Immunology and Infectious Disease Commons^™

Ruthenium-Azole Complexes As Chemotherapeutic Agents Against Leishmaniasis, Eva Iniguez

Open Access Theses & Dissertations

Leishmaniasis is a neglected disease that affects millions of people worldwide. Poor efficacy and high toxicity of the limited treatment options demonstrate the need for the development of new chemotherapeutic agents to treat this disease. In order to respond this concern, the development of novel Ru-azole complexes as chemotherapeutic agents by inhibiting the cytochrome P-450 dependent C14-α-demethylation of lanosterol to ergosterol which is essential for the parasite survival. In addition, Ruthenium would enhance the activity of the parental drug, by helping ketoconazole/clotrimazole to cross the parasite membrane, together presenting low toxicity. The viability and citotoxicity of the Ru-azole compunds was …

Neutralizing Antibodies Against The Ricin Toxin Binding Subunit (Rtb), Anastasiya Yermakova

Legacy Theses & Dissertations (2009 - 2024)

Ricin is a toxin that is naturally produced by the seeds of the castor bean plant Ricinus communis, and is part of a family of A-B toxins that includes Shiga, cholera, and anthrax toxins. The toxin consists of two subunits, RTA and RTB, which are linked by a disulfide bond. RTA is an RNA N-glycosidase that selectively targets and inactivates 28S ribosomal RNA, thereby arresting protein synthesis and leading to cell death. RTB is a galactose/ N-acetylgalactosamine-specific lectin that mediates attachment, entry, and intracellular trafficking of ricin in host cells. Currently, there is no approved vaccine or therapeutics available against …

Equine Serum Antibody Responses To Streptococcus Equi And Streptococcus Zooepidemicus, Rafaela De Negri

Theses and Dissertations--Veterinary Science

Streptococcus zooepidemicus (Sz) and Streptococcus equi (Se) share 98% DNA sequence homology, but display different pathogenic properties. Infection by one organism does not cross-protect against the other. To better understand pathogenic differences between these organisms and gain information about which proteins are expressed in horses infected experimentally with Se, intrauterine Sz or naturally with respiratory Sz we compared antibody specificities of convalescent sera using ELISA. These comparisons were based on sets of 8 and 14 immunoreactive recombinant proteins of Se strain CF32 and Sz strain NC78, respectively. Sera from donkeys that were previously naturally affected with strangles and later developed …

Understanding Amphibian Decline: The Role Of Pesticides And The Pathogenic Chytrid Fungus On Amphibians And Aquatic Communities, Taegan A. Mcmahon

USF Tampa Graduate Theses and Dissertations

Amphibians are the most threatened taxon on the planet. Declines have been associated with over-exploitation, habitat loss, pollution, and pathogenic diseases, but of these factors, pollution and disease have been relatively under-studied. Here, I investigated: 1) the impacts of commonly used pesticides on aquatic communities, 2) the effect of these pesticides on amphibian susceptibility to the pathogenic chytrid fungus, Batrachochytrium dendrobatidis (Bd), and 3) whether there are non-amphibian hosts of Bd and 4) how to best quantify the survival of Bd through ontogeny of the host.

In my first research chapter, I quantified the effects of environmentally relevant concentrations of …

Innate Immune Responses To Respiratory Syncytial Virus: Age-Associated Changes, Terianne Maiko Wong

USF Tampa Graduate Theses and Dissertations

Respiratory syncytial virus (RSV) infection causes ~64 million cases of respiratory disease and 200,000 deaths annually worldwide, yet there is no broadly effective prophylactic or treatment regimen. RSV can produce acute respiratory illness in patients of all ages but strikes the age extremes, infants and the elderly, with highest frequency presumably due to innate immune deficiencies. A higher morbidity and mortality has been reported for the elderly above 65 years of age, which has been attributed to immune senescence. Efforts to generate an effective vaccine have thus far been unsuccessful.

