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Identification Of Rickettsia Prowazekii Methionine Aminopeptidase Inhibitors And Development Of Thermal Shift Assays For Burkholderia Pseudomallei Ispf And Sars-Cov-2 3cl Protease, Ishpriya Sharma

Graduate Research Theses & Dissertations

There is a crucial need for new antibacterial agents to combat the increase in antibiotic resistance. Methionine aminopeptidase (MetAp) is an enzyme that removes the amino-terminal methionine residue from newly synthesized proteins, an important step in the maturation of proteins. As such, MetAp is a target for the development of antibacterial and anticancer agents. One such bacterial target is Rickettsia prowazekii (Rp), the causative agent of epidemic typhus. To discover new inhibitors of RpMetAp1, the MMV Malaria Box, which is a collection of 400 compounds with drug-like and probe-like compounds, was screened using a high throughput fluorescence-based RpMetAp1 enzyme inhibition …

Environmental Toxicants And Human B Cells: Insights From Crispr Editing And Genomic Sequencing, Clayton Allex-Buckner

Browse all Theses and Dissertations

The human immunoglobulin heavy chain gene locus (IGH) has two 3 prime regulatory regions (3’IGHRR), each containing three enhancers (hs3, hs1.2, hs4). In animal models, the 3’IghRR regulates IgH expression and class switch recombination (CSR) to different Ig isotypes. The 3’IGHRR hs1.2 enhancer in humans is polymorphic in that an invariant sequence (IS) can be repeated one to four times in tandem. The hs1.2 polymorphism is of interest due to its association with several human autoimmune disorders and its potential sensitivity to exogenous substances such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin). In mouse models, TCDD inhibits the hs1.2 enhancer and 3’IghRR …

Surveillance And Monitoring Of Amphibian Pathogens And Evaluating The Impacts Of An Associated Course-Based Undergraduate Research Experience (Cure), Jennifer Perez

EWU Masters Thesis Collection

Amphibians are a highly diverse class of vertebrates and crucial for natural ecosystems, inhabiting both aquatic and terrestrial environments at different life stages. However, amphibians are facing devastating declines largely due to the disease chytridiomycosis, caused by the fungal pathogens Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal). This disease can lead to population declines, biodiversity loss, and species extinction. However, resources to study and mitigate this disease are limited and an opportunity to assist in these efforts has been created in the form of a course-based undergraduate research experience (CURE). Chapter 1 of my thesis used Roger's Diffusion of Innovations …

Evaluating Efficacy Of Anti-Batrachochytrium Dendrobatidis Probiotic Treatment On Pacific Chorus Frogs (Pseudacris Regilla) At Current And Modeled Climate Change Temperatures, Autumn N. Holley

EWU Masters Thesis Collection

Amphibian populations are declining due to a variety of threats, including the chytrid fungal pathogen, Batrachochytrium dendrobatidis (Bd), the causative agent of the disease chytridiomycosis. Climate change and other stressors can have complicated interactions with amphibian disease. Some amphibian populations are less susceptible to chytridiomycosis due to factors such as symbiotic skin microbes that may inhibit Bd through secondary metabolites. There have been several attempts to develop probiotics from these symbiotic, antifungal bacteria to provide protection against Bd infection, but these studies have had mixed success. Our study evaluated anti-Bd bacteria isolated from the skin of Pacific chorus frogs (Pseudacris …

Ovarian Inflammation Mediated By Toll-Like Receptor 4 Increased Transcripts Of Maternal Effect Genes And Decreased Embryo Development, Alison F. Ermisch, Katie L. Bidne, Scott G. Kurz, Kerri A. Bochantin, Jennifer R. Wood

Department of Animal Science: Faculty Publications

Obese women are subfertile and have reduced assisted reproduction success, which may be due to reduced oocyte competence. We hypothesize that consumption of a high-fat/high-sugar diet induces ovarian inflammation, which is a primary contributor to decreased oocyte quality and pre-implantation embryo development. To test this hypothesis, C57BL/6 (B6) mice with a normal inflammatory response and C3H/HeJ (C3H) mice with a dampened inflammatory response due to dysfunctional Toll-like receptor 4 were fed either normal chow or high-fat/high-sugar diet. In both B6 and C3H females, high-fat/high-sugar diet induced excessive adiposity and hyperglycemia compared to normal chow-fed counterparts. Conversely, ovarian CD68 levels and …

