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Investigating Streptococcus Pneumoniae And Adenovirus Co-Infections Of Lung Epithelial Cells, Mark Nicholas Calabro

Browse all Theses and Dissertations

Co-infection is common among viruses and bacteria in the human respiratory system. Adenovirus (AdV) and Streptococcus pneumoniae are clinically relevant respiratory pathogens that cause morbidity and mortality in a variety of patient populations with the highest morbidity occurring among immunocompromised individuals, but also prevalent in infants and the elderly. Acute respiratory distress syndrome may become severe in healthy individuals when co-infection with S. pneumoniae and AdV occurs due to synergistic effects of the pathogens on the host. I hypothesized that S. pneumoniae infection decreases AdV transduction of airway epithelia. To test this hypothesis, we utilized the polarized immortalized airway epithelial …

Why Do Antibiotics Exist?, Fabrizio Spagnolo, Monica Trujillo, John J. Dennehy

Publications and Research

In the struggle with antibiotic resistance, we are losing. There is now a serious threat of moving into a postantibiotic world. High levels of resistance, in terms of both frequency and strength, have evolved against all clinically approved antibiotics worldwide. The usable life span of new clinically approved antibiotics is typically less than a decade before resistance reaches frequencies so high as to require only guarded usage. However, microbes have produced antibiotics for millennia without resistance becoming an existential issue. If resistance is the inevitable consequence of antibiotic usage, as has been the human experience, why has it not become …

Substrate Trafficking Within The Type Vii Secretion Systems Of Pathogenic Mycobacteria, Zachary A. Williamson

Theses and Dissertations--Molecular and Cellular Biochemistry

Tuberculosis (TB), primarily caused by infection of Mycobacterium tuberculosis (Mtb) in the lungs, is the deadliest infectious bacterial disease killing 1.5 million people annually. A major determinant of virulence is active secretion through three specialized type VII secretion (ESX) systems; ESX-1, ESX-3, and ESX-5. A large group of substrates exported by the ESX systems is the PE (Proline-Glutamine) and PPE (Proline-Proline-Glutamate) families of proteins, which are highly expanded in the pathogenic species of Mycobacteria and encompass over 7% of Mtb’s genome coding capacity. PE and PPE proteins interact together to form PE-PPE heterodimers, and are secreted through …

Investigating Streptococcus Pneumoniae And Adenovirus Co-Infections Of Lung Epithelial Cells, Mark Nicholas Calabro

Browse all Theses and Dissertations

Co-infection is common among viruses and bacteria in the human respiratory system. Adenovirus (AdV) and Streptococcus pneumoniae are clinically relevant respiratory pathogens that cause morbidity and mortality in a variety of patient populations with the highest morbidity occurring among immunocompromised individuals, but also prevalent in infants and the elderly. Acute respiratory distress syndrome may become severe in healthy individuals when co-infection with S. pneumoniae and AdV occurs due to synergistic effects of the pathogens on the host. I hypothesized that S. pneumoniae infection decreases AdV transduction of airway epithelia. To test this hypothesis, we utilized the polarized immortalized airway epithelial …

High Prevalence Of Pre-Existing Serological Cross-Reactivity Against Severe Acute Respiratory Syndrome Coronavirus-2 (Sars- Cov-2) In Sub-Saharan Africa, For Yue Tso, Salum Lidenge, Phoebe B. Peña, Ashley A. Clegg, John R. Ngowi, Julius Mwaiselage, Owen Ngalamika, Peter Julius, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective: Significant morbidity and mortality have occurred in the USA, Europe, and Asia due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whereas the numbers of infections and deaths in sub-Saharan Africa (SSA) have remained comparatively low. It has been hypothesized that exposure of the population in SSA to other coronaviruses prior to the COVID-19 pandemic resulted in some degree of cross-protection against SARS-CoV-2 infection and pathogenesis. We evaluated this hypothesis by comparing SARS-CoV-2 cross-reactive antibodies in pre-pandemic plasma samples collected from SSA and the USA.

