Immunology and Infectious Disease Commons^™

Comparison Of Two Diagnostic Assays For The Detection Of Serum Neutralizing Antibody To Porcine Epidemic Diarrhea Virus, Justin Brown, Korakrit Poonsuk, Ting-Yu Cheng, Chris Rademacher, Erin Kalkwarf, Liying Tian, Lauren A. Mckeen, Chong Wang, Luis Gimenez-Lirola, David Baum, Locke A. Karriker

School of Veterinary and Biomedical Sciences: Faculty Publications

Lactogenic immunity is important for the protection of piglets against many pathogens including porcine epidemic diarrhea virus. Circulating neutralizing antibodies levels in sow sera may help determine if a detectable immune response could confer protection to piglets. Neutralizing antibodies can be detected through various diagnostic assays. This study evaluated the diagnostic characteristics of two neutralizing antibody assays for porcine epidemic diarrhea virus neutralizing antibodies in serum of challenged gilts. Four treatment groups, control, non-vaccinated, vaccinated prior to challenge, and vaccinated following challenge, were comprised of 20 gilts. Serum sample were collected from each gilt prior to and following challenge with …

Cd5 Expression By Dendritic Cells Directs T Cell Immunity And Sustains Immunotherapy Responses, Mingyu He, Kate Roussak, Feiyang Ma, Nicholas Borcherding, Vince Garin, Mike White, Charles Schutt, Trine I Jensen, Yun Zhao, Courtney A Iberg, Kairav Shah, Himanshi Bhatia, Daniel Korenfeld, Sabrina Dinkel, Judah Gray, Alina Ulezko Antonova, Stephen Ferris, David Donermeyer, Cecilia Lindestam Arlehamn, Matthew M Gubin, Jingqin Luo, Laurent Gorvel, Matteo Pellegrini, Alessandro Sette, Thomas Tung, Rasmus Bak, Robert L Modlin, Ryan C Fields, Robert D Schreiber, Paul M Allen, Eynav Klechevsky

Faculty, Staff and Student Publications

The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1c+CD5+ DCs are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T cell priming and improved survival after ICB therapy. CD5+ DC numbers increased during ICB therapy, and low interleukin-6 (IL-6) concentrations promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5hi T helper and CD8+ T cells; further, deletion of CD5 from T …

Fgl2-Targeting T Cells Exhibit Antitumor Effects On Glioblastoma And Recruit Tumor-Specific Brain-Resident Memory T Cells, Qingnan Zhao, Jiemiao Hu, Lingyuan Kong, Shan Jiang, Xiangjun Tian, Jing Wang, Rintaro Hashizume, Zhiliang Jia, Natalie Wall Fowlkes, Jun Yan, Xueqing Xia, Sofia F Yi, Long Hoang Dao, David Masopust, Amy B Heimberger, Shulin Li

Faculty, Staff and Student Publications

Although tissue-resident memory T (TRM) cells specific for previously encountered pathogens have been characterized, the induction and recruitment of brain TRM cells following immune therapy has not been observed in the context of glioblastoma. Here, we show that T cells expressing fibrinogen-like 2 (FGL2)–specific single-chain variable fragments (T-αFGL2) can induce tumor-specific CD8+ TRM cells that prevent glioblastoma recurrence. These CD8+ TRM cells display a highly expanded T cell receptor repertoire distinct from that found in peripheral tissue. When adoptively transferred to the brains of either immunocompetent or T cell-deficient naïve mice, these CD8+ TRM cells reject glioma cells. Mechanistically, T-αFGL2 …

The Landscape Of Immunotherapy For Retroperitoneal Sarcoma, Alicia A Gingrich, Elise F Nassif, Christina L Roland, Emily Z Keung

Faculty, Staff and Student Publications

Significant multidisciplinary scientific effort has been undertaken to understand the heterogeneous family of neoplasms that comprise soft tissue sarcomas. Within this family of neoplasms, outcomes for retroperitoneal sarcomas (RPS) are currently limited given a lack of effective therapies. In this review, we focus on immunotherapy and its relationship with the common RPS histologic subtypes. Although initial outcomes for RPS patients with immune checkpoint inhibition alone have been somewhat disappointing, subsequent analyses on histologies, the tumor microenvironment, sarcoma immune class, tumor infiltrating lymphocytes and genetic analysis for tumor mutational burden have yielded insight into the interplay between sarcomas and immunotherapy. Such …