Does Tssh Deletion In Paraburkholderia Bonniea Affect Its Symbiosis With Dictyostellum Discoideum?, Anna Chen

Honors Theses

Paraburkholderia are amoeba resistant, gram negative bacteria that form facultative symbiotic relationships with D. discoideum, a soil dwelling amoeba host. Three species of Paraburkholderia, P. agricolaris, P. hayleyella, and P. bonniea are able to persistently infect nonnative, or symbiont free, D. discoideum. These three species share a type III secretion system (T3SS) and type VI secretion system (T6SS) that is absent in other close relatives We hypothesized that the ability to persistently infect D. discoideum may be partially attributed to the T3SS and T6SS shared across the three species of Paraburkholderia.

The goal was to test the phenotypic effect of …

New Insights On Epidemiology Of Infectious Bronchitis Virus In Iran By Comparing Two Genotyping Methods, Arash Ghalyanchilangeroudi, Hossein Hosseini, Zahra Ziafati Kafi, Naser Sadri, Ali Hojabr Rajeoni, Hamideh Najafi

Turkish Journal of Veterinary & Animal Sciences

Different genotypes of infectious bronchitis virus (IBV) in poultry are circulating worldwide. The most efficient classification system for IBV genotypes is based on the complete sequencing of S1 gene, and the target organ can be trachea, kidney, oviduct, lung, esophagus, proventriculus, intestine, liver, spleen, bursa, cecal tonsils, cloaca, and testis. In Iran, IBV genotyping is usually performed by partial sequencing of S1 gene, and the trachea is often selected for sampling. This study applies a different genotyping method, and compares the results with the routine method of genotyping. Samples were collected from the trachea and kidneys of 50 broiler flocks …

Hmgb2 Regulates The Differentiation And Stemness Of Exhausted Cd8+ T Cells During Chronic Viral Infection And Cancer, Emily N. Neubert, Julia M. Derogatis, Sloan A. Lewis, Karla M. Viramontes, Pedro Ortega, Monique L. Henriquez, Rémi Buisson, Ilhem Messaoudi, Roberto Tinoco

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chronic infections and cancers evade the host immune system through mechanisms that induce T cell exhaustion. The heterogeneity within the exhausted CD8⁺ T cell pool has revealed the importance of stem-like progenitor (Tpex) and terminal (Tex) exhausted T cells, although the mechanisms underlying their development are not fully known. Here we report High Mobility Group Box 2 (HMGB2) protein expression is upregulated and sustained in exhausted CD8⁺ T cells, and HMGB2 expression is critical for their differentiation. Through epigenetic and transcriptional programming, we identify HMGB2 as a cell-intrinsic regulator of the differentiation and maintenance of Tpex cells during …

Can Host Traits And Environmental Conditions Predict Helminth Fecundity And Length?, Finley Melnikoff

Pitzer Senior Theses

Helminths are some of the most common parasites in the world, infecting anything from humans to plants to mice. These parasites can play a massive role in determining a host's fitness and ultimately can have consequences on their body condition, reproductive ability, and infection transmission potential. Many factors influence the potential burden helminths have on their hosts–from host traits to environmental conditions–yet helminth fecundity and length have been studied very little in relation to these factors. Helminth fecundity–or how many eggs each female worm has in its ovaries–determines the transmission of the parasite, and helminth length is correlated with fecundity, …

Profiling The Cell Wall Polysaccharides Of Hemp (Cannabis Sativa L.) Inflorescence And Hempseed And Exploring Their Application As Ruminant Feed Ingredients, Miranda Agbana

