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Gut Commensals Modulate Siv/Shiv Pathogenesis And Therapeutics, Samuel Johnson

Theses & Dissertations

Despite significant advancements in combination antiretroviral therapy (cART), ongoing inflammation in the brain and gut remain two of the most significant hurdles in the health of people living with human immunodeficiency virus (HIV). Additionally, a viral reservoir in each compartment inhibits cure efforts by allowing rapid viral rebound following cART interruption. Emerging understanding of the gut-brain axis (GBA) implicates each compartment in the modulation of the other in a complex bi-directional interaction mediated by vagus innervation, circulating lymphocytes, and microbiome composition and biproducts. Using multiple models of the simian (and simian-human) immunodeficiency virus (SIV/SHIV) and therapeutic intervention, I present how …

Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib

Theses & Dissertations

Posttraumatic stress disorder (PTSD) is a devastating psychiatric disorder characterized by distinctive symptom clusters, including intrusive memories (i.e., flashbacks), avoidance of related stimuli, affective changes, and hyperarousal. Strikingly, patients with PTSD face a significantly increased risk for a number of inflammation-driven pathologies, ranging from cardiovascular to autoimmune disease. Yet, the exact etiology of this increased risk remains unknown. The immune system is known to be strongly influenced by the sympathetic nervous system, and sympathetic overactivity is a hallmark of PTSD. Lymphoid organs, such as the spleen, are richly innervated by sympathetic nerve fibers which terminate near adaptive immune …

The Role Of Calprotectin In T-Lymphocyte Driven Inflammation In A Mouse Model Of Psychological Trauma, Cassandra Moshfegh

Theses & Dissertations

Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that affects nearly 45 million Americans. This mental disorder is characterized by behavioral symptoms such as learned helplessness, hyperarousal, withdrawal, and flashbacks. The deleterious effects of PTSD are far-reaching and go beyond behavioral dysfunction, as these individuals are at a three-fold higher risk of comorbid inflammatory diseases. Autonomic, metabolic, and cardiovascular diseases plague these individuals later in their lifetime, however, the mechanistic link connecting psychological trauma to this systemic peripheral immunological dysfunction remains elusive. T-lymphocyte-induced inflammation plays a significant role in all these disease pathologies. Previous work from our laboratory demonstrated …

Innate Immunity In The Pathobiology And Treatment Of Infectious And Neurodegenerative Diseases, Mai Mostafa

Theses & Dissertations

Mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells) are the governors of innate immunity which is the body’s first line of defense against microbial pathogens. They act beneficial or detrimental. They are crucial for an effective non-specific immune response to invading pathogens by engulfing, destroying, then eliciting an adaptive specific immune response. Given their pivotal functions in the host immune defense, studying MP immune responses in disease is paramount important for understanding disease pathobiology and uncovering therapeutic strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the driver of acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) amongst …

The Effects Of Climate Change On The Transmission Of Lyme Disease, Schuyler Hedican, Katherine Kistler, Iveth Martinez Granados

Celebrating Scholarship and Creativity Day (2018-)

Lyme disease currently affects approximately 300,000 people annually in the United States, but climate change threatens to increase this number. Rising temperatures, humidity, and levels of rainfall are impacting the relationship and interactions between the bacterium that causes Lyme disease (Borrelia burgdorferi), its vectors, and associated hosts. Climate change models predict a northward expansion of these disease-carrying vectors and hosts into new territories in North America, as formerly unsuitable territories become more hospitable, most notably in Canada. Human exposure to the bacteria through the bite of an infected tick can lead to the characteristic symptoms of Lyme disease, such as …

Why Plasmodium Vivax And Plasmodium Falciparum Are So Different? A Tale Of Two Clades And Their Species Diversities, Ananias A. Escalante, Axl S. Cepeda, M. Andreína Pacheco

Harold W. Manter Laboratory of Parasitology: Library Materials

The global malaria burden sometimes obscures that the genus Plasmodium comprises diverse clades with lineages that independently gave origin to the extant human parasites. Indeed, the differences between the human malaria parasites were highlighted in the classical taxonomy by dividing them into two subgenera, the subgenus Plasmodium, which included all the human parasites but Plasmodium falciparum that was placed in its separate subgenus, Laverania. Here, the evolution of Plasmodium in primates will be discussed in terms of their species diversity and some of their distinct phenotypes, putative molecular adaptations, and host–parasite biocenosis. Thus, in addition to a current …

Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong

Pharmaceutical Sciences (PhD) Dissertations

Human cutaneous melanoma is the most aggressive form of skin cancer and the incidence rates have continued to increase over the years. Neuronal nitric oxide synthase (nNOS) produces nitric oxide (NO) has been found to be overexpressed in human melanoma and the expression of nNOS is induced by interferon-gamma (IFN-γ). In our studies, nNOS has been implicated in IFN-γ-stimulated melanoma progression and the inhibition of nNOS using novel inhibitors effectively inhibited IFN-γ-stimulated tumor growth in a xenograft mouse model. Programmed death-ligand 1 (PD-L1) is overexpressed in melanoma and plays an important role in suppressing the immune system ^12-14. Our …

Characterization Of Gangliosides And Fatty Acids In Extracellular Vesicles From Human Milk, Aliya Amin

Food Science (MS) Theses

Extracellular vesicles (EVs) are bioactive components of human milk that may impact functionality to regulate growth, cognitive development, metabolism, and immunity in newborns. The biogenesis of EVs and the mechanism by which EVs elicit biologic effects in vivo have not been characterized entirely. Gangliosides and fatty acids are integral in the formation, release, stability, and functionalities of EVs. Presumably, EV function is related to EV composition and lipids in EVs influence the bioavailability of EV cargo and downstream functions of EVs. The objective of this research was to characterize the fatty acid and ganglioside composition of EVs in human milk. …

Time Course Investigation Of The Dermal Leukocyte Response To Lipoteichoic Acid In Chickens, Ian Gilbert

Animal Science Undergraduate Honors Theses

Lipoteichoic acid (LTA) is component of the cell wall of Gram-positive bacteria that stimulates inflammation during bacterial infection. However, few studies have investigated the in vivo immune response to LTA, and none of the in vivo studies done have been performed in birds. For this project, the pulp (a skin-derivative) of growing feathers (GFs) of chickens were used as a test site to investigate the in vivo effects of intradermally injected LTA. In Study 1, the pulp of 12 GFs of 11-week-old Light-brown Leghorn (LBL) males were injected with 10 μL of differing concentrations of LTA (0.1, 1.0, 10, 100 …

Native And Non-Native Ant Impacts On Soil Microbes, Hannah A. Stewart

Biology Theses

Organisms produce chemical weapons for defense, but target organisms can develop resistance. In their introduced range, non-native species may bring “novel weapons” against which native organisms have not co-evolved resistance. The invasive European fire ant (Myrmica rubra) may have brought antimicrobial secretions to the Northeastern United States that are novel weapons against native fungal and bacterial soil organisms. I hypothesized that M. rubra would better inhibit seed pathogens resulting in greater emergence of native myrmecochorous Viola sororia seeds and, as a side effect, more strongly inhibit arbuscular mycorrhizal fungi than a native seed dispersing ant (Aphaenogaster picea …

Aggregatibacter Actinomycetemcomitans Exploits And Modulates The Immune Response By Human Neutrophils For Survival In The Anaerobic Environment., Hazel Ozuna

Electronic Theses and Dissertations

Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative facultative anaerobe and an opportunistic oral pathogen, strongly associated with localized periodontitis and other inflammatory diseases. Periodontitis is a chronic inflammation of the periodontium resulting from the inflammatory response of the host towards the dysbiotic microbial community present at the gingival crevice. The host immune response creates a hostile environment for microorganisms; therefore, it is important for Aa to be able to regulate the necessary genes to survive and thrive in such an environment. Aaexpresses several virulence factors such as a cytolethal distending toxin (Cdt), lipopolysaccharide (LPS) and leukotoxin A (LtxA), …

Structural Formation And Functionality Of The Spoiie Protein In Clostridium Difficile, Rachel Siebenmorgen

Biological Sciences Undergraduate Honors Theses

My research efforts were directed toward the structure and functionality of a protein, designated SpoIIE [11], which previously has been shown to regulate C. difficile peptide utilization in addition to sporulation and toxin release. The SpoIIE protein is found in all spore-forming gram-positive bacteria and is a crucial component in activation of transcription factors and septum formation thus affecting the regulation and timing of spore development [11,12]. A truncated form of the SpoIIE protein named SpoIIE∆TM was used in an effort to determine the structure of an important but uncharacterized linker domain of the protein. If the structure and specific …

Increasing Human Papillomavirus Vaccination Intent And Knowledge Through An Educational Intervention, Angelica E. Musumeci

