Digital Commons Network^™

Role Of Pseudomonas Aeruginosa Exoenzymes S, T, And Y In The Modulation Of Intrinsic Apoptosis In Pulmonary Microvascular Endothelial Cells, Andrea M. Vavrinek

Honors Theses

P. aeruginosa is the most common cause of ventilator-associated pneumonia in ICU patients. P. aeruginosa uses a type III secretion system to inject exoenzymes S, T, U, and Y into host cells, exhibiting unique effects. Pulmonary microvascular endothelial cells (PMVECs) are used to evaluate cellular changes caused by exoenzymes. ExoY infection of PMVECs leads to cell rounding but does not lead to cell death, unlike ExoS/T. The current study evaluated the exoenzyme-induced modulation of intrinsic apoptosis in endothelial cells. Strain PAK, producing ExoS, T, and Y, was compared to isogenic strains expressing either S, SY, T, TY, Y, or none …

Impacts Of Dietary Restriction On A Drosophila Model Of Werner Syndrome, Eileen Sember

College of Arts & Sciences Senior Theses

Werner syndrome (WS) is an autosomal recessive disorder that results in premature aging and occurs in 1 in 1,000,0000 to 1 in 10,000,000 people. In humans, WS is the result of mutations that render the WRN gene, that contains a helicase and an exonuclease domain, non-functional. Currently, there is no cure for WS in humans, making dietary and lifestyle interventions attractive for increasing the quality and longevity of lives. Diet restriction (DR) has been shown to extend the lifespan of several model organisms, including Drosophila melanogaster, making it a strong candidate for WS treatment. In this thesis, mutant flies …

A Meta-Analysis Of The Correlation Between Historical Trauma And Health Outcomes In The Native American Population, Taylen Day

Psychological Science Undergraduate Honors Theses

Native Americans experience significant health disparities such as increased rates of
cardiovascular disease, diabetes, and mental illness. Recent research has suggested that historical trauma may be a contributing factor. This meta-analysis examined the association between historical trauma and health outcomes in Native Americans in the United States and Canada. Data from 14 studies (N = 14,698, 35 effect sizes) examining the physical health, mental health, and substance use domains and using the Historical Loss Scale were collected for analysis. Possible moderating factors were also examined. Overall, a small, significant association (r =.124) was found between historical trauma and health outcomes. …

A Systematic Review Of Research On Treatment & Prevention Of The Neglected Tropical Disease Leishmaniasis, Aryn Akerberg

All Theses

Leishmaniasis is a life-threatening neglected tropical disease that is caused by the protozoa parasite, Leishmania. Over one million new human leishmaniasis cases occur each all over the world, affecting most the deeply impoverished regions of the world. The disease presents in three different forms: cutaneous leishmaniasis, mucocutaneous (mucosal) leishmaniasis, and visceral leishmaniasis. Symptoms can range from self-limiting lesion to more life-threatening conditions such as fever, kidney disease, and anemia. The Leishmania parasite is transmitted via the bite of the female phlebotomine sandfly and can infect many other mammals such as canines, rodents, bats, etc. The canine leishmaniasis epidemic is also …

Investigating Gene-Diet Interactions Impacting The Association Between Macronutrient Intake And Glycemic Traits, Kenneth E Westerman, Maura E Walker, Sheila M Gaynor, Jennifer Wessel, Daniel Dicorpo, Jiantao Ma, Alvaro Alonso, Stella Aslibekyan, Abigail S Baldridge, Alain G Bertoni, Mary L Biggs, Jennifer A Brody, Yii-Der Ida Chen, Joseé Dupuis, Mark O Goodarzi, Xiuqing Guo, Natalie R Hasbani, Adam Heath, Bertha Hidalgo, Marguerite R Irvin, W Craig Johnson, Rita R Kalyani, Leslie Lange, Rozenn N Lemaitre, Ching-Ti Liu, Simin Liu, Jee-Young Moon, Rami Nassir, James S Pankow, Mary Pettinger, Laura M Raffield, Laura J Rasmussen-Torvik, Elizabeth Selvin, Mackenzie K Senn, Aladdin H Shadyab, Albert V Smith, Nicholas L Smith, Lyn Steffen, Sameera Talegakwar, Kent D Taylor, Paul S De Vries, James G Wilson, Alexis C Wood, Lisa R Yanek, Jie Yao, Yinan Zheng, Eric Boerwinkle, Alanna C Morrison, Miriam Fornage, Tracy P Russell, Bruce M Psaty, Daniel Levy, Nancy L Heard-Costa, Vasan S Ramachandran, Rasika A Mathias, Donna K Arnett, Robert Kaplan, Kari E North, Adolfo Correa, April Carson, Jerome I Rotter, Stephen S Rich, Joann E Manson, Alexander P Reiner, Charles Kooperberg, Jose C Florez, James B Meigs, Jordi Merino, Deirdre K Tobias, Han Chen, Alisa K Manning

