Life Sciences Commons^™

Retroviral Infection Dynamics In Maine's Wild Turkeys, Stephanie A. Shea

Electronic Theses and Dissertations

Widespread wild turkey reintroductions in the late 1900s have led to increases in population density and geographic distribution across North America. This rapid population expansion has put them into proximity with closely-related wild and domestic avian species, increasing the risks of pathogen transmission. Lymphoproliferative disease virus (LPDV) is an avian oncogenic retrovirus detected in wild turkeys in 2009, and previously known to infect domestic turkeys. Following its initial detection, surveys reported variable LPDV prevalence across eastern North America with most wild turkeys being asymptomatic, however diagnostic cases revealed 10% mortality of LPDV-infected individuals. Given its recent detection, little is known …

Immunological Factors Associated With Siv/ Shiv Persistence In Diverse Tissue Niches, Omalla A. Olwenyi

Theses & Dissertations

The significant challenge towards a successful HIV cure lies in eradicating persistent viral reservoirs across diverse tissue niches. As a result, HIV-infected individuals have to resort to lifelong antiretroviral therapy. Recent news of supposed HIV eradication in a second patient has further re-invigorated the fields of HIV cure. However, a few barriers remain, such as the lack of currently available assays to accurately quantify viral reservoirs, limited information on cellular factors associated with persistence, and varied dynamics of the viral reservoir in various body compartments. Lastly, HIV-infected individuals live different lifestyles stemming from comorbid substance abuse including consumption of morphine, …

Intrinsically Disordered Protein Regions In Human Evolution And As Therapeutic Targets, Karen Paco Mendivil

KGI Theses and Dissertations

Intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) fail to form stable structures but have important biological functions via interacting with various molecular partners (proteins, DNA, RNA, glycosaminoglycans). We hypothesized that IDPRs are potential targets for therapeutics development because they are reservoirs of evolutionary innovation, and they play crucial roles in adaptation to pathogens.

We first studied the evolution of IDPRs in the human proteome and compared it with the proteome of non-human primates. We have found that evolutionary young protein-coding genes have included low conserved regions in the N-terminal part of proteins, and such regions are linked to high …

Dicer Represses Antiviral Innate Immunity Pathways In Mouse Embryonic Stem Cells, Chandan Gurung

Dissertations

Recent studies have demonstrated that embryonic stem cells (ESCs) are deficient in expressing type I interferons (IFN), the cytokines that play key roles in antiviral responses. However, the underlying molecular mechanisms and biological implications of this finding are poorly understood. In this study, I used a synthetic RNA-based assay that can simultaneously assess multiple forms of antiviral responses in ESCs. Dicer is an enzyme essential for RNA interference (RNAi), which is used as a major antiviral mechanism in invertebrates but not clear in vertebrates. RNAi activity is detected in wild-type ESCs but is abolished in Dicer knockout ESCs (D−/−ESCs) as …

Osmr Signaling Induces Tamp-Specific Bbb Dysfunction Following Autoimmune-Mediated Neutrophil Recruitment, Travis Scott Wertz

Boise State University Theses and Dissertations

Integrity of the brain microvessels that form the blood-brain barrier (BBB) is maintained through fine-tuned regulation of endothelial tight junction proteins, chiefly represented by claudin 5 and the tight junction-associated MARVEL protein (TAMP) occludin. Under proinflammatory conditions in autoimmune-mediated multiple sclerosis (MS), autoreactive effector T cells are activated in white matter regions of the brain and spinal cord and release cytokines to recruit circulating neutrophils that, in turn, release neurotoxic substances. Lack of tight junctions in peripheral blood vessels allows neutrophils to exit blood vessels unhindered, but BBB tight junctions must first be downregulated before neutrophils can transmigrate into the …

Kshv Susceptibility And Transmission Within Tonsillar Specimens, Farizeh Aalam

Pharmaceutical Sciences (PhD) Dissertations

Despite nearly three decades of research, not much is known regarding the early stages of development for KSHV lymphoproliferative disorders, hindering our ability to develop prophylactic measures or effective treatments. This dissertation will focus on the host and viral factors influencing the magnitude and dynamics of KSHV infection in the human tonsil to pave the way for future interventions directed at limiting person-to-person transmission of KSHV.