UNLV Theses, Dissertations, Professional Papers, and Capstones

Human papillomavirus (HPV) is a widely discussed topic in healthcare as it affects patients of all genders and ages who partake in sexual activity. The most significant concern it poses to those at risk is HPV-related cancer. Fortunately, a vaccination exists that targets specific strains associated with these types of cancers. Despite evidence-based research supporting the vaccination’s efficacy and safety, lack of awareness and misinformation diminish the receipt of the vaccine and drive the lack of protection. Thus, educational interventions directed at parents and caregivers, which aims to improve their understanding of HPV and the vaccination’s benefits, is key to …

A Mechanistic Study On The Immunological Effects Of A Novel Anti-Schistosomal Compound, Caleb M. Sandall, Paul H. Davis

Theses/Capstones/Creative Projects

Schistosomiasis is a condition caused by a parasitic worm infection that is one of the primary neglected tropical diseases. It infects approximately 250 million people every year, and it causes the second largest economic impact from any parasitic disease. There exists a treatment for Schistosomiasis; however, it is ineffective against the juvenile stages of the worm. A novel drug has been developed that has been illustrated to have efficacy against all stages of worm infection. However, before this drug can be utilized, its method of action must be determined. Preliminary single cell transcriptomic data from our lab suggests that our …

Genomic Tools And Models For Investigating The Role Of Germline Diversity In Mouse Antibody Repertoire Development., Justin T. Kos

Electronic Theses and Dissertations

Given the diversity and complexity within immunoglobulin (IG) loci, effective mouse models first require characterization of intra-strain differences and construction of high-quality reference assemblies for IG loci in several representative strains. To understand light chain germline diversity across biomedically significant mouse strains, we profiled the expressed IGK and IGL repertoires of 18 commonly used laboratory mouse strains using AIRR-seq. Across strains, we observed germline IGKV sequences shared by three different IGK haplotypes and a more conserved IGLV germline repertoire among common laboratory strains. Pacific Biosciences (PacBio) Single-Molecule Real-Time (SMRT) sequencing was used to sequence and assemble bacterial artificial chromosomes (BAC) …

Atr-Mediated Cd47 And Pd-L1 Upregulation Restricts Radiotherapy-Induced Immune Priming And Abscopal Responses In Colorectal Cancer, Cheng-En Hsieh, Cheng-En Hsieh

Dissertations and Theses (Open Access)

Radiotherapy of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, incidences of abscopal tumor remission are extremely rare, and the post-irradiation immune escape mechanisms in CRC remain elusive. We report that CRC cells utilize a common DNA repair signaling pathway — ATR/Chk1/STAT3 — to upregulate both CD47 and PD-L1 in response to radiotherapy, which through engagement of SIRPα and PD-1 suppresses the capacity of antigen-presenting cells to phagocytose them thereby preventing TAA cross-presentation and innate immune activation. This post-irradiation CD47 and PD-L1 upregulation can be observed across various human solid tumor cells. Concordantly, …

Spike Protein Structural Dynamics Of Sars-Cov-2 Coronaviruses Studied Using Molecular Dynamics, William Strickland

Biological Sciences Undergraduate Honors Theses

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has overwhelmingly impacted the global population, accounting for millions of confirmed infections and deaths over the last year. The virus’s influence on the health and safety of individuals, the economy, and daily life has been disruptive and devastating. While SARS-CoV-2 and SARS-CoV-1, two closely related members of the SARS coronaviruses, have shown the ability to cross the species barrier and infect humans, SARS-CoV-2 has predominantly been the virus responsible for the number of infections presently known. SARS-CoV-2 has also proven to be volatile, as many variants have …

Innate Lymphoid Cell Characterization And Ilc2s In Neuroinflammation In Aging And Sex Differences, Alexis Mobley, Alexis S. Mobley

Dissertations and Theses (Open Access)

Aging affects immunologic responses by a global immune system suppression, including dysregulation of cytokine mediators, leading to increased inflammation throughout all systems, termed inflammaging. However, understanding healthy aging mechanisms can bypass this effect. Inflammaging also leads to poor outcomes during brain injury, making immune-targeting therapeutics tantamount to overall brain health and longevity. Moreover, sex affects disease etiology and severity through hormonal and chromosomal sex, as the X chromosome contains most immunology-based genes. Androgens have a generally suppressive effect on the immune system. Additionally, when immune responses are mounted, males are better at CD4+ T cell type (Th1) responses, while females …

Macrophage Rac2 Promotes Suppression Of Germination During Aspergillus Fumigatus Infection, Chris D. Tanner

