Digital Commons Network^™

Phase 1a Clinical Study For Q-Griffithsin Intranasal Spray For Prevention Of Coronavirus, Megan Bezold, Kenneth Palmer, Nobuyuki Matoba, Elizabeth Cash

Posters-at-the-Capitol

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus that causes acute respiratory disease with possible long-term complications, known as coronavirus disease 2019 (COVID-19). Griffithsin (GRFT; including the oxidation-resistant variant Q-GRFT used in this study) is an algal carbohydrate-binding protein exhibiting antiviral effects against many enveloped viruses, including all major variants of SARS- CoV-2 reported to date. Q-GRFT has been recombinantly manufactured in Nicotiana benthamiana plants, thoroughly purified, and formulated as an intranasal spray designed to be developed as a non-vaccine broad-spectrum prophylactic product for acute use. This is the first-in-human, randomized, double-blind, placebo-controlled study. The …

A Dynamical System Model Of Dengue Transmission For Rio De Janeiro, Brazil, Gregory Schmidt, Benjamin Whipple, Vinodh Chellamuthu, Xiaoxia Xie

Spora: A Journal of Biomathematics

The dengue virus is a serious concern in many parts of the world, including Brazil. As data indicates, a prominent vector for dengue is the mosquito Aedes aegypti. By using the dengue incidence records from the Brazilian SINAN database, we estimate the population of A. aegypti within the city of Rio de Janeiro. Using historical climate data for Rio de Janeiro and the computed population estimates, we extend an existing model for the population dynamics of mosquitoes to incorporate precipitation in aquatic stages of development for A. aegypti.

Molecular Regulation Of The Salicylic Acid Hormone Pathway In Plants Under Changing Environmental Conditions, Christina A. M. Rossi, Eric J. R. Marchetta, Jong Hum Kim, Christian Castroverde

Biology Faculty Publications

Salicylic acid (SA) is a central plant hormone mediating immunity, growth, and development. Recently, studies have highlighted the sensitivity of the SA pathway to changing climatic factors and the plant microbiome. Here we summarize organizing principles and themes in the regulation of SA biosynthesis, signaling, and metabolism by changing abiotic/biotic environments, focusing on molecular nodes governing SA pathway vulnerability or resilience. We especially highlight advances in the thermosensitive mechanisms underpinning SA-mediated immunity, including differential regulation of key transcription factors (e.g., CAMTAs, CBP60g, SARD1, bHLH059), selective protein–protein interactions of the SA receptor NPR1, and dynamic phase separation of the recently identified …

Serving Two Masters: Conflicts Between Physician Employment Contracts And The Physician's Duty Of Care, Steven L. Hendler, M.D.

Annals of Health Law and Life Sciences

No abstract provided.

Alcohol Consumption And Its Effects On The Liver, Eveline Weinreb

The Science Journal of the Lander College of Arts and Sciences

Thousands of people die each year in the United States from alcohol related deaths. Why does the metabolism of alcohol cause severe damage to the body? Ethanol enters the body in the form of wine, and other alcoholic beverages and travels through the digestive system and then to the liver where it is metabolized. There are a series of steps involved in the breakdown of ethanol, and toxic byproducts are formed such as reactive oxygen species (ROS). These oxygen radicals can lead to damaged deoxyribonucleic acid (DNA) and to the formation of adducts. Chronic alcohol consumption can lead to liver …

A Novel Therapeutic Approach To Regulate Carex8 Protein Expression Through E6-Conjugated Cell Penetrating Peptides, Jared D. Compaleo

Browse all Theses and Dissertations

Adenovirus is a human pathogen that causes cold like symptoms in healthy individuals, which could be lethal in pediatrics and the immunocompromised. In polarized epithelia, adenovirus uses the eight-exon isoform of the Coxsackievirus and Adenovirus Receptor (CAREx8) on the apical surface, to facilitate infection. CAREx8 protein expression level is regulated by the scaffolding protein MAGI-1, using two of its PSD95/Dlg-1/ZO-1 (PDZ) domains: PDZ2 and PDZ4. We previously showed that CAREx8 is degraded after interaction with PDZ4 and rescued following interaction with PDZ2. We then developed a PDZ2 binding decoy molecule (E6) that blocks the interaction between CAREx8 and PDZ2, which …

The Role Of Schwann Cells In Nerve Injury: Forskolin-Mediated Camp Activation Upregulates Tnfα Expression Despite Nf-Κb Downregulation In Lps-Treated Schwann Cells, Caitlyn E. Henry, Angela L. Asirvatham Ph.D.