To understand the contribution of host factors to KSHV susceptibility in B lymphocytes, we generated a library of 40 tonsillar specimens. Our results indicate that the immunological composition of tonsillar lymphocytes varies across our …

Trained Immunity Enhances The Immune Response And Maintains Microbiome Diversity In Aging And Sepsis, P. Spencer Gill

Electronic Theses and Dissertations

The global population is rapidly aging. It is estimated that over the next thirty years, the number of individuals >60 years of age will increase by over a billion, and the number of individuals over age 80 may increase by 300 million. As humans age, our immune system becomes progressively weaker through a process called immune senescence. This age-related decrease in immune function increases susceptibility to infection and chronic diseases. Sepsis is a leading cause of death worldwide. Over the past two decades, there has been an increased incidence of sepsis which is due, in part, to our aging population …

Enhancing Adoptive Cell Therapy By Augmenting Fitness And Anti-Tumor Function Of Tumor-Infiltrating Lymphocytes, Parin Shah

Dissertations & Theses (Open Access)

The success of immune checkpoint inhibitors (ICIs) has established the importance of cancer immunotherapy in solid cancers, where it has been adopted as one of the standards of care for advanced melanoma and lung cancer. It is currently being investigated to treat other solid cancers. However, a large fraction of patients do not respond to ICIs and relapse. ICI therapy offers an in vivo approach to activate tumor-specific T cells, albeit in some cases, this modality does not create a sufficiently robust anti-tumor response. Thus, ex vivo approaches employing manipulation of immune cells, such as Adoptive Cell Therapy (ACT) using …

Genital Chlamydia Infection Is Influenced By The Female Sex Hormones Estrogen And Progesterone In Vivo, Amy Gail Gravitte

Electronic Theses and Dissertations

Chlamydia is the most common bacterial sexually transmitted infection in the United States and worldwide. It often goes unnoticed due to lack of symptoms and left untreated it can ascend the female genital tract to cause sequelae like pelvic inflammatory disease and irreversible tubal infertility. In reproductive-aged women, female sex hormones estrogen (E2) and progesterone (P4) concentrations fluctuate during the menstrual cycle and are influenced by hormonal contraceptives and hormone replacement therapy. E2 and P4 influence genital Chlamydia infection in women and mice, but these multifactorial interactions are not entirely mapped out. The complex interplay of E2 and P4 with …

Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells, Taylor Chrisikos

Dissertations & Theses (Open Access)

Conventional dendritic cells (cDCs) are an essential immune population, responsible for controlling adaptive immunity and tolerance. Recently, type I cDCs (cDC1s) have been delineated as a distinct cDC subset, uniquely responsible for coordinating T cell-mediated immunity against pathogens and tumors. Although the importance of cDC1s is now well established, the mechanisms that regulate cDC1 function remain largely unknown. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of interleukin 10 (IL-10), an immunosuppressive cytokine. Therefore, we hypothesized that STAT3 and IL-10 inhibit cDC1 function and induction of T cell-mediated immunity. Herein, we show that IL-10 inhibits polyinosinic:polycytidylic …

Comprehensive Study Of Human Pathogenic Trypanosomatids: From Chemotherapies To Disease Ecology, Felipe Rodriguez

Open Access Theses & Dissertations

The vector-borne diseases Leishmaniasis and Chagas disease, caused by the kinetoplastid parasites Leishmania spp. and Trypanosoma cruzi respectively, are among the most important parasitic diseases in the group of neglected tropical diseases. Even though the two diseases are endemic to the Americas, they affect millions of people worldwide. Leishmaniasis and Chagas disease cause a great array of symptoms and some of them can be fatal if left undiagnosed and untreated. Current treatment regimens are becoming less effective, vaccines are still not available, and diagnosis needs to be improved. Vector control has been responsible for a decrease of diseases in endemic …

Q-Griffithsin Interactions And Utility For The Prevention And Treatment Of Mucosal Infections., Henry Nabeta

Electronic Theses and Dissertations

Griffithsin (GRFT) is a carbohydrate binding agent (lectin) that was originally identified in the red alga Griffithsia sp. Q-Griffithsin (Q-GRFT) is an oxidation stable analog of GRFT. GRFT has demonstrated inhibitory activity against HIV-1, Coronaviruses, Hepatitis C, influenza and Ebola viruses. The broad-spectrum activity suggests the potential utility of this lectin in a wide range of viral infections. However, the lectin’s activity in mucosal infections has not been extensively studied. Using in vitro, ex vivo and in vivo assays, we have demonstrated that Q-GRFT maintains the ability to bind glycosylated ligands following incubation in murine, macaque and human rectal …

