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Evaluation Of Interleukin-3 In Blood-Stage Immunity Against Murine Malaria Plasmodium Yoelii, Haley E. Davis 2016 James Madison University

Evaluation Of Interleukin-3 In Blood-Stage Immunity Against Murine Malaria Plasmodium Yoelii, Haley E. Davis

Senior Honors Projects, 2010-current

Malaria is a mosquito-borne infection caused by the parasitic protozoan Plasmodium. This disease infects over 200-300 million people and causes nearly 400,000 deaths every year. Our laboratory previously examined malarial infection caused by Plasmodium berghei NK65, a lethal rodent strain that induces symptoms similar to those observed in humans. The results of this previous study indicated that the hematopoietic growth factor and immunoregulatory cytokine interleukin-3 (IL-3) suppressed protective immunity against infection with P. berghei NK65. However, the extent to which IL-3 contributes to host defense against blood-stage malaria infection caused by other Plasmodium species remains to be determined. In ...


Rnai-Mediated Gene Knockdown By Microinjection In The Model Entomopathogenic Nematode Heterorhabditis Bacteriophora., Ramesh Ratnappan, Jonathan Vadnal, Melissa Keaney, Ioannis Eleftherianos, Damien O'Halloran, John M. Hawdon 2016 George Washington University

Rnai-Mediated Gene Knockdown By Microinjection In The Model Entomopathogenic Nematode Heterorhabditis Bacteriophora., Ramesh Ratnappan, Jonathan Vadnal, Melissa Keaney, Ioannis Eleftherianos, Damien O'Halloran, John M. Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Parasitic nematodes threaten the health of humans and livestock and cause a major financial and socioeconomic burden to modern society. Given the widespread distribution of diseases caused by parasitic nematodes there is an urgent need to develop tools that will elucidate the genetic complexity of host-parasite interactions. Heterorhabditis bacteriophora is a parasitic nematode that allows simultaneous monitoring of nematode infection processes and host immune function, and offers potential as a tractable model for parasitic nematode infections. However, molecular tools to investigate these processes are required prior to its widespread acceptance as a robust model organism. In this paper we ...


Study Of Potential Risk Of Dengue Disease Outbreak In Sri Lanka Using Gis And Statistical Modelling, Sumith Pathirana, Masato Kawabata, Rohitha Goonatilake 2015 Southern Cross University

Study Of Potential Risk Of Dengue Disease Outbreak In Sri Lanka Using Gis And Statistical Modelling, Sumith Pathirana, Masato Kawabata, Rohitha Goonatilake

Adjunct Associate Professor Sumith Pathirana

The increasing incidence of dengue fever has become a priority health issue for Sri Lanka. Recent dengue outbreaks in Sri Lanka show two trends: yearly increase of total number of dengue incidence and increasing dengue outbreaks outside the endemic urbanised areas in the south and the west. Identification of factors responsible for dengue outbreaks and the mapping of potential risk areas in Sri Lanka are long overdue. This study examines the association between weekly rainfall patterns and dengue outbreaks in the western province between 2000 and 2004. Methods: The study develops a model to quantitatively assess the relationship between rainfall ...


Dynamical Features Of The Plasmodium Falciparum Ribosome During Translation, Ming Sun, Wen Li, Karin Blomqvist, Sanchaita Das, Yaser Hashem, Jeffrey D. Dvorin, Joachim Frank 2015 Columbia University

Dynamical Features Of The Plasmodium Falciparum Ribosome During Translation, Ming Sun, Wen Li, Karin Blomqvist, Sanchaita Das, Yaser Hashem, Jeffrey D. Dvorin, Joachim Frank

Open Access Articles

Plasmodium falciparum, the mosquito-transmitted Apicomplexan parasite, causes the most severe form of human malaria. In the asexual blood-stage, the parasite resides within erythrocytes where it proliferates, multiplies and finally spreads to new erythrocytes. Development of drugs targeting the ribosome, the site of protein synthesis, requires specific knowledge of its structure and work cycle, and, critically, the ways they differ from those in the human host. Here, we present five cryo-electron microscopy (cryo-EM) reconstructions of ribosomes purified from P. falciparum blood-stage schizonts at sub-nanometer resolution. Atomic models were built from these density maps by flexible fitting. Significantly, our study has taken ...


Viability Of Developmental Stages Of Schistosoma Mansoni Quantified With Xcelligence Worm Real-Time Motility Assay (Xworm)., Gabriel Rinaldi, Alex Loukas, Paul J. Brindley, Jeff T. Irelan, Michael J. Smout 2015 George Washington University

Viability Of Developmental Stages Of Schistosoma Mansoni Quantified With Xcelligence Worm Real-Time Motility Assay (Xworm)., Gabriel Rinaldi, Alex Loukas, Paul J. Brindley, Jeff T. Irelan, Michael J. Smout

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infection with helminth parasites causes morbidity and mortality in billions of people and livestock worldwide. Where anthelmintic drugs are available, drug resistance is a major problem in livestock parasites, and a looming threat to public health. Monitoring the efficacy of these medicines and screening for new drugs has been hindered by the lack of objective, high-throughput approaches. Several cell monitoring technologies have been adapted for parasitic worms, including video-, fluorescence-, metabolism enzyme- and impedance-based tools that minimize the screening bottleneck. Using the xCELLigence impedance-based system we previously developed a motility-viability assay that is applicable for a range of helminth parasites ...