Student Research Poster Presentations 2023

Although Schwann cells are known to play a role in axonal regeneration following nerve injury and inflammation, the exact mechanism is unknown. This study explores two potential mechanisms: the NF-κB and cAMP pathways. The NF-κB pathway produces cytokines, such as TNFα, to regulate inflammation, whereas the cAMP pathway is anti-inflammatory and regulates Schwann cell proliferation via AKAP95 and cyclin D3. Although it is well-known that NF-κB and cAMP are involved in inflammation, not much is known regarding the effects of forskolin-mediated cAMP activation on LPS-mediated NF-κB activation in Schwann cells. In this study, RT4-D6P2T immortalized rat Schwann cells were treated …

Local-Scale Impacts Of Water Hyacinth On Water Quality In A Hypereutrophic Lake, J. R. Corman, A. Z. Roegner, Z. Ogari, T. R. Miller, C. M. Aura

School of Natural Resources: Documents and Reviews

No abstract provided.

Comparing The Performance Of A Targeted Pull-Down Assay To Shotgun Sequencing For Improving Respiratory Infectious Disease Surveillance, Monica R. Christian

Browse all Theses and Dissertations

Current surveillance focuses on well characterized pathogens such as influenza. Since 2000, there have been multiple outbreaks of respiratory disease. These outbreaks have demonstrated the need for robust and collaborative global efforts to identify, monitor, and contain novel respiratory viruses. This study aims to improve the ability of public health agencies to monitor and respond to respiratory disease outbreaks. Using five respiratory pathogens, this study compares a molecular capture technology from Twist Biosciences to the shotgun sequencing approach of whole transcriptome amplification (WTA, Qiagen) with the goal of determining which method is most effective using cost, usability, and sequencing quality …

Fair Domestic Allocation Of Monkeypox Virus Countermeasures, Govind C. Persad, R. J. Leland, Trygve Ottersen, Henry S. Richardson, Carla Saenz, G. Owen Schaefer, Ezekiel J. Emanuel

Sturm College of Law: Faculty Scholarship

Countermeasures for mpox (formerly known as monkeypox), primarily vaccines, have been in limited supply in many countries during outbreaks. Equitable allocation of scarce resources during public health emergencies is a complex challenge. Identifying the objectives and core values for the allocation of mpox countermeasures, using those values to provide guidance for priority groups and prioritisation tiers, and optimising allocation implementation are important. The fundamental values for the allocation of mpox countermeasures are: preventing death and illness; reducing the association between death or illness and unjust disparities; prioritising those who prevent harm or mitigate disparities; recognising contributions to combating an outbreak; …

Lead And Mercury Exposure In Eastern Whooping Cranes: Cause For Concern?, Barry K. Hartup, Anne E. Lacy, Hillary L. Thompson

Proceedings of the North American Crane Workshop

The dietary uptake of lead (Pb) and mercury (Hg) risks limiting population growth of reintroduced whooping cranes (Grus americana) in the Eastern Migratory Population (EMP). We evaluated these potentially toxic trace elements in blood and marginal covert feathers of wild-hatched juvenile and adult cranes sampled in the Wisconsin breeding range between 2016 and 2023. Samples were obtained at live capture events, and analyzed using inductively coupled plasma/mass spectrometry for Pb and Total Hg (THg). Blood Pb concentrations from adults were greater than those of juveniles, but feather Pb concentrations were similar between age classes. Blood and feather THg concentrations were …

Genome-Scale Quantification Of Target Vulnerability In Mycobacterium Tuberculosis, Barbara Bosch

Student Theses and Dissertations

Essential bacterial genes orchestrate core biological processes and represent the targets of nearly all antibacterial drugs. Traditional genetic approaches such as knockout studies and transposon mutagenesis have cataloged hundreds of essential bacterial genes but provide no basis on which to identify the most attractive targets for antibiotics. In contrast to the binary definition of gene essentiality, the gene vulnerability is an expression that relates the magnitude of gene inhibition with the resulting impact on bacterial fitness. Partial gene inhibition results in stronger fitness costs for vulnerable genes than invulnerable genes. Understanding vulnerability is critical for prioritizing targets for drug development …

Building Consensus Around The Assessment And Interpretation Of Symbiodiniaceae Diversity, Cawa Tran, Et Al.