Method: Pre-COVID-19 pandemic plasma samples from SSA and the USA were collected and tested by …

The 20th Anniversary Meeting Of The Rocky Mountain Virology Association, Joel Rovnak, Laura A. St Clair, Carley Mcalister, Chinemerem P. Ogbu, Jessica Smolenske, Randall J. Cohrs, Rushika Perera

Nebraska Center for Virology: Faculty Publications

Due to the COVID-19 pandemic and multiple devastating forest fires, the 2020 meeting of the Rocky Mountain Virology Association was held virtually. The three-day gathering featured talks describing recent advances in virology and prion research. The keynote presentation described the measles virus paradox of immune suppression and life-long immunity. Special invited speakers presented information concerning visualizing antiviral effector cell biology in mucosal tissues, uncovering the T-cell tropism of Epstein-Barr virus type 2, a history and current survey of coronavirus spike proteins, a summary of Zika virus vaccination and immunity, the innate immune response to flavivirus infections, a discussion concerning prion …

Chlorovirus Pbcv-1 Multidomain Protein A111/114r Has Three Glycosyltransferase Functions Involved In The Synthesis Of Atypical N-Glycans, Eric Noel, Anna Notaro, Immacolata Speciale, Garry A. Duncan, Cristina De Castro, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life. All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars. A combination of ge- netic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each. Here, in addition to in silico sequence …

Strategies Targeting Hemagglutinin As A Universal Influenza Vaccine, Brianna L. Bullard, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Influenza virus has significant viral diversity, both through antigenic drift and shift, which makes development of a vaccine challenging. Current influenza vaccines are updated yearly to in- clude strains predicted to circulate in the upcoming influenza season, however this can lead to a mismatch which reduces vaccine efficacy. Several strategies targeting the most abundant and im- munogenic surface protein of influenza, the hemagglutinin (HA) protein, have been explored. These strategies include stalk-directed, consensus-based, and computationally derived HA immunogens. In this review, we explore vaccine strategies which utilize novel antigen design of the HA protein to improve cross-reactive immunity for development …

Zika Virus Infection Induces Endoplasmic Reticulum Stress And Apoptosis In Placental Trophoblasts, Philma Glora Muthuraj, Prakask K. Sahoo, Madison Kraus, Taylor Bruett, Arun S. Annamalai, Aryamav Pattnaik, Asit K. Pattnaik, Siddappa N. Byrareddy, Sathish Kumar Natarajan

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV) infection to a pregnant woman can be vertically transmitted to the fetus via the placenta leading to Congenital Zika syndrome. This is characterized by microcephaly, retinal defects, and intrauterine growth retardation. ZIKV induces placental trophoblast apoptosis leading to severe abnormalities in the growth and development of the fetus. However, the molecular mechanism behind ZIKV-induced apoptosis in placental trophoblasts remains unclear. We hypothesize that ZIKV infection induces endoplasmic reticulum (ER) stress in the trophoblasts, and sustained ER stress results in apoptosis. HTR-8 (HTR-8/SVneo), a human normal immortalized trophoblast cell and human choriocarcinoma-derived cell lines (JEG-3 and JAR) were …

Molecular And Genetic Studies On A Sipd/Ipad-Related Virulence Spike Protein From Immune-Suppressive Particles Of A Drosophila Parasitoid, Carlo Miguel A. Sevilla

Dissertations and Theses

Parasitoid wasps are effective biological control agents that have evolved intricate host immune suppression strategies to overcome host immune defenses. The most important anti-parasite defense mechanism is encapsulation, where the host’s blood cells surround the wasp egg. In the Drosophila/Leptopilina host-parasitoid system, extracellular vesicles (EVs) are oviposited along with the wasp egg. The EVs possess spikes and contain hundreds of proteins, some of which enable wasp eggs to escape encapsulation by changing the morphology and function of hemocytes, or killing them. Previous studies have identified an abundant surface/spike protein (SSp40) from Leptopilina heterotoma EVs. While p40, a predicted …