Faculty, Staff and Student Publications

Few studies have demonstrated reproducible gene-diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient-glycemia relationship in genetically and culturally diverse cohorts. We analyzed 33,187 participants free of diabetes from 10 National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program cohorts with whole-genome sequencing, self-reported diet, and glycemic trait data. We fit cohort-specific, multivariable-adjusted linear mixed models for the effect of diet, modeled as an isocaloric substitution of carbohydrate …

Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska

Student Theses and Dissertations

Buildup of oxidative stress and mitochondrial dysfunction are well known characteristics of both sporadic and hereditary amyotrophic lateral sclerosis (ALS). While both forms of the disease seem to arise from common cellular dysfunction, the genetic disease is studied to a much greater extent. Engineering novel animal models of the sporadic form of the disease is crucial for development of druggable targets to treat ALS and understand the underlying mechanisms. Interestingly, accumulation of oxidative stress by exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a hallmark of both hereditary and sporadic ALS. Previous work by our laboratory showed …

Development Of A Computational Model To Investigate Pathways And The Effects Of Treatment In Fanconi Anemia, Sabrina Kellett

Biological Sciences Undergraduate Honors Theses

Fanconi Anemia (FA) is a rare type of anemia that is not easily studied and can have very detrimental effects. This disease compromises the bone marrow, resulting in decreased hemopoiesis. Symptoms of FA also include abnormalities in the brain and spinal cord, incorrect formation of the kidneys, abnormal formation of the heart and lungs, and a dramatically increased risk of developing cancer. FA can be caused by various mutations in any of the 22 genes that encode for proteins involved in what is called the FA DNA repair pathway. In healthy individuals, this pathway specifically repairs interstrand cross-links (ICLs) recognized …

Laboratory Evaluation Of An Enzyme Immunoassay To Detect Coccidioides Galactomannan Antigens In Serum Samples, Anneliese Ahrens

Biological Sciences Undergraduate Honors Theses

Introduction: Coccidioidomycosis (cocci) is an infection caused by fungal pathogens in soil of dry and arid regions in the Southwestern states of the United States. The disease can present itself anywhere in the body, but usually is found in the lungs. The symptoms are very similar to the symptoms of a bacterial or viral respiratory infection, which is one of the reasons it is commonly misdiagnosed or left untreated. The CDC reports cases to have increased 143% from 2014 to 2019, with a mortality rate of 200 deaths per year, however this is likely underreported because of the inadequacies of …

Exploring The Plausibility Of Human Ecosystem Disruption Being The Cause For Increased Viral Prevalence, Andrew Ventura

University Honors Theses

Viral diseases and their prevalence--including both the number of cases and the appearance of new viruses--has increased in the last century, and these diseases have become an increasing threat to human health and well-being. The influenza and COVID-19 pandemics served both as introductions and reminders respectively to the power these viruses have to destroy and disrupt human life. As such, it intimates a necessity to investigate possible causes for the increase in these deadly diseases. Among these plausible causes is the dilution effect hypothesis, which states that decreasing the biodiversity of an ecosystem increases a pathogen's ability to infect, both …

Investigating Novel Chemotherapeutics Against The Parasite Toxoplasma Gondii, Braydon Dreher

Theses/Capstones/Creative Projects

Toxoplasma gondii, an intracellular protozoan, is a globally prevalent parasite due to the infectivity of T. gondii with nearly 2.5 billion people affected worldwide. Toxoplasma gondii can cause toxoplasmosis, which is a disease acquired through the consumption of undercooked meat or found in the feces of felines, and often leads to profound neuropathology and potentially death. Currently, acute toxoplasmosis is treated with pyrimethamine and sulfadiazine, which is a combination of an antiprotozoal and a sulfonamide. This combination of drugs directly targets the acute stage of infection but has failed to eliminate or impact the chronic carriage of bradyzoites while …

Dengue Virus And Blood Safety: A Mini-Review Of Research Publications, Festus Mulakoli, George Gachara, Eric Ndombi, Samoel Khamadi

