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The Effect Of Antibiotics On Immune Cell Infiltration Of Colon In A Mouse Model Of Early Onset Colorectal Cancer, Valerie Hinsch

Theses and Dissertations

Early onset colorectal cancer (EOCRC) is an aggressive form of colorectal cancer diagnosed before the age of 50. While colorectal cancer cases in patients 50 years and older have been declining, EOCRC cases have been steadily increasing globally in the last few decades, and the cause is unknown. Many agents, called exposomes, have been associated with EOCRC based on their emergence and prevalence prior to and in parallel with the rise in EOCRC cases. Among these are antibiotics (Abx). Abx are indispensable in our fight against infectious diseases, however their overuse is becoming a global epidemic. They are prescribed globally, …

The Emerging Oral Pathogen, Filifactor Alocis, Modulates Antimicrobial Responses Of Primed Human Neutrophils., Ian J. Snider, Aruna Vashishta, Richard J. Lamont, Silvia M. Uriarte

The Cardinal Edge

Almost 50% of the adult population older than 30 years of age suffers from some form of periodontitis, a chronic inflammatory disease of the periodontal tissue caused by microbial subversion of the host immune response. Neutrophils are the most abundant leukocyte present in the oral mucosa. In periodontitis, periodontal pathogens have developed strategies to evade neutrophil antimicrobial responses and promote bacterial growth. Among these oral pathogens is Filifactor alocis which can modulate neutrophils’ antimicrobial responses by preventing phagosome maturation. During inflammation, neutrophils that reach the gingival tissue are primed by cytokines and chemokines. However, the response of primed human neutrophils …

The Phylogeny Predicts Potential New Sources Of Antibiotics From Plants, Malini Anna Prasad, Jeanmaire Molina

Discovery Day

The evolution and spread of antibiotic resistance has been the greatest threat to successful antibiotic treatment, and hence the driving force behind the search for new therapies. None of our modern pharmaceutical antibiotics have been developed from plants, albeit plants have been used since antiquity in traditional medicine to fight bacterial infections. We phylogenetically analyzed 138 plant species with antibacterial activity and found 5 plant families that are disproportionately important, with confamilials exerting similar antibacterial mechanisms, as expected due to common ancestry. Myrtaceae (guava family) was shown to inhibit quorum sensing, disrupting bacterial communication implicated in pathogenicity, due to its …

The Role Of Gardnerella In Bacterial Vaginosis And Facilitating Colonization By Neisseria Gonorrhoeae, Sydney Rose Morrill

Arts & Sciences Graduate Student Theses and Dissertations

Bacterial vaginosis (BV) is a condition of vaginal flora that affects about 1/3 of reproductive age women. The optimal vaginal microbiome is thought to be one dominated by Lactobacillus species. In the BV-positive microbiome, this lactobacillus-dominance is replaced by an outgrowth of diverse anaerobic bacteria. BV has been clinically linked to a number of negative health outcomes, including preterm birth, infertility, cervical dysplasia, and an increased risk of sexually-transmitted infections (STIs) such as gonorrhea. The underlying cause(s) of BV have been debated in the literature for over half a century. In 1955, it was first reported that a bacterium now …

Heterogeneity Of Human Tissue-Resident Lymphocytes, Natalia Jaeger

Arts & Sciences Graduate Student Theses and Dissertations

The immune system plays a critical role in maintaining tissue homeostasis and defending against pathogens. Recent discoveries have highlighted the significance of tissue-resident memory T cells (TRM) and Innate Lymphoid Cells (ILCs) in tissue immunity. TRM exhibit memory-like properties, persist long-term in various tissues, and express markers such as CD69, CD103, and transcription factors like Hobit and Blimp-1. Similarly, ILCs, considered the innate counterparts of T cells, are abundant at barrier organs and mucosal sites, sharing similar markers and transcriptional factors with TRM, and rapidly responding to insults. Unraveling the heterogeneity and function of tissue-resident lymphocytes is crucial for understanding …