Theses and Dissertations--Animal and Food Sciences

Hemp (Cannabis sativa L.) is used in the United States as a source of CBD oil, fiber, and grain. While hempseeds are consumed whole or as dehulled hemp hearts, hempseed oil is also a desirable seed oil in human nutrition. The process of collecting hempseed oil leaves behind hempseed cakes that are abundant in protein and fiber. Feeding of hempseed cakes to animals, including ruminants, has only initially been explored. Extraction of CBD from hemp inflorescences generates organic waste that may find a second purpose as a fiber feed for cattle. Little is known about the exact fiber composition …

Monoclonal Antibody Therapy Of Breastfeeding Patient Infected With Sars-Cov-2: A Case Report, Nicole E. Marshall, Madison B. Blanton, Brianna M. Doratt, Delphine C. Malherbe, Monica Rincon, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Introduction: Although safety data demonstrated the efficacy and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination for all individuals over 6 months of age, including pregnant and breastfeeding individuals, optimal treatment courses for symptomatic pregnant and lactating individuals infected with SARS-CoV-2 remain to be defined. Case Description: A coronavirus disease 2019 (COVID-19)-vaccinated breastfeeding woman received anti-SARS-CoV-2 monoclonal antibody treatment casirivimab–imdevimab 5 days after diagnosis of a symptomatic breakthrough SARS-CoV-2 infection. Results and Conclusions: The patient did not present with obvious defects in innate or adaptive cellular subsets, but compared with controls had minimal maternal antibody response to recommended …

Mild/Asymptomatic Covid-19 In Unvaccinated Pregnant Mothers Impairs Neonatal Immune Responses, Brianna M. Doratt, Suhas Sureshchandra, Heather E. True, Monica Rincon, Nicole E. Marshall, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Maternal SARS-CoV-2 infection triggers placental inflammation and alters cord blood immune cell composition. However, most studies focus on outcomes of severe maternal infection. Therefore, we analyzed cord blood and chorionic villi from newborns of unvaccinated mothers who experienced mild/asymptomatic SARS-CoV-2 infection during pregnancy. We investigated immune cell rewiring using flow cytometry, single-cell RNA sequencing, and functional readouts using ex vivo stimulation with TLR agonists and pathogens. Maternal infection was associated with increased frequency of memory T and B cells and nonclassical monocytes in cord blood. Ex vivo T and B cell responses to stimulation were attenuated, suggesting a tolerogenic state. …

Assessing The Relationship Between Binding Kinetics And Subcellular Protection Of Ribosomes By Single-Domain Antibodies, Mara Bureau

Legacy Theses & Dissertations (2009 - 2024)

Assessing the ability of VHHs to protect ribosomes from the depurination activity of Ricin toxin’s(RT) enzymatic subunit, RTA, can provide insights regarding binding placement, epitopes of interest and role of affinity in neutralization is critical for the development of anti-toxin countermeasures. Determining the level of correlation between binding strength, binding location and elicited protection can be useful for future and ongoing research. Ricin is easily manufactured and considered one of the most toxic biological agents known. Without an approved vaccine, continued research to design and optimize therapeutic countermeasures is essential. Over the past decade single-domain antibodies (VHHs) have been recognized …

Refugia From White-Nose Syndrome: Ecology And Behavior Of Northern Myotis Coastal Populations, Samantha Hoff

Legacy Theses & Dissertations (2009 - 2024)

Recent increases in anthropogenic environmental change have been directly linked to the global loss of biodiversity and are a primary driver of disease emergence in wildlife populations. Infectious diseases interact with other threats to cause population declines and changes in community composition, potentially resulting in local or global extinctions. Yet, outcomes are variable across the landscape, leading some host populations to persist at low numbers. One of the biggest challenges in conserving species threatened by disease is determining whether persisting populations can remain viable into the future once they have been driven to low abundance. White-nose syndrome (WNS) is one …

Climatic Stress Decreases Tick Survival But Increases Rate Of Host-Seeking Behavior, Caleb Nielebeck, Sang Hyo Kim, Antonio Pepe, Lucian Himes, Zachary Miller, Sophia Zummo, Mary Tang, Javier D. Monzón