School of Nursing & Midwifery, East Africa

The growing demand for donated whole blood and blood products to save lives has both health benefits and health risks for blood recipients at the same time. Dengue virus, a re-emerging viral disease poses a threat to blood safety, and it has spread to over 128 countries in the world. Several studies have documented transfusion-transmitted (TT) dengue, with the first cases being reported in China in 2002 and Singapore in 2008. To understand the magnitude and broader picture of the dengue virus and blood safety, we conducted a mini-review of published literature from the Scopus database. The review focused on …

Examining Ndufab1 Expression In Head And Neck Squamous Cell Carcinoma, Addison L. Stevens

Honors Theses

Head and neck squamous cell carcinoma (HNSCC) accounts for around 4% of all cancers in the USA. HNSCC includes cancers of the oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx. Reprogramming of mitochondrial metabolism has been known to promote oncogenesis. NDUFAB1, a nuclear encoded subunit of respiratory complex I (RCI) in the inner mitochondrial membrane, is abundantly expressed at the mRNA level in HNSCC patients. Based on this finding, we hypothesize that NDUFAB1 protein expression is high in HNSCC and that NDUFAB1 expression predicts a poor prognosis in HNSCC patients. We determined NDUFAB1 expression in HNSCC using immunohistochemistry and pathology guided …

Attitudes Towards Gluten Free Foods And Celiac Disease In Italy, Joellyn Speredelozzi

Senior Honors Projects

This project addresses the perception and realities of living with Celiac’s Disease in Italy. I combine a literature review with my own anecdotal experiences as an individual with Celiac’s Disease who has lived and studied in Italy. In my paper, I first describe the high awareness of gluten-free living that I noted the first time I studied abroad, being the impetus of this project. I follow this with the history and science of Celiac’s Disease for those who may be unaware of this serious chronic medical condition. I then continue to describe personal experiences I had while living in Naples, …

Sexual Dimorphism Of Glomerular Capillary Morphology In Rats, Zackarias Coker

Undergraduate Honors Theses

Chronic kidney disease (CKD) progresses faster in males than females; however, the underlying mechanisms remain poorly understood. Sex differences in glomerular capillary morphology has been hypothesized to contribute, in part, to the increased susceptibility to hypertension-induced renal injury and CKD progression in males, but this has not been investigated. The goal of the present study was to assess glomerular capillary morphology in male vs. female rats with intact kidneys and after uninephrectomy (UNX). We hypothesized that glomerular capillary radii (R_CAP) and length (L_CAP) would be greater in male rats.

Male (n=4) and female (n=4) with intact …

Irritable Bowel Syndrome: Proposed Mechanisms Of Pathophysiology And The Underlying Dysregulation Of Brain-Gut Interaction, Hailey Haddix

Senior Honors Theses

Irritable bowel syndrome (IBS) is a disease of the gastrointestinal tract affecting approximately 11-21% of people worldwide (Xiao et al., 2021). This research focuses on the dysregulation of gut homeostasis in IBS and explains how the pathophysiology of the gut is controlled by the bidirectional brain-gut axis. The mechanisms of the brain-gut axis consist of neuro-immune cross talk, neuro-hormone cross talk, microbiome-gut signaling, and the HPA-axis. Each of these contribute to one or more of the possible phenotypes of gut pathophysiology, which could include intestinal permeability, visceral hypersensitivity, and motility disturbance (Xiao et al., 2021). Stress is also an important …

Incidence And Risk Factors For Clinically Confirmed Secondary Bacterial Infections In Patients Hospitalized For Coronavirus Disease 2019 (Covid-19), Hiromichi S. Park, Caitlin M. Mccracken, Noah Lininger, Cara D. Varley, Multiple Additional Authors

OHSU-PSU School of Public Health Faculty Publications and Presentations

Objective: The true incidence and risk factors for secondary bacterial infections in coronavirus disease 2019 (COVID-19) remains poorly understood. Knowledge of risk factors for secondary infections in hospitalized patients with COVID-19 is necessary to optimally guide selective use of empiric antimicrobial therapy. Design: Single-center retrospective cohort study of symptomatic inpatients admitted for COVID-19 from April 15, 2020, through June 30, 2021. Setting: Academic quaternary-care referral center in Portland, Oregon. Patients: The study included patients who were 18 years or older with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) PCR test up to 10 days prior to admission. Methods: …

Cytochrome P450 1b1 And 12/15 Lipoxygenase Interaction In Paraventricular Nucleus In Angiotensin Ii-Induced Hypertension In Females, Shubha Ranjan Dutta

Theses and Dissertations (ETD)