Biology: Faculty Scholarship

Within microeukaryotes, genetic variation and functional variation sometimes accumulate more quickly than morphological differences. To understand the evolutionary history and ecology of such lineages, it is key to examine diversity at multiple levels of organization. In the dinoflagellate family Symbiodiniaceae, which can form endosymbioses with cnidarians (e.g., corals, octocorals, sea anemones, jellyfish), other marine invertebrates (e.g., sponges, molluscs, flatworms), and protists (e.g., foraminifera), molecular data have been used extensively over the past three decades to describe phenotypes and to make evolutionary and ecological inferences. Despite advances in Symbiodiniaceae genomics, a lack of consensus among researchers with respect to interpreting genetic …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

UROP Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Clonal Diversity, Antibiotic Resistance, And Virulence Factor Prevalence Of Community Associated Staphylococcus Aureus In Southeastern Virginia, Katelyn D. Cranmer, Mohan D. Pant, Suzanne Quesnel, Julia A. Sharp

EVMS School of Health Professions Faculty Publications

Staphylococcus aureus is a significant human pathogen with a formidable propensity for antibiotic resistance. Worldwide, it is the leading cause of skin and soft tissue infections (SSTI), septic arthritis, osteomyelitis, and infective endocarditis originating from both community- and healthcare associated settings. Although often grouped by methicillin resistance, both methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) strains are known to cause significant pathologies and injuries. Virulence factors and growing resistance to antibiotics play major roles in the pathogenicity of community-associated strains. In our study, we examined the genetic variability and acquired antibiograms of 122 S. aureus clinical isolates from SSTI, blood, and urinary …

Investigation Of Fungal Pathogens And Woodboring Beetles Of Sugarbush Stands In The Central Appalachian Region, Molly A. Sherlock

Graduate Theses, Dissertations, and Problem Reports (ETD)

The production of maple syrup is a valuable source of income and cultural identity for many rural communities throughout the central Appalachian region. Regardless, maple syrup producers face difficulties maintaining the health and productivity
of their stands due to various impacts of climate change, which have given rise to extreme weather events that exacerbate damage caused by pests and diseases. To ensure the long-term sustainability of the maple syrup industry, it is crucial to obtain a comprehensive understanding of the current biotic threats within the region, particularly woodboring insects and fungal pathogens. However, insufficient information exists regarding the community assemblages …

Understanding Inflammation, Immunity, And Infection, Jeff Vasiloff, Md, Mph

OHIO Open Faculty Textbooks

Inflammation, immunity, and infection explained by Jeffrey Vasiloff, MD, MPH, Associate Clinical Professor, PA Program; Adjunct Professor, PT Program, College of Health Sciences and Professions, Ohio University Dublin Medical Campus; Physician Consultant: Ohio Association of Physician Assistants; Physician Volunteer: Franklin County & Columbus Medical Reserve Corps; Board Certification: Internal Medicine & Diabetes and Endocrinology.

Interrogation And Manipulation Of The Igg Fc Glycan, Aaron Keshav Gupta

Student Theses and Dissertations

Antibody signaling is a cardinal feature of successful adaptive immune responses. The magnitude and direction of this signaling is determined by the structure of a given antibody's fragment crystallizable (Fc) domain, which interfaces with cells of the immune system. Often considered a constant region, the immunoglobulin G (IgG) Fc protein backbone and conserved N-linked glycan combine to introduce structural diversity in IgG molecules that in turn, triggers divergent humoral responses. These N-glycans are variably constructed, ultimately leading to families of highly related, but non-equivalent glycoproteins known as glycoforms. Despite burgeoning interest in understanding the complexities of IgG Fc glycoforms and …

Rarely Acquired Type Ii-A Crispr-Cas Spacers Mediate Anti-Viral Immunity Through The Targeting Of A Non-Canonical Pam Sequence, Claire T. Kenney