Comparison Of Two Diagnostic Assays For The Detection Of Serum Neutralizing Antibody To Porcine Epidemic Diarrhea Virus, Justin Brown, Korakrit Poonsuk, Ting-Yu Cheng, Chris Rademacher, Erin Kalkwarf, Liying Tian, Lauren A. Mckeen, Chong Wang, Luis Gimenez-Lirola, David Baum, Locke A. Karriker

School of Veterinary and Biomedical Sciences: Faculty Publications

Lactogenic immunity is important for the protection of piglets against many pathogens including porcine epidemic diarrhea virus. Circulating neutralizing antibodies levels in sow sera may help determine if a detectable immune response could confer protection to piglets. Neutralizing antibodies can be detected through various diagnostic assays. This study evaluated the diagnostic characteristics of two neutralizing antibody assays for porcine epidemic diarrhea virus neutralizing antibodies in serum of challenged gilts. Four treatment groups, control, non-vaccinated, vaccinated prior to challenge, and vaccinated following challenge, were comprised of 20 gilts. Serum sample were collected from each gilt prior to and following challenge with …

Fibrinogen-Like Protein 2: Its Biological Function Across Cell Types And The Potential To Serve As An Immunotherapy Target For Brain Tumors, Sheng Zhang, Ganesh Rao, Amy Heimberger, Shulin Li

Faculty, Staff and Student Publications

Brain tumors are among the 10 leading causes of cancer-related death and present unique treatment challenges due to their critical location, genetic heterogeneity, and the blood-brain barrier. Recent advances in targeted immunotherapy and immune checkpoint blocking therapy provide alternative therapeutic strategies for brain tumors. Fibrinogen-like protein 2 (FGL2), which induces transformation from low-grade glioma to high-grade glioblastoma, is a type II membrane protein that is highly expressed in both host immune cells and tumor cells. Studies have uncovered multiple forms of FGL2 proteins with a broad range of roles in inducing immune tolerance and avoiding immune surveillance in tumor cells. …

Ifn-Γ Production By Brain-Resident Cells Activates Cerebral Mrna Expression Of A Wide Spectrum Of Molecules Critical For Both Innate And T Cell-Mediated Protective Immunity To Control Reactivation Of Chronic Infection With Toxoplasma Gondii, Yasuhiro Suzuki, Jenny Lutshumba, Kuey Chu Chen, Mohamed H. Abdelaziz, Qila Sa, Eri Ochiai

Markey Cancer Center Faculty Publications

We previously demonstrated that brain-resident cells produce IFN-g in response to reactivation of cerebral infection with Toxoplasma gondii. To obtain an overall landscape view of the effects of IFN-g from brain-resident cells on the cerebral protective immunity, in the present study we employed NanoString nCounter assay and quantified mRNA levels for 734 genes in myeloid immunity in the brains of T and B cell-deficient, bone marrow chimeric mice with and without IFN-g production by brain-resident cells in response to reactivation of cerebral T. gondii infection. Our study revealed that IFN-g produced by brain-resident cells amplified mRNA expression for the molecules …

Inhibition Of Myeloperoxidase Enhances Immune Checkpoint Therapy For Melanoma, Tracy W Liu, Seth T Gammon, Ping Yang, Wencai Ma, Jing Wang, David Piwnica-Worms

Faculty, Staff and Student Publications

BACKGROUND: The presence of a highly immunosuppressive tumor microenvironment has limited the success of immune checkpoint therapy (ICT). Immune suppressing myeloid cells with increased production of reactive oxygen species are critical drivers of this immunosuppressive tumor microenvironment. Strategies to limit these immune suppressing myeloid cells are needed to enhance response to ICT.