Background: Angiotensin (Ang) II releases arachidonic acid (AA) from tissue phospholipids that is metabolized by 12/15-lipoxygenase (ALOX15) generating 12(S)- and 15(S)-hydroxyeicosatetraenoic acid (HETE) which have been implicated in cardiovascular and renal diseases. This study was conducted to investigate a) the contribution of ALOX15 to Ang II-induced hypertension and associated pathogenesis in female mice, and b) the interaction between the cytochrome P450 (CYP)1B1-generated metabolite of 17β-estradiol (E2) (2-methoxyestradiol, 2-ME) and ALOX15 in the paraventricular nucleus (PVN) as a mechanism that protects against Ang II-induced hypertension and its associated pathogenesis in female mice. Methods: Experiments were conducted in intact and ovariectomized (OVX) …

A Review Of Staphylococcus Aureus Pathogenesis, Global Impact, And The Rise Of Antibiotic-Resistant Clones, Anders Kleinbeck

Honors Scholar Theses

Staphylococcus aureus is a pathogen of grave concern to global public health. The pathogen has shown an unrivaled propensity to obtain resistance to nearly every antibiotic drug approved and prescribed for its treatment. This review will provide an overview of the history and evolution of S. aureus, including an analysis of its transition from the nosocomial setting to the community and the factors contributing to the species’ innate pathogenicity. This paper will also discuss the molecular mechanisms by which resistance to a wide range of popular antibiotic substances was obtained and will provide insight into the evolutionary patterns exhibited by …

Identification Of Molecular Markers Associated With Copd In Non-Smokers And Smokers: A Bioinformatics Analysis, Agede O. Ayodele, Isa M. Wasagu, Ademola E. Fawibe, Alakija K. Salami

The University of Louisville Journal of Respiratory Infections

Background

Even though the proportional burden of COPD among never-smokers is significant in both developing and developed nations, accounting for around 30% of all COPD in the community, there is little awareness of the prevalence of COPD in this population. Understanding the molecular processes that underlie COPD in nonsmokers is essential.

Methods

Dataset (GSE146560) was acquired from the Gene Expression Omnibus (GEO). The limma and clusterProfiler software tools were used to identify differentially expressed genes (DEGs) and conduct a functional enrichment analysis respectively.

Results

In all, 10,583 DEGs were found, of which 1,065 were up-regulated and 9,518 were down-regulated. The …

Inhibiting Survival Of Salmonella During Desiccation Through The Use Of Naturally Occurring Signals, Joseph Headrick

Electronic Theses and Dissertations

A rising problem in agriculture is the increase of antibiotic-resistant Salmonella cases associated with chicken eggs, which transmit infection to humans. To counter this, new approaches to combat Salmonella in chickens and desiccated on eggshells are vital in the prevention of human foodborne illness. Disrupting signaling pathways with naturally occurring compounds provides a potential novel avenue for prevention of Salmonella infections, as this would disrupt sensing of these environments and inhibit subsequent optimal gene expression. Starting with signals identified in previous studies, salicylic acid was found to inhibit Salmonella desiccation survival on both eggshells and plastic. To expand upon this, …

The Effects Of Radiation On Cancer Stem Cells In Glioblastoma And Ovarian Cancer, Aaron Keniston

Electronic Theses, Projects, and Dissertations

High grade serous ovarian cancer (HGSOC) and glioblastoma multiforme (GBM) are some of the most aggressive forms of cancer with poor patient survival. Despite successful cancer therapies, these malignancies have high recurrence rates which can be attributed to cancer stem cells (CSC) due to innate tumor initiating properties. In this study, we investigated the response of CSC populations to proton and photon radiation by quantification of core stem cell transcription factors Sox2 and Oct4. This was carried out utilizing a Sox2/Oct4 green fluorescent protein based reporter designated as SORE6-GFP measured by flow cytometry. We hypothesize that proton and photon irradiation …

Effect Of Temperature On The Microbiome Of A Laboratory-Reared Colony Of Haemaphysalis Longicornis Ticks, Brianna L. Mitchell

Honors Theses

Haemaphysalis longicornis ticks are invasive to the United States with potential to transmit several tick-borne pathogens that are native to the United States. Based on existing locations of H. longicornis in its native regions in Asia, as well as its invasive populations that are established in the United States, several geographic range prediction models have been produced to help understand future range expansion and distribution of this invasive tick in North America. Unfortunately, these models do not all agree and there is uncertainty associated with the potential geographic range expansion of H. longicornis ticks in North America. Climate can affect …

The Cx3cl1-Cx3cr1 Chemokine Axis Contributes To Tumor Immune Evasion And Its Blockade Enhances Responses To Anti-Pd-1 Immunotherapy, Apoorvi Chaudhri

Dissertations and Theses (Open Access)

