Immunology and Infectious Disease Commons^™

Discovery Of Exosomes From Tick Saliva And Salivary Glands Reveals Therapeutic Roles For Cxcl12 And Il-8 In Wound Healing At The Tick-Human Skin Interface, Wenshuo Zhou, Faizan Tahir, Joseph Che-Yen Wang, Michael Woodson, Michael B. Sherman, Shahid Karim, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Ticks secrete various anti-coagulatory, anti-vasoconstrictory, anti-inflammatory, and anti-platelet aggregation factors in their saliva at the bite site during feeding to evade host immunological surveillance and responses. For the first time, we report successful isolation of exosomes (small membrane-bound extracellular signaling vesicles) from saliva and salivary glands of partially fed or unfed ixodid ticks. Our data showed a novel role of these in vivo exosomes in the inhibition of wound healing via downregulation of C-X-C motif chemokine ligand 12 (CXCL12) and upregulation of interleukin-8 (IL-8). Cryo-electron microscopy (cryo-EM) analysis revealed that tick saliva and salivary glands are composed of heterogeneous populations …

A Simple, Inexpensive Method For Mark-Recapture Of Ixodid Ticks, Alexis White, Robin Minch, Lindsey Bidder, Holly Gaff

Biological Sciences Faculty Publications

Mark-recapture techniques have been widely used and specialized to study organisms throughout the field of biology. To mark-recapture ticks (Ixodida), we have created a simple method to mark ticks using nail polish applied with an insect pin secured in a pencil that allows for a variety of questions to be answered. For measuring tick control efficacy, estimating population estimates, or measuring movement of ticks, this inexpensive mark-recapture method has been easily applied in the field and in the lab to provide useful data to answer a variety of questions about ticks.

The Heat Is On: Comparison Of Thermoregulatory Behavior In Parasitised Versus Unparasitized Caterpillars Of The Tobacco Hornworm, Manduca Sexta (L.) [Lepidoptera: Sphingidae], Jessica M. Johnston

Theses and Dissertations

Insect thermoregulatory research has demonstrated evidence of variation occurring within and among species with respect to infection, pathogens, and parasitism, but few studies have examined differences in thermoregulatory behavior in a host-parasite system with a coevolved symbiotic virus. I investigated the role of parasitism by Cotesia congregata (Say) (Hymenoptera: Braconidae) on the thermoregulatory behavior of Manduca sexta (L.) (Lepidoptera: Sphingidae) using an experimental design in a thermal gradient chamber and a complementary observational field study on wild M. sexta collected from tobacco farms. Parasitism and larval age were not found to have a significant effect on the preferred body temperature …

Isolation And Characterization Of Α-Gal-Containing Extracellular Vesicles (Evs) From Three Major Genotypes Of Trypanosoma Cruzi: Potential Biomarkers Of Chagas Disease, Nasim Karimi Hosseini

Open Access Theses & Dissertations

Chagas disease (ChD) is a neglected tropical disease (NTD) caused by the protozoan parasite, Trypanosoma cruzi. It is transmitted by the insect-vector triatomine (popular known as kissing bug), blood transfusion, organ transplantation, congenitally, and contaminated foods and juices. T. cruzi has evolved several strategies to invade the host cells, including the release extracellular vesicles (EVs), which assist pathogen survival and its replication within the host. T. cruzi is covered with highly glycosylated surface molecules such as glycoproteins and glycolipids, which are shown to be involved in the interaction with host immune cells. These molecules are highly immunogenic and reactive with …

Host Relationships And Geographic Distribution Of Species Of Blanchard, 1848 (Onchoproteocephalidea, Onchobothriidae) In Elasmobranchs: A Metadata Analysis, Francisco Zaragoza-Tapia, Griselda Pulido-Flores, Scott L. Gardner, Scott Monks