Student Theses and Dissertations

Viruses that infect prokaryotes, called bacteriophages or phages, are thought to outnumber bacteria by a ratio of 10:1 and provide a constant threat to their hosts. In response, bacteria have evolved numerous defense mechanisms, attacking all major steps of the phage infection and replication cycle. In turn, phages have evolved their own counter defenses. One phage defense system, only recently characterized, has proved revolutionary for our understanding of prokaryote-phage dynamics and our ability to edit genomes of nearly any cell type. CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated genes) functions as an adaptive immune system by identifying and …

Bioorthogonal Tethering Of Drug Fragments To Engineered G Protein-Coupled Receptors, Jordan M. Mattheisen

Student Theses and Dissertations

G protein-coupled receptors (GPCRs) modulate diverse cellular signaling pathways and are important drug targets. Despite the availability of high-resolution structures for nearly 100 discrete GPCRs in complex with various ligands, discovering allosteric drugs that can modulate receptor signaling remains challenging. In principle, allosteric ligands have certain advantages because they bind to pockets on the receptor that do not directly impact the orthosteric site for agonist ligands, but still tune downstream signaling pathways. But identifying and validating allosteric ligands remains difficult partly due to the dynamic nature of GPCRs in native membranes. Of the more than 3700 distinct FDA-approved drugs, there …

Development Of Improved Genetic Methods For Enterococcus Faecium, Victor Chen

Student Theses and Dissertations

Enterococcus faecium is a ubiquitous Gram-positive bacterium that has been recovered from the environment, food, and microbiota of mammals. Enterococcus faecium is widely recognized as an emerging public health threat with the rise of drug resistance and nosocomial infections. Antibiotic usage has afforded antibiotic-resistant and pathogenic isolates from livestock and humans. Nevertheless, commensal Enterococcus strains possess beneficial health functions in mammals to upregulate host immunity and prevent microbial infections. However, the dissection of E. faecium functions and mechanisms has been restricted by inefficient genetic methods. Current genetic engineering methods in E. faecium still require passive homologous recombination from plasmid DNA. …

A Chemical-Genetic Map Of Drug Resistance In Mycobacterium Tuberculosis, Nicholas Poulton

Student Theses and Dissertations

Tuberculosis (TB) is the leading cause of death from any single infectious disease, killing over 1.5 million people each year. Treatment of TB is extraordinarily difficult, requiring at least 6 months of combination antibiotic therapy to cure patients. Even with this prolonged treatment, 5 to 10% of patients are not fully cured and experience disease relapse. Mycobacterium tuberculosis (Mtb), the causative agent of TB, is intrinsically resistant to most antibiotics and can acquire an additional level of antibiotic resistance through specific chromosomal mutations. A better understanding of intrinsic and acquired drug resistance in Mtb is essential to develop faster treatments …

Noteworthy Parasites (Trematoda, Cestoda, Phthiraptera) Of Three Birds (Aves: Passeriformes; Pelecaniformes; Piciformes) From Arkansas, C.T. Mcallister, H.W. Robison

Journal of the Arkansas Academy of Science

Between November 2020 and March 2021, three species of birds, one each of a tufted titmouse (Baeolophus bicolor), pileated woodpecker (Dryocopus pileatus), and great blue heron (Ardea herodias) were salvaged from Lawrence and Polk counties, Arkansas, and examined for parasites. Found were four taxa of parasites, including a dicrocoeliid trematode, a cyclophyllidean cestode, and species of philopterid and menoponid lice. We document new host and distributional records for these parasites from select birds of the state.

Longitudinal Variations In Antibody Responses Against Sars-Cov-2 Spike Epitopes Upon Serial Vaccinations, Dicle Yalcin, Sydney J. Bennett, Jared Sheehan, Amber J. Trauth, For Yue Tso, John T. West, Michael E. Hagensee, Alistair J. Ramsay, Charles Wood

School of Biological Sciences: Faculty Publications

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted healthcare, the workforce, and worldwide socioeconomics. Multi-dose mono- or bivalent mRNA vaccine regimens have shown high efficacy in protection against SARSCoV- 2 and its emerging variants with varying degrees of efficacy. Amino acid changes, primarily in the receptor-binding domain (RBD), result in selection for viral infectivity, disease severity, and immune evasion. Therefore, many studies have centered around neutralizing antibodies that target the RBD and their generation achieved through infection or vaccination. Here, we conducted a unique longitudinal study, analyzing the effects of a three-dose mRNA vaccine …

Immune Checkpoint Inhibitors: Friend Or Foe, Antonio Cordova, Md, Jesse Powell, Md, Whitney Elg-Salsman, Md, Caroline Mcculley, Md

Poster Presentations

No abstract provided.