METHODS: To evaluate the contribution of myeloperoxidase (MPO), a myeloid lineage-restricted enzyme and a major source of reactive oxygen species, to mediating ICT response, we compared treatment outcome and immune composition in wild-type, MPO-deficient (

RESULTS: Tumor growth and survival studies demonstrated that either host deficiency (

CONCLUSION: …

Fucosylation Of Hla-Drb1 Regulates Cd4+ T Cell-Mediated Anti-Melanoma Immunity And Enhances Immunotherapy Efficacy, Daniel K Lester, Chase Burton, Alycia Gardner, Patrick Innamarato, Krithika Kodumudi, Qian Liu, Emma Adhikari, Qianqian Ming, Daniel B Williamson, Dennie T Frederick, Tatyana Sharova, Michael G White, Joseph Markowitz, Biwei Cao, Jonathan Nguyen, Joseph Johnson, Matthew Beatty, Andrea Mockabee-Macias, Matthew Mercurio, Gregory Watson, Pei-Ling Chen, Susan Mccarthy, Carlos Moransegura, Jane Messina, Kerry L Thomas, Lancia Darville, Victoria Izumi, John M Koomen, Shari A Pilon-Thomas, Brian Ruffell, Vincent C Luca, Robert S Haltiwanger, Xuefeng Wang, Jennifer A Wargo, Genevieve M Boland, Eric K Lau

Faculty, Staff and Student Publications

Immunotherapy efficacy is limited in melanoma, and combinations of immunotherapies with other modalities have yielded limited improvements but also adverse events requiring cessation of treatment. In addition to ineffective patient stratification, efficacy is impaired by paucity of intratumoral immune cells (itICs); thus, effective strategies to safely increase itICs are needed. We report that dietary administration of l-fucose induces fucosylation and cell surface enrichment of the major histocompatibility complex (MHC)-II protein HLA-DRB1 in melanoma cells, triggering CD4+ T cell-mediated increases in itICs and anti-tumor immunity, enhancing immune checkpoint blockade responses. Melanoma fucosylation and fucosylated HLA-DRB1 associate with intratumoral T cell abundance …

Pkr Induces Tgf-Β And Limits Oncolytic Immune Therapy, Bangxing Hong, Upasana Sahu, Matthew P Mullarkey, Evan Hong, Guangsheng Pei, Yuanqing Yan, Yoshihiro Otani, Yeshavanth Banasavadi-Siddegowda, Huihui Fan, Zhongming Zhao, Jianhua Yu, Michael A Caligiuri, Balveen Kaur

Faculty, Staff and Student Publications

BACKGROUND: Mammalian cells have developed multiple intracellular mechanisms to defend against viral infections. These include RNA-activated protein kinase (PKR), cyclic GMP-AMP synthase and stimulation of interferon genes (cGAS-STING) and toll-like receptor-myeloid differentiation primary response 88 (TLR-MyD88). Among these, we identified that PKR presents the most formidable barrier to oncolytic herpes simplex virus (oHSV) replication in vitro.

METHODS: To elucidate the impact of PKR on host responses to oncolytic therapy, we generated a novel oncolytic virus (oHSV-shPKR) which disables tumor intrinsic PKR signaling in infected tumor cells.

RESULTS: As anticipated, oHSV-shPKR resulted in suppression of innate antiviral immunity and improves virus …

Autonomic Function Recovery And Physical Activity Levels In Post-Covid-19 Young Adults After Immunization: An Observational Follow-Up Case-Control Study, Ana Paula Coelho Figueira Freire, Shaan Amin, Fabio Santos Lira, Ana Elisa Von Ah Morano, Telmo Pereira, Manuel-João Coelho-E-Silva, Armando Caseiro, Diego Giulliano Destro Christofaro, Vanessa Ribeiro Dos Santos, Osmar Marchioto Júnior, Ricardo Aurino Pinho, Bruna Spolador De Alencar Silva

All Faculty Scholarship for the College of Education and Professional Studies

Coronavirus disease 2019 (COVID-19) has detrimental multi-system consequences. Symptoms may appear during the acute phase of infection, but the literature on long-term recovery of young adults after mild to moderate infection is lacking. Heart rate variability (HRV) allows for the observation of autonomic nervous system (ANS) modulation post-SARS-CoV-2 infection. Since physical activity (PA) can help improve ANS modulation, investigating factors that can influence HRV outcomes after COVID-19 is essential to advancements in care and intervention strategies. Clinicians may use this research to aid in the development of non-medication interventions. At baseline, 18 control (CT) and 20 post-COVID-19 (PCOV) participants were …

