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Sertraline, Paroxetine, And Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable Of Clinical Repurposing., Janis C Weeks, William M Roberts, Caitlyn Leasure, Brian M Suzuki, Kristin J Robinson, John M Hawdon, +several additional authors 2018 George Washington University

Sertraline, Paroxetine, And Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable Of Clinical Repurposing., Janis C Weeks, William M Roberts, Caitlyn Leasure, Brian M Suzuki, Kristin J Robinson, John M Hawdon, +Several Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. To expedite drug discovery, we screened a small-molecule library of compounds with histories of use in human clinical trials for anthelmintic activity against the soil nematode Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs sertraline, paroxetine, and chlorpromazine kill C. elegans at multiple life stages including embryos, developing larvae and gravid adults. These drugs act rapidly to inhibit C. elegans feeding within minutes of exposure. Sertraline, paroxetine, and chlorpromazine also decrease motility of adult Trichuris muris whipworms, prevent hatching ...


Lipophosphoglycan Polymorphisms Do Not Affect Leishmania Amazonensis Development In The Permissive Vectors Lutzomyia Migonei And Lutzomyia Longipalpis, Paula M. Nogueira, Agna C. Guimarães, Rafael R. Assis, Jovana Sadlova, Jitka Myskova, Katerina Pruzinova, Jana Hlavackova, Salvatore J. Turco, Ana C. Torrecilhas, Petr Volf, Rodrigo P. Soares 2017 Instituto René Rachou/FIOCRUZ, Brazil

Lipophosphoglycan Polymorphisms Do Not Affect Leishmania Amazonensis Development In The Permissive Vectors Lutzomyia Migonei And Lutzomyia Longipalpis, Paula M. Nogueira, Agna C. Guimarães, Rafael R. Assis, Jovana Sadlova, Jitka Myskova, Katerina Pruzinova, Jana Hlavackova, Salvatore J. Turco, Ana C. Torrecilhas, Petr Volf, Rodrigo P. Soares

Molecular and Cellular Biochemistry Faculty Publication

Background: Lipophosphoglycan (LPG) is a dominant surface molecule of Leishmaniapromastigotes. Its species-specific polymorphisms are found mainly in the sugars that branch off the conserved Gal(β1,4)Man(α1)-PO4 backbone of repeat units. Leishmania amazonensis is one of the most important species causing human cutaneous leishmaniasis in the New World. Here, we describe LPG intraspecific polymorphisms in two Le. amazonensis reference strains and their role during the development in three sand fly species.

Results: Strains isolated from Lutzomyia flaviscutellata (PH8) and from a human patient (Josefa) displayed structural polymorphism in the LPG repeat units, possessing side chains ...


A Molecular Diagnostic Survey Of Pathogens And Parasites Of Honey Bees, Apis Mellifera L., From Arkansas And Oklahoma, Dylan Cleary 2017 University of Arkansas, Fayetteville

A Molecular Diagnostic Survey Of Pathogens And Parasites Of Honey Bees, Apis Mellifera L., From Arkansas And Oklahoma, Dylan Cleary

Theses and Dissertations

The health and viability of colonies of the honey bee, Apis mellifera, in the United States have fluctuated dramatically over the past decade. This poses a substantial threat to agricultural production in this country. Currently, no single factor has been identified for this decline. Rather, it has been suggested that the interaction between multiple biotic and abiotic stressors may be responsible. Among these factors are pesticides, habitat loss, climate and weather, parasites and pathogens, and colony management techniques. For this reason, it is important to examine the prevalence of honey bee parasite and pathogen infection at the state level in ...


Recombinant Subunit Vaccines For Soil-Transmitted Helminths, Jason B. Noon, Raffi V. Aroian 2017 University of Massachusetts Medical School

Recombinant Subunit Vaccines For Soil-Transmitted Helminths, Jason B. Noon, Raffi V. Aroian

Open Access Articles

Soil-transmitted helminths (STHs) collectively infect one fourth of all human beings, and the majority of livestock in the developing world. These gastrointestinal nematodes are the most important parasites on earth with regard to their prevalence in humans and livestock. Current anthelmintic drugs are losing their efficacies due to increasing drug resistance, particularly in STHs of livestock and drug treatment is often followed by rapid reinfection due to failure of the immune system to develop a protective response. Vaccines against STHs offer what drugs cannot accomplish alone. Because such vaccines would have to be produced on such a large scale, and ...