Scott L. Gardner Publications

Species of Acanthobothrium have been documented as parasites of the spiral intestine of elasmobranchs. Results of a metadata analysis indicate that 114 species of elasmobranchs have been reported as hosts of 200 species of Acanthobothrium. The metadata analysis revealed that 3.7% of species of sharks and 14.9% of species of rays that have been reported as hosts to date; some species are parasitized by more than one species of Acanthobothrium. This work provides a Category designation, as proposed by Ghoshroy and Caira (2001), for each species of Acanthobothrium. These Category designations are a tool to facilitate comparisons …

Obituary: Sydney Anderson (1927–2018), Scott Lyell Gardner, Robert M. Timm, Nancy Olds, Hugh H. Genoways

Scott L. Gardner Publications

On August 12, 2018, the American Society of Mammalogists (ASM) lost one of its giants of the latter half of the 20th century when Sydney Anderson quietly passed away at his home in Birmingham, Alabama, at the age of 91. “Syd,” to his many friends and colleagues, was born on January 11, 1927 in Topeka, Kansas, to Robert Grant and Evelyn Fern (Hunt) Anderson.

Anderson began his professional career at the University of Kansas, where for four years (1955–1959) he served as Assistant Curator in charge of mammals in the Museum of Natural History, and Instructor in the Department of …

Using Phytoglycogen-Based Nanoparticles To Enhance Inosine Monophsophate Delivery Using Rainbow Trout And Bovine Models, Kristof Jenik

Theses and Dissertations (Comprehensive)

Recently, there has been interest in the use of nucleotides in industrials feeds, with inosine monophosphate showing the most promising effects on growth and immunity. Rainbow trout and Alberta cattle are two of Canadas most profitable farmed animals, if their growth rates and immunity could be enhanced this would further improve their value. The impacts of IMP, a phytoglycogen-based nanoparticle (NP) and inosine monophosphate cationically bound to the phytoglycogen-based nanoparticle (IMP-NP) were characterized in rainbow trout in vivo and in vitro and in vitro in bovine cells. Rainbow trout that were fed an IMP-NP containing feed on average had higher …

Investigation Of Rna Interference (Rnai)-Mediated Gene Silencing In Rainbow Trout, Sarah Au

Theses and Dissertations (Comprehensive)

RNA interference (RNAi) was first characterized in plants and invertebrates as an antiviral innate immune response. It is a natural antiviral defence mechanism to degrade viral RNA by virus-induced gene silencing. Studies showed synthetic long double-stranded RNA (dsRNA; >30bp) degraded Caenorhabditis elegans messenger RNA (mRNA) transcripts, resulting in sequence-dependent gene silencing. Currently, there is only limited research on RNAi in fish, particularly the use of long dsRNA to trigger sequence-specific gene silencing. This is because studies have shown long dsRNAs trigger interferon response that could mask gene-specific RNAi effects. This thesis explored long dsRNA-mediated RNAi pathways in rainbow trout cells …

Identification Of A Novel Single Amino Acid Substitution (V666g) Of Jak1 From A Patient With Acute Lymphoblastic Leukemia Impairs Jak3 Mediated Il-2 Signaling, Alice Hernandez Grant

Open Access Theses & Dissertations

The Janus kinase (JAK) family, notably JAK1, JAK2 and JAK3 are recognized as oncogenic drivers in high risk Acute Lymphoblastic Leukemia (ALL). The bulk of activating JAK mutations are thought to occur within functional hot-spots across Janus Homology (JH) domains. The most frequently mutated regions is the JH2 pseudo-kinase, which provides a negative regulatory role to the adjacent catalytically active JH1 kinase domain. Despite the prevalence of JAK activating mutations and a need for new therapeutic inhibitors, there is a lack of understanding in the allosteric regulation of JAK kinases. Here we sought to identify mutations involved in driving ALL …

Mosquito Diversity And Positive Pools For The West Nile Virus In Forested Versus Non-Forested Areas, Elizabeth C. Paul

Honors Projects

The West Nile virus (WNV) is one of the leading causes of mosquito borne illness in the United States (CDC, 2018). This virus is a neurotropic pathogen that can cause fever and encephalitis. It is known that the Culex species is the primary vector for WNV. Humans infected with the WNV are typically asymptomatic. There is a small portion of individuals that experience West Nile fever which could include symptoms like high fever, vision loss, and coma (CDC, 2018). Previous studies have shown that mosquitoes tend to favor forests and wetlands (Hay et al., 1998), however, it is unknown if …