All Theses

Aspergillus fumigatus is a fungus found ubiquitously in the environment including in the air we breathe. Though not a threat to most people, immunodeficient or immunosuppressed individuals are at risk for developing severe infection, including the life-threatening condition of invasive aspergillosis. The hematopoietic cell specific GTPase protein Rac2 is associated with major roles in innate immune defense. Currently Rac2 has been demonstrated to be crucial for survival against a variety of infections. Here, we use a rac2 null mutant zebrafish line and morpholino approaches to elucidate roles of Rac2 in mounting the macrophage host defense response against A. fumigatus infection. …

Lipid Rafts, Exosomal Vesicles And Anti-Giardial Therapies, Brian Ivan Grajeda

Open Access Theses & Dissertations

Giardia lamblia, a protozoan parasite, is a major cause of waterborne infection, worldwide. While the trophozoite form of this parasite induces pathological symptoms in the gut, the cyst forms transmit the infection via contaminated water. Since Giardia is a non-invasive parasite, the actual mechanism by which it causes infection remains elusive. We have previously reported that Giardia assembles cholesterol and GM1 glycolipid-enriched lipid rafts (LRs) that participate in encystation and cyst production. To further delineate the role of LRs in pathogenesis, we isolated LRs from Giardia and subjected them to proteomic analysis. Various cellular proteins including the virulent proteins—e.g., giardins, …

The Plague: A Contemporary Lens, Khawaja Ahmed, Delaney Collier, Will Plumb

Student Research

The Plague by Albert Camus bears witness to the town of Oran amidst the spread of the plague from the beginning to the end of the quarantine placed on the town. Although it is a direct comparison to the COVID-19 pandemic, Camus’s themes expressed in his novel resonates with other contemporary worldly issues that may or may not have an explanation. These other contemporary issues include war and the climate crisis. From our 2022 perspective, we have seen the COVID pandemic play out firsthand. We have witnessed from afar the threat of World War III and the current war in …

What Is The Prevalence Of Dirofilaria Immitis (Dog Heartworm) In Invasive Aedes Mosquitoes?, Leen Yousef, Johan Espinoza Corrales, Daniela H. Dolar, Taylor K. Trieu, Aisha Popalzai, Agamchat Dhami

Pacific Undergraduate Research and Creativity Conference (PURCC)

No abstract provided.

Covid Susceptibility And Severity Correlation With The Ace2 Gene, Natalie Taylor

Thinking Matters Symposium

A wide spectrum of susceptibility and severity of infection has been observed among COVID-19 patients. While some individuals remain unaffected by the Sars-Cov-2 virus, others have contracted the virus multiple times with varying levels of severity. This poster reviews some of the research demonstrating a link between the susceptibility of the Sars-Cov- 2 virus and the severity of infection, and a specific gene called ACE2. The ACE2 gene encodes an angiotensin-converting enzyme that acts as a functional receptor for the spike glycoprotein receptor binding domain of the coronavirus and severe acute respiratory syndrome coronaviruses. ACE2 presents numerous amino acid variants …

The Effect Of Covid-19 On The Low-Wage Workforce Nationwide, Katie Gilbertson

Undergraduate Research Symposium Podium Presentations

Key Takeaways: 1. Each low-wage occupation pays less than the mean hourly wage in their respective MSA. 2. Least amount of wage variance among MSAs in 2019. 3. In Las Vegas 2/3 of occupational wages increased, but employment dropped in 14/15 occupations. Leisure and hospitality occupations hardest hit and slowest to recover.

Temporal Trends In Outcomes In Patients With Adrenocortical Carcinoma: A Multidisciplinary Referral-Center Experience, Marilyne Daher, Jeena Varghese, Stephen K Gruschkus, Camilo Jimenez, Steven G Waguespack, Sara Bedrose, Lina Altameemi, Hadil Bazerbashi, Aung Naing, Vivek Subaiah, Matthew T Campbell, Amishi Y Shah, Miao Zhang, Rahul A Sheth, Jose A Karam, Christopher G Wood, Nancy D Perrier, Paul H Graham, Jeffery E Lee, Mouhammed Amir Habra

Faculty, Staff and Students Publications

CONTEXT: Reporting temporal trends in adrenocortical carcinoma (ACC) helps guide management strategies.

OBJECTIVE: This work aimed to report the trends in disease burden and clinical outcomes over time that cannot be adequately captured from individual clinical trials.

METHODS: A retrospective study was held of ACC patients seen at a referral cancer center between February 1998 and August 2019. Clinical outcomes were compared between an early cohort (February 1998-June 2007) and a late cohort (July 2007-August 2019).