Displaying And Delivering Viral Membrane Antigens Via Ww Domain–Activated Extracellular Vesicles, Sengjin Choi, Zhiping Yang, Qiyu Wang, Zhi Qiao, Maoyun Sun, Joshua Wiggins, Shi-Hua Xiang, Quan Lu

School of Veterinary and Biomedical Sciences: Faculty Publications

Membrane proteins expressed on the surface of enveloped viruses are conformational antigens readily recognized by B cells of the immune system. An effective vaccine would require the synthesis and delivery of these native conformational antigens in lipid membranes that preserve specific epitope structures. We have created an extracellular vesicle–based technology that allows viral membrane antigens to be selectively recruited onto the surface of WW domain–activated extracellular vesicles (WAEVs). Budding of WAEVs requires secretory carrier-associated membrane protein 3, which through its proline-proline-alanine-tyrosine motif interacts with WW domains to recruit fused viral membrane antigens onto WAEVs. Immunization with influenza and HIV viral …

Vaccines Against Group B Coxsackieviruses And Their Importance, Kiruthiga Mone, Ninaad Lasrado, Meghna Sur, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

The group B coxsackieviruses (CVBs) exist in six serotypes (CVB1 to CVB6). Disease associations have been reported for most serotypes, and multiple serotypes can cause similar diseases. For example, CVB1, CVB3, and CVB5 are generally implicated in the causation of myocarditis, whereas CVB1 and CVB4 could accelerate the development of type 1 diabetes (T1D). Yet, no vaccines against these viruses are currently available. In this review, we have analyzed the attributes of experimentally tested vaccines and discussed their merits and demerits or limitations, as well as their impact in preventing infections, most importantly myocarditis and T1D.

Personalized Matched Targeted Therapy In Advanced Pancreatic Cancer: A Pilot Cohort Analysis, Justin Shaya, Shumei Kato, Jacob J. Adashek, Hitendra Patel, Paul T. Fanta, Gregory P. Botta, Jason K. Sicklick, Razelle Kurzrock

School of Veterinary and Biomedical Sciences: Faculty Publications

Despite progress, 2-year pancreatic cancer survival remains dismal. We evaluated a biomarker-driven, combination/N-of-one strategy in 18 patients (advanced/metastatic pancreatic cancer) (from Molecular Tumor Board). Targeted agents administered/ patient = 2.5 (median) (range, 1–4); first-line therapy (N = 5); second line, (N = 13). Comparing patients (high versus low degrees of matching) (matching score ≥50% versus <50%; reflecting number of alterations matched to targeted agents divided by number of pathogenic alterations), survival was significantly longer (hazard ratio [HR] 0.24 (95% confidence interval [CI], 0.078–0.76, P = 0.016); clinical benefit rates (CBR) (stable disease ≥6 months/partial/complete response) trended higher (45.5 vs 0.0%, P = 0.10); progression-free survival, HR, 95% CI, 0.36 (0.12–1.10) (p = 0.075). First versus ≥2nd-line therapy had higher CBRs (80.0 vs 7.7%, P = …

Antibody-Dependent Enhancement Activity Of A Plant-Made Vaccine Against West Nile Virus, Amber M. Paul, Haiyan Sun, Dhiraj Acharya, Huafang Lai, Junyun He, Fengwei Bai, Qiang Chen

Publications

West Nile virus (WNV) causes annual outbreaks globally and is the leading cause of mosquito-borne disease in Unite States. In the absence of licensed therapeutics, there is an urgent need to develop effective and safe human vaccines against WNV. One of the major safety concerns for WNV vaccine development is the risk of increasing infection by related flaviviruses in vaccinated subjects via antibody-dependent enhancement of infection (ADE). Herein, we report the development of a plant-based vaccine candidate that provides protective immunity against a lethal WNV challenge mice, while minimizes the risk of ADE for infection by Zika (ZIKV) and dengue …

