Immunology and Infectious Disease Commons^™

A Potent Antimalarial Benzoxaborole Targets A Plasmodium Falciparum Cleavage And Polyadenylation Specificity Factor Homologue., Ebere Sonoiki, Caroline L. Ng, Marcus C. S. Lee, Denghui Guo, Yong-Kang Zhang, Yasheen Zhou, M. R. K. Alley, Vida Ahyong, Laura M. Sanz, Maria Jose Lafuente-Monasterio, Chen Dong, Patrick G. Schupp, Jiri Gut, Jenny Legac, Roland A. Cooper, Francisco-Javier Gamo, Joseph Derisi, Yvonne R. Freund, David A. Fidock, Philip J. Rosenthal

Natural Sciences and Mathematics | Faculty Scholarship

Benzoxaboroles are effective against bacterial, fungal and protozoan pathogens. We report potent activity of the benzoxaborole AN3661 against Plasmodium falciparum laboratory-adapted strains (mean IC50 32 nM), Ugandan field isolates (mean ex vivo IC50 64 nM), and murine P. berghei and P. falciparum infections (day 4 ED90 0.34 and 0.57 mg kg-1, respectively). Multiple P. falciparum lines selected in vitro for resistance to AN3661 harboured point mutations in pfcpsf3, which encodes a homologue of mammalian cleavage and polyadenylation specificity factor subunit 3 (CPSF-73 or CPSF3). CRISPR-Cas9-mediated introduction of pfcpsf3 mutations into parental lines recapitulated AN3661 resistance. PfCPSF3 homology models placed these …

The Evaluation Of Carbon Dioxide-Independent Media For Toxoplasma Gondii Growth, Matthew C. Martens

UNO Student Research and Creative Activity Fair

Toxoplasma gondii is a human pathogen that plays a role as the causative agent of toxoplasmosis, a disease that produces many deleterious effects for immunocompromised individuals and infants. Current research involving this intracellular parasite requires the use and continues maintenance of costly cell incubators attached to bulky carbon dioxide canisters. To reduce laboratory costs and space requirements, we, therefore, propose a novel procedure by which human foreskin fibroblasts, as well as Toxoplasma gondii tachyzoites, may be grown in a commercially available carbon dioxide-independent media. Growth assays utilizing resazurin dye or relative fluorescence from parasites modified with a red fluorescent protein …

Foxo3 Increases Mir-34a To Cause Palmitate-Induced Cholangiocyte Lipoapoptosis, Sathish Kumar Natarajan, Bailey A. Stringham, Ashley M. Mohr, Cody J. Wehrkamp, Sizhao Lu, Mary Anne Phillippi, Duygu Dee Harrison-Findik, Justin L. Mott

School of Veterinary and Biomedical Sciences: Faculty Publications

Nonalcoholic steatohepatitis (NASH) patients have elevated plasma saturated free fatty acid levels. These toxic fatty acids can induce liver cell death and our recent results demonstrated that the biliary epithelium may be susceptible to lipotoxicity. Here, we explored the molecular mechanisms of cholangiocyte lipoapoptosis in cell culture and in an animal model of NASH. Treatment of cholangiocytes with palmitate (PA) showed increased caspase 3/7 activity and increased levels of cleaved poly (ADP-ribose) polymerase and cleaved caspase 3, demonstrating cholangiocyte lipoapoptosis. Interestingly, treatment with PA significantly increased the levels of microRNA miR-34a, a pro-apoptotic microRNA known to be elevated in NASH. …

A Blueprint To Evaluate One Health, Simon R. Rüegg, Barry J. Mcmahon, Barbara Häsler, Roberto Esposito, Helen O'Shea, Et Al

Department of Biological Sciences Publications

One Health (OH) positions health professionals as agents for change and provides a platform to manage determinants of health that are often not comprehensively captured in medicine or public health alone. However, due to the organization of societies and disciplines, and the sectoral allocation of resources, the development of transdisciplinary approaches requires effort and perseverance. Therefore, there is a need to provide evidence on the added value of OH for governments, researchers, funding bodies, and stakeholders. This paper outlines a conceptual framework of what OH approaches can encompass and the added values they can provide. The framework was developed during …

