Immunology and Infectious Disease Commons^™

The Role Of The Host Factor Sptbn1 In Hiv-1 Infection Of Microglial Cells, Marc Gordon Havlicek

Graduate Theses/Dissertations

HIV-1 is the etiological agent that cause AIDS. Since the 1980’s when HIV-1 was discovered, much has been discovered, however a cure for HIV-1 has eluded researchers. Effective therapeutics do exist but can have adverse side effects including HAND/HAD which leads to neurodegeneration in patients regardless of viral suppression. One area of research that holds the possibility of discovering new viral targets and therapeutics is host factor interaction within the replication process. One host factor that can cause a decrease in HIV-1 infectivity is SPTBN1. SPTBN1 is a cytoskeletal protein that was shown to bind to the capsid and nucleocapsid …

The Comparison Of Three Different Fecal Egg Counting Techniques And Their Ability To Perform A Fecal Egg Count Reduction Test, Diana J. Summitt

Graduate Theses/Dissertations

A comprehensive gastrointestinal parasite control program includes an understanding of common parasites, application of chemotherapeutic agents, as well as frequent and appropriate diagnostic testing. An effective control program is essential for facilities such as animal shelters, that deal with large populations of transient canines with unknown parasite exposure and deworming history. The identification of a sensitive flotation method to evaluate anthelmintic efficacy is critical in monitoring parasite populations for drug resistance. The objective of the current study was to compare three different fecal egg counting technologies and their ability to perform a fecal egg reduction test. The flotation techniques evaluated …

The Role Of Ly49 Receptors In Maintaining Healthy Murine Pregnancy, Michelle Belmont

Master's Theses

Natural Killer (NK) cells are abundant in pregnancy and contribute to the health of the fetus. Uterine NK (uNK) cells provide less cytotoxic function than their conventional NK (cNK) cell counterparts. Various combinations of Killer Immunoglobulin Receptor (KIR)- Human Leukocyte Antigen (HLA) on maternal NK and fetally derived cells, respectively, can have different effects on the health of pregnancy in humans. Murine NK cells contain Ly49 receptors, an equivalent to KIRs. Therefore, Ly49 receptor interactions with fetally-derived MHC-I molecules can be a valuable model for studying the role of NK cells in pregnancy. The process of spiral artery remodeling can …

Social Determinants Of Disease: Hiv And Covid-19 Experiences, Raiza M. Beltran, Ian W. Holloway, Chenglin Hong, Ayako Miyashita, Luisita Cordero, Elizabeth Wu, Katherine Burris, Paula M. Frew

Epidemiology & Biostatistics Faculty Research

Purpose of Review: The differential impact of the COVID-19 and HIV pandemics on marginalized communities has renewed calls for more robust and deeper investigation into structural and social causes of health inequities contributing to these infections, including underlying factors related to systematic racism. Using the Social Determinants of Health (SDOH) framework, we analyzed parallel and divergent factors associated with COVID-19 and HIV/AIDS and the prevalence of disparate disease in diverse communities. We utilized PRISMA guidelines to identify relevant literature (N = 210 articles) that resulted in a review of 125 articles included in our synthesis. Recent Findings: With racial health …

Rickettsial Pathogen Perturbs Tick Circadian Gene To Infect The Vertebrate Host, Supreet Khanal, Vikas Taank, John F. Anderson, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Ixodes scapularis is a medically important tick that transmits several microbes to humans, including rickettsial pathogen Anaplasma phagocytophilum. In nature, these ticks encounter several abiotic factors including changes in temperature, humidity, and light. Many organisms use endogenously generated circadian pathways to encounter abiotic factors. In this study, we provide evidence for the first time to show that A. phagocytophilum modulates the arthropod circadian gene for its transmission to the vertebrate host. We noted a circadian oscillation in the expression of arthropod clock, bmal1, period and timeless genes when ticks or tick cells were exposed to alternate 12 h …

Editorial: Tick Saliva: Secret To Blood Feeding Success, Daniel E. Sonenshine, Patricia A. Nuttall, Sukanya Narasimhan

Biological Sciences Faculty Publications

No abstract provided.