Role Of Topoisomerase Ii Alpha In Dna Topology And T Cell Responses During Chronic Viral Infections, Stella Chinyere Ogbu

Electronic Theses and Dissertations

The clearance of viruses is largely dependent upon the activation of T cells to generate a robust immune response. However, host responses are suppressed during chronic viral infections. In this thesis, we explored the role of Top2α in DNA topology in individuals with chronic HBV, HCV, and HIV infections. We found that Top2α protein expression and activity were low in T cells derived from chronically virus-infected individuals compared to healthy subjects. Using CD4⁺ T cells treated with Top2α inhibitor or poisoner as a model, we demonstrated that Top2α inhibition disrupts the DNA topology, suppresses DNA repair kinase (ATM), and …

Immune Gene Diversity And Populations Structure Of Reticulated Flatwoods Salamander (Ambystoma Bishopi), Steven Tyler Williams

LSU Master's Theses

Reticulated flatwoods salamander (Ambystoma bishopi) populations began decreasing dramatically in the late 1900s. Contemporary populations are small, isolated, and may be susceptible to inbreeding and reduced adaptive potential because of low genetic variation. Genetic variation at immune genes is especially important as it influences disease susceptibility and adaptation to emerging infectious pathogens, a central conservation concern for declining amphibians. Connectivity between isolated populations is also vital to maintain genetic diversity and avoid inbreeding. I collected tissue samples from across the extant range of this salamander to examine genetic variation and population structure in: immune genes broadly (immunome), the …

Extracellular Vesicle-Mediated Macrophage Activation: An Insight Into The Mechanism Of Thioredoxin-Mediated Immune Activation, Chontida Yarana, Hannah Thompson, Luksana Chaiswing, D. Allan Butterfield, Heidi L. Weiss, Subbarao Bondada, Sara S. Alhakeem, Suriyan Sukati, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Extracellular vesicles (EVs) generated from redox active anticancer drugs are released into the extracellular environment. These EVs contain oxidized molecules and trigger inflammatory responses by macrophages. Using a mouse model of doxorubicin (DOX)-induced tissue injury, we previously found that the major sources of circulating EVs are from heart and liver, organs that are differentially affected by DOX. Here, we investigated the effects of EVs from cardiomyocytes and those from hepatocytes on macrophage activation. EVs from H9c2 rat cardiomyocytes (H9c2 EVs) and EVs from FL83b mouse hepatocytes (FL83 b EVs) have different levels of protein-bound 4-hydroxynonenal and thus different immunostimulatory effects …

Role Of Host Cell Β-Catenin During Toxoplasma Gondii Infection, Cameron H. Ranken

Biology ETDs

The microbial pathogen Toxoplasma gondii is an intracellular protozoan that actively invades host cells and simultaneously creates a specialized parasitophorous vacuole within which the parasite lives and replicates. The parasite molecular machinery that drives establishment of the intracellular niche is relatively well known. However, it is now emerging that Toxoplasma exploits less well-understood host cell components to enable successful infection. Here, we examined the role of host Wnt/β-catenin during T. gondii infection. Using human fibroblasts and a mouse dendritic cell line, we found that infection with Toxoplasma stimulated both upregulation and nuclear localization of β-catenin. Using a transwell experimental approach, …

Development Of A Prolyl Endopeptidase Expression System In Lactobacillus Reuteri To Reduce The Clinical Manifestation Of Celiac Disease, Kara Lynn Jew

Master's Theses

Celiac Disease (CD) is an autoimmune disorder that emerges due to the ingestion of gluten, a protein found in a variety of common grains such as wheat, rye, and barley. Approximately 1 in 100 individuals in the US suffer from CD, making it the most commonly diagnosed gastrointestinal disorder (Ciclitira et. al., 2005). These proline-rich gluten peptides are resistant to proteolysis and accumulate in the duodenum of the small intestine. Once in the duodenum, these peptides illicit an autoimmune response resulting in villous atrophy. Current treatment for CD requires a rigorous adherence to a gluten-free diet. Nevertheless, gluten-containing grains are …