Elevated Prevalence Of Helicobacter Species And Virulence Factors In Opisthorchiasis And Associated Hepatobiliary Disease., Raksawan Deenonpoe, Eimorn Mairiang, Pisaln Mairiang, Chawalit Pairojkul, Yaovalux Chamgramol, Gabriel Rinaldi, Alex Loukas, Paul J. Brindley, Banchob Sripa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Recent reports suggest that Opisthorchis viverrini serves as a reservoir of Helicobacter and implicate Helicobacter in pathogenesis of opisthorchiasis-associated cholangiocarcinoma (CCA). Here, 553 age-sex matched cases and controls, 293 and 260 positive and negative for liver fluke O. viverrini eggs, of residents in Northeastern Thailand were investigated for associations among infection with liver fluke, Helicobacter and hepatobiliary fibrosis. The prevalence of H. pylori infection was higher in O. viverrini-infected than uninfected participants. H. pylori bacterial load correlated positively with intensity of O. viverrini infection, and participants with opisthorchiasis exhibited higher frequency of virulent cagA-positive H. pylori than those free of …

Advances In Neglected Tropical Disease Vaccines: Developing Relative Potency And Functional Assays For The Na-Gst-1/Alhydrogel Hookworm Vaccine., Jill B. Brelsford, Jordan L Plieskatt, Anna Yakovleva, Amar Jariwala, Brian P Keegan, Jin Peng, Pengjun Xia, Guangzhao Li, Doreen Campbell, Maria Victoria Periago, Rodrigo Correa-Oliveira, Maria Elena Bottazzi, Peter J. Hotez, David Diemert, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

A new generation of vaccines for the neglected tropical diseases (NTDs) have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. The current manuscript focuses on the often overlooked critical aspects of NTD vaccine product development, more specifically, vaccine stability testing programs. A key measure of vaccine stability testing is "relative potency" or the immunogenicity of the vaccine during storage. As with most NTD vaccines, the Na-GST-1/Alhydrogel Hookworm Vaccine was not developed by attenuation or inactivation of the pathogen (Necator americanus), so conventional methods for measuring relative potency are …

Immune Responses In Hibernating Little Brown Myotis (Myotis Lucifugus) With White-Nose Syndrome, Thomas M. Lilley, Jenni M. Prokkola, Elisabeth Jeanine Rogers, Sarah Gronsky, Allen Kurta, Deeann Reeder, Kenneth A. Field

Faculty Journal Articles

White-nose syndrome (WNS) is a fungal disease responsible for decimating many bat populations in North America. Pseudogymnoascus destructans (Pd), the psychrophilic fungus responsible for WNS, prospers in the winter habitat of many hibernating bat species. The immune response that Pd elicits in bats is not yet fully understood; antibodies are produced in response to infection by Pd, but they may not be protective and indeed may be harmful. To understand how bats respond to infection during hibernation, we studied the effect of Pd inoculation on the survival and gene expression of captive hibernating Myotis lucifugus with varying …

The Effects Of Camelina Sativa Meal On Haemonchus Contortus In Breeding Age Ewes, Nicole Julia Nichols

Student Theses and Dissertations

Gastrointestinal parasites (GIP) are one of the greatest threats to sheep production in the United States. Increased resistance to traditional anthelmintics has created the need for alternative methods to control GIP. The objective of this study was to determine if Camelina sativa (CS) meal could be fed as part of a daily ration to reduce infection rates of the GIP Haemonchus contortus during two 28-day trials. Forty-eight ewes were sorted and fed a 14% crude protein (CP) supplement with or without 10% CS as part of their daily ration. All ewes grazed a mixture of Bermuda (Cynodon dactylon) and tall …

Parasite Infection, Carcinogenesis And Human Malignancy., Hoang Van Tong, Paul J. Brindley, Christian G Meyer, Thirumalaisamy P Velavan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in …

Habitat And Community Associations And The Population Dynamics Of A Temporary Coral-Reef Fish Ectoparasite, John Michael Artim

Student Theses and Dissertations

Coral reef is habitat constructed by the scleractinian coral after which the habitat is named. While scleractinian coral colonies are often meters in extent, they are composed of small individual organisms—typically on the scale of millimeters across. Coral reefs that include an abundance of many coral species support a diverse abundance of fish and conspicuous invertebrate life. These macro constituents of coral reefs—coral colonies, reef fish and conspicuous invertebrates—have been the primary focus for much of the existing body of coral reef ecology research. One of the inconspicuous and understudied coral reef invertebrate constituents are gnathiid isopod fish parasites. These …