Prevalence And Antibiotic Resistance Profile Of Secondary Bacterial Pneumonia And Bloodstream Infections Among Hospitalized Covid-19 Patients And Their Relation To Procalcitonin, Azhin D. Aziz, Adel K. Khider

Polytechnic Journal

Background and Objectives: in COVID-19 patients, secondary bacterial infections (SBIs) are a known complication of viral respiratory infections and are significantly associated with poorer outcomes.Our study aimed to determine the prevalence, clinical profile, antimicrobial resistance profile, and patient outcomes of secondary bacterial pneumonia and blood infections in COVID-19 hospitalized patients and their correlation with procalcitonin (PCT) levels.Method: During 7 months’ study, 260 clinical samples (blood and respiratory specimens) were collected from 130 hospitalized COVID-19 patients, of which 90 were from intensive care units (ICUs) and 40 from non-ICU departments, at six hospitals in Erbil city, Iraq. All samples were applied …

Computational Analysis Of Plasma Lipidomics From Mice Fed Standard Chow And Ketogenic Diet, Amy L. Seufert, James W. Hickman, Jaewoo Choi, Brooke A. Napier

Biology Faculty Publications and Presentations

Dietary saturated fatty acids (SFAs) are upregulated in the blood circulation following digestion. A variety of circulating lipid species have been implicated in metabolic and inflammatory diseases; however, due to the extreme variability in serum or plasma lipid concentrations found in human studies, established reference ranges are still lacking, in addition to lipid specificity and diagnostic biomarkers. Mass spectrometry is widely used for identification of lipid species in the plasma, and there are many differences in sample extraction methods within the literature. We used ultra-high performance liquid chromatography (UPLC) coupled to a high-resolution hybrid triple quadrupole-time-of-flight (QToF) mass spectrometry (MS) …

Identifying Sources Of Antibiotic Resistance Genes In The Environment Using The Microbial Find, Inform, And Test Framework, Corinne Wiesner-Friedman, Rachelle E. Beattie, Jill R. Stewart, Krassimira R. Hristova, Marc L. Serre

Biological Sciences Faculty Research and Publications

Introduction: Antimicrobial resistance (AMR) is an increasing public health concern for humans, animals, and the environment. However, the contributions of spatially distributed sources of AMR in the environment are not well defined.

Methods: To identify the sources of environmental AMR, the novel microbial Find, Inform, and Test (FIT) model was applied to a panel of five antibiotic resistance-associated genes (ARGs), namely, erm(B), tet(W), qnrA, sul1, and intI1, quantified from riverbed sediment and surface water from a mixed-use region.

Results: A one standard deviation increase in the modeled contributions of elevated AMR from bovine sources or land-applied waste sources [land application …

The Dangers Of Staphylococcus Aureus And Antimicrobial Resistance, Madison Pines

Graduate Student Dissertations, Theses, Capstones, and Portfolios

Methicillin-resistant Staphylococcus aureus (MRSA) is the etiological agent responsible for many problematic infections. The signs and symptoms of an infection caused by MRSA differ based on the route of transmission and type of infection. Staphylococcus aureus can secrete toxins that act as virulence factors and aid host invasion. Obesity, old age, being a health care worker, playing contact sports, living in a crowded place, hospitalization, recent antibiotic use, and HIV patients are more at risk of developing an infection caused by MRSA. An abundance of factors has contributed to antimicrobial resistance, like misuse of antibiotics in clinical and agricultural settings …

Developing A Safe And Effective Papillomavirus Screen To Be Used On College Students At A South Carolina University, Owen R. Smith, Nicole E. Frantz, Emily E. Bishop, Rahjai G. Thomas, Paul E. Richardson

Journal of the South Carolina Academy of Science

No abstract provided.