Characterizing A Novel Cocksackievirus B3 Protease Mutant And Its Response To Polyamine Depletion, Bridget Hulsebosch

Master's Theses

Enteroviruses, including Coxsackievirus B3 (CVB3), are pervasive pathogens that cause significant disease, including cardiomyopathies. Unfortunately, no treatments or vaccines are available for infected individuals. We identified the host polyamine pathway as a potential drug target, as inhibiting polyamine biosynthesis significantly reduces enterovirus replication in vitro and in vivo. Here, we show that CVB3 is sensitive to polyamine depletion through the polyamine analog diethylnorspermidine (DENSpm) which enhances polyamine catabolism through induction of polyamine acetylation. We demonstrate that CVB3 acquires resistance to DENSpm via mutation of the 2A protease, which enhances proteolytic activity in the presence of DENSpm. Resistance to DENSpm occurred …

Review: Formation And Metabolic Function Of Coral Rubble Biofilms In The Reef Ecosystem, Andres Sanchez-Quinto, Luisa I. Falcon

Gulf and Caribbean Research

When coral dies, their calcareous skeletons constitute coral rubble in conjunction with the cementing activity of coralline algae and bacteria, creating a secondary reef structure which takes from years to decades to form. Healthy coral reefs differ from coral—rubble dominated reefs in microbial taxonomic composition and metabolic functional roles. The metabolisms of healthy reefs are dominated by autotrophic pathways, where carbon and nitrogen fixation dominate, while the metabolism of rubble—dominated reefs predominate in degradation of organic matter. Nitrogen fixation is 3 orders of magnitude lower in rubble—dominated reefs than in healthy reefs. Coral—rubble harbors a vast diversity of microbes that …

Chga-Depleted Urothelial Amp And Immune Response During Urinary Tract Infection, Theadora Jane Ceccarelli

Master's Theses

Women are 8 times more likely than men to experience a urinary tract infection (UTI) with up to 60% of women reporting a UTI in their lifetime. This significant healthcare burden is caused by the infection of uropathogenic Escherichia coli in the urinary tract. At this time, treatment is limited to antibiotic therapy, which is challenged by antibiotic-resistance. These factors make UTIs an NIH priority and are motivation for our research.CgA is a protein of the granin family co-released with catecholamines from neuroendocrine cells throughout the body. Pro-hormone convertases post-translationally cleave CgA into peptides, like catestatin, which can have antimicrobial …

Assessing The Role Of The Interaction Between Polyamines And Heparan Sulfate In Coxsackievirus B3 Viral Infection, Oreoluwa Omoba

Master's Theses

Non-polioenteroviruses are highly infectious viruses that typically cause mild asymptomatic cases but can cause severe disease such as aseptic meningitis and dilated cardiomyopathy. Coxsackievirus B3 (CVB3) is a member of this group and is prevalent in the United States and Eastern Asia. Viruses like CVB3 rely on the host cell for many molecules in order to replicate. One such set of molecules is the polyamines. Polyamines are small, positively charged molecules that play a role in a multitude of cellular processes including RNA/DNA stabilization, gene expression, translation, and regulating membrane fluidity. Previous studies have shown CVB3 relies on polyamines for …

Il-36g Cytokine Induction In Oral Epithelial Cells Triggered By Treponema Denticola And Their Role In Chronic Periodontitis, Christopher Blake

Theses and Dissertations

Periodontal disease is a polymicrobial disease affecting 10-15% of the population. Periodontal disease affects the quality of life by reducing mastication and potentially causing tooth loss. Periodontal disease is also linked to more severe, systemic diseases such as cardiovascular disease and rheumatoid arthritis. Development of the diseased state occurs when the plaque biofilm shifts from healthy to dysbiotic. The shift to a dysbiotic biome brings with it a shift in bacterial presence, specifically an increase in gram-negative bacteria, such as T. denticola. T. denticola is a gram-negative, anaerobic spirochete whose relationship with oral epithelial cells is poorly understood. Preliminary data …