The innate immune system provides the first line of defense …

The Effect Of Exogenous Leptin On Dendritic Cell Migration And Interactions With T Cells, Amanda L. Gonzales

Open Access Theses & Dissertations

Obesity is a complex, chronic disease that has reached epidemic proportions in the United States and shows no indication of receding. It is a state of chronic low-grade inflammation that is initiated by morphological changes in large accumulations of adipose tissue. Leptin is a pleiotropic hormone secreted by adipose tissue, presenting a possible link between obesity and inflammation. In this study, we assessed the effect of leptin on bone marrow-derived (BM) dendritic cells (DC) (BM-DC) function, antigen presenting cells vital for the activation of naí¯ve T cells. Previous data produced in our laboratory established that the addition of leptin to …

Identification Of Chemotherapeutic Agents Against Leishmaniasis And Chagas' Disease, Miguel Abran Vasquez

Open Access Theses & Dissertations

Patients with clinical manifestations of leishmaniasis and Chagas' disease rely on few drugs that have limited efficacy and considerable side effects. Expanding the diversity of available chemotherapeutic drugs for these diseases is of extreme medical importance. Enones or á,í¢-unsaturated ketones, initially developed as anti-cancer agents, are a worthy of class of compounds to test for activity against Leishmania major and Trypanosoma cruzi as these eukaryotic parasites share many of the characteristics exhibited by cancer cells. The anti-parasitic activity of a library of á,í¢-unsaturated ketones (136 derivatives) was screened against L. major as well as in mammalian cells. Three compounds (NC901, …

Worms, Nematoda, Scott Lyell Gardner

Scott L. Gardner Publications

Nematodes are the most speciose phylum of metazoa on earth. Not only do they occur in huge numbers as parasites of all known animal groups, but also they are found in the soils, as parasites of plants, and in large numbers in the most extreme environments, from the Antarctic dry valleys to the benthos of the ocean. They are extremely variable in their morphological characteristics, with each group showing morphological adapta­tions to the environment that they inhabit. Soil-dwelling forms are extremely small; many marine species have long and complex setae; and parasitic species man­ifest amazingly great reproductive potential and large …

Mutations In Stat3 Associated With Human Hyper Ige Syndrome Enhance Nfκb And Mapk-Mediated Gene Expression, Nathaniel Greeley

Dissertations and Theses (Open Access)

Hyper IgE syndrome (HIES) is a multisystem disorder resulting in bone and immune system abnormalities. It is associated with mutations in STAT3, which disrupt protein domains responsible for transcriptional function. Patients with HIES display osteoporosis and enhanced inflammatory cytokine production similar to hematopoietic Stat3-deficient mice. Since osteoclast and inflammatory cytokine genes are NFκB targets, these observations indicate a possible deregulation of NFκB signaling in both mice and humans with STAT3-deficiency. Here, we sought to examine the role of STAT3 in the regulation of NFκB-mediated gene expression through analysis of three HIES STAT3 point mutations in both hematopoietic and non- hematopoietic …

Regulation Of To Xin Synthesis By Clostridium Difficile, Charles Darkoh

Dissertations and Theses (Open Access)

Clostridium difficile is the leading definable cause of nosocomial diarrhea worldwide due to its virulence, multi-drug resistance, spore-forming ability, and environmental persistence. The incidence of C. difficile infection (CDI) has been increasing exponentially in the last decade. Virulent strains of C. difficile produce either toxin A and/or toxin B, which are essential for the pathogenesis of this bacterium. Current methods for diagnosing CDI are mostly qualitative tests that detect the bacterium, the toxins, or the toxin genes. These methods do not differentiate virulent C. difficile strains that produce active toxins from non-virulent strains that do not produce toxins or produce …

Pathogen Response Genes Mediate Caenorhabditis Elegans Innate Immunity, Hannah L. Anthony

Celebration

Innate immunity is crucial in the response and defense against pathogens for invertebrates and vertebrates alike. The soil nematode Caenorhabditis elegans is a useful model to study the eukaryotic innate immune response to microbial pathogenesis. Prior research indicates that the protein receptor FSHR-1 plays an important role in the innate recognition of intestinal infection due to pathogen consumption. Determining what genes are controlled by FSHR-1 may uncover an unknown pathway that could increase not only the comprehension of the C. elegans immune system but also innate immunity generally. To characterize the function of FSHR-1, four candidate pathogen response genes that …