Tick Transmission Of Borrelia Burgdorferi To The Murine Host Is Not Influenced By Environmentally Acquired Midgut Microbiota, Sukanya Narasimhan, Nallakkandi Rajeevan, Morven Graham, Ming-Jie Wu, Kathleen Deponte, Solenne Marion, Orlanne Masson, Anya J. O'Neal, Daniel E. Sonenshine, Erol Fikrig

Biological Sciences Faculty Publications

Background

Ixodes scapularis is the predominant tick vector of Borrelia burgdorferi, the agent of Lyme disease, in the USA. Molecular interactions between the tick and B. burgdorferi orchestrate the migration of spirochetes from the midgut to the salivary glands—critical steps that precede transmission to the vertebrate host. Over the last decade, research efforts have invoked a potential role for the tick microbiome in modulating tick-pathogen interactions.

Results

Using multiple strategies to perturb the microbiome composition of B. burgdorferi-infected nymphal ticks, we observe that changes in the microbiome composition do not significantly influence B. burgdorferi migration from the midgut, invasion of …

Methods For Characterization Of Cl-001 Derived Exosomes As A Stimulating Agent For Nk Cells For Immunotherapy, Ilana Gomez Diaz

Honors Undergraduate Theses

The immune system is a complex set of cells in the body that work to prevent disease or infection by recognizing and eliminating foreign material or unhealthy cells. One essential type of immune cell that is part of the innate immune response are Natural Killer (NK) cells. These cytotoxic effector lymphocytes can detect certain unhealthy cells, such as cancer cells, that normal B and T cells would miss. For example, many tumor cells have evolved to bypass immune system surveillance by not expressing major histocompatibility complex class I molecules (MHC class I), on their surface, reducing recognition by cytotoxic T …

Dissecting The Role Of Actin-Myosin Motor And Calcium – Based Organelle Secretion In Motility Of Sarcocystis Neurona, Parul Suri

Theses and Dissertations--Veterinary Science

Sarcocystis neurona is a protozoan parasite that causes a rare neurological disorder in horses called Equine Protozoal Myeloencephalitis (EPM). Apicomplexa use actin-myosin based motor and organelle secretion to interact with the host cell and invade it. Despite the importance of motility and invasion-needed factors, the mechanisms by which S. neurona employs host cell association strategies to interact remains largely undefined. To address this knowledge gap, we hypothesize that just like other Apicomplexa, S. neurona utilizes actin polymerization for substrate-dependent gliding. Moreover, we also hypothesize that micronemes of S. neurona secrete proteins that are calcium-dependent. Based on previous studies in T. …

The Microbiome Of The Equine Roundworm, Parascaris Spp., Jennifer Lynn Cain

Theses and Dissertations--Veterinary Science

Parasitic nematodes, including the large roundworms colloquially known as ascarids, affect the health and well-being of livestock animals worldwide. The equine ascarid, Parascaris spp., was the first ascarid parasite to develop wide-spread anthelmintic drug resistance, with other species slowly following suit. There are no new classes of anthelmintics currently in development, and a solution to the ever-increasing prevalence of resistance is desperately needed. The microbiome has been shown to be an important factor in the fitness and health of many organisms and changes to microbiome composition have been associated with a plethora of diseases. The microbiome is also important to …

The Influence Of Political Party Affiliation And Park Accessibility On Covid-19 Case Incidence, Sascha Wolf-Sorokin

CMC Senior Theses

This paper examines the joint effect of political party affiliation and the urban landscape, as measured by access to parks, on case rates during the COVID-19 pandemic in the United States. The 2016 and 2020 U.S. Presidential Election returns are used as a proxy for a county’s political party affiliation prior to and during the COVID-19 pandemic. A county population’s spatial relationship to its parks encapsulates the green open space within an urban environment. The data set controls for features of the built environment, socioeconomic and demographic characteristics (race, gender, income, education), COVID-19 government regulations, and presidential election returns. Using …

Avian Haemosporidian Blood Parasite Diversity, Prevalence, And Distribution In Michigan’S Western Upper Peninsula, Maria M. Ferrer

