysis, and identified multiple proteins that are differentially regulated in licensed and unlicensed human NK cells before and after inhibition by killer-cell immunoglobulin-like receptors (KIRs) and activation by the NKp46 natural cytotoxicity …

Age-Structured And Vaccination Models Of Devil Facial Tumor Disease, Christopher D. Bruno, Timothy Comar, Megan O. Powell, Adjo Tameklo

Spora: A Journal of Biomathematics

Tasmanian devil populations have been devastated by devil facial tumor disease (DFTD) since its first appearance in 1996. The average lifespan of a devil has decreased from six years to three years. We present an age-structured model to represent how the disease has affected the age and breeding structures of the population. We show that with the recent increase in the breeding of juvenile devils, the overall devil population will increase but not nearly to pre-DFTD levels. The basic reproductive number may be increased with the influx of young breeding devils. In addition, our model shows that the release of …

Cd80 Expressed By Cd8+ T Cells Contributes To Pd-L1-Induced Apoptosis Of Activated Cd8+ T Cells, Meagan R. Rollins, Rachel M. Gibbons Johnson

Biology Publications

Tumor cells are capable of limiting antitumor CD8+ T cell responses through their cell surface expression of PD-L1. In addition to PD-1 expressed by CD8+ T cells, PD-L1 also binds to CD80 expressed by CD8+ T cells. The influence of the PD-L1/CD80 interaction on CD8+ T cell function has not been fully characterized, so we sought to investigate the impact of the PD-L1/CD80 interaction on PD-L1-induced apoptosis of activated CD8+ T cells. We found that CD8+ T cells that lacked CD80 expression got activated to the same extent as wild-type CD8+ T cells, but when cultured with anti-CD3 and PD-L1/Fc …