A Thesis On The Human Genetic Basis Of Severe Pneumococcal Infection In Papua New Guinea, Emma Catherine Walker

Arts & Sciences Graduate Student Theses and Dissertations

Pneumonia remains a major cause of childhood mortality, especially in under-resourced communities. The profound morbidity of pediatric pneumonia in Papua New Guinea (PNG) compels innovative approaches to ameliorate disease. While the high incidence of pneumonia has been ascribed to environmental factors, we here identify a heritable allele increasing risk of severe pneumonia. In a pilot study, whole exome sequencing reveals a single nucleotide variant (SNV) in coenzyme Q6 (COQ6), a mitochondrial enzyme essential for ubiquinone biosynthesis. Significant association of SNV homozygosity with pneumonia replicates in an independently recruited cohort (p=0.036). Mice homozygous for the murine variant exhibit increased mortality after …

Automated Processing Of Metabolomics Data For Population-Scale Studies, Ethan Stancliffe

Arts & Sciences Graduate Student Theses and Dissertations

The growth of untargeted metabolomic profiling technology has prompted the upstart of many large cohort studies. Metabolomics serves as an informative complement to other more established ‘omics (e.g., genomics, transcriptomics, proteomics). As a younger discipline, however, experimental and computational workflows are non-standardized and at times inadequate for large-scale studies. Two primary limitations in analysis of untargeted metabolomics data are 1) the poor performance and scalability of the algorithms applied to detect metabolite signals from the raw LC/MS data and 2) inefficient and arduous metabolite identification, which is the process of determining the biochemical structures that correspond to the detected LC/MS …

Cytokine Profiles In Peruvian Pinnipeds And Their Relationships With Environmental Stressors, Mykenzee L. Munaco

All HCAS Student Capstones, Theses, and Dissertations

Large colonies of two vulnerable, sympatric pinniped species, Peruvian fur seals (Arctocephalus australis Peruvian subpopulation; PFS) and South American sea lions (Otaria byronia; SASL), reside and reproduce in Punta San Juan, Peru (PSJ) where they are exposed to stressors such as environmental contaminants and El Niño-Southern Oscillation (ENSO) events. Cytokine concentrations can be indicative of an animal’s health and immune function by allowing for immunoresponse characterization as Th1 or Th2 dominant. Utilizing an archived pinniped plasma collection of samples from 2009-2019 (n=148), 13 cytokines were analyzed in PFS and SASL: GM-CSF, IFN-γ, KC-like, MCP-1, TNF-α, IL-2, IL-6, …

Distinct Roles For Ltα3 And Ltα1Β2 Produced By B Cells Contribute To Their Multi-Faceted Impact On Ileitis, Emma Claire Erlich

Arts & Sciences Graduate Student Theses and Dissertations

Crohn’s disease, one of the most common forms of inflammatory bowel disease, is marked by local intestinal inflammation. However, pathology in CD patients is not strictly limited to the gastrointestinal system, and almost 50% of CD patients exhibit extraintestinal manifestations of disease. Many, though not all, of these systemic pathologies are linked to intestinal inflammation and, thus, resolution of local gastrointestinal disease also ameliorates systemic disease. How the connection between local and systemic inflammation is mediated is not well understand, nor is why only some patients exhibit these extraintestinal manifestations of disease. Blocking dissemination of inflammatory signals generated in the …

Evaluating The Immunogenicity Of Colonization Proteins Of S. Pneumoniae For Identification Of Vaccine Candidates, Isidora Fereday

Theses and Dissertations

Streptococcus pneumoniae is typically an asymptomatic colonizer of the upper respiratory tract but can cause invasive disease in susceptible populations. Pneumococcal vaccines which are currently in use have failed to significantly reduce colonization by S. pneumoniae. To control invasive pneumococcal disease, novel strategies must be utilized. One such strategy is to reduce or eradicate colonization by pneumococcus. Supplementary vaccination with pneumococcal proteins important for colonization could serve to prime the immune system against these targets. This study serves as an initial step towards identification of crucial pneumococcal colonization proteins which may previously have been uncharacterized. Assessing the immune reactivity …