CX3CL1 secreted in the tumor microenvironment serves as a chemoattractant playing a critical role in metastasis of CX3CR1 expressing cancer cells. While CX3CR1 can be expressed in both cancer and immune-inhibitory myeloid cells to facilitate their migration, the mechanisms employed by this axis on these cells to mediate immune suppression remain poorly understood. Here, we explore the immune evasion strategies implemented by this axis and find that it initiates a resistance program in cancer cells that results in 1) facilitation of tumor cell migration, 2) secretion of soluble mediators to generate a pro-metastatic niche, 3) secretion of mediators to attract …

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations and Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

The Diagnostic Odyssey Of Hypermobile Eds Patients: Diagnosis, Clinical Expectations, And Psychosocial Concerns, Madeline Alpar

Dissertations and Theses (Open Access)

Background: Ehlers-Danlos syndrome (EDS) is a highly variable, heritable connective tissue disorder. Hypermobile EDS (hEDS) is the most common subtype of EDS and has no identifiable underlying genetic etiology. Patients with clinical features of hEDS face a long diagnostic odyssey due to lack of genetic testing and wide clinical heterogeneity. Additionally, recent research has shown that genetic institutions limit evaluations for suspected hEDS, adding another barrier to care.

Methods: We developed an online patient survey to explore the diagnostic odyssey of hEDS for those who were diagnosed with or suspicious for hEDS. This survey included sections on demographics, diagnostic information …

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations and Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …

Multiparametric Magnetic Resonance Imaging Artificial Intelligence Pipeline For Oropharyngeal Cancer Radiotherapy Treatment Guidance, Kareem Wahid

Dissertations and Theses (Open Access)

Oropharyngeal cancer (OPC) is a widespread disease and one of the few domestic cancers that is rising in incidence. Radiographic images are crucial for assessment of OPC and aid in radiotherapy (RT) treatment. However, RT planning with conventional imaging approaches requires operator-dependent tumor segmentation, which is the primary source of treatment error. Further, OPC expresses differential tumor/node mid-RT response (rapid response) rates, resulting in significant differences between planned and delivered RT dose. Finally, clinical outcomes for OPC patients can also be variable, which warrants the investigation of prognostic models. Multiparametric MRI (mpMRI) techniques that incorporate simultaneous anatomical and functional information …

Uncovering Novel Mechanism Of Immune Modulation Of Invariant Natural Killer T Cells By Liposomal Α-Galactosylceramide, Alexandra S. Flegle

Dissertations and Theses (Open Access)

Invariant Natural Killer T cells (iNK-T cells) are a powerful regulatory immune cell that can recruit both innate and adaptive immune cells. Unlike conventional T cells (CD4⁺ and CD8α⁺), they recognize glycolipid antigens via the MHC-class-I like molecule, CD1d. A synthetically derived glycolipid from the marine sponge, Agelas mauritianus, alpha-Galactosylceramide (α-GalCer) potently activates iNK-T cells. Within a few hours after activation, iNK-T cells produce high quantities of T_H1 and T_H2 type cytokines, thus shape subsequent adaptive immunity towards inflammation (T_H1) or immune-suppression (T_H2). Structural modification of α-GalCer’s phytosphingosine …

Perceived Utility Of Genetic Carrier Screening In A Diverse Patient Population, Jack A. Colleran

Dissertations and Theses (Open Access)

Carrier screening assesses whether an individual may carry variants in select genes associated with autosomal recessive and X-linked inheritance. Recent American College of Medical Geneticists (ACMG) guidelines call for utilization of expanded screening that analyzes carrier status for up to hundreds of conditions. In these guidelines, clinical utility is based on alterations to reproductive decision-making. However, clinical utility study cohorts cited by these guidelines were largely white, highly educated, of high income, and were often receiving preconception counseling. There is a lack of research on the perspectives of patients from diverse backgrounds, whose perceptions may be more reflective of those …

The Impact Of Treatment With Palynziq® On Quality Of Life For Individuals With Pku, Teresa Heller

Dissertations and Theses (Open Access)

Management for phenylketonuria (PKU) has traditionally involved adhering to a strict low-protein diet to maintain phenylalanine (Phe) levels within the recommended range (μmol/L). The time commitment and financial, emotional, and social burdens of adhering to a restrictive diet, as well as the neurocognitive symptoms associated with elevated Phe levels, make it challenging to manage PKU and lead to reductions in quality of life. Palynziq^® is an enzyme substitution therapy used to lower blood Phe levels and liberate individuals with PKU from their restrictive diets. Previous studies have demonstrated the safety and efficacy of Palynziq^®, but our study …