All Faculty Open Access Publications

Ticks are vectors of many diseases and are expanding in geographic distribution. However, how ticks will fare in their new environments, where they may experience stressful climatic conditions at the expansion front, remains unclear. Since there is a trade-off in ticks between behaviors that promote longevity and behaviors that promote reproduction, we hypothesized that extreme climatic stress reduces the survivorship of ticks but increases the frequency of tick host-seeking behavior, or questing. Here, we used a novel method to simulate climatic stress on individual ticks of three species—Amblyomma americanum, Dermacentor variabilis, and Ixodes scapularis—to evaluate their survival, physiology, and questing …

The Effect Of Larval Competition On Adult Life History Traits And The Immune Response Of Adult Cat Fleas (Ctenocephalides Felis), Piper N. Zellner, Lisa D. Brown

Honors College Theses

In holometabolous insects, conditions during the larval stage can affect the adult stage. For instance, in mosquitoes, reduced larval food and high density can make adults more susceptible to infection. Fleas (Siphonaptera), like mosquitoes, go through complete metamorphosis and have adult stages that exclusively feed on the blood of vertebrates, including humans. However, flea larvae have chewing mandibles and rely on nutrients from dried fecal matter containing vertebrate blood proteins. Their limited mobility and unique nutritional needs confine their development to specific areas, likely leading to frequent larval competition in natural conditions. Yet, the influence of larval density on the …

Elafibranor Modulates Ileal Macrophage Polarization To Restore Intestinal Integrity In Nash: Potential Crosstalk Between Ileal Il-10/Stat3 And Hepatic Tlr4/Nf-Κb Axes, Andrew Hakeem, Mohamed M. Kamal, Rasha A. Radwan, Basma A. Abdelrahman, Olfat A. Hammam, Mohey M. Elmazar, Aiman S. El-Khatib, Yasmeen M. Attia

Pharmacy

Experimental and clinical evidence implicate disrupted gut barrier integrity in provoking innate immune responses, specifically macrophages, towards the progression of non-alcoholic steatohepatitis (NASH). Peroxisome proliferator-activated receptors (PPARs), a subset of the nuclear receptor superfamily, act to fine-tune several metabolic and inflammatory processes implicated in NASH. As such, the current study was carried out to decipher the potential role of dual PPAR α/δ activation using elafibranor (ELA) on ileal macrophage polarization (MP) and its likely impact on the liver in a NASH setting. To achieve this aim, an in vitro NASH model using fat-laden HepG2 cells was first used to validate …

Redescription Of Adults And First Description Of The Larva Of Haemaphysalis (Rhipistoma) Adleri Feldman-Muhsam, 1951 (Acari: Ixodidae), Parasite Of Carnivorans In Western Asia, Cole Anderson

Honors College Theses

The adult ticks of Haemaphysalis (Rhipistoma) adleri Feldman-Muhsam, 1951 (Acari: Ixodidae) are redescribed and the larva of this species is described for the first time here. The adults of H. adleri that we studied were collected from various canid, felid and hyaenid carnivorans (Carnivora: Canidae, Felidae, Hyaenidae) as well as a hedgehog (Erinaceomorpha: Erinaceidae) in Iraq, Israel and West Bank. The males, females and larvae of H. adleri can be differentiated from Haemaphysalis (Rhipistoma) species occurring in the Palearctic portion of West Asia and Egypt as well those in the H. asiatica subgroup by the length of idiosomal …

Presumptive Hepatogenous Photosensitization In Beef Cattle Winter Grazing A Cover Crop Containing Brassica Spp. Turnips, Matthew M. Hille, Scott A. Fritz, Breanna C. Brown

School of Veterinary and Biomedical Sciences: Faculty Publications

Over a period of ~2 wk, 5 adult beef cows developed severe necrotizing skin lesions on the face and neck shortly after being moved to a field with a cover crop of Brassica spp. turnips. We describe here the clinical signs, hematology, and serum chemistry results, as well as gross and histopathologic findings, from this outbreak. We made a presumptive diagnosis of Brassica-associated liver disease (BALD) based on the similarities in the history and diagnostic findings observed with previously reported cases of BALD from elsewhere in the world. BALD has not been reported previously in cattle in North America, …