A Rapid Viability And Drug‑Susceptibility Assay Utilizing Mycobacteriophage As An Indicator Of Drug Susceptibilities Of Anti‑Tb Drugs Against Mycobacterium Smegmatis Mc2 155, Gillian Catherine Crowley, Jim O'Mahony, Aidan Coffey, Riona G. Sayers, Paul D. Cotter

Department of Biological Sciences Publications

Background: A rapid in-house TM4 mycobacteriophage-based assay, to identify multidrug resistance against various anti-tuberculosis drugs, using the fast-growing Mycobacterium smegmatis mc² 155 in a microtiter plate format was evaluated, based on phage viability assays. Methods: A variety of parameters were optimized before the study including the minimum incubation time for the drugs, phage and M. smegmatis mc² 155 to be in contact. An increase in phage numbers over 2 h was indicative that M. smegmatis mc² 155 is resistant to the drugs under investigation, however when phage numbers remained static, M. smegmatis mc² 155 found to …

Htlv-1 Latency-Maintenance Factor P30ii Modulates Tax-Induced Nf-Kappa B Signaling Through A P53-Regulated Mechanism, Aditi Malu

Biological Sciences Theses and Dissertations

The human T-cell leukemia virus type-1 (HTLV-1) infects CD4+ T-cells and is the etiological agent of adult T-cell leukemia/lymphoma (ATL), an aggressive and often-fatal lymphoproliferative neoplastic disease. The major transactivator protein, Tax, drives proviral gene expression and replication and plays a key role during the early-stage immortalization of T-cells by HTLV-1. Tax has also been shown to regulate many host cellular signaling pathways, including CREB/ATF, SRF, and NFκB. Another accessory viral protein p30_II acts as a latency-maintenance factor and negatively regulates proviral gene expression and replication. The p30^II protein counters Tax-dependent gene expression at the transcriptional and posttranscriptional …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

The Endosymbiotic Gut Fungus Zancudomyces Culisetae Influences Transstadial Transmission Of Host-Associated Microbiota In The Yellow Fever Mosquito (Aedes Aegypti), Jonas Frankel-Bricker

Boise State University Theses and Dissertations

Mosquitoes are vectors for a variety of human pathogens and have a significant impact on human health worldwide. There is growing evidence that host-associated microbiota influence mosquito vector competence for certain viruses. Transstadial transmission of bacteria from larvae through pupae to adults could affect these interactions, though further studies are needed to fully unravel the mechanisms involved. Current microbiome research primarily focuses on bacterial communities, whereas the potential role endosymbiotic gut fungi have in transstadial transmission dynamics remains largely unknown. Trichomycetes is an ecological group of endosymbiotic microfungi that colonize the digestive tracts of arthropod hosts, including the Yellow Fever …

Cross-Presentation Is A Source Of Tumor Antigens For Multiple Myeloma Immunotherapy, Alexander A. Perakis

Dissertations and Theses (Open Access)

Cross-presentation is an essential bridge between the innate and adaptive arms of the immune system where antigen presenting cells (APCs) prime cytotoxic T cell responses. We have recently identified cross-presentation as a mechanism by which solid tumors present exogenous antigens. We therefore hypothesized that multiple myeloma would be capable of cross-presentation as these cells are derived from B cells, known APCs. We explored the capacity of multiple myeloma to cross-present PR1, a human leukocyte antigen (HLA)-A2 nonameric peptide that is derived from neutrophil elastase (NE) and proteinase 3 (P3), and the ability to treat multiple myeloma using PR1-targeting immunotherapies. Here …

Enhancing Immunotherapeutic Interventions For Treatment Of Chronic Lymphocytic Leukemia, Kamira K. Maharaj

