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Assessing The Role Of Arsenic Exposure And Mirna-186 In Skin Tumorigenesis And Chromosomal Instability., Angeliki Lykoudi Dec 2021

Assessing The Role Of Arsenic Exposure And Mirna-186 In Skin Tumorigenesis And Chromosomal Instability., Angeliki Lykoudi

Electronic Theses and Dissertations

Chronic arsenic exposure through drinking water is a global health issue, affecting more than 200 million people. Arsenic is a group I human carcinogen and causes chromosomal instability (CIN). Arsenic exposure is the second most cause of skin cancer after UV radiation. MiR-186 is overexpressed in arsenic-induced squamous cell carcinoma relative to premalignant hyperkeratosis. Predicted targets of miR-186 are cell cycle regulators. Thus, we hypothesize that miR-186 overexpression drives malignant transformation of HaCaT cells by induction of CIN. Stable clones of HaCaT transfected with pEP-miR-186 expression vector or empty vector were maintained under puromycin selection were exposed to 0 or …


Preclinical Development Of Epicertin, A Novel Biotherapeutic For The Treatment Of Ulcerative Colitis., Micaela Ann Reeves Dec 2021

Preclinical Development Of Epicertin, A Novel Biotherapeutic For The Treatment Of Ulcerative Colitis., Micaela Ann Reeves

Electronic Theses and Dissertations

Epicertin (EPT) is a recombinant variant of the cholera toxin B subunit with a C-terminal KDEL endoplasmic retention motif. Previously, orally administered EPT demonstrated mucosal healing activity in acute and chronic dextran sulfate sodium colitis models, indicating its therapeutic potential for ulcerative colitis (UC) treatment. However, oral dosing with EPT requires neutralization of gastric acid prior to administration, hindering its facile application in the treatment of chronic diseases like UC. One solution to this issue is that EPT may also be administered intracolonically without losing efficacy. This work describes the determination of a target intracolonic dose of EPT for future …


An Analysis Of Taste Neuron Morphological Variability: Influences Of Neuron Type And Plasticity., Lisa Christina Ohman Dec 2021

An Analysis Of Taste Neuron Morphological Variability: Influences Of Neuron Type And Plasticity., Lisa Christina Ohman

Electronic Theses and Dissertations

Taste neurons are functionally and molecularly diverse, but their morphological diversity was, until recently, completely unexplored. Taste neurons were considered relay cells, communicating information from taste-transducing cells to the brain without variation in morphology. Instead, individual taste neurons are tremendously morphologically variable. To determine how differences in branching relate to the number and types of taste-transducing cells providing neuronal input, I combined sparse cell genetic labeling with a whole-mount immunohistochemistry and analysis workflow. I found that the maximum number of taste-transducing cells capable of providing convergent input onto individual gustatory neurons varied with a range of 1-22 taste-transducing cells. Consistently, …


Hospital-Based Professional Spiritual Care: Evaluating The Utilization, Availability, And Impact Of Chaplains., Kelsey B. White Dec 2021

Hospital-Based Professional Spiritual Care: Evaluating The Utilization, Availability, And Impact Of Chaplains., Kelsey B. White

Electronic Theses and Dissertations

BACKGROUND: The Affordable Care Act, enacted in 2010, transformed healthcare policy and forced hospitals to reevaluate traditional methods for care delivery. Researcher advocated for patient-centered models of care to reduce costs, address inequitable access to services, and improve service quality. These models prioritize patient values, preferences, and beliefs inclusive of patients’ religious and spiritual needs. Professional chaplains provide religious and spiritual care within many hospital settings. This dissertation explored the characteristics of hospitalized persons using chaplains, the factors associated with a hospital reporting a chaplaincy department, and how those services impacted patient satisfaction. METHODS: The first analysis used a two-part …


Impact Of Pank1 Deletion On Mitochondrial Acetylation And Cardiac Function During Pressure Overload., Timothy N. Audam Dec 2021

Impact Of Pank1 Deletion On Mitochondrial Acetylation And Cardiac Function During Pressure Overload., Timothy N. Audam