A Comparison Of The Quality Of Informed Consent For Clinical Trials Of An Experimental Hookworm Vaccine Conducted In Developed And Developing Countries., David J. Diemert, Lucas Lobato, Ashley Styczynski, Maria Zumer, Amanda Soares, Maria Flávia Gazzinelli

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Informed consent is one of the principal ethical requirements of conducting clinical research, regardless of the study setting. Breaches in the quality of the informed consent process are frequently described in reference to clinical trials conducted in developing countries, due to low levels of formal education, a lack of familiarity with biomedical research, and limited access to health services in these countries. However, few studies have directly compared the quality of the informed consent process in developed and developing countries using the same tool and in similar clinical trials. This study was conducted to compare the quality of the informed …

Detection Of Strongylus Vulgaris In Equine Faecal Samples By Real-Time Pcr And Larval Culture – Method Comparison And Occurrence Assessment, A. Kaspar, K. Pfister, Martin K. Nielsen, C. Silaghi, H. Fink, M. C. Scheuerle

Veterinary Science Faculty Publications

Background: Strongylus vulgaris has become a rare parasite in Germany during the past 50 years due to the practice of frequent prophylactic anthelmintic therapy. To date, the emerging development of resistance in Cyathostominae and Parascaris spp. to numerous equine anthelmintics has changed deworming management and the frequency of anthelmintic usage. In this regard, reliable detection of parasitic infections, especially of the highly pathogenic S. vulgaris is essential. In the current study, two diagnostic methods for the detection of infections with S. vulgaris were compared and information on the occurrence of this parasite in German horses was gained. For this purpose, …

Identification Of Candidate Infection Genes From The Model Entomopathogenic Nematode Heterorhabditis Bacteriophora., Jonathan Vadnal, Ramesh Ratnappan, Melissa Keaney, Eric Kenney, Ioannis Eleftherianos, Damien O'Halloran, John M. Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Despite important progress in the field of innate immunity, our understanding of host immune responses to parasitic nematode infections lags behind that of responses to microbes. A limiting factor has been the obligate requirement for a vertebrate host which has hindered investigation of the parasitic nematode infective process. The nematode parasite Heterorhabditis bacteriophora offers great potential as a model to genetically dissect the process of infection. With its mutualistic Photorhabdus luminescens bacteria, H. bacteriophora invades multiple species of insects, which it kills and exploits as a food source for the development of several nematode generations. The ability to culture …

Isolation, Culture And Characterization Of Hirsutella Sinensis Mycelium From Caterpillar Fungus Fruiting Body, Yun-Fei Komi, Jian-Ching Liau, Chien-Sheng Lee, Chen-Yaw Chiu, Jan Martel, Chuan-Sheng Lin, Shan-Fu Tseng, David M. Ojcius, Chia-Chen Lu, Hsin-Chih Lai, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

The caterpillar fungus Ophiocordyceps sinensis (previously called Cordyceps sinensis) has been used for centuries in Asia as a tonic to improve health and longevity. Recent studies show that O. sinensis produces a wide range of biological effects on cells, laboratory animals and humans, including anti-fatigue, anti-infection, anti-inflammatory, antioxidant, and anti-tumor activities. In view of the rarity of O. sinensis fruiting bodies in nature, cultivation of its anamorph mycelium represents a useful alternative for large-scale production. However, O. sinensis fruiting bodies harvested in nature harbor several fungal contaminants, a phenomenon that led to the isolation and characterization of a large number …

Genomes Of Fasciola Hepatica From The Americas Reveal Colonization With Neorickettsia Endobacteria Related To The Agents Of Potomac Horse And Human Sennetsu Fevers., Samantha N Mcnulty, Jose F Tort, Gabriel Rinaldi, Bruce A Rosa, Victoria H. Mann, Patricia S. Latham, Paul J. Brindley, +Several Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Food borne trematodes (FBTs) are an assemblage of platyhelminth parasites transmitted through the food chain, four of which are recognized as neglected tropical diseases (NTDs). Fascioliasis stands out among the other NTDs due to its broad and significant impact on both human and animal health, as Fasciola sp., are also considered major pathogens of domesticated ruminants. Here we present a reference genome sequence of the common liver fluke, Fasciola hepatica isolated from sheep, complementing previously reported isolate from cattle. A total of 14,642 genes were predicted from the 1.14 GB genome of the liver fluke. Comparative genomics indicated that F. …