Dissertations, Master's Theses and Master's Reports

Avian haemosporidian parasites, known as avian malaria (phylum Apicomplexa) can diminish an individual bird’s fitness by causing parasitemia, anemia, and reduced survival. Climate change is predicted to increase the spread of malarial parasites into more northerly latitudes where little is known about community compositions of these parasites. I assessed the prevalence and diversity of haemosporidian parasites in the first-ever community-level sampling of malaria in songbirds across the western Upper Peninsula of Michigan. In total, 179 blood samples were collected from birds representing 17 species, at five locations in the Upper Peninsula, including a mature forest, an early successional forest, and …

In Situ Vaccination Using Plant Viral Particles As A Novel Approach For Cancer Immunotherapy, Chenkai Mao

Dartmouth College Ph.D Dissertations

Non-infectious to mammals, genetically, and physically stable plant virus-based nanoparticles have been increasingly studied as a novel platform for cancer vaccine and adjuvants due to their immunogenic properties. Our prior work showed that, empty cowpea mosaic virus (eCPMV), a plant virus-like particle (VLP) that is composed of a separated capsid, is an excellent in situ vaccine (ISV) for cancer immunotherapy; however, little is known about the mechanisms linked to their activities regarding recognition and antigen presentation.

In the present studies, we report cowpea mosaic virus (CPMV) and RNA-lacking CPMV (empty, eCPMV) are both toll like receptor (TLR) agonists for TLRs …

Simulation Of An Inflammatory Model Using Schwann Cells, Caitlyn E. Henry, Peyton Kimmel, Mackenzie Wilcox, Angela Asirvatham

SURF Posters 2022

Schwann cells are a type of glial cell in the peripheral nervous system that produce the myelin sheath surrounding neuronal axons. This myelin insulates the neurons and promotes the rapid conduction of electrical impulses throughout the body. Schwann cells have also been found to play a critical role in neuron repair following nerve injury. During nerve injury, the myelin sheath is damaged, stimulating Schwann cells to release cytokines, or inflammatory mediators, that recruit immune cells to the site of injury so that the myelin debris can be cleared, and repair can take place.1 Then neuronal growth is facilitated by heregulin …

Factors Influencing Intestinal Parasite In Black-And-White Ruffed Lemurs (Varecia Variegata), Eliette Noromalala

All Master's Theses

Ecological factors, such as feeding behavior and climatic seasonality, might influence intestinal parasite infection and patterns in non-human primates. Here, we examined if frugivory levels and climate (i.e., temperature and rainfall) were associated with parasite patterns in black-and-white ruffed lemurs (Varecia variegata). Feeding data using 5-min focal sampling, climate data, and fecal samples from V. variegata (n = 23) at the “Mangevo” site were collected from February through May 2019. Microscopic examinations of fecal flotation and sedimentation were done to identify and count parasites. Nematoda (Callistoura vauceli, and Strongyloides sp.) Ciliophora (Balantidium sp.), Coccidia ( …

Investigating The Interplay Of The Immune System, Skin Barrier, And Microbiome Following Dermal Exposure To Triclosan, Rachel Baur

Graduate Theses, Dissertations, and Problem Reports (ETD)

Triclosan is an antimicrobial chemical used in healthcare products that are applied to the skin. However, exposure to triclosan has been positively associated with food allergy, aeroallergy, and asthma severity in humans. In mice, dermal triclosan exposure, although not directly sensitizing, has been shown to augment the allergic response in a model of asthma. Furthermore, exposure to triclosan on mouse skin has been demonstrated to be immunomodulatory through the activity of thymic stromal lymphopoietin and S100 calcium-binding protein A8. The skin barrier and microbiome are known to interact with the immune system and disruptions in barrier integrity and the microbiome …

Novel Molecular Approaches To Diagnostic And Epidemiological Analyses Of Cryptosporidiumspp.Implicated In Clinical Infection, Jennifer K. O'Leary