A Review Of The Molecular Mediators Of Host-Baculovirus Interactions In Lepidoptera, Olivia Crouse

Honors Program Theses

Iowa farmlands occupy approximately 85% of its 35.7 million acres, and Iowa leads the United States in corn and soybean production, with an estimated 2.58 billion and 502 million bushels of corn and soybean produced in 2019, respectively. This successful trend in annual yields has span forty plus years and been consequential to the simultaneous implementation of agricultural- and science-based practices. Genetically modified corn and soybean crop varieties express genes from Bacillus thuringiensis (Bt) which encode insecticidal proteins that protect, with high specificity, against insect pests. While researchers continue to study the molecular mechanism(s) of Bt extensively, alternative environmentally safe …

Multistrain Hiv-1 Elimination: A Crispr-Cas9 And Theranostics-Based Approach, Jonathan Herskovitz

Theses & Dissertations

A critical barrier to achieving a functional cure for infection by human immunodeficiency virus type one (HIV-1) rests in the presence of latent proviral DNA integrated in the nuclei of host CD4+ T cells and mononuclear phagocytes. Accordingly, HIV-1-infected patients must adhere to lifelong regimens of antiretroviral therapy (ART) to prevent viral rebound, CD4+ T cell decline, and progression to acquired immunodeficiency syndrome (AIDS). Gene editing using clustered regularly interspersed short palindromic repeat (CRISPR)-Cas9 technology stands as one means to inactivate integrated proviral DNA. We devised a mosaic gRNA CRISPR-Cas9 system- TatDE- that targets viral transcriptional regulator genes tat / …

Impact Of Endangered Animal Protection Rights, Policies, And Practices On Zoonotic Disease Spread, Daniella Fedak-Lengel

Honors Projects

Building on field research in Costa Rica and Belize, this honors project analyzes environmental and endangered animal protection policies, rights, and practices in Central America and the Caribbean, and assesses the impact of veterinary science and biological research and practice, particularly conservation biology, on animal welfare concerns. Informed by the recent surge in awareness regarding zoonoses and zoonotic disease transmission, prevention and control, resulting from the current global pandemic of SARS-CoV-2, the project assesses the need for new and innovative types of collaboration, particularly involving conservation biologists, environmental scientists, public health experts, law and policy makers, and global trade and …

Climate Warming’S Alteration Of Host-Parasite Dynamics, Ting-Hsuan Wu

Binghamton University Undergraduate Journal

Parasites and pathogens have significant roles in host population control, and thus host-parasite interactions affect biodiversity. The important question reviewed in this paper is how changes in temperature due to climate change affect host-parasite interactions. There is mounting evidence that elevated temperatures have both beneficial and detrimental effects on parasites and independently on hosts. These independent changes result in altered host-parasite dynamics through various mechanisms. If elevated temperatures enhance parasite survival, risk of disease transmission among hosts is enhanced as well. This enhancement is dependent on temperature-induced shifts in the host lifecycle, as asynchrony in host and parasite development can …

Malaria, Microbes, And Mice: The Role Of The Gut Microbiota On The Immune Response To Plasmodium Infection And The Treatment Potential Of Microbiota Modulation., Morgan L. Waide

Electronic Theses and Dissertations

Plasmodium infection leads to over 200 million cases of malaria and 400,000 deaths worldwide each year. These deaths are largely in children under the age of five and pregnant women [1]. Caused by transmission of Plasmodium parasites by the female Anopheles mosquito, malaria poses a risk for over 40 percent of the world’s population [1]. Despite worldwide efforts to eradicate malaria leading to a decrease in malaria-associated mortalities in the early 2000s [2], growing resistance to the available antimalarials and the lack of an effective, long-lasting vaccine has caused this decrease to plateau in recent years [1, 3-6]. Furthermore, malaria …