Antibody Duration After Infection From Sars-Cov-2 In The Texas Coronavirus Antibody Response Survey, Michael D Swartz, Stacia M Desantis, Ashraf Yaseen, Frances A Brito, Melissa A Valerio-Shewmaker, Sarah E Messiah, Luis G Leon-Novelo, Harold W Kohl, Cesar L Pinzon-Gomez, Tianyao Hao, Shiming Zhang, Yashar Talebi, Joy Yoo, Jessica R Ross, Michael O Gonzalez, Leqing Wu, Steven H Kelder, Mark Silberman, Samantha Tuzo, Stephen J Pont, Jennifer A Shuford, David Lakey, Eric Boerwinkle

Faculty, Staff and Student Publications

Understanding the duration of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that causes COVID-19 is important to controlling the current pandemic. Participants from the Texas Coronavirus Antibody Response Survey (Texas CARES) with at least 1 nucleocapsid protein antibody test were selected for a longitudinal analysis of antibody duration. A linear mixed model was fit to data from participants (n = 4553) with 1 to 3 antibody tests over 11 months (1 October 2020 to 16 September 2021), and models fit showed that expected antibody response after COVID-19 infection robustly increases for 100 days postinfection, and predicts …

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 …

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; …

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 …

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.

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

Poster Presentations

No abstract provided.

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. …

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 …

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, …

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 …

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 …

Multipatch Stochastic Epidemic Model For The Dynamics Of A Tick-Borne Disease, Milliward Maliyoni, Holly D. Gaff, Keshlan S. Govinder, Faraimunashe Chirove

Biological Sciences Faculty Publications

Spatial heterogeneity and migration of hosts and ticks have an impact on the spread, extinction and persistence of tick-borne diseases. In this paper, we investigate the impact of between-patch migration of white-tailed deer and lone star ticks on the dynamics of a tick-borne disease with regard to disease extinction and persistence using a system of Itô stochastic differential equations model. It is shown that the disease-free equilibrium exists and is unique. The general formula for computing the basic reproduction number for all patches is derived. We show that for patches in isolation, the basic reproduction number is equal to the …

Anti-Tick Vaccine Candidate Subolesin Is Important For Blood Feeding And Innate Immune Gene Expression In Soft Ticks, Krittika Nandy, Comfort Tamakloe, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Subolesin is a conserved molecule in both hard and soft ticks and is considered as an effective candidate molecule for the development of anti-tick vaccine. Previous studies have reported the role of subolesin in blood feeding, reproduction, development, and gene expression in hard ticks. However, studies addressing the role of subolesin in soft ticks are limited. In this study, we report that subolesin is not only important in soft tick Ornithodoros turicata americanus blood feeding but also in the regulation of innate immune gene expression in these ticks. We identified and characterized several putative innate immune genes including Toll, Lysozyme …

Relative Adrenal Insufficiency In Sepsis, Dan Hao

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death in children. Glucocorticoid (GC) therapy had been strongly recommended for the pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. Relative adrenal insufficiency (RAI) is a condition characterized by impaired inducible glucocorticoid (iGC) production in response to stress. It develops in 32.8% of pediatric septic patients. Unfortunately, little is known about the pathogenesis of RAI in pediatric sepsis, and whether GC therapy should be based on the status of RAI is controversial. In this study, we utilized 21-day-old SF1CreSRBI^fl/fl mice as the first …

Vitamin D Enhanced Vitamin D Receptor (Vdr) Inhibition Of Nlrp3 Inflammasome Activation Can Attenuate The Development Of Autoimmune Thyroiditis, Alexzon Mandac

Capstone Showcase

Autoimmune Thyroiditis (AIT) is a prevalent autoimmune disease affecting approximately 2% of the population. Characterized by the gradual loss of thyroid function through an autoimmune attack on the thyroid gland, the disease manifests symptoms that negatively affect one’s quality of life. The mechanisms behind the disease’s pathophysiology are not fully understood; however, researchers are examining the involvement of the NLRP3 inflammasome in the disease. This thesis will address the question of whether Vitamin D can act as an inhibitor of the NLRP3 inflammasome and attenuate the progression of AIT in mouse model. Current investigations explore the effects of NLRP3 inhibition …