Histomonas Elisa, Jessica L Martinez 2017 University of Tennessee, Knoxville

Histomonas Elisa, Jessica L Martinez

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

Histomonas meleagridis is a protozoan parasite of avians and is the causative agent in Histomonosis, commonly known as Blackhead Disease. Current methods for diagnosing the presence of H. meleagridis are limited to parasite culture or Polymerase Chain Reaction (PCR) to amplify target DNA. This project aims to develop an enzyme-linked immunosorbent assay (ELISA) for faster and more sensitive diagnosis of Histomonas infections. Cultures of H. meleagridis parasites were purified, and surface antigens were extracted using a spectrum of chemical solutions. The various antigen solutions were subjected to an ELISA, with serum from birds immunized for H. meleagridis as positive controls ...


Differential Roles For Inner Membrane Complex Proteins Across Toxoplasma Gondii And Sarcocystis Neurona Development, Rashmi Dubey, Brooke Harrison, Sriveny Dangoudoubiyam, Giulia Bandini, Katherine Cheng, Aziz Kosber, Carolina Agop-Nersesian, Daniel K. Howe, John Samuelson, David J. P. Ferguson, Marc-Jan Gubbels 2017 Boston College

Differential Roles For Inner Membrane Complex Proteins Across Toxoplasma Gondii And Sarcocystis Neurona Development, Rashmi Dubey, Brooke Harrison, Sriveny Dangoudoubiyam, Giulia Bandini, Katherine Cheng, Aziz Kosber, Carolina Agop-Nersesian, Daniel K. Howe, John Samuelson, David J. P. Ferguson, Marc-Jan Gubbels

Gluck Equine Research Center Faculty Publications

The inner membrane complex (IMC) of apicomplexan parasites contains a network of intermediate filament-like proteins. The 14 alveolin domain-containing IMC proteins in Toxoplasma gondii fall into different groups defined by their distinct spatiotemporal dynamics during the internal budding process of tachyzoites. Here, we analyzed representatives of different IMC protein groups across all stages of the Toxoplasma life cycle and during Sarcocystis neurona asexual development. We found that across asexually dividing Toxoplasma stages, IMC7 is present exclusively in the mother’s cytoskeleton, whereas IMC1 and IMC3 are both present in mother and daughter cytoskeletons (IMC3 is strongly enriched in daughter buds ...


The Role Of Intermittent Preventive Treatment For Malaria In Saving Lives And Promoting Drug Resistance, Carrie Manore 2017 Illinois State University

The Role Of Intermittent Preventive Treatment For Malaria In Saving Lives And Promoting Drug Resistance, Carrie Manore

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Bottom-Up Control Of Parasites, David S. Johnson, Richard Heard 2017 Virginia Institute of Marine Science

Bottom-Up Control Of Parasites, David S. Johnson, Richard Heard

VIMS Articles

Parasitism is a fundamental ecological interaction. Yet we understand relatively little about the ecological role of parasites compared to the role of free-living organisms. Bottom-up theory predicts that resource enhancement will increase the abundance and biomass of free-living organisms. Similarly, parasite abundance and biomass should increase in an ecosystem with resource enhancement. We tested this hypothesis in a landscape-level experiment in which salt marshes (60,000 m2 each) received elevated nutrient concentrations via flooding tidal waters for 11 yr to mimic eutrophication. Nutrient enrichment elevated the densities of the talitrid amphipod, Orchestia grillus, and the density and biomass of its ...


Transmission Pattern Of Major Clonal Lineages Of Toxoplasma Gondii, Pooja Saraf 2017 University of Tennessee, Knoxville

Transmission Pattern Of Major Clonal Lineages Of Toxoplasma Gondii, Pooja Saraf

Doctoral Dissertations

Toxoplasma gondii is the most successful zoonotic pathogen known today. One-third of people are chronically infected worldwide. Different strains of T. gondii shows variability in mouse virulence which may potentially correlate with disease manifestation in humans. As a result, mouse is used as the model organism to study the virulence of T. gondii strains. To study the virulence on a global scale, it is necessary to establish a standardized approach for mice virulence assays. Thus, we review the methodologies used in different labs and put forth standardized approaches to study the T. gondii virulence in mice (Chapter 1). Recent advances ...


Checklist Of Helminths Of Bats From Mexico And Central America, F. Agustín Jiménez, Juan M. Caspeta-Mandujano, Said B. Ramírez-Chávez, Silvia E. Ramírez-Díaz, Marissa G. Juárez-Urbina, Jorge L. Peralta-Rodríguez, José A. Guerrero 2017 Southern Illinois University Carbondale

Checklist Of Helminths Of Bats From Mexico And Central America, F. Agustín Jiménez, Juan M. Caspeta-Mandujano, Said B. Ramírez-Chávez, Silvia E. Ramírez-Díaz, Marissa G. Juárez-Urbina, Jorge L. Peralta-Rodríguez, José A. Guerrero

MANTER: Journal of Parasite Biodiversity

Based on original data obtained from fieldwork conducted from January 2008 to December 2015 and from previous records from published accounts, an updated checklist of helminth parasites of bats from Mexico and Central America is presented. The checklist has been organized in four ways, first as a helminth-host list in the state of Morelos, second as a helminth-host list with taxonomic and geographic distributional information, third as a bat-helminth list with references, and last, as a summary of the host-helminth association. A total of 105 records and 67 helminth taxa (26 trematodes, 4 cestodes, and 37 nematodes [33 adult and ...