Roles Of Type I Interferon Signaling In Drug Resistant Mycobacterium Tuberculosis Infection, Suhas Bobba

Arts & Sciences Graduate Student Theses and Dissertations

Tuberculosis (TB) is a global health threat, with 10 million people developing active TB disease and a million deaths attributed to TB annually. Emergence of drug resistance in Mycobacterium tuberculosis (Mtb), the causative agent of TB, has led to half a million cases of drug resistant (DR) TB annually. Further, clinical reports suggest dysregulation and suppression of immune responses in DR TB patients as compared with DS TB patients. However, we do not understand how acquisition of drug resistance-conferring mutations can drive broad and systemic differences in immune responses of DR TB patients. We found that rpoB-H445Y a specific DR …

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …

Investigating How Sterol Transport Affects Survival Of The Pathogenic Fungus Cryptococcus Neoformans In Host-Like Conditions, Hau Lam Choy

Arts & Sciences Graduate Student Theses and Dissertations

Cryptococcus neoformans is an opportunistic fungal pathogen that has an enormous impact on global health and is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. With a mortality rate of 10-75%, cryptococcal meningitis results in over 100,000 deaths per year, comprising 18% of all AIDS-related deaths worldwide. These numbers emphasize the need to understand the basic biology and pathogenesis of this fungus. During infection, spores or desiccated yeast cells are inhaled, resulting in primary pulmonary infection. In immunocompetent hosts, these infections are asymptomatic and are either quickly cleared or remain latent. In immunocompromised patients, …

Dna-Encoded Chemical Libraries Yield Non-Covalent And Non-Peptidic Sars-Cov-2 Main Protease Inhibitors, Ravikumar Jimmidi, Srinivas Chamakuri, Shuo Lu, Melek Nihan Ucisik, Peng-Jen Chen, Kurt M Bohren, Seyed Arad Moghadasi, Leroy Versteeg, Christina Nnabuife, Jian-Yuan Li, Xuan Qin, Ying-Chu Chen, John C Faver, Pranavanand Nyshadham, Kiran L Sharma, Banumathi Sankaran, Allison Judge, Zhifeng Yu, Feng Li, Jeroen Pollet, Reuben S Harris, Martin M Matzuk, Timothy Palzkill, Damian W Young

Faculty, Staff and Students Publications

The development of SARS-CoV-2 main protease (Mpro) inhibitors for the treatment of COVID-19 has mostly benefitted from X-ray structures and preexisting knowledge of inhibitors; however, an efficient method to generate Mpro inhibitors, which circumvents such information would be advantageous. As an alternative approach, we show here that DNA-encoded chemistry technology (DEC-Tec) can be used to discover inhibitors of Mpro. An affinity selection of a 4-billion-membered DNA-encoded chemical library (DECL) using Mpro as bait produces novel non-covalent and non-peptide-based small molecule inhibitors of Mpro with low nanomolar Ki values. Furthermore, these compounds demonstrate efficacy against mutant forms of Mpro that …

Microglial Response To Glucocorticoids During Chronic Sleep Fragmentation, Christian Chelson

Masters Theses & Specialist Projects

Sleep is one of the body’s greatest and most basic needs. Chronic sleep loss (<6 hours a day) is linked to many cardiovascular issues, diabetes, and inflammatory conditions and has been shown to lower life expectancy. Obstructive sleep apnea (OSA) is a complication that causes sleep fragmentation in >8% of adults from developed countries, and many with OSA may be unaware of their condition. Having long-term OSA is linked to neuroinflammation caused by activated microglia in the brain, but the mechanics of this inflammation are not well understood. It is known that glucocorticoids, steroid hormones produced and released from the adrenal glands, have a suppressive effect on microglia. The purpose of this study is to explore the role that glucocorticoids have upon microglia activation induced by chronic sleep fragmentation (SF). C57BL/6J mice were …