Diversity Of Antimicrobial Peptides In Silkworm, Pooja Makwana, Kamidi Rahul, Katsuhiko Ito, Bindu Subhadra

Faculty Publications - Biological Sciences

Antimicrobial resistance is a phenomenon that the present-day world is witnessing that poses a serious threat to global health. The decline in the development of novel therapeutics over the last couple of decades has exacerbated the situation further. In this scenario, the pursuit of new alternative therapeutics to commonly used antibiotics has gained predominance amongst researchers across the world. Antimicrobial peptides (AMPs) from natural sources have drawn significant interest in the recent years as promising pharmacological substitutes over the conventional antibiotics. The most notable advantage of AMPs is that microorganisms cannot develop resistance to them. Insects represent one of the …

The Relationship Between Parasite Infection, Body Condition, And Migration In White-Crowned Sparrows And California Towhees, Madeline Galbraith

CMC Senior Theses

Long-distance animal migration plays a large role in the spread of infectious disease, potentially causing an increase or a decrease in infection. These outcomes can be serious, as infection has the ability to induce a variety of effects on the host, all which may impact their overall health. The consequences of infection on a host can be measured using body condition. Changes to an individual’s body condition are central to the mechanisms involved in migration’s ability to both increase (ex: susceptibility) and decrease infection (ex: migratory culling). Therefore, when assessing potential migratory effects, it is important to consider relationships between …

Visualization And Characterization Of The Immunological Synapse Between Chlorotoxin Chimeric Antigen (Cltx-Car) Redirected T Cells And Targeted Glioblastoma Tumors, Arianna Livi

CMC Senior Theses

Chimeric Antigen Receptor T (CAR-T) cells have demonstrated anti-tumor activity against aggressive and invasive cancers such as glioblastoma (GBM); however, clinical response rates remain low in clinical trial studies. Tumor heterogeneity and tumor microenvironment conditions pose significant challenges for treatment of GBM, thus continuous optimization of CAR-T cell therapies and identification of novel, widely expressed, and highly specific GBM antigens are vital to better patient outcomes. A newly developed CAR-T cell construct incorporating chlorotoxin (CLTX) as the targeting domain exhibited broad GBM-targeting capabilities and elicited potent cytotoxic effects during preclinical studies and is currently being tested in a phase I …

The Effects Of Nausea And Vomiting On Mother And Child, Mayane Bensoussan

The Science Journal of the Lander College of Arts and Sciences

Nausea and vomiting are common side effects that can occur during pregnancy. On one hand, it can lead to its severe form called hyperemesis gravidarum, which can lead to hospitalization for electrolyte imbalances, dehydration, muscle weakness, or arrhythmias. On the other hand, nausea and vomiting may be an indication of a statistically healthier fetus. Benefits of maternal nausea and emesis to the developing fetus include improved neural development, decreased risk for congenital heart defects, and decreased incidence of miscarriages. Additionally, benefits to the mother include decreased risk for lung, cervical, and rectal cancer. The mothers also had an overall decreased …

Examining The Immune Regulation Of Nlrp12 Through Novel Protein Interactions, Catherine Rippe

Graduate Theses/Dissertations

NOD-like receptors (NLRs) are intracellular proteins that play an important role in the regulation of the innate immune response to pathogens. Since being identified, various functions for NOD-like receptor pyrin domain containing 12 (NLRP12) have been suggested. It has been shown to negatively regulate the inflammatory response through canonical and noncanonical NF-kB signaling pathways, control tumorigenesis and gut homeostasis and exacerbate inflammation through the formation of a multi-protein complex called an inflammasome. Due to the varying roles established for NLRP12, the mechanisms by which it functions remain poorly understood. In this study, I sought to confirm a novel protein-protein interaction …

Cul3 Negatively Regulates Nlrp12-Mediated Inhibition Of The Canonical Nf-Κb Signaling Pathway, Inyeong Lee