Assessment Of Grain Safety In Developing Nations, Jose R. Mendoza

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Grains are the most widely consumed foods worldwide, with maize (Zea mays) being frequently consumed in developing countries where it feeds approximately 900 million people under the poverty line of 2 USD per day. While grain handling practices are acceptable in most developed nations, many developing nations still face challenges such as inadequate field management, drying, and storage. Faulty grain handling along with unavoidably humid climates result in recurrent fungal growth and spoilage, which compromises both the end-quality and safety of the harvest. This becomes particularly problematic where there is little awareness about health risks associated with poor …

Role Of Β-Glucan Structure In Dectin-1 Homo- And Hetero-Oligomerization In Innate Anti-Fungal Immunity, Eduardo U. Anaya

Biomedical Sciences ETDs

Dectin-1A is a C-type Lectin innate immunoreceptor that recognizes β-(1,3)-glucan, a structural component of Candida species cell walls. Dectin-1 has eight alternative splice isoforms including, A and B. Innate immunocytes can express one or both isoforms, but neither their relative responsiveness to β-glucan nor the potential for inter-isoform signaling cross-talk is well understood. In this study, we determine how the different structures of soluble β-glucans affect both isoforms and unravel how differences in glucan structure impact the earliest events in Dectin-1 signaling. Using quantitative microscopy techniques, we explored the role of glucan structure on Dectin-1A oligomerization, which is thought to …

Exploring The Niche Of Rickettsia Montanensis (Rickettsiales: Rickettsiaceae) Infection Of The American Dog Tick (Acari: Ixodidae), Using Multiple Species Distribution Model Approaches, Catherine A. Lippi, Holly Gaff, Alexis L. White, Heidi K. St. John, Allen L. Richards, Sadie J. Ryan

Biological Sciences Faculty Publications

The American dog tick, Dermacentor variabilis (Say) (Acari: Ixodidae), is a vector for several human diseasecausing pathogens such as tularemia, Rocky Mountain spotted fever, and the understudied spotted fever group rickettsiae (SFGR) infection caused by Rickettsia montanensis. It is important for public health planning and intervention to understand the distribution of this tick and pathogen encounter risk. Risk is often described in terms of vector distribution, but greatest risk may be concentrated where more vectors are positive for a given pathogen. When assessing species distributions, the choice of modeling framework and spatial layers used to make predictions are important. …

A Pharmacological Strategy Against African Sleeping Sickness, Wahaj Zuberi

Dissertations and Theses (Open Access)

Trypanosoma brucei is a parasitic eukaryote and is the causal agent of the disease known as African sleeping sickness, transmitted via the bite of a tsetse fly. If left untreated, the parasite ultimately crosses the blood-brain eventually leading to death. Currently there are 5 approved drugs used to treat it, each with toxic side effects and effective at specific disease stages. A more effective and less toxic drug candidate is highly sought after. The essential enzyme, dUTPase, is an excellent drug target in the parasite while utilizing S. cerevisiae as a model system.

dUTPase is essential in T. brucei (tbdUTPase), …

Comprehensive Survey Of The Litter Bacterial Communities In Commercial Turkey Farms, Bishnu Adhikari, Guillermo Tellez-Isaias, Tieshan Jiang, Brian Wooming, Young Min Kwon

Poultry Science Faculty Publications and Presentations

The importance of microbiota in the health and diseases of farm animals has been well-documented for diverse animal species. However, studies on microbiotas in turkey and turkey farms are relatively limited as compared to other farm animal species. In this study, we performed a comprehensive survey of the litter microbiotas in 5 commercial turkey farms in the Northwest Arkansas (H, M, V, K, and R farms) including one farm with positive incidence of cellulitis (R farm). Altogether 246 boot swabs were used for 16S rRNA gene profiling of bacterial communities. At phylum level, 11 major bacterial phyla (≥0.01%) were recovered. …