Molecular Investigation Of Minor Genomic Populations And Biological Exposures In Human Health, Brandon Ned Johnson

Dissertations and Theses

The study of genetics has contributed to countless discoveries related to human health and disease. However, the complexities of human biology reside not only in the genome but also in the contributions from environmental exposures, as measured via the classical twin design. To understand the influence of biological exposures, I implemented study designs to explore both the health associations and propagation of foreign genetic material. Microchimerism has been studied for association with several clinical conditions, and I further investigated if male microchimerism could elucidate the etiology of Mayer-Rokitansky-Küster-Hauser syndrome. Prevalence of male microchimerism in women with no history of pregnancy …

Investigation Of Bacterial Infection And Immunity In The Body Louse, Lauren Mae Kress

Dissertations and Theses

The human body louse (Pediculus humanus humanus) is a host-specific hematophagous ectoparasite that frequently infests populations experiencing a breakdown of hygienic conditions. Body lice are vectors for several bacterial human pathogens, including Borrelia recurrentis (relapsing fever), Rickettsia prowazekii (epidemic typhus) and Bartonella quintana (trench fever) (Badiaga & Brouqui 2012, Amanzougaghene et al. 2020). Today, louse-borne relapsing fever and epidemic typhus are largely geographically restricted to small foci in East Africa. However, B. quintana is a re-emerging and underappreciated pathogen throughout the globe, especially in urban environments (Mai 2022). Transmission of B. quintana is known to occur via inoculation of infectious …

Writing New Normals: A Study Of American Pandemic Fiction In The Wake Of Covid-19, Riley E. Droppleman

Gaines Fellow Senior Theses

The purpose of this thesis is to explore the aspects of pandemic fiction that extend beyond the illness itself. In this thesis, I show that while the disease that spreads is a large focus of pandemic fiction, the truths that spring from these novels reveal larger societal issues, such as class hierarchies, racial inequalities, and failings of the government to fight the pandemic. In fact, pandemics act as catalysts for the uncovering of these societal ills, and the authors of pandemic fictions bring these greater faults of society to the forefront of their novels. I analyze three novels from the …

Relative Adrenal Insufficiency Is A Risk Factor And Endotype Of Sepsis - A Proof-Of- Concept Study To Support A Precision Medicine Approach To Guide Glucocorticoid Therapy For Sepsis, Chia-Hua Wu, Ling Guo, Dan Hao, Qian Wang, Xiang Ye, Misa Ito, Bin Huang, Chieko Mineo, Philip W. Shaul, Xiang-An Li

Saha Cardiovascular Research Center Faculty Publications

Introduction: 25-60% of septic patients experience relative adrenal insufficiency (RAI) and glucocorticoid (GC) is frequently used in septic patients. However, the efficacy of GC therapy and whether GC therapy should be based on the status of RAI are highly controversial. Our poor understanding about the pathogenesis of RAI and a lack of RAI animal model present significant barriers to address these critical issues.

Methods: Scavenger receptor BI (SR-BI) regulates stress-induced GC (iGC) production in response to stress. We generated SF1CreSR-BIfl/fl mice and utilized the mice as a RAI model to elucidate the pathogenesis of RAI and GC therapy in sepsis. …

Differential Diagnosis Of Dna Viruses Related To Reproductive Disorder On Sows By Multiplex-Pcr Technique, T N. Nguyen, H T T Le, H L X Vu, P X. Dinh

Department of Animal Science: Faculty Publications

The newly emerged diseases caused by ASFV and PCV3 and their confirmed prevelance in Vietnam whereas most of available common commercial methods such as ELISA or realtime PCR designed for detecting single pathogen per reaction, highlighted a necessity for another diagnostic method to simultaneously detect and differentiate DNA viruses that are related to reproductive failures in sow herds including PCV2, PCV3, PPV, ASFV. In this communication, a diagnostic multiplex-PCR (mPCR) was established with pathogen-specific primers selected from previous studies and another set of primers designed for COX1 gene serving as an internal amplification control (IAC). The predicted products of PCV2, …