Graduate Theses/Dissertations

Nod-like receptor family pyrin domain-containing protein 12 (NLRP12) is mainly known for its inhibitory function on NF-κB signaling in innate immune cells, and more recently, for its ability to regulate chemokine signaling and ubiquitination of the immune receptor RIG-I. Through a yeast 2-hybrid screen, the Lupfer lab previously discovered that NLRP12 interacts with other ubiquitin-associated proteins including Cullin 3 (CUL3) and RING finger protein 2 (RNF2). This research was conducted to mainly investigate the interaction between NLRP12 and CUL3 in human cells and examine the role in regulating NF-κB signaling. Previously, co-immunoprecipitation, followed by western blot analysis, and confocal microscopy …

Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas

Graduate Theses/Dissertations

The first line of defense against bodily insults, like pathogen invasion, is the innate immune system. Innate immunity sets in motion countless cascades that result in inflammation. Inflammation simultaneously affects multiple biological processes like metabolism and gene expression. Males and females react differently to inflammation. To understand both molecular and physiological sex differences in inflammation, we examined how inflammation affects gene expression and glucose metabolism. Adenosine deaminase acting on RNA (ADAR1) is upregulated by inflammation and catalyzes RNA editing, a process where nucleotides encoded by the genome are modified. ADAR1 also controls the innate immune reaction by decreasing activity of …

Influence Of Cell Cycle On Aim2 Inflammasome Activation, Ashok Kumar Dubey

Graduate Theses/Dissertations

A cell cycle's progression has a significant role in the development of a disease. All the signaling pathways and inflammatory reactions are maintained in a healthy mode if cell cycle checkpoints are precisely regulated and kept in homeostasis. AIM2 inflammasome is a cytoplasmic double-stranded DNA sensor. Upon activation, it elicits an inflammatory reaction with the release of pro-inflammatory cytokines such as IL-1β and IL-18 and they are cleaved by the proteases, Caspase-1 from their inactive form. Also, the AIM2 inflammasome helps in regulating cell division and inhibits cell proliferation; thus, leading to a cell death called pyroptosis. Here, I examined …

The Covid-19 Pandemic And Its Influence On The Human Immune System, Nicole L. Riha

Undergraduate Honors Theses

COVID-19 rapidly infected the world, and scientists continue to research how the disease spread and killed as many as it did by analyzing how it affects the human immune system and referring to past pandemics. Since the pandemic is ongoing, scientists do not fully understand how the virus works and if lockdowns were effective. Nevertheless, a discussion on what is known about COVID-19's influence on the human immune system is needed. With an understanding of the COVID-19 pandemic, scientists can make more effective treatments for COVID-19 and learn how to manage future pandemics.

Pharmaceuticals From Natural Products: The Utility Of The Phylogeny, Shaimaa Magdy Saad

Selected Full-Text Master Theses 2021-

About 60% of approved drugs during the last 30 years are either directly or indirectly from natural products. Previous studies have shown that the phylogeny has predictive utility in drug discovery. In this study the pharmacological applications of various naturally-derived drugs were mapped on the phylogeny reconstructed from DNA sequences of the source organisms to decipher phylogenetic patterns that may facilitate drug discovery. A multi-step approach was employed starting with a literature search to compile a comprehensive list of pharmaceutical drugs derived from natural sources. A phylogeny was reconstructed from the source organisms and their pharmacological uses mapped on the …

Experiences With Covid-19 Stress Among Hispanic/Latino Farmworkers, Brenda Berumen-Flucker, Hadiza Galadima, Sylvia Shangani, Michele Kekeh, Muge Akpinar-Elci

Community & Environmental Health Faculty Publications

BACKGROUND: Hispanics/Latinos, particularly those that identify as foreign-born, are overrepresented in the agricultural sector in the U.S. Over the course of the COVID-19 pandemic, this subpopulation of farmworkers was recognized as an invaluable group of essential workers unable to implement COVID-19 protections.

METHODS: Previously validated COVID-19 stress scale measures were identified, adapted, and translated to collect COVID-19 stress data from Hispanic/Latino agricultural workers in two heavily agricultural counties in northeastern North Carolina. Participants were recruited using purposive convenience sampling. Data collection took place from June to November of 2021.

RESULTS: The majority of Hispanic/Latino agricultural workers surveyed reported experiencing worries …