Investigation Of Histomoniasis Prevention In Poultry, Lesleigh Beer

Graduate Theses and Dissertations

Histomonas meleagridis is the etiological agent of histomoniasis, also commonly known as blackhead disease. This protozoal disease of poultry is detrimental to turkeys with flock mortalities often reaching 80-100%, although other gallinaceous birds are susceptible. Since the voluntary removal of nitarsone in 2015, the poultry industry is suffering with no approved prophylactics, therapeutics, or vaccines for this disease. The objectives of this dissertation were to evaluate multiple methods for prevention or control of histomoniasis, including dietary chemoprophylaxis and vaccination. Specifically, this research evaluated quinine as a chemoprophylactic candidate (Chapter 3) or live-attenuated H. meleagridis as vaccine candidates (Chapter 4) in …

Structural Analysis And Vaccine Efficacy Of Hla Mutants, Kelly Tomaszewski

Arts & Sciences Electronic Theses and Dissertations

Staphylococcus aureus is a commensal of the human skin and also a major human pathogen. Currently, there has been no successful vaccine despite many approaches over the last two decades. S. aureus α-hemolysin (Hla), a potent cytotoxin, plays an important role in the pathogenesis of S. aureus diseases, through the activation of its receptor, ADAM10. We utilized three distinct Hla mutants with differing structural and ADAM10 binding properties to examine for vaccine efficacy. Our studies have demonstrated immunization with each vaccine candidate antigens provided significant protection against S. aureus skin infection yet elicited distinguishable immune responses. We have also generated …

Livestock Ticks In The Uae: Prevalence, Distribution, Population Dynamics, And Associated Microorganisms, Nighat Perveen

Dissertations

Ticks are important vectors of an array of viral, bacterial, and protozoan pathogens resulting in a wide range of animal and human diseases in the Middle East and North Africa (MENA). In this study, ticks were collected from camels, cows, sheep, and goats in Abu Dhabi, Dubai, and Sharjah in the United Arab Emirates (UAE). The objectives of the study were to (1) identify tick species of livestock through taxonomic keys and using molecular markers, and determine their prevalence and distribution in the UAE, (2) assess Hyalomma dromedarii seasonal population fluctuation over a year under common camel breeding and management …

Exogenous Surfactant As A Delivery Vehicle For Intrapulmonary Therapeutics, Brandon J. Baer

Electronic Thesis and Dissertation Repository

As an organ system, the lung has unique advantages and disadvantages for direct drug delivery. Its contact with the external environment allows for the airways to be easily accessible to intrapulmonary delivery. However, its complex structure, which divides into more narrow airways with each branch, can make direct delivery to the remote alveoli challenging. The objective of this thesis was to overcome this issue by using exogenous surfactant, a lipoprotein complex used to treat neonatal respiratory distress syndrome, as a carrier for pulmonary therapeutics. It was hypothesized that therapeutics administered with a surfactant vehicle would display enhanced delivery to the …

Understanding The Effect Of Dietary Palmitic Acid On Glycolysis During Innate Immune Memory In Macrophages, Khaleda A. Aqaei

University Honors Theses

Trained immunity is long-term innate immune memory induced by a primary stimulus, which leads to hyper-inflammation upon secondary stimulation with a homologous or heterologous ligand. Trained immunity is mediated by epigenetic and metabolic reprogramming of the target cell and leads to modification of gene expression and cellular function. Classically, trained immunity is initiated by β-glucans, an inflammatory molecule found on the exterior of fungal species. Interestingly, our lab has recently described that dietary fatty acids can initiate trained immunity, working through similar pathways as β-glucans. Specifically, our data show that a pre-treatment with a specific dietary saturated fatty acid (SFA), …

Assesment Of Antibiotic Resistant Gene Expression In Clinical Isolates Of Pseudomonas Aeruginosa, Dustin Esmond

Biology Theses

Increasing prevalence of nosocomial infections by antimicrobial resistant pathogens resulting in higher mortality rates and financial burden is of great concern. Pseudomonas aeruginosa represents one of six highly virulent “ESKAPE” pathogens that exhibit considerable intrinsic drug resistance as well as mechanisms for acquiring further resistance. As many of these mechanisms are regulated through gene expression, we sought to identify regulatory strategies and patterns at play in 23 clinical isolates collected from Baku, Azerbaijan and Tyler, Texas, USA. Real-time quantitative polymerase chain reaction was performed on six gene targets implicated in resistance and contrasted with antibiotic phenotypes. We found AmpC cephalosporinase …