Electronic Theses and Dissertations

Recent studies have associated elevated protein acetylation levels with heart failure in humans. Although mechanisms promoting elevated acetylation levels are not fully known, excess acetyl-CoA may drive enzyme-independent acetylation of cardiac proteins. Accumulation of acetyl-CoA depends on the availability of sufficient CoA, whose production is regulated by pantothenate kinases in the CoA biosynthetic pathway. We show that cardiac proteins are hyperacetylated during heart failure in humans and tested in mice whether limiting CoA abundance would improve ventricular remodeling during pressure overload-induced hypertrophy. We limited cardiac CoA levels by deleting the rate-limiting enzyme in CoA biosynthesis, Pank1 (one of three PANK-encoding …


The Impact Of Statin Use On Outcomes Of Diabetic Adult Patients Hospitalized For Community Acquired Pneumonia., Joel Lanceta Dec 2021

The Impact Of Statin Use On Outcomes Of Diabetic Adult Patients Hospitalized For Community Acquired Pneumonia., Joel Lanceta

Electronic Theses and Dissertations

BACKGROUND: Statins, a class of drugs that treat hyperlipidemia, may have an immunosuppressive effect for patients with community acquired pneumonia (CAP). Retrospective and in vitro studies have suggested an immunomodulatory, antioxidative and anticoagulant effects from statin use in patients with Type 2 Diabetes Mellitus (T2DM) hospitalized for CAP. Prospective studies that have tested any effect of statin therapy on patients with T2DM and CAP have not been found literature. To date, prospective studies showing of the effects statin therapy may have on T2DM patients hospitalized for CAP are not available. METHODS: This dissertation is a secondary analysis using deidentified data …


Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge Dec 2021

Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge

Electronic Theses and Dissertations

It is generally believed that the tear film lipid surface film inhibits the rate of evaporation (Revap) of the underlying tear aqueous. It is also generally believed that changes in the composition of the tear film lipid layer is responsible for an increase in Revap in patients with dry eye. Both of these ideas have never been proven. The purpose of the current studies was to test these ideas. Revap was measured in vitro gravimetrically. Lipid spreading was measured using Raman spectroscopy and microscopy. The influence of the following surface films on the Revap of the sub phase of physiologically …


Collaborative Human-Machine Interfaces For Mobile Manipulators., Shamsudeen Olawale Abubakar Dec 2021

Collaborative Human-Machine Interfaces For Mobile Manipulators., Shamsudeen Olawale Abubakar

Electronic Theses and Dissertations

The use of mobile manipulators in service industries as both agents in physical Human Robot Interaction (pHRI) and for social interactions has been on the increase in recent times due to necessities like compensating for workforce shortages and enabling safer and more efficient operations amongst other reasons. Collaborative robots, or co-bots, are robots that are developed for use with human interaction through direct contact or close proximity in a shared space with the human users. The work presented in this dissertation focuses on the design, implementation and analysis of components for the next-generation collaborative human machine interfaces (CHMI) needed for …


Perceived Social Support, Family Relationships, And Health-Related Quality Of Life Among Women With Breast Cancer In Jordan., Hedaya Rateb Hina Dec 2021

Perceived Social Support, Family Relationships, And Health-Related Quality Of Life Among Women With Breast Cancer In Jordan., Hedaya Rateb Hina

Electronic Theses and Dissertations

Introduction: Breast cancer is the most common cancer among Jordanian women. Perceived social support (PSS) and family relationships are strongly associated with positive psychosocial outcomes and health-related quality of life (HRQoL). This area was widely explored in Western countries, but little attention was devoted to investigate this area in Middle East region. Purpose: to investigate the interrelationships among PSS, family relationships, and HRQoL of women with breast cancer in Jordan using an exploratory cross-sectional design. Method: The contextual model of HRQoL designed by Ashing-Giwa (2005) provided the foundation for this study. A total of 140 women were …


Effects Of Chemosensory Experience And Context On Consummatory Behaviors., Saphira M. Chiu Dec 2021

Effects Of Chemosensory Experience And Context On Consummatory Behaviors., Saphira M. Chiu

Electronic Theses and Dissertations

Eating food generates associations between odors and tastes (i.e., flavor) that guide future choices. Experience with an odor-taste mixture links an odor with a taste’s quality and hedonic value, resulting in a preference for an odor paired with a palatable taste over an odor paired with an unpalatable taste. However, experience with a neutral stimulus (i.e., latent inhibition) or environment (i.e., context) can influence the formation of conditioned associations. Here, I used a two-bottle brief-access task to determine whether rats display an innate preference between unpaired odors (isoamyl acetate and benzaldehyde), how preexposure to the unpaired odors impacts mixture-dependent consummatory …