Genetic Variation In Potentially Virulent Vibrio Parahaemolyticus From The Northern Gulf Of Mexico, Nicholas Felix Noriea Iii

Dissertations

Vibrio parahaemolyticus (V_p) is a gram-negative bacterium found naturally in marine and estuarine environments. V_p is found in oysters including those which are later consumed by the public. Sub-populations of potentially virulent Vp contain specific virulence factors and are relevant human pathogens capable of causing gastroenteritis, wound infection, and death. The tdh and trh genes, both encoding hemolysins, have been correlated with the majority of clinical V_p isolates but have not been shown to be the definitive virulence factors.

A total of 146 V_p isolates from the northern Gulf of Mexico were collected and probed …

Signaling Pathways And Genetic Interactions That Lead To Metastatic Cancer In Drosophila Melanogaster, Amanda Cole

Renée Crown University Honors Thesis Projects - All

Cancer is a complex and multigenic disease, which is typically initiated by genetic mutations in tumor suppressor genes that regulate homeostatic mechanisms within cells. Oncogenic promoter mutations, like those involved in signal transduction pathways, also have the potential to induce cancer in an otherwise healthy organism. Transformation is highly dependent upon mutations to both tumor suppressor and oncogenes, as neither mutation is exclusive in its ability to generate malignant tumors. In the model organism, Drosophila melanogaster, I have generated metastatic cancer through the genetic effect of overactive Raf signaling, in conjugation with silencing selected tumor suppressor genes using RNA …

Clam (Corbicula Fluminea) As A Potential Sentinel Of Human Norovirus Contamination In Freshwater, Xunyan Ye

Dissertations

The purpose of this study was to evaluate and validate the use of the clam Corbicula fluminea as a sentinel of human noroviruses (HuNoV) contamination in freshwater. The first specific aim was to develop a new method to extract HuNoV RNA from contaminated bivalves (e.g. oysters, clams) that would be much faster than existing methods. The procedure developed includes an initial total RNA extraction using TRI Reagent, followed by HuNoV RNA concentration and purification using biotinylated probe-capture technology. HuNoV RNA is finally detected by real-time RT-PCR. Using bivalve homogenates spiked with HuNoV, 100 PCR detection units of the virus was …

Polyglutamine Toxicity Is Controlled By Prion Composition And Gene Dosage In Yeast, He Gong, Nina V. Romanova, Kim D. Allen, Pavithra Chandramowlishwaran, Kavita Gokhale, Gary P. Newnam, Piotr Miceczkowski, Michael Y. Sherman, Yury O. Chernoff

Publications and Research

Polyglutamine expansion causes diseases in humans and other mammals. One example is Huntington’s disease. Fragments of human huntingtin protein having an expanded polyglutamine stretch form aggregates and cause cytotoxicity in yeast cells bearing endogenous QN-rich proteins in the aggregated (prion) form. Attachment of the proline(P)-rich region targets polyglutamines to the large perinuclear deposit (aggresome). Aggresome formation ameliorates polyglutamine cytotoxicity in cells containing only the prion form of Rnq1 protein. Here we show that expanded polyglutamines both with (poly-QP) or without (poly-Q) a P-rich stretch remain toxic in the presence of the prion form of translation termination (release) factor Sup35 (eRF3). …

Thoughts On Quorum Sensing And Fungal Dimorphism, Kenneth W. Nickerson, Audrey L. Atkin, Jessica C. Hargarten, Ruvini U. Pathirana, Sahar Hasim

Papers in Microbiology

Farnesol has been best studied for its role in regulating fungal dimorphism. However, farnesol is also a lipid and in this review we analyze data relevant to farnesol’s function and synthesis from the perspective of farnesol and bacterial endotoxins acting as membrane active compounds. This analysis implicates the possible roles of: (1) endotoxins in the regulation of farnesol production by C. albicans; (2) farnesol in the interactions between C. albicans and the host during disseminated infections; and (3) ubiquinones in the mechanisms for unusually high resistance to farnesol by some C. albicans cell types. Finally we discuss the implications …