Theses

Cryptosporidium remains an underestimated, yet highly prevalent, parasitic agent of gastrointestinal illness worldwide. In clinical settings, diagnosis has previously relied on microscopic techniques. However, enteric parasite targeting molecular tools, such as real-time PCR panels, have superseded microscopy in recent years. This body of work examines the nature, implications and opportunities of this paradigm shift. This thesis is divided into seven chapters that consist of a literature review chapter, five experimental chapters focusing on the molecular diagnosis and epidemiological analysis of Cryptosporidium spp., and a final summary chapter. Chapter I provides the contextual narrative and supportive reasoning behind the research undertaken …

Ifn-Γ Increases The Expression Of Sars-Cov-2 Receptors On Vero E6 Cells, Bindu Madhavi Madabattula

Browse all Theses and Dissertations

Respiratory epithelial cells are the initial target for SARS-CoV-2 infection. IFN-γ is known to increase the expression of ACE-2, an initial receptor for SARS-CoV-2, on epithelial cells. This study focuses on examining the effect of IFN-γ for ACE-2, TMPRSS2, and neuropilin-1 on Vero E6 cells using two immunofluorescence methods, namely, direct (membrane) fluorescence method and Cytation5 method. Direct fluorescence was determined using an Accu-Scope and ImageJ analysis. Using this method, significance (p<0.023) was observed only for ACE-2 when Vero E6 cells were treated with IFN-γ. Cytation5 fluorescence was determined using a Bio-tek Cytation5 plate reader. The results showed that IFN-γ significantly increased (p<0.001) the expression of ACE-2, neuropilin-1, and TMPRSS2. These results indicate Cytation5 is a more sensitive method for determining the expression of receptors on Vero E6 cells. The elevated levels of SARS-CoV-2 receptors expression resulting from IFN-γ treatment makes the epithelial cells more susceptible targets of SARS-CoV-2 infection. IFN-γ is most likely provided by innate immune cells in the initial COVID-19 infection, consequently contributing to the severity of disease.

Expression Of Sars Cov2 Receptors Influenced Upon Cytokine Polarizations (Il-4 And Ifnγ) In Hemangioendothelioma Cells, Chandra Lekha Koopari

Browse all Theses and Dissertations

Endothelial cells are distinct multifunctional cells with essential metabolic and synthetic roles along with their ability to function as selective permeability barrier. Endothelial cells (ECs), the major component of blood vessels, essentially interact directly yet differently with inflammatory cytokines. ECs are well recognized to be polarized cells, but little is known about the potential function of inflammatory mediators. Covid 19 may have long-term health effects on par with chronic illnesses. Vascular inflammatory disease and coagulopathy linked to COVID-19 are exacerbated by endothelial cell (EC) dysfunction. SARS-CoV-2 enters the host cell through the Angiotensin Converting Enzyme 2 (ACE2) receptor and primes …

Tetramerization Of Stat5 Has Opposing Roles In Governing Autoimmune Pathogenesis, Kelly Lynn Monaghan

Graduate Theses, Dissertations, and Problem Reports (ETD)

Signal transducers and activators of transcription 5 (STAT5A and STAT5B) are members of the STAT protein family. STAT5 plays a critical role in mediating cellular responses following cytokine stimulation. Critical STAT5 signaling is achieved following functional dimerization, which occurs via SH2 domain interactions. The binding of two STAT5 dimers to tandemly linked TTCN₃GAA γ-interferon-activated sequence (GAS) motifs and N-terminal domain interactions, facilitates functional tetramerization. The biological role of STAT5 tetramers has been investigated using the Stat5a-Stat5b N-domain double knock-in (DKI) mouse strain, in which STAT5 tetramers cannot be formed due to substitutions in critical amino acid …

Utilizing The K18-Hace2 Mouse Model To Develop Protective Covid-19 Vaccines, Ting Y. Wong

Graduate Theses, Dissertations, and Problem Reports (ETD)

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the respiratory virus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Similar to other respiratory viruses, SARS-CoV-2 is transmitted through inhalation of respiratory droplets and aerosols from infected individuals. Once inhaled, SARS-CoV-2 utilizes the receptor binding domain (RBD) on the spike protein to bind to human Angiotensin Converting Enzyme 2 (hACE2) receptor to gain entrance into host cells to begin viral replication. SARS-CoV-2 infection can result in mild to severe cases of COVID-19 ranging from asymptomatic infections, cold or flu like symptoms to respiratory failure. The onset of the pandemic in …