Exploring The Contextual Factors And Decision-Making Process Of Risky Sexual Behavior Among Homeless Adults In Louisville, Kentucky., Sarah C. Van Heiden Dec 2021

Exploring The Contextual Factors And Decision-Making Process Of Risky Sexual Behavior Among Homeless Adults In Louisville, Kentucky., Sarah C. Van Heiden

Electronic Theses and Dissertations

Homelessness is a complex public health issue; individuals who experience homelessness are said to engage in risky sexual behaviors at an increased rate and experience a higher prevalence of sexually transmitted infection (STI). While the sexual behaviors of homeless adolescents are commonly studied, little is known about the sexual behaviors of the growing population of older adults, or how they make decisions to engage in sex. Three aims guided this research: 1) to describe the sexual behaviors and sexual decision-making process of homeless older adults, 2) to examine how homeless older adults evaluate the outcomes associated with engaging in risky …


The Association Between Depression And Anxiety With Covid-19 Outcomes., Erica Miller Dec 2021

The Association Between Depression And Anxiety With Covid-19 Outcomes., Erica Miller

Electronic Theses and Dissertations

Previous studies have shown that mental disorders affect COVID-19 mortality. This study investigated the effect of depression and/or anxiety on COVID-19 outcomes. Depression/anxiety was defined by actively taking medication and/or diagnosis. The outcomes were ICU admission; ventilation; mortality; and time to mortality. Of 698 hospitalized patients, there were 204 (29%) defined to have either depression or anxiety. There were 109 deaths, and of those, 52 (48%) were diagnosed with depression/anxiety. Multivariable logistic regression and Cox proportional hazards models were used to examine associations. ICU admission and ventilation were not significantly associated with depression/anxiety. Depression/anxiety was associated with mortality (OR: 1.84, …


Multilateration Index., Chip Lynch Aug 2021

Multilateration Index., Chip Lynch

Electronic Theses and Dissertations

We present an alternative method for pre-processing and storing point data, particularly for Geospatial points, by storing multilateration distances to fixed points rather than coordinates such as Latitude and Longitude. We explore the use of this data to improve query performance for some distance related queries such as nearest neighbor and query-within-radius (i.e. “find all points in a set P within distance d of query point q”). Further, we discuss the problem of “Network Adequacy” common to medical and communications businesses, to analyze questions such as “are at least 90% of patients living within 50 miles of a covered emergency …


Decreased Kidney Mitochondrial Content And Pgc-1Α Following Repeated Low-Dose Cisplatin-Induced Kidney Injury., Andrew Joseph Orwick Aug 2021

Decreased Kidney Mitochondrial Content And Pgc-1Α Following Repeated Low-Dose Cisplatin-Induced Kidney Injury., Andrew Joseph Orwick

Electronic Theses and Dissertations

Cisplatin is highly effective and one of the most commonly used chemotherapeutic agents in the treatment of a number of different solid organ tumors. Unfortunately, the dose-limiting nephrotoxicity occurs in up to 30% of patients, which requires alterations to treatment regimens that are often less effective. The kidney’s function is to provide fluid homeostasis, and this is an energy-intensive process. Proper renal function is dependent on functional mitochondria. PGC-1α regulates mitochondrial number, respiratory capacity, and mitochondrial proteins in proximal tubule cells. We delivered low-dose cisplatin to mice via intraperitoneal injections once a week for 4 weeks. The mice were then …


Oligodendrocyte Responses After Spinal Cord Injury., George Zach Wei Aug 2021

Oligodendrocyte Responses After Spinal Cord Injury., George Zach Wei

Electronic Theses and Dissertations

Recent studies demonstrate that neuroprotection strategies targeting the proteostasis network and components of its effector signaling pathways improve cell survival and motor recovery outcomes in several models of neuronal injury and degeneration. However, the individual contributions of these signaling pathways to the pathogenesis of spinal cord injury (SCI), white matter damage, and motor recovery have not yet been determined. Here, I explored the role of the HIF prolyl hydroxylase domain proteins (PHD/EGLN), effectors that can modulate stress responses activated by the proteostasis network, on motor function recovery after SCI. Furthermore, I identified previously unknown candidate mechanisms in an unbiased manner …


Development And Validation Of Biosafety Climate Scale And Survey-Based Analyses Of Safety Perceptions In Biological Research And Teaching Laboratories At Public Universities In The Usa., Sivarchana Mareedu Aug 2021