USF Tampa Graduate Theses and Dissertations

Chronic lymphocytic leukemia (CLL) is the most common leukemia in developed countries. It is characterized by the accumulation of CD5+ B lymphocytes in the peripheral blood, bone marrow, and lymphoid tissues of affected patients. Patients experience lymphadenopathy, fatigue, and are severely immunocompromised. Management of disease and symptoms is possible with chemo-immunotherapy for higher risk patients; however, CLL remains incurable unless bone marrow transplant is performed. Identification of novel targets and optimization of current therapeutics is therefore still necessary. The new targeted therapies are at the forefront of development for CLL treatment, but it remains challenging to maximize their efficacies while …

The Sucking Louse Fauna Of Mongolian Rodents: Host Associations, Molecular Phylogenetics And Description Of Two New Species, Chase N. Robinson

Honors College Theses

This study aimed to screen Mongolian rodents for sucking lice (Insecta: Phthiraptera: Anoplura) to better understand host-parasite associations for this understudied region. Nine species, including 3 previously undescribed, from 4 genera were identified. A molecular phylogeny based on 2 mitochondrial genes of collected louse specimens is included.

The Ecological Niche Of Echinococcus Multilocularis In North America: Understanding Biotic And Abiotic Determinants Of Parasite Distribution With New Records In New Mexico And Maryland, United States, Sebastian Botero-Cañola, Altangerel Tsogtsaikhan Dursahinhan, Sara E. Rácz, Parker V. Lowe, John E. Ubelaker, Scott Lyell Gardner

Scott L. Gardner Publications

English abstract: Understanding the factors shaping the niche of parasites and its expression over geographical space and through time continues to be a modern scientific challenge with the results of research in this area directly influencing both theoretical and applied biology. This is especially important for proactive management of zoonotic parasites such as Echinococcus multilocularis, the etiologic agent of alveolar echinococcosis. Echinococcus multilocularis has a Holarctic distribution; with its geographic range and prevalence increasing recently in areas of the western Palearctic, while its distribution dynamics are poorly understood in the Nearctic. In this paper, we use an ecological niche …

Impact Of Intrinsic Physiological Factors In The Population Recovery Of Myotis Lucifugus (Little Brown Myotis) From White-Nose Syndrome, Caroline Burke, Caitlin Looney, Alissah Sillah, Christopher Richardson

Lesley University Community of Scholars Day

White-nose Syndrome (WNS) has decimated populations of hibernating bats in the US. In particular, Myotis lucifugus (little brown myotis) has been one of the most affected. We investigated the energetic cost of innate immune response and Pseudogymnoascus destructans (Pd) fungal activity on post-hibernating little brown myotis and the link with the recovery of local populations in New England from WNS. We captured bats at one of each of 4 colonies in Eastern Massachusetts and Southern New Hampshire, consecutively, every 14 days to minimize disturbance to the colony. Blood samples were collected from each bat. Respirometry trials were performed on each …

Mrub_3019 Casa Gene Is An Ortholog To E. Coli B2760, Kelsey Heiland, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This research is part of the Meiothermus ruber genome annotation project which aims to predict gene function with various bioinformatics tools. We investigated the function of Mrub_3019, which encodes the CasA protein involved in the multi-subunit effector complex for the CRISPR-Cas immunity system and predicted it to be an ortholog of E. coli K12 MG1655 b2760 (casA). We predicted that Mrub_3019 encodes the protein CasA, which is involved in PAM recognition of CRISPR interference pathway. Foreign DNA will bind to CasA, which signals Cas3 for helicase-mediated DNA degradation. Our hypothesis is supported by low E-values for pairwise alignment in NCBI …

Structural And Functional Determinants Of Rodent And Human Surfactant Protein A: A Synthesis Of Binding And Computational Data, Armen Nalian, Todd M. Umstead, Ching-Hui Yang, Patricia Silveyra, Neal J. Thomas, Joanna Floros, Francis X. Mccormack, Zissis C. Chroneos