RESULTS: A total of 621 patients included with a median age at diagnosis of 49.3 years (range, 0.5-86.6 years). There were 285 (45.9%) patients …

Physician's Attitudes On Pulmonary Rehabilitation Following Covid-19: A Brief Perspective From A Developing Country, Ivan Cherrez-Ojeda, Emanuel Vanegas, Miguel Felix, María José Farfán Bajaña, Azza Sarfraz, Zouina Sarfraz, Genesis Camacho, Alanna Barrios-Ruiz, Jack Michel

Department of Paediatrics and Child Health

Despite the uncertainty about the follow up of COVID-19 survivors, there is a growing body of evidence supporting specific interventions including pulmonary rehabilitation, which may lead to a reduced hospital stay and improved overall respiratory function. The aim of this short report was to assess the attitudes toward pulmonary rehabilitation following COVID-19 among Ecuadorian physicians. A cross-sectional study was conducted, in which a 5-question survey was used to assess the level of agreement to specific statements with a 5-point Likert scale. Out of the 282 participants, 48.2% (n=136) were male, with a mean of 12.6 (SD=11.3) years of experience. More …

Adaptive Coping For Covid-Related Stress, Sandra Maloy

Undergraduate Research Conference

The restrictions placed on society by the COVID- 19 pandemic for the purpose of limiting spread of the disease appear to have produced a different set of potential chronic health issues. Through lockdown and social distancing measures the general public lost access to key elements of daily life. The literature and qualitative interview data primarily support a negative association between participation in spiritual and physical activity and COVID-19 related stress. These findings are not surprising based on previous research investigating coping and other chronic stressors.

Exploiting 4–1bb Immune Checkpoint To Enhance The Efficacy Of Oncolytic Virotherapy For Diffuse Intrinsic Pontine Gliomas, Virginia Laspidea, Montserrat Puigdelloses, Sara Labiano, Lucía Marrodán, Marc Garcia-Moure, Marta Zalacain, Marisol Gonzalez-Huarriz, Naiara Martínez-Vélez, Iker Ausejo-Mauleon, Daniel De La Nava, Guillermo Herrador-Cañete, Javier Marco-Sanz, Elisabeth Guruceaga, Carlos E De Andrea, María Villalba, Oren Becher, Massimo Squatrito, Verónica Matía, Jaime Gállego Pérez-Larraya, Ana Patiño-García, Sumit Gupta, Candelaria Gomez-Manzano, Juan Fueyo, Marta M Alonso

Faculty, Staff and Student Publications

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors, and patient survival has not changed despite many therapeutic efforts, emphasizing the urgent need for effective treatments. Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was engineered to express the costimulatory ligand 4-1BBL to potentiate the antitumor immune response of the virus. Delta-24-ACT induced the expression of functional 4-1BBL on the membranes of infected DIPG cells, which enhanced the costimulation of CD8+ T lymphocytes. In vivo, Delta-24-ACT treatment of murine DIPG orthotopic tumors significantly improved the survival of treated mice, leading to long-term survivors that developed …

Investigating Alternative Induction Of The S. Aureus 80a Prophage, Jody Caretti

Student Scholar Showcase

Widespread antibiotic resistance has quickly become one of the most concerning crises affecting modern medicine, especially in cases of Staphylococcal infections, which have become resistant to all ��-lactam antibiotics. As a result, research into alternative forms of treatment for bacterial infections is a top priority. Bacteriophage therapy is a popular candidate for replacing antibiotics, due to the way the viruses interact with the bacteria. The 80�� prophage integrates its DNA into Staphylococcus aureus strain 10616 via the lysogenic cycle, and replicates with the bacterial cell. When stressed, the bacteria stop replicating and the prophage stimulates the lytic cycle, activating transcription …

Feasibility Of Tubulin As A Control For Gene Expression Following Transfection In Mouse Monocyte/Macrophage-Like Cells, Ankita Chabra

Honors Program Theses and Research Projects

Transfection, which is the ability to modify host cells’ genetic content, has broad application in studying normal cellular processes, molecular mechanism of disease and gene therapy. There are several transfection techniques, and all require either a control or a reference gene. Commonly used controls for transfection experiments are housekeeping genes, which maintain expression for a given cell/tissue, experimental conditions, and treatment. However, recent research has uncovered that expression levels of housekeeping genes may vary depending on the gene, cell type and experimental conditions. A growing body of evidence demonstrates that housekeeping genes are inadequate internal standards for measuring gene expression …