Development And Validation Of Biosafety Climate Scale And Survey-Based Analyses Of Safety Perceptions In Biological Research And Teaching Laboratories At Public Universities In The Usa., Sivarchana Mareedu

Electronic Theses and Dissertations

Biosafety plays a key role in ensuring safety of researchers’ as well as the public from unintentional exposures to infectious agents. However, the occurrence of lab acquired infections, exposures, and safety lapses in biological laboratories underscores challenges in biosafety program management. The raise in emerging and reemerging infectious diseases and the ongoing COVID-19 pandemic reiterates the need for biosafety and research community to work together. Literature recommends the application of safety climate in measuring safety culture. The goal of this dissertation is to quantify biosafety climate and examine associated factors to understand the gaps between research and biosafety professionals in …


Trends In Hysterectomy In Hospital And Ambulatory Settings In Kentucky 2017-2020., Felicia A. Pugh Aug 2021

Trends In Hysterectomy In Hospital And Ambulatory Settings In Kentucky 2017-2020., Felicia A. Pugh

Electronic Theses and Dissertations

Hysterectomy is the most common treatment for benign uterine conditions in the United States. Data suggest that one in nine women will have the procedure in their lifetime (1). Previous studies indicate that abdominal hysterectomy rates for non-malignancies are declining as alternative methods are increasing for decades; however, those trends do not apply for all women in the country (2-5). In this cross-sectional study, hysterectomy procedures completed between 2017-2020 are described in Kentucky Cabinet for Health and Family Services data. Multivariable logistic regression is used to assess the odds of abdominal hysterectomy for benign indications in Kentucky. Conclusion: Rates of …


Concurrent Reporting Of Adverse Childhood Experiences Among Perspectives Of Adolescents And Caregivers., Katie J. Berghuis Aug 2021

Concurrent Reporting Of Adverse Childhood Experiences Among Perspectives Of Adolescents And Caregivers., Katie J. Berghuis

Electronic Theses and Dissertations

The consequences of Adverse Childhood Experience (ACE) events in youth have predominantly been studied through retrospective studies that assess adults’ first 18 years of life or caregiver report of ACEs in youth. Reliance on only caregiver report to discern ACEs is a limitation amongst prior studies as research has found that caregivers tend to underestimate ACEs among their children, and there is even a greater discrepancy of reporting between caregivers and youth 12 years and older. Therefore, this study investigated concurrent reporting of self-report ACE scores in adolescents – defined in this study as 12 to 20 years old – …


Metabolic-Epigenetic Regulation Of Macrophage Polarization., Jordan T. Noe Aug 2021

Metabolic-Epigenetic Regulation Of Macrophage Polarization., Jordan T. Noe

Electronic Theses and Dissertations

Tumor-associated macrophages polarized to an M2 phenotype (M2-TAMs) promote neo-angiogenesis, tumor-stromal matrix remodeling, and immuno-evasion, which, collectively, contribute to immunotherapeutic resistance and reduced cancer patient survival. Highly glycolytic “Warburg” cancer cells produce lactate that independently drives naïve M0→immunosuppressive M2 (M0→M2) macrophage polarization, but the mechanisms have not been fully elucidated. The atypical cytokine macrophage migration inhibitory factor (MIF) is a fundamental underlying requirement for immunosuppressive M2 macrophage polarization. Still, it is unknown whether a molecular link exists between lactate-supported and MIF-dependent M2 macrophage polarization. Using a combination of gene expression assays, chromatin immunoprecipitation, and metabolomic analyses, we identified that M2 …


“And The Next Day, You Are In Charge”: Policy Recommendations Stemming From A Qualitative Investigation Into The Professional Development Of Early Career Peer Support Specialists In Kentucky., Diane Zero Aug 2021

“And The Next Day, You Are In Charge”: Policy Recommendations Stemming From A Qualitative Investigation Into The Professional Development Of Early Career Peer Support Specialists In Kentucky., Diane Zero

Electronic Theses and Dissertations

Over the last twenty years, the peer support segment of the behavioral health workforce has grown rapidly. However, few researchers have studied the effects on individuals from transitioning into the role. Likewise, there is limited research examining the professional development process of early career peer support specialists. To begin to fill these gaps in the literature, I conducted a qualitative research study examining workforce development experiences of peer support specialists in Kentucky. This dissertation reports on its findings and includes a policy paper with recommendations for improving policy and practice. Chapter one offers an introduction to the peer support workforce …