Identification Of Epitopes On Ricin Toxin's Enzymatic Subunit (Rta) Critical For Eliciting Neutralizing Antibodies And Protective Immunity, Joanne Marie O'Hara

Legacy Theses & Dissertations (2009 - 2024)

Ricin toxin's enzymatic subunit (RTA) is a 267 amino acid RNA N-glycosidase that selectively depurinates eukaryotic ribosomal RNA and arrests protein synthesis. The crystal structure of RTA revealed that the protein assumes three distinct folding domains (FD). Residues within FD1 and FD2 form RTA's active site pocket and are proposed to interface with ribosomal proteins, while FD3's primary function is to associate with ricin's B subunit (RTB). In this study I sought to identify the regions of RTA that are important in eliciting toxin-neutralizing antibodies (TNA), as this information is critical for current efforts to develop RTA-based subunit vaccines. I …

In Vitro Propagation Of Candidatus Rickettsia Andeanae Isolated From Amblyomma Maculatum, Alison Luce-Fedrow, Chelsea Wright, Holly D. Gaff, Daniel E. Sonenshine, Wayne L. Hynes, Allen L. Richards

Biological Sciences Faculty Publications

Candidatus Rickettsia andeanae was identified during an investigation of a febrile outbreak in northwestern Peru (2002). DNA sequencing from two ticks (Amblyomma maculatum, Ixodes boliviensis) collected during the investigation revealed a novel Rickettsia agent with similarity to the spotted fever group rickettsiae. Since then, Candidatus R. similar to andeanae has been detected in A. maculatum ticks collected in the southeastern and southcentral United States, Argentina, and Peru. To date, Candidatus R. andeanae has not been successfully cultivated in the laboratory. We present evidence for the continuous cultivation in three cell lines of Candidatus R. similar to …

Evaluation Of Protection Induced By Dna Vaccine Candidate Against Leishmania Mexicana In Balb/C Mice Model, Rosina Rodarte

Open Access Theses & Dissertations

Background and Significance. The leishmaniases are a diverse group of diseases with four major clinical manifestations: cutaneous, mucocutaneous, visceral, and diffuse. Approximately 21 Leishmania species and 30 sandfly vectors have been implicated in human leishmaniasis. Leishmaniasis is endemic in 88 countries, 72 are developing countries. Currently, 350 million people live in leishmaniasis-endemic areas around the world. The true incidence of the disease is not known. However, the estimated incidence for visceral leishmaniasis is 500,000 cases per year, and for cutaneous and mucocutaneous leishmaniasis 1.5-2 million cases per year. Visceral leishmaniasis causes 70,000 deaths each year. In the Americas region, …

A New Genus And A New Species Of Cladorchiidae (Digenea: Dadayiinae) From Podocnemis Expansa (Chelonia) Of The Neotropical Region, State Of Pará, Brazil, Marcelo Knoff, Daniel Rusk Brooks, Maria Cristina Mullins, Delir Corrêa Gomes

Harold W. Manter Laboratory of Parasitology: Faculty Publications

A new species of amphistome digenean from the stomach and intestine of Podocnemis expansa (Pelomedusidae), of the tropical rain forest, from the State of Pará, Brazil, is described and allocated to a new genus (Oriximinatrema noronhae). The new species is characterized by the presence of an esophageal bulb, an esophageal extension uncovered by an extension of the pharyngeal sacs, a well-developed cirrus sac, post-bifurcal genital sucker, a ventro-terminal acetabulum with an anterior lip, and medium-sized eggs. This is the first report of a Dadayiinae trematode infecting a reptilian host.