Ectoparasitic Mites Of The Genus Gigantolaelaps (Acari: Mesostigmata: Laelapidae) Associated With Small Mammals Of The Genus Nephelomys (Rodentia: Sigmodontinae), Including Two New Species From Peru, Donald D. Gettinger, Scott Lyell Gardner 2017 University of Nebraska - Lincoln

Ectoparasitic Mites Of The Genus Gigantolaelaps (Acari: Mesostigmata: Laelapidae) Associated With Small Mammals Of The Genus Nephelomys (Rodentia: Sigmodontinae), Including Two New Species From Peru, Donald D. Gettinger, Scott Lyell Gardner

Scott Gardner Publications & Papers

An extensive survey of small mammals and ectoparasites along an altitudinal transect in the Manu Biodiversity Reserve in Peru found the sigmodontine rodent genus Nephelomys infested by mites of the genus Gigantolaelaps Fonseca, 1939. Two distinct species co-occurred exclusively in the pelage of Nephelomys keaysi, G. inca Fonseca and G. minima n. sp. Nephelomys levipes, which replaces N. keaysi at higher elevations, was infested exclusively with a single new species, G. nebulosa n. sp. In this paper, we formally describe these new mite species, and provide more information on the morphology of G. inca.


Helminth Infection-Induced Malignancy., Paul J Brindley, Alex Loukas 2017 George Washington University

Helminth Infection-Induced Malignancy., Paul J Brindley, Alex Loukas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infectious diseases cause more than 20% of cancers in the developing world [1]. About a dozen pathogens including Epstein-Barr virus and human T cell lymphocytotropic virus 1 are among the well-known examples. In addition, infection with several trematodes, which are eukaryotes, can cause malignancy. The International Agency for Research on Cancer categorizes infection with the fish-borne trematodes Opisthorchis viverrini and Clonorchis sinensis and the blood fluke Schistosoma haematobium as Group 1 biological carcinogens [2]. In addition to parasitism directly damaging development, health, and prosperity of infected populations, infection with these helminths leads to cholangiocarcinoma (CCA) (bile duct cancer) and squamous ...


American Society Of Parasitologists Newsletter, Volume 39, Number 1, Summer 2017, Scott Lyell Gardner 2017 University of Nebraska - Lincoln

American Society Of Parasitologists Newsletter, Volume 39, Number 1, Summer 2017, Scott Lyell Gardner

Newsletter of the American Society of Parasitologists

Summer 2017 issue of the ASP newsletter.


Subsets Of Inflammatory Cytokine Gene Polymorphisms Are Associated With Risk Of Carcinogenic Liver Fluke Opisthorchis Viverrini-Associated Advanced Periductal Fibrosis And Cholangiocarcinoma., Arpa Surapaitoon, Sutas Suttiprapa, Eimorn Mairiang, Narong Khuntikeo, Chawalit Pairojkul, Jeffrey Bethony, Paul J Brindley, Banchob Sripa 2017 George Washington University

Subsets Of Inflammatory Cytokine Gene Polymorphisms Are Associated With Risk Of Carcinogenic Liver Fluke Opisthorchis Viverrini-Associated Advanced Periductal Fibrosis And Cholangiocarcinoma., Arpa Surapaitoon, Sutas Suttiprapa, Eimorn Mairiang, Narong Khuntikeo, Chawalit Pairojkul, Jeffrey Bethony, Paul J Brindley, Banchob Sripa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF−, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-1β ...


Evolutionary Genetic Aspects Of Host Association In Generalist Ectoparasites, Benoit Talbot 2017 The University of Western Ontario

Evolutionary Genetic Aspects Of Host Association In Generalist Ectoparasites, Benoit Talbot

Electronic Thesis and Dissertation Repository

Despite the use of the host for dispersal by most parasite species, the extremely loose relationship typical between highly mobile hosts and generalist ectoparasites may lead to very different gene flow patterns between the two, leading in turn to different spatial genetic structure, and potentially different demographic history. I examined how similar gene flow patterns are between Cimex adjunctus, a generalist ectoparasite of bats present throughout North America, and two of its key bat hosts. I first analyzed the continent-scale genetic structure and demographic history of C. adjunctus and compared it to that of two of its hosts, the little ...