Exploring Opportunities For Prevention Of Child Sexual Abuse In A Diverse American Muslim Community., Rishtya Meena Kakar Aug 2021

Exploring Opportunities For Prevention Of Child Sexual Abuse In A Diverse American Muslim Community., Rishtya Meena Kakar

Electronic Theses and Dissertations

Recognizing the significant mental, emotional, developmental and health consequences for victims of child sexual abuse (CSA) and sociopolitical consequences for families and communities in every cultural, ethnic, and religious group around the world, this study sought to determine key opportunities for prevention of CSA in a diverse American Muslim community using a public health socioecological lens, rooted in aspects of critical theory. While there is considerable research on situational and individual-level risk factors related to CSA cases, there is less research on the societal and community-level processes related to the primary prevention of CSA, especially among minoritized communities. Responding to …


Histone Deacetylases In Alcohol Associated Liver Disease., Srineil Bodduluri Aug 2021

Histone Deacetylases In Alcohol Associated Liver Disease., Srineil Bodduluri

Electronic Theses and Dissertations

Alcohol abuse is endemic worldwide and there is no FDA approved treatment for Alcohol-Associated Liver Disease (ALD). Many scholars have posited that targeting Histone Deacetylases (HDAC) may be therapeutic in ALD intervention. In this study, the changes in hepatic gene expression and immune phenotyping of mice undergoing chronic plus binge alcohol exposure was examined. The characterization of relative mRNA levels for all 18 HDAC were performed. Results showed decreased expression of the genes HDAC 1,7,9,10,11 and Sirtuin enzymes (SIRT) 3,4,5,7. Other pathways related to lipid metabolism as well as systemic inflammation and hepatic injury also exhibited significant changes. These altered …


Development And Evaluation Of A Body Weight Support Treadmill For Use With Locomotor Training On Pediatric Spinal Cord Injury Patients., Winston T Rauch Aug 2021

Development And Evaluation Of A Body Weight Support Treadmill For Use With Locomotor Training On Pediatric Spinal Cord Injury Patients., Winston T Rauch

Electronic Theses and Dissertations

The consequences of spinal cord injury (SCI) are devastating regardless of the age of a patient. When the injury occurs in children five years old or younger, however, the impact is magnified due to the inevitable development of scoliosis (96%) and hip dysplasia (57%) (Schottler et al., 2012). To reduce occurrence of these complications and improve the quality of life for these patients, specialized activity-based therapies such as locomotor training (LT) are being increasingly used to improve overall trunk control and muscle activity in the lower extremities (Harkema et al., 2012; Howland et al., 2014). The aim of this therapy …


Development Of 3d-Bioprinted Scaffolds For Oral Probiotic Application., Jhanvi Patel Aug 2021

Development Of 3d-Bioprinted Scaffolds For Oral Probiotic Application., Jhanvi Patel

Electronic Theses and Dissertations

Background: Porphyromonas gingivalis adheres to and invades gingival epithelial cells, resulting in decreased cell viability. Previous studies have indicated that probiotics are effective against dental pathogens; however, few approaches provide sustained-delivery of active agents in the oral cavity. Hypothesis: Probiotics will limit P. gingivalis effects on Telomerase Immortalized Gingival Keratinocyte (TIGK) cells and 3D-printed scaffolds will prolong probiotic release. Methods: Lactobacillus acidophilus, Lactobacillus reuteri, and Bifidobacterium bifidum were assessed with adhesion and antibiotic protection assays to limit P. gingivalis effects on TIGKs. Scaffolds were printed with a select probiotic and evaluated for release kinetics. Results: Free L.a., …


Genetic And Functional Analysis Of Rat Mammary Cancer Susceptibility., Emily L Duderstadt May 2021

Genetic And Functional Analysis Of Rat Mammary Cancer Susceptibility., Emily L Duderstadt

Electronic Theses and Dissertations

Breast cancer genetic susceptibility is modulated by high to low penetrance risk alleles. Population frequencies of high and moderate penetrant predisposing mutations are rare and responsible for a small percentage of population cases. Most genetic variation in breast cancer susceptibility is low penetrance common variants where causal genes and risk-associated mechanisms are largely unknown. Comparative genetics uses animal models to isolate and mechanistically evaluate genetic susceptibility to human disease. Rat strains have different susceptibility phenotypes to chemical-induced carcinogenesis. Selective breeding and genetic linkage analysis using a 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis model have identified Mammary carcinoma susceptibilityquantitative trait loci …


Covid-19 Serological Diagnostic Development Using A Sars-Cov-2 Rbd Foldon Fusion, Joey Emery Breckenridge Jr. May 2021

Covid-19 Serological Diagnostic Development Using A Sars-Cov-2 Rbd Foldon Fusion, Joey Emery Breckenridge Jr.