Influence Of Detritus Levels And Organic Pollution On Interspecific Resource Competition, Oviposition Behavior, And Larval Survival Of Two Tire-Inhabiting Mosquito Species (Diptera: Culicidae), David Wayne Allgood

Master's Theses

Mosquitoes (Diptera: Culicidae) are vectors of disease in the adult stage, but understanding the factors affecting distributions of the immature stages is important to the understanding and control of adult populations. Discarded automobile tires comprise important larval mosquito habitats. The Asian tiger mosquito (Aedes albopictus) and the southern house mosquito (Culex quinquefasciatus) are two medically important species commonly found in tires, but factors affecting their larval distributions in tires have not been studied, nor have their interspecific interactions. I investigated the effects of chemicals associated with organic pollution on oviposition preferences and larval survival of both …

Avian Influenza In Migratory Birds In The United States, 2007–2009, And Effects Of September Hunting Seasons On Survival, Harvest, And Recovery Rates Of Canada Geese Banded In Southeast Nebraska, Scott R. Groepper

School of Natural Resources: Dissertations, Theses, and Student Research

Highly-pathogenic avian influenza virus (HPAIV H5N1) poses risks to wild birds, poultry, and humans. Personnel with the United States Department of Agriculture-Animal Plant Health Inspection Service-Wildlife Services, state, and tribal wildlife agencies collected 168,940 samples from migratory birds from 2007 to 2009 to test for presence of HPAIV H5N1. No HPAIV was found, but other subtypes were discovered, including H5 and H7. I estimated prevalence of avian influenza virus by flyway and found prevalence was lowest each year in the Atlantic Flyway (6.7%–8.3%), highest in the Pacific Flyway in 2007 (13.3%) and 2008 (13.4%), and highest in the Mississippi Flyway …

Upregulation Of Reactive Oxygen Species During The Retrovirus Life Cycle And Their Roles In A Mutant Of Moloney Murine Leukemia Virus, Ts1-Mediated Neurodegeneration, Soo Jin Kim

Dissertations and Theses (Open Access)

Viral invasion of the central nervous system (CNS) and development of neurological symptoms is a characteristic of many retroviruses. The mechanism by which retrovirus infection causes neurological dysfunction has yet to be fully elucidated. Given the complexity of the retrovirus-mediated neuropathogenesis, studies using small animal models are extremely valuable. Our laboratory has used a mutant moloney murine leukemia retrovirus, ts1-mediated neurodegneration. We hypothesize that astrocytes play an important role in ts1-induced neurodegeneration since they are retroviral reservoirs and supporting cells for neurons. It has been shown that ts1 is able to infect astrocytes in vivo and in …

Role Of Porcine Reproductive And Respiratory Syndrome Virus Non-Structural Protein 1 In Viral Replications And Pathogenesis, Lalit Kumar Beura

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Porcine reproductive and respiratory syndrome virus (PRRSV) is an infectious agent of significant concern to the global swine industry. PRRSV infection of pigs is initiated by a long viremia after which the virus enters in an extended persistent phase of 3-4 months that ultimately is resolved by the immune system. The delayed and weak host adaptive response is responsible for the protracted convalescence period. An initial sub-optimal innate immune response is postulated to be the reason behind such meager adaptive immune response. A major focus of the studies undertaken in this dissertation was to identify the viral non-structural proteins (nsps) …

Mathematical Modeling And Dynamical Analysis Of The Operation Of The Hypothalamus - Pituitary - Thyroid (Hpt) Axis In Autoimmune (Hashimoto's) Thyroiditis, Balamurugan Pandiyan

Dissertations (1934 -)

This thesis is a mathematical modeling study of the operation of the negative feedback control through the hypothalamus-pituitary- thyroid (HPT) axis in autoimmune (Hashimoto's) thyroiditis. Negative feedback control through the HPT axis is a mechanism in which the high levels of thyroid hormone; free thyroxine (FT4) in the blood inhibits the secretion of the pituitary hormone, thyroid stimulating hormone (TSH) into the blood. Similarly, the low levels of free thyroxine (FT4) sensed by the pituitary gland and then it secretes thyroid stimulating hormone (TSH) into the blood. Autoimmune (Hashimoto's) thyroiditis is a disease in which the immune system turns against …

Estrogenic Regulation Of The Immune System In A Murine Model For Systemic Lupus Erythematosus, Matthew James Zuber