Whole Genome Analysis Of A Schistosomiasis-Transmitting Freshwater Snail., Coen M Adema, LaDeana W Hillier, Catherine S Jones, Eric S Loker, Matty Knight, Patrick Minx, +several additional authors 2017 George Washington University

Whole Genome Analysis Of A Schistosomiasis-Transmitting Freshwater Snail., Coen M Adema, Ladeana W Hillier, Catherine S Jones, Eric S Loker, Matty Knight, Patrick Minx, +Several Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify several potential targets ...


The Role Of Rna Interference In The Control Of Leishmania Rna Virus 1 Infection, Erin Acino Brettmann 2017 Washington University in St. Louis

The Role Of Rna Interference In The Control Of Leishmania Rna Virus 1 Infection, Erin Acino Brettmann

Arts & Sciences Electronic Theses and Dissertations

The presence of Leishmania RNA virus 1 (LRV1) in parasites of the Leishmania (Viannia) subgenus increases the virulence of the parasite in mouse models of leishmaniasis and is correlated with treatment failure, relapse, and the development of mucocutaneous disease in humans. LRV1 is not shed or infectious; rather, the infection is persistent, and as yet it is unknown how the parasite controls virus levels. Many eukaryotic organisms use RNA interference (RNAi) to limit virus replication, and Leishmania (Viannia) parasites have an active RNAi pathway. To determine whether Leishmania are capable of using RNAi to control LRV1, we sequenced sRNAs from ...


The Role Of Histidine Rich Protein Ii In Cerebral Malaria, Priya Pal 2017 Washington University in St. Louis

The Role Of Histidine Rich Protein Ii In Cerebral Malaria, Priya Pal

Arts & Sciences Electronic Theses and Dissertations

Human malaria is caused by five species of Plasmodium. Of these, P. falciparum is the deadliest and is the only species that causes cerebral malaria (CM). CM is a disease of the vascular endothelium characterized by parasite sequestration, increased inflammatory cytokine production, vascular leakage and leukocyte infiltration. A distinguishing feature of P. falciparum infection is the parasite’s production and secretion of histidine-rich protein II (HRPII). HRPII accumulates to high concentrations (up to 100 µg/ml) in serum, which correlates with disease severity. Due to high serum levels of this protein, HRPII has classically been considered a biomarker for P ...


Amphibian Risk Assessment In Montana: An Evaluation Of Chytridiomycosis In Columbia Spotted Frogs (Lithobates Luteiventris), Alex Kurtz 2017 Carroll College, Helena, MT

Amphibian Risk Assessment In Montana: An Evaluation Of Chytridiomycosis In Columbia Spotted Frogs (Lithobates Luteiventris), Alex Kurtz

Life and Environmental Sciences Undergraduate Theses

The fungus, Batrachochytrium dendrobatidis, has been found to negatively impact amphibian populations around the world. This fungus can have multiple effects on frog physiology, including changes in osmotic regulation that may lead to death. B. dendrobatidis has been shown to be the driving force for many amphibian population crashes and extinctions around the world. The purpose of this project was to build a predictive model of B. dendrobatidis infection, one that would be used to assess population susceptibility in order to identify populations of amphibians at risk of infection. This was accomplished by statistical analyses of several components that contribute ...


A Variant Pfcrt Isoform Can Contribute To Plasmodium Falciparum Resistance To The First-Line Partner Drug Piperaquine, Satish K. Dhingra, Devasha Redhi, Jill M. Combrinck, Tomas Yeo, John Okombo, Philipp P. Henrich, Ann N. Cowell, Purva Gupta, Matthew L. Stegman, Jonathan M. Hoke, Roland A. Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J. Egan, David A. Fidock 2017 Department of Microbiology and Immunology, Columbia University Medical Center

A Variant Pfcrt Isoform Can Contribute To Plasmodium Falciparum Resistance To The First-Line Partner Drug Piperaquine, Satish K. Dhingra, Devasha Redhi, Jill M. Combrinck, Tomas Yeo, John Okombo, Philipp P. Henrich, Ann N. Cowell, Purva Gupta, Matthew L. Stegman, Jonathan M. Hoke, Roland A. Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J. Egan, David A. Fidock

Collected Faculty and Staff Scholarship

Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisininbased combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nucleasebased gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites. Resistance was demonstrated as significantly higher PPQ concentrations causing 90% inhibition of parasite growth (IC90) or 50% parasite killing (50% lethal dose [LD50]). This mutation also reversed Dd2-mediated CQ ...


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