Electronic Theses and Dissertations

Serological tests are conducted to assess humoral response against viral protein antigens, to assess viral exposure and protection from pathogens. The rapid development and modularity of serological assays have proven critical to managing the current SARS-CoV-2 pandemic. The receptor binding domain of SARS-CoV-2 is within the trimeric Spike protein and serves as a highly immunogenic target for potentially neutralizing antibodies. Current receptor binding domain serological assays use recombinant monomers or dimers of the receptor binding domain. The receptor binding domain is presented to the immune system natively in the context of the Spike protein trimer. Therefore, a recombinant trimeric receptor …


Sex-Based Differences In Microbiota Composition And Metabolomic Profiles Associated With Altered Macrophage Function And Protection From Lupus In Bwf1 Mice., James William Harder May 2021

Sex-Based Differences In Microbiota Composition And Metabolomic Profiles Associated With Altered Macrophage Function And Protection From Lupus In Bwf1 Mice., James William Harder

Electronic Theses and Dissertations

Systemic lupus erythematosus (SLE) is a complex and an insidious disease that is still not completely understood, and has very few treatment options. Those that are available are ineffective and/or have serious side effects. Both genetic and environmental factors contribute to the susceptibility and resistance to SLE, and understanding the environmental factors underlying this disease could lead to more effective prevention and/or treatment strategies. Like most autoimmune diseases, SLE is much more prevalent in females than males. While there are numerous factors that contribute to this lupus susceptibility, there is increasing evidence that the microbiota can strongly influence lupus progression, …


Role Of Kvβ2 Subunits In Regulation Of Resistance Arterial Tone., Sean M Raph May 2021

Role Of Kvβ2 Subunits In Regulation Of Resistance Arterial Tone., Sean M Raph

Electronic Theses and Dissertations

Voltage-gated potassium (Kv) channels control vascular resistance and facilitate the augmentation of myocardial blood flow in response to increases in cardiac workload (i.e., metabolic hyperemia). Native sarcolemmal Kv1 channels in arterial myocytes associate with a heteromeric auxiliary complex consisting of intracellular Kvβ1 and Kvβ2 proteins. The Kvβ proteins differentially regulate the function of heterologously expressed Kv channels, as well as native Kv1 channels in excitable cells of the cardiovascular and nervous systems. The physiological importance of vascular Kvβ proteins in mediating vasodilation remains unknown. In this study, I tested the hypothesis that Kvβ proteins functionally regulate vascular tone in response …


Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller May 2021

Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller

Electronic Theses and Dissertations

Despite the success of immunotherapy in many types of cancer, pancreatic adenocarcinoma (PDAC) has yet to benefit. Innate immune cells are critical to antitumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Though trained innate immunity has mostly been investigated in the context of infection, the induction of trained innate immunity could also protect against tumors, and specifically pancreatic tumors. Here, we demonstrate that yeast-derived particulate β-glucan, a known inducer of trained immunity, traffics to the pancreas following IP administration. This causes …


The Importance Of Noncapped Viral Genomic Rna To Alphaviral Infection And Pathogenesis., Autumn Lapointe May 2021

The Importance Of Noncapped Viral Genomic Rna To Alphaviral Infection And Pathogenesis., Autumn Lapointe

Electronic Theses and Dissertations

Alphaviruses are mosquito-borne arboviruses that have a positive sense, single-stranded RNA genome, which are capable of causing severe disease and thus pose a significant burden to public health. During alphaviral replication, significant quantities of viral genomic RNAs that lack the canonical alphaviral 5’ cap structure are produced and packaged into viral particles, despite the fact that these noncapped genomes cannot be translated and are essentially noninfectious. The production and packaging of the noncapped genomes has been found to be true for infections across multiple vertebrate and invertebrate cell lines and alphavirus species, although the proportion of ncgRNA produced differs. Despite …