Schistosoma Mansoni Reinfection: Analysis Of Risk Factors By Classification And Regression Tree (Cart) Modeling., Andréa Gazzinelli, Roberta Oliveira-Prado, Leonardo Ferreira Matoso, Bráulio M Veloso, Gisele Andrade, Helmut Kloos, Jeffrey M Bethony, Renato M Assunção, Rodrigo Correa-Oliveira

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Praziquantel (PZQ) is an effective chemotherapy for schistosomiasis mansoni and a mainstay for its control and potential elimination. However, it does not prevent against reinfection, which can occur rapidly in areas with active transmission. A guide to ranking the risk factors for Schistosoma mansoni reinfection would greatly contribute to prioritizing resources and focusing prevention and control measures to prevent rapid reinfection. The objective of the current study was to explore the relationship among the socioeconomic, demographic, and epidemiological factors that can influence reinfection by S. mansoni one year after successful treatment with PZQ in school-aged children in Northeastern Minas …

Ancylostoma Ceylanicum Infective Third-Stage Larvae Are Activated By Co-Culture With Ht-29-Mtx Intestinal Epithelial Cells, Caitlin Feather, John M. Hawdon, John March

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Human hookworm larvae arrest development until they enter an appropriate host. This makes it difficult to access the larvae for studying larval development or host-parasite interactions. While there are in vivo and in vitro animal models of human hookworm infection, there is currently no human, in vitro model. While animal models have provided much insight into hookworm biology, there are limitations to how closely this can replicate human infection. Therefore, we have developed a human, in vitro model of the initial phase of hookworm infection using intestinal epithelial cell culture.

Results

Co-culture of the human hookworm Ancylostoma ceylanicum with …

H-Ipse Is A Pathogen-Secreted Host Nucleus Infiltrating Protein (Infiltrin) 3 Expressed Exclusively By The Schistosoma Haematobium Egg Stage, Luke Pennington, Abdulaziz Alouffi, Evaristus Mbanefo, Debalina Ray, David Heery, Theodore Jardetzky, Michael Hsieh, Franco Falcone

Urology Faculty Publications

Urogenital schistosomiasis, caused by the parasitic trematode Schistosoma haematobium, affects over 112 million people worldwide. As with S. mansoniinfections, the pathology in urogenital schistosomiasis is mainly related to the egg stage, which induces granulomatous inflammation of affected tissues. Schistosoma eggs and their secretions have been studied extensively for the related S. mansoniorganism which is more amenable to laboratory studies. Indeed, we have shown that IPSE/alpha-1 (M-IPSE herein), a major protein secreted from S .mansoni eggs, can infiltrate host cells. Although M-IPSE function is unknown, its ability to translocate to their nucleus and bind DNA suggests a possible …

The Effect Of Gram-Positive Staphylococcus Aureus Cell Wall Components Lipoteichoic Acid And Peptidoglycan On Cytokine Production, Cytoskeletal Arrangement, And Cell Viability On Raw 264.7 Murine Macrophages, Gabrielle String

Browse all Theses and Dissertations

In this study, gram positive Staphylococcus aureus cell wall components such as lipoteichoic acid (LTA) and peptidoglycan (PGN) were used to study the potential inflammatory and anti-inflammatory cytokine response, cytoskeletal arrangement and cell viability on RAW264.7 murine macrophages over 24 hours. The effect of S.aureus LTA and PGN (5 µg/mL) on RAW 264.7 macrophages was evaluated every six hours for twenty-four hours. Inflammatory cytokine (TNF-a) production peaked at 6 hours before decreasing over time. Anti-inflammatory cytokine (IL-10) production peaked between 12 and 18 hours. During the first twenty-four hours, cytotoxicity of treated macrophages, as defined as the release of lactate …

Effects Of Socs1 And Socs3 Peptide Mimetics On Macrophage Phagocytosis Of Malignant Cells, Colt Dylan Capan

Browse all Theses and Dissertations

Macrophages play a key role in both the innate and adaptive immune system responses to foreign materials. Suppressors of cytokine signaling (SOCS) proteins are known as regulators of the immune response through various JAK/STAT pathways. This study examined the roles of SOCS1 and SOCS3 peptide mimetics on the phagocytosis of fluorescently labeled malignant target cell by RAW264.7 murine macrophages. The malignant cells used were Neuro-2a cells, a murine neuroblastoma cell line. A prominent "eat me" signal found in neuroblastoma cells is calreticulin (CRT), which permits macrophages to recognize and then phagocytize the malignant cells. When M1 (pro-inflammatory) polarized macrophages were …