Biology Honors Papers

Systemic Lupus Erythematosus is a damaging autoimmune disease afflicting millions of people worldwide. Lupus is characterized by an overabundance of autoantibodies, proteins directing the immune system to destroy a person's own body, what it would normally be protecting. The molecular mechanisms, environmental influences, and genetic predispositions of Lupus are not yet fully understood. However, nine out of ten Lupus patients are women between the age of puberty and menopause, when estrogen levels are highest. The fact that women are significantly more prone to suffer from Lupus than men leads experts to believe that the sex hormone estrogen which is present …

Assessment Of Pathways For The Introduction And Spread Of Mycobacterium Bovis In The United States, Katie Portacci, Jason Lombard, Lauren Abrahamsen, Eric Bush, Charles Fossler, Robert Harris, Kamina Johnson, Ryan S. Miller, Dianna Mitchell, Randy Pritchard, Steven Sweeney, Todd Weaver

Zoonotics and Wildlife Disease: Publications

Bovine tuberculosis (TB) was responsible for more losses among U.S. farm animals in the early 20th century than all other infectious diseases combined. The Cooperative State-Federal Tuberculosis Eradication Program (established in 1917 and administered by APHIS, State animal health agencies, and U.S. livestock producers) has nearly eradicated bovine TB from the nation’s livestock population. However, despite the many accomplishments of the program, bovine TB remains a serious and costly disease of livestock in the United States. In 1992, VS conducted an assessment to identify pathways for the introduction and spread of bovine TB, in order to develop the most effective …

Fascin1 Promotes Cell Migration Of Mature Dendritic Cells, Michael Lipscomb

Department of Biology Faculty Publications

Dendritic cells (DCs) play central roles in innate and adaptive immunity. Upon maturation, DCs assemble numerous veil-like membrane protrusions, disassemble podosomes, and travel from the peripheral tissues to lymph nodes to present Ags to T cells. These alterations in morphology and motility are closely linked to the primary function of DCs, Ag presentation. However, it is unclear how and what cytoskeletal proteins control maturation-associated alterations, in particular, the change in cell migration. Fascin1, an actin-bundling protein, is specifically and greatly induced upon maturation, suggesting a unique role for fascin1 in mature DCs. To determine the physiological roles of fascin1, we …

The Impact Of Tricaine Methanesulfonate, 2-Phenoxyethanol, And Carvone-Methyl Salicylate On The Innate Immune Response Of Zebrafish (Danio Rerio), Charles R. Wulff

Honors Theses

Anesthesia plays a vital role in the maintenance of aquaculture species, where it is used to minimize stress during complex handling tasks such as transport, assessment, and harvesting. However, anesthetics have been shown to suppress the innate immune response, which could impact immunity and increase risk of infection. Tricaine methanesulfonate (MS-222) and 2-Phenoxyethanol (2-PE) represent two of the most commonly used anesthetics in aquaculture, with R-(+)-carvone, in the form of carvone-methyl salicylate (CMS) has recently been proposed as an alternative anesthetic for food fish. These three anesthetics were used to assess the influence of anesthetics on the immune system of …

Preventing Mother-To-Child Transmission Of Human Immunodeficiency Virus-1 (Hiv-1): Effects Of Intrapartum And Neonatal Single-Dose Nevirapine Prophylaxis And Subsequent Hiv-1 Drug Resistance At Antiretroviral Treatment Initiation, Amanda L. Harmon

CMC Senior Theses

The prevention of mother-to-child transmission is one of the most powerful tools in human immunodeficiency virus type 1 (HIV-1) prevention and has huge potential to improve both maternal and child health. In the absence of any preventative measures, infants born to and breastfed by their HIV-positive mothers have roughly a one-in-three chance of acquiring the infection themselves. HIV can be passed on from mother-to-child during pregnancy, during labor and delivery, and even after during breastfeeding.

Intrapartum and neonatal single-dose nevirapine (sd-NVP) is the foundation of preventing mother-to-child transmission in lower resource settings where it has been used alone or as …