Mucosa-Associated Invariant T Cells Undergo Phenotypic Changes Following Fecal Microbiota Transplantation, Jenna M. Benoit

Electronic Thesis and Dissertation Repository

Fecal microbiota transplantation (FMT) has emerged as the most effective therapy for recurrent Clostridioides difficile infections (rCDI); yet the role of immune cells in the response to FMT remains poorly understood. Mucosa-associated invariant T (MAIT) cells are bacterial metabolite-reactive T cells found in the peripheral blood and mucosal tissues. We posited that MAIT cells are in the perfect position to respond to the influx of microbial metabolites associated with FMT. We collected peripheral blood from rCDI patients prior to FMT, 1-week post-FMT, and 1-month post-FMT, to explore if MAIT cell phenotypic characteristics or functions change following treatment. Following FMT, MAIT …

The Immunoregulation Of Autoimmune Diabetes, Hao Hu

Arts & Sciences Electronic Theses and Dissertations

How autoimmune diseases are regulated is a long-term research topic in the autoimmunity field. We use autoimmune diabetes as a model to study this. Autoimmune diabetes is a T cell-dependent autoimmune syndrome. The functions of T cells are regulated during their development and activation. Developmentally, T cells will undergo a stringent thymic selection: a process that self-reactive T cells are tolerized to become thymic derived Tregs or can be deleted by apoptosis based on binding affinity and avidity between the TCRs and self-peptide:MHC complexes. After T cells mature, they can also be tolerized in the periphery in many other ways, …

Investigating The Role Of Bladder Epithelial Stem Cells In Bladder Mucosal Remodeling And Defense Against Infection, Seongmi Kim Russell

Arts & Sciences Electronic Theses and Dissertations

Urinary tract infections (UTIs) can be highly recurrent, and the mechanism(s) governing recurrence susceptibility are mostly unknown. Here I demonstrate bladder epithelial (urothelial)-intrinsic trained immunity as part of a differential mucosal remodeling response to an initial UTI. I established urothelial stem cell (USC) lines from isogenic mice with different UTI histories (naïve, chronic, or self-resolving) and discovered 2880 differential genome-accessible regions, indicating differential epigenetic reprogramming dependent on infection history. Differentiation of USC lines in vitro resulted in polarized urothelial cultures that recapitulated distinct remodeling morphologies seen in vivo and exhibited altered gene expression, including genes involved in cell death pathways. …

Investigation Of Ifnγ-Induced Control Of Intracellular Pathogens, Michael Mcallaster

Arts & Sciences Electronic Theses and Dissertations

Genes required for the lysosomal degradation pathway of autophagy play key roles in topologically distinct cellular processes with significant physiologic importance. One of the first-described of these ATG gene-dependent processes is the requirement for a subset of ATG genes in interferon-γ (IFNγ)-induced inhibition of norovirus and Toxoplasma gondii replication. In this dissertation we identified novel components that are required for or that negatively regulate this immune mechanism. Enzymes involved in the conjugation of UFM1 to target proteins including UFC1 and UBA5, negatively regulated IFNγ-induced inhibition of norovirus replication via effects of Ern1. We identified and confirmed that IFNγ-induced inhibition of …

Metabolic Control And Immune Barriers Of Hematopoietic Stem Cells, Hannah Pizzato

Arts & Sciences Electronic Theses and Dissertations

Hematopoietic stem cells (HSCs) have the unique ability to self-renew for life, to differentiate into mature blood lineages, and to readily engraft upon intravenous transplantation. As such, they are the only types of stem cells in routine clinical use. Understanding HSCs and hematopoietic development can provide many lessons for other types of stem cells as they near clinical utility. Through bone marrow transplantation, it was discovered that cells exist with regenerative potential. This led to the search to purify these cells and to determine the function of other hematopoietic cells. By isolating and transplanting cells expressing different combinations of surface …

Regulation Of Host-Microbe Interactions In Autoimmunity And Antiviral Immunity By Cytosolic Nucleic Acid Sensing And Interferon Signaling, Derek Jerome Platt

Arts & Sciences Electronic Theses and Dissertations

Cytosolic nucleic acid sensing and interferon (IFN) signaling are central to the host immune response to microbial pathogens. However, dysregulation of immunological pathways such as these can result in devastating autoimmune disease. In order to provide a robust immune response to pathogen without causing harm to self, the host immune system must engage in a delicate balancing act, interacting with microbes and determining whether they are commensal or pathogenic. The cGAS-STING pathway is a key regulator of host-microbe interactions by cytosolic nucleic sensing and IFN signaling. Loss of function in the cGAS-STING pathway leads to increased susceptibility to pathogenic threats, …

Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc

Arts & Sciences Electronic Theses and Dissertations

Rapid cell proliferation is a hallmark feature of adaptive immune cells lymphocytes. It is essential for the establishment of diverse antigen receptor repertoires and amplification of antigen-specific immune responses. While such proliferation is beneficial for host protection from infections and cancers, it inevitably elevates the risk of oncogenic transformation. In developing and germinal center B lymphocytes, the risk is further increased by endogenous, genomic insults due to antigen receptor rearrangements and somatic mutations, with which expression of the proto-oncogene c-MYC is closely associated. Nonetheless, frequencies of cancers originated from B lymphocytes are relatively low, suggesting that they are protected from …

Peripheral Nerve Macrophages And Their Implications In Neuroimmunity, Peter Leon Wang

Arts & Sciences Electronic Theses and Dissertations

Macrophages are innate immune cells that protect against pathogens and maintain tissue integrity. In vertebrates, macrophages reside in every tissue where they perform specific functions from early development through adulthood. While macrophages provide important functions across all tissues, a major focus in recent years has been the role of resident brain macrophages, known as microglia, in neurodegeneration. As microglia have been shown to affect brain development, homeostasis, and disease, they demonstrate how immune cells critically mediate neurological health and point to the broader significance of neuroimmune interactions, or the coordinated actions of the nervous and immune systems for maintaining tissue …

Development Of Macromolecular Prodrug Of Sinomenine For The Treatment Of Rheumatoid Arthritis, Roshni Mukundan

Theses & Dissertations

Inflammation is a natural response of the body to infections or any potential threat to the body. But, sometimes the immune system attacks its own body causing persistent inflammation leading to inflammatory diseases. One of the common chronic inflammatory diseases is rheumatoid arthritis (RA) which causes inflammation of the synovial membrane. The current treatments for RA are effective in controlling the symptoms but they come with severe side effects and economic burden. Further, the management of pain is still a problem with these drugs. Sinomenine is a natural alkaloid obtained from the Chinese medicinal plant Sinomenium acutum that has been …

Roles Of A Bradykinin Storm And A Cytokine Storm In Covid-19 Cases, Nouha H. Odeh

Honors College Theses

In the light of recent events, it is imperative to understand the key inflammatory response elements that appear to be the source of more severe ailments resulting from a SARS-CoV-2 viral infection known as Covid-19 The more severe cases of Covid-19 are characterized by a severe inflammatory response resulting in tissue damage. My research proposal aims to investigate the two possible culprits of this response: a bradykinin (BK) storm and an interleukin-6 (IL-6) mediated cytokine storm. In both systems respectively, the excess release of these signals subsequently signals the production of even more of the same response element, resulting in …

The Regulation Of Pannexin1 And Pannexin2 In The Skin In Health And Disease, Rafael E. Sanchez Pupo

Electronic Thesis and Dissertation Repository

Pannexins (PANX1, 2, 3) are a family of channel-forming glycoproteins that mediate intracellular and paracrine signaling. In contrast to PANX2, PANX1 has been extensively investigated in the skin, modulating cell differentiation, wound healing, and melanoma development. PANX1 and PANX2 can co-exist in the same cell and form mixed channels where their glycosylation seems to regulate their intermixing. N-glycosylation and caspase cleavage have been proposed as modulators of the function of PANX1, but their effects on PANX2 are unknown. We explored the PANX2 expression in mouse skin and showed that a Panx2 splice variant (PANX2-202) is continuously expressed throughout aging skin. …

Intranasal Hpv Peptide Vaccine Formulation Induces Potent Cytotoxic Cd8 T Cell Immunity For The Treatment Of Genital Hpv Tumors, Gloria Sierra

Dissertations & Theses (Open Access)

Human Papillomavirus (HPV) induced cancers continue to affect millions of women worldwide, with the five year survival rate hovering just under 60% in some demographics. Therefore there is an unmet need to develop effective, yet, easily administered therapies to treat established HPV genital lesions. Even though immune checkpoint therapy (ICT) is a promising treatment option in some HPV+ cancers, the high cost and associated toxicities are still major concerns for their widespread application. HPV cancers are textbook candidates for therapeutic vaccination intervention because they’re driven by the expression of viral oncoproteins E6 and E7, which serve as ideal tumor specific …