Long-Term Spring Through Fall Capture Data Of Eptesicus Fuscus In The Eastern Usa Before And After White-Nose Syndrome, Molly Simonis, Lynn K. Hartzler, Joshua Campbell, Timothy C. Carter, Lisa Noelle Cooper, Katelin Cross, Katherine Etchison, Traci, R. Andrew King, Richard J. Reynolds, Yasmeen Samar, Michael Yasmeen, Sarah Stankavich, Gregory G. Turner, Megan A. Rúa

Biological Sciences Faculty Publications

Emerging infectious diseases threaten wildlife populations. Without well monitored wildlife systems, it is challenging to determine accurate population and ecosystem losses following disease emergence. North American temperate bats present a unique opportunity for studying the broad impacts of wildlife disease emergence, as their federal monitoring programs were prioritized in the USA throughout the 20 th century and they are currently threatened by the invasive fungal pathogen, Pseudogymnoascus destructans ( Pd ), which causes white-nose syndrome. Here we provide a long-term dataset for capture records of Eptesicus fuscus (big brown bat) across the eastern USA, spanning 16 years before and 14 …

Molecular Mechanisms That Regulate The Stress Response In A. Baumannii, Feroz Ahmed

Biology Dissertations - Archive

Acinetobacter baumannii is particularly problematic in hospital settings, where infections can occur in a range of tissues. This bacterium can endure extreme stress from various antimicrobial agents, biocides, host immune response etc. Not much is known about how these bacteria react to such high stress. A. baumannii also possesses a unique ability to inactivate lipooligosaccharide (LOS) biosynthesis, which is an essential molecule in most Gram-negative bacteria. LOS is enriched in the outer membrane and is the targeted by the last-resort antibiotic, colistin. LOS-deficient A. baumannii is highly resistant to the list-line antimicrobial. Previously, our lab discovered that a two-component system, …

Modeling The Egyptian Goose (Alopochen Aegyptiaca) Invasion; And Future Concerns, Percival Matzinger Marshall

Graduate Theses and Dissertations

In an increasingly interconnected world, the ecological and financial cost of invasive species is expected to continue to climb through the movement of exotic biota. Understanding the driving forces behind how a species invades, what environments promote their establishment, and what impacts they are likely to have on the invaded environment are all critical for management. Waterfowl, order Anseriformes, are one such category of invasive species of concern due to their popularity of accidental introduction, ease of movement, and propensity to affect both terrestrial and aquatic ecosystems. The Egyptian Goose (Alopochen aegyptiaca) is a native to the African continent that …

Functional Analysis Of Two Campoletis Sonorensis Ichnovirus Vinnexins In Drosophila Melanogaster, Peng Zhang

All Dissertations

Campoletis sonorensis Ichnovirus (CsIV) is produced by the ichneumonid parasitoid Campoletis sonorensis (the primary host). Female parasitoid wasps restrictedly replicate viruses in their ovaries and inject them into a larval lepidopteran (secondary host) during oviposition. This symbiotic virus of C. sonorensis is essential for successful parasitization. CsIV is characterized by having a large, segmented double-stranded DNA genome with a large number of genes, many of which are associated with one of five multigene families. The CsIV vinnexin gene family is one of them and has four members, including CsIV-vnxD and CsIV-vnxG. Vinnexins are homologues of insect Innexins, which form gap …

Understanding The Environmental And Genetic Influence On Fluctuating Asymmetry And Developmental Instability In Primates, Ashly N. Romero

Graduate Theses and Dissertations

This dissertation explored the impact of environmental factors on the development and perpetuation of fluctuating asymmetry (FA) and sought to understand the role evolution may play in the FA exhibited in two primate populations: the free-ranging Cayo Santiago rhesus macaques (Macaca mulatta) and the Southwest National Primate Research Center olive baboons (Papio hamadryas anubis). Demographic, ontogenetic, secular, external, and genetic factors were examined. Specifically, this dissertation investigated FA over all ontogenetic stages, across decades, between sexes, in association with ecological catastrophes, and with tooth pathology to try and tease apart factors that may influence FA and developmental instability. This dissertation …