Structural Variant-Based Pangenome Construction Has Low Sensitivity To Variability Of Haplotype-Resolved Bovine Assemblies, Alexander S. Leonard, Danang Crysnanto, Zih-Hua Fang, Michael P. Heaton, Brian L. Vander Ley, Carolina Herrera, Heinrich Bollwein, Derek M. Bickhart, Benjamin D. Rosen, Hubert Pausch

School of Veterinary and Biomedical Sciences: Faculty Publications

Advantages of pangenomes over linear reference assemblies for genome research have recently been established. However, potential effects of sequence platform and assembly approach, or of combining assemblies created by different approaches, on pangenome construction have not been investigated. Here we generate haplotype-resolved assemblies from the offspring of three bovine trios representing increasing levels of heterozygosity that each demonstrate a substantial improvement in contiguity, completeness, and accuracy over the current Bos taurus reference genome. Diploid coverage as low as 20x for HiFi or 60x for ONT is sufficient to produce two haplotype-resolved assemblies meeting standards set by the Vertebrate Genomes Project. …

Does Swab Type Matter? Comparing Methods For Mannheimia Haemolytica Recovery And Upper Respiratory Microbiome Characterization In Feedlot Cattle, William B. Crosby, Lee Pinnell, John T. Richeson, Cory Wolfe, Jake Castle, John Dustin Loy, Sheryl P. Gow, Keun Seok Seo, Sarah F. Capik, Amelia R. Woolums, Paul S. Morley

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Bovine respiratory disease (BRD) is caused by interactions among host, environment, and pathogens. One standard method for antemortem pathogen identification in cattle with BRD is deep-guarded nasopharyngeal swabbing, which is challenging, costly, and waste generating. The objective was to compare the ability to recover Mannheimia haemolytica and compare microbial community structure using 29.5 inch (74.9 cm) deep-guarded nasopharyngeal swabs, 16 inch (40.6 cm) unguarded proctology swabs, or 6 inch (15.2 cm) unguarded nasal swabs when characterized using culture, real time-qPCR, and 16S rRNA gene sequencing. Samples for aerobic culture, qPCR, and 16S rRNA gene sequencing were collected from the …

Creating A Pre-Illness Covid-19 Action Plan: A Web-Based Public Education Initiative, Brian S. Hustad

DNP Research Projects

Abstract

Background: The COVID-19 pandemic took the world by storm in the beginning stages of 2020. Public health agencies were overwhelmed, undermanned, and therefore slow to respond. Information began to flow at an unprecedented rate. Yet, very limited resources were put into place to present this information or to instruct the public on evidence-based prevention, treatment, or care at home during active infection.

Intervention: A project website was created and accessed through a QR code on the project flyer or by entering the URL into any browser. Participants were able to access three evidence- based video modules, which introduced the …

Amblyomma Quadricavum (Schulze, 1941) (Acari:Ixodidae): First Description Of The Nymphal Stage And Phylogenetic Assessment Of Its Taxonomic Status, Ashleigh V. Riggs

College of Graduate Studies: Theses & Dissertations

The hard tick (Acari: Ixodidae) Amblyomma quadricavum (Schulze, 1941) is a parasite of snakes and is endemic to the Caribbean region. Morphological characters of this species, namely its rudimentary eye structures, have led to debate about its taxonomic status. The species was originally assigned to the genus Aponomma. However, with revisions of the genus Aponomma, and the recent creation of new genera created for some basal former-Aponomma, it has been suggested that perhaps Amblyomma quadricavum might be a close relative of Robertsicus elaphensis, the Trans-Pecos rat snake tick of the southwest United States and New Mexico, another eyeless former-Aponomma species …

Genomic Approaches To Uncovering The Coevolutionary History Of Parasitic Lice [Review], Kevin P. Johnson