Faculty Publications

Surfactant protein A (SP-A) provides surfactant stability, first line host defense, and lung homeostasis by binding surfactant phospholipids, pathogens, alveolar macrophages (AMs), and epithelial cells. Non-primates express one SP-A protein whereas humans express two: SP-A1 and SP-A2 with core intra- and inter-species differences in the collagen-like domain. Here, we used macrophages and solid phase binding assays to discern structural correlates of rat (r) and human (h) SP-A function. Binding assays using recombinant rSP-A expressed in insect cells showed that lack of proline hydroxylation, truncations of amino-terminal oligomerization domains, and site-directed serine (S) or alanine (A) mutagenesis of cysteine 6 (C6S), …

Dynamics Of Two Pathogens In A Single Tick Population, Alexis White, Elsa Schaefer, Chelsea Wright-Thompson, Christopher M. Kribs, Holly Gaff

Biological Sciences Faculty Publications

A mathematical model for a two-pathogen, one-tick, one-host system is presented and explored. The goal of this model is to determine how long an invading pathogen persists within a tick population in which a resident pathogen is already established. The numerical simulations of the model demonstrate the parameter ranges that allow for coexistence of the two pathogens. Sensitivity analysis highlights the importance of vector-borne, tick-to-host, transmission rates on the invasion reproductive number and persistence of the pathogens over time. The model is then applied to a case study based on a reclaimed swampland field site in southeastern Virginia using field …

Multistate Survey Of American Dog Ticks (Dermacentor Variabilis) For Rickettsia Species, Joy A. Hecht, Michelle E.J. Allerdice, Elizabeth A. Dykstra, Laura Mastel, Rebecca J. Eisen, Tammi L. Johnson, Holly D. Gaff, Andrea S. Varela-Stokes, Jerome Goddard, Benedict B. Pagac, Christopher D. Paddock, Sandor E. Karpathy

Biological Sciences Faculty Publications

Dermacentor variabilis, a common human-biting tick found throughout the eastern half and along the west coast of the United States, is a vector of multiple bacterial pathogens. Historically, D. variabilis has been considered a primary vector of Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever. A total of 883 adult D. variabilis, collected between 2012 and 2017 from various locations in 12 states across the United States, were screened for rickettsial DNA. Tick extracts were evaluated using three real-time PCR assays; an R. rickettsii-specific assay, a Rickettsia bellii-specific assay, and a Rickettsia genus-specific …

Prime-Boost Vaccine Regimen For Sjtpl And Sjc23 Schistosome Vaccines, Increases Efficacy In Water Buffalo In A Field Trial In China, Akram A. Da'dara, Changlin Li, Xinling Yu, Mao Zheng, Jie Zhou, Lisa M. Shollenberger, Yue-Sheng Li, Donald A. Ham

Biological Sciences Faculty Publications

Schistosomiasis remains a serious zoonotic disease in China and the Philippines. Water buffalo and cattle account for the majority of transmission. Vaccination of water buffalo is considered a key strategy to reduce disease prevalence. Previously, we showed that vaccination of water buffalo with SjC23 or SjCTPI plasmid DNA vaccines, induced 50% efficacy to challenge infection. Here, we evaluated several parameters to determine if we can develop a two dose vaccine that maintains the efficacy of the three dose vaccine. We performed four trials evaluating: (1) lab produced vs. GLP grade vaccines, (2) varying the time between prime and boost, (3) …

Parasitic Dinoflagellate Hematodinium Perezi Prevalence In Larval And Juvenile Blue Crabs Callinectes Sapidus From Coastal Bays Of Virginia, H. J. Small, J. P. Huchin-Mian, K. S. Reece, K. M. Pagenkopp Lohan, Mark J. Butler Iv, J. D. Shields

Biological Sciences Faculty Publications

The parasitic dinoflagellate Hematodinium perezi infects the American blue crab Callinectes sapidus and other decapods along the Eastern seaboard and Gulf of Mexico coast of the USA. Large juvenile and adult blue crabs experience high mortality during seasonal outbreaks of H. perezi, but less is known about its presence in the early life history stages of this host. We determined the prevalence of H. perezi in megalopae and early benthic juvenile crabs from multiple locations along the Virginia portion of the Delmarva Peninsula. The DNA of H. perezi was not detected in any megalopae collected from several locations within …