Microsporidian Spores And The Integrin Binding Loop Of The Madam Protein Are Important For Integrin Signaling And Attachment To Host Cells, Cindy L. Barrett

Electronic Theses and Dissertations

Microsporidia are a distant fungal pathogen that have severe clinical consequences for the immunocompromised. Previous work identified a microsporidian pathogen protein termed Microsporidian ADAM or MADAM. This protein has close sequence homology to other ADAM proteins (A Disintegrin and Metalloproteinase) in two microsporidian species, Encephalitozoon intestinalis and E. cuniculi. ADAM proteins have a wide range of functions, including binding to integrins and host signaling. It is known that many pathogens manipulate integrins to invade host cells, and it is predicted that microsporidia are also exploiting this host target. Previous work with the MADAM protein demonstrated that this protein has a …

Heterogeneity Among Harveyi Clade-Specific Virulence Genes And Attribution Of These Genes To Possible Environmental Carriers, Cameron Brown

Biology Theses

In the face of global warming, waterborne pathogens are evolving rapidly and expanding geographically. The Vibrio Harveyi clade encompasses a number of human and aquatic organism pathogens, and due to their physiology, they may benefit from ongoing changes in the temperature, pH, and salinity of the global Ocean. With this, the Southeastern United States might become an accommodating environment for Harveyi clade species, and it is imperative to monitor for their abundance and distribution in the environment. A qPCR assay was developed for the detection and quantification of clade-specific virulence genes toxRvh, hly, toxR, luxR, srp, vhha, vhh, and vhp …

Comparing Four Indices Of Physiological Stress In An Urban-Adapted Songbird Between Urban And Rural Habitats, Rachel Kaplan

Master of Science in Integrative Biology Theses

Birds show tremendous variation in the extent to which different species tolerate life in urban habitats, yet it remains unclear why some species thrive while others cannot. My work explores possible phenotypes that make an urban-adapted species, the European starling (Sturnus vulgaris), so successful in both rural and urban areas. Literature on stress-urbanization relationship remains highly equivocal partly due to an array of different study systems being compared as well as to key methodological differences. The present study quantified metrics of both acute stress (i.e., stress-induced corticosterone and breath rate) and chronic stress (i.e., baseline corticosterone and total …

Cardiovascular Sars-Cov-2 Tropism And Immunopathology, Oleksandr Dmytrenko

Arts & Sciences Graduate Student Theses and Dissertations

Coronavirus Disease 2019 (COVID-19) is caused by SARS-CoV-2, a member of beta-coronaviridae family. This single-stranded RNA virus is transmitted through a respiratory route, binds to a host receptor ACE2 and enters lung pneumocytes, causing fulminant pulmonary disease in a subset of patients. In addition to pulmonary disease, SARS-CoV-2 can also lead to extrapulmonary manifestations, affecting brain, kidneys, blood vessels and heart. Cardiac complications are common in COVID-19 patients with both mild and severe clinical courses. However, it remains unclear which cardiac cell types are susceptible to SARS-CoV-2 and what the consequences of their infection are. In this work, I identified …

Long-Chain Fatty Acid Sensing And Catabolism In Commensal Escherichia Coli Impact Murine Gut Colonization, Tessa Carolina Cox

Theses and Dissertations

The gastrointestinal tract is home to trillions of microbes that collectively influence host physiology, immunity, nutrient metabolism, and infectious disease. The overgrowth of naturally-occurring Escherichia coli in the gut is a common signifier of microbiome dysfunction and occurs in many chronic diseases including obesity. Recent studies have shown that higher fat intake is associated with increased gut E. coli growth. However, it remains unknown whether gut E. coli utilize lipids such as long chain fatty acids (LCFAs) as carbon sources to colonize the mammalian gut. Therefore, the central objective of my dissertation was to utilize bacterial genetics and various mouse …