Harold W. Manter Laboratory of Parasitology: Library Materials

Next-generation sequencing technologies are revolutionizing the fields of genomics, phylogenetics, and population genetics. These new genomic approaches have been extensively applied to a major group of parasites, the lice (Insecta: Phthiraptera) of birds and mammals. Two louse genomes have been assembled and annotated to date, and these have opened up new resources for the study of louse biology. Whole genome sequencing has been used to assemble large phylogenomic datasets for lice, incorporating sequences of thousands of genes. These datasets have provided highly supported trees at all taxonomic levels, ranging from relationships among the major groups of lice to those among …

Methodology To Estimate Natural- And Vaccine-Induced Antibodies To Sars-Cov-2 In A Large Geographic Region, Stacia M Desantis, Luis G León-Novelo, Michael D Swartz, Ashraf S Yaseen, Melissa A Valerio-Shewmaker, Yashar Talebi, Frances A Brito, Jessica A Ross, Harold W Kohl, Sarah E Messiah, Steve H Kelder, Leqing Wu, Shiming Zhang, Kimberly A Aguillard, Michael O Gonzalez, Onyinye S Omega-Njemnob, David Lakey, Jennifer A Shuford, Stephen Pont, Eric Boerwinkle

Faculty, Staff and Student Publications

Accurate estimates of natural and/or vaccine-induced antibodies to SARS-CoV-2 are difficult to obtain. Although model-based estimates of seroprevalence have been proposed, they require inputting unknown parameters including viral reproduction number, longevity of immune response, and other dynamic factors. In contrast to a model-based approach, the current study presents a data-driven detailed statistical procedure for estimating total seroprevalence (defined as antibodies from natural infection or from full vaccination) in a region using prospectively collected serological data and state-level vaccination data. Specifically, we conducted a longitudinal statewide serological survey with 88,605 participants 5 years or older with 3 prospective blood draws beginning …

Antibiotic Permeation In Gram-Negative Bacteria And Contribution Of Inflammasome Activation And Pyroptosis In Pathogenesis Of Salmonella Systemic Infection, Ankit Pandeya

Theses and Dissertations--Chemistry

Antibiotic resistance is one of the major global issues in the field of public health and medicine. Good antibiotic candidates need to be selectively toxic, inhibit cellular target, and effectively penetrate and accumulate in bacterial cells. The last factor is a formidable barrier in the development of antimicrobials effective in Gram-negative bacteria, due to the presence of two layers of cell envelope. The first half of my thesis focuses on understanding the permeation of small molecules through this formidable cell envelope, distribution inside the cell of Gram-negative bacteria, and design of novel methods to make small molecules effectively cross the …

Cell-Engineered Vesicles For Therapeutic Delivery And Immunomodulatory Applications, Khaga Neupane

Theses and Dissertations--Chemistry

Development of a new kind of drug delivery system (DDS) that could efficiently deliver therapeutics to the cell of interest would allow us to accomplish cell-specific drug delivery while eliminating systemic toxicity. Although nanocarriers including endogenously released extracellular vesicles (EEVs), liposomes, and small molecules seem to be promising drug delivery systems, biological challenges persist for their use in clinical applications. Here, we demonstrate nanovesicles engineered by fragmenting cellular membranes can be exploited as versatile DDSs for therapeutics delivery as well as immunomodulatory functions. Cell-engineered vesicles were produced by cavitating cells using nitrogen gas at high pressure followed by serial centrifugation. …

Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila R. Kunuthuru, Laura Graham, Harry D. Bear Md, Phd

UROP Posters

Breast cancer has the highest incidence rate of all cancers globally in women, and those of African descent, especially West African females, face higher rates of triple-negative breast cancer (TNBC), a more aggressive form of breast cancer. Immunotherapy for breast cancer is a relatively new treatment option, and research is ongoing to identify the best combination treatments for increasing survival of those diagnosed with TNBC. Eganelisib (IPI-549: a PI3K-gamma inhibitor that works to shift M2 macrophages to M1 to augment T cell function) with other combinatory treatments has shown promising results in reducing tumor growth and increasing survival in mice. …