Drivers Of Rickettsial Pathogen Transmission And Spillover In Local Tick Populations In Southeastern Virginia, Alexandra Cumbie

Biomedical Sciences Theses & Dissertations

Cases of spotted fever group rickettsiosis are becoming more prevalent in the United States. In Virginia, there are three human-biting ticks which are largely responsible for the spread of rickettsial pathogens and the increase in disease cases. These species include Dermacentor variabilis, Amblyomma americanum, and Amblyomma maculatum; all of which are vectors of rickettsial agents to vertebrate hosts. These species are sympatric as adults and have the potential to share large and small mammal hosts. Their interactions on and off host and their associated rickettsiae were the focus of this dissertation work. Amblyomma americanum is the vector …

Copper And Cobalt Metal Conjugation Enhances Flaviviral Replication, And Denv/Zikv Caused Thrombocytopenia Suppresses Integrin Signaling, Shovan Dutta

Biomedical Sciences Theses & Dissertations

Vector control is a global concern, and effective strategies have been on the way. Among the many different strategies, insect repellents to protect us from blood-feeding arthropods are very common. Food processing or preservatives in food expose us to several chemicals associated with insect repellents, insecticides, and pesticides. Using metallic conjugation with plant extracts or essential oils has become a widespread strategy to increase their efficacy. But it is worth it to be aware that some of those metallic compounds like Cobalt or Copper upon conjugation with thiosemicarbazone ligands derived from Citral and 2-acetylethiazole at the center coordination enhance both …

Acute Ischemic Stroke As The Presenting Feature Of Covid-19 In The Young And Pregnant, Nermila A. Ballmick, Jiri F. Kubac, Hossein Akhondi

HCA Healthcare Journal of Medicine

Introduction: Coronavirus disease (COVID-19) is an emerging and rapidly evolving public health issue that has become globally widespread and an overwhelming pandemic. Clinical manifestations of the disease include asymptomatic carrier states, acute respiratory distress syndrome, and even multiorgan dysfunction. Here, we present a unique and rare case of an acute ischemic stroke (AIS) in an asymptomatic pregnant woman with no predisposing medical illnesses.

Discussion: An 18-year-old G2P1 African American woman at 7 weeks gestational age with no significant medical or family history presenting to the Emergency Department during the initial phases of the pandemic with complaints of new onset left …

Development Of Novel Methodology For The Molecular Differentiation Of Cryptosporidium Parvum Gp60 Subtypes Via High Resolution Melting Analysis, Jennifer K. O'Leary, Liam Blake, Gerard D. Corcoran, Roy D. Sleator, Brigid Lucey

Department of Biological Sciences Publications

Cryptosporidium species subtypes are generally identified via DNA sequencing of the gp60 gene tandem repeat motif region. Due to the immunogenic nature of its glycoprotein products, gp60 is subject to host selective pressures, genetic recombination and evolutionary processes that drive extensive polymorphism at this locus. The elucidation of the polymorphic nature of this gene has led to the current mainstay in Cryptosporidium subtyping nomenclature.

This study aimed to develop a real-time polymerase chain reaction based method utilising a post-PCR application, high resolution melting (HRM) analysis, in conjunction with the abovementioned gp60 nomenclature system, in order to differentiate between Cryptosporidium parvum …

Increasing Antibiotic Resistance In Shigella Bacteria In The United States, William J. Pharr

The Corinthian

Shigella bacteria cause half a million infections, 6,000 hospitalizations, and 70 deaths annually in the United States. These bacteria are of particular concern due to their high survivability, low infectious dose, and high adaptability. Cases of shigellosis from Shigella sonnei are becoming a more prevalent issue in the U.S. as the bacteria continues to develop higher resistance to today’s strongest antibiotics. Much of this resistance is connected to the exchange of genes between strains of Shigella due to insertion sequences (IS), intercontinental travel, and men who have sex with men (MSM). As a result of increased resistance, the use of …