Open Educational Resources: A Catalyst For Innovation, Dominic Orr, Michele Rimini, Dirk Van Damme 2015 Organisation for Economic Cooperation and Development

Open Educational Resources: A Catalyst For Innovation, Dominic Orr, Michele Rimini, Dirk Van Damme

Concepts in Animal Parasitology Textbook

Foreword:

Open educational resources (OER) are rapidly becoming a major phenomenon in education across OECD countries and beyond. Initiated largely at the level of institutions by pioneers and technology advocates, the OER community has grown considerably over the past ten years and the impact of OER on educational systems has become an issue of public policy. The open education community is increasingly well organised and enjoys support from various institutions and foundations. National governments have developed, or are in the process of developing, open policies to support access to and use of OER.

It is the task of the OECD ...


Dna-Containing Immunocomplexes Promote Inflammasome Assembly And Release Of Pyrogenic Cytokines By Cd14+ Cd16+ Cd64high Cd32low Inflammatory Monocytes From Malaria Patients, Isabella C. Hirako, Carolina Gallego-Marin, Marco A. Ataide Oswalso Cruz Founda, Warrison A. Andrade, Humberto Gravina, Bruno C. Rocha, Rosane B. de Oliveira, Dhelio B. Pereira, Joseph Vinetz, Betty Diamond, Sanjay Ram, Douglas T. Golenbock, Ricardo T. Gazzinelli 2015 Oswaldo Cruz Foundation

Dna-Containing Immunocomplexes Promote Inflammasome Assembly And Release Of Pyrogenic Cytokines By Cd14+ Cd16+ Cd64high Cd32low Inflammatory Monocytes From Malaria Patients, Isabella C. Hirako, Carolina Gallego-Marin, Marco A. Ataide Oswalso Cruz Founda, Warrison A. Andrade, Humberto Gravina, Bruno C. Rocha, Rosane B. De Oliveira, Dhelio B. Pereira, Joseph Vinetz, Betty Diamond, Sanjay Ram, Douglas T. Golenbock, Ricardo T. Gazzinelli

Open Access Articles

High levels of circulating immunocomplexes (ICs) are found in patients with either infectious or sterile inflammation. We report that patients with either Plasmodium falciparum or Plasmodium vivax malaria have increased levels of circulating anti-DNA antibodies and ICs containing parasite DNA. Upon stimulation with malaria-induced ICs, monocytes express an NF-kappaB transcriptional signature. The main source of IC-induced proinflammatory cytokines (i.e., tumor necrosis factor alpha [TNF-alpha] and interleukin-1beta [IL-1beta])in peripheral blood mononuclear cells from acute malaria patients was found to be a CD14(+) CD16 (FcgammaRIIIA)(+) CD64 (FcgammaRI)(high) CD32 (FcgammaRIIB)(low) monocyte subset. Monocytes from convalescent patients were predominantly of ...


Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes To Adopt A Tumorigenic Phenotype, Sujittra Chaidayet, Javier Sotillo, Michael Smout, Cinzia Cantacessi, Malcolm Jones, Paul J. Brindley, Jeffrey M. Bethony, +9 additional authors 2015 George Washington University

Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes To Adopt A Tumorigenic Phenotype, Sujittra Chaidayet, Javier Sotillo, Michael Smout, Cinzia Cantacessi, Malcolm Jones, Paul J. Brindley, Jeffrey M. Bethony, +9 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. Throughout Asia there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes including chronic inflammation and secretion of parasite proteins into the biliary epithelium drive infection towards cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown.

Methods. Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterised the EV proteome and associated changes in cholangiocytes after EV uptake, and detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and IL-6 ...


Advances In The Diagnosis Of Human Opisthorchiasis: Development Of Opisthorchis Viverrini Antigen Detection In Urine, Chanika Worasith, Christine Kamamia, Anna Yakovleva, Kunyarat Duenngai, Chompunoot Wangboon, Jeffrey M. Bethony, +8 additional authors 2015 George Washington University

Advances In The Diagnosis Of Human Opisthorchiasis: Development Of Opisthorchis Viverrini Antigen Detection In Urine, Chanika Worasith, Christine Kamamia, Anna Yakovleva, Kunyarat Duenngai, Chompunoot Wangboon, Jeffrey M. Bethony, +8 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Many strategies to control opisthorchiasis have been employed in Thailand, but not in the other neighbouring countries. Specific control methods include mass drug administration (MDA) and health education to reduce raw fish consumption. These control efforts have greatly shifted the epidemiology of Opisthorchis viverrini (OV) infection over the last decade from presenting as densely concentrated "heavy" infections in single villages to widespread "light" OV infections distributed over wide geographical areas. Currently, the "gold standard" detection method for OV infection is formalin ethyl-acetate concentration technique (FECT), which has limited diagnostic sensitivity and diagnostic specificity for light OV infections, with OV ...


Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing And Potentially Promotes Neoplasia., Michael J. Smout, Javier Sotillo, Thewarach Laha, Atiroch Papatpremsiri, Gabriel Rinaldi, Rafael N. Pimenta, Paul J. Brindley, +11 more 2015 James Cook University, Cairns, QLD, Australia

Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing And Potentially Promotes Neoplasia., Michael J. Smout, Javier Sotillo, Thewarach Laha, Atiroch Papatpremsiri, Gabriel Rinaldi, Rafael N. Pimenta, Paul J. Brindley, +11 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated ...


Release Of Small Rna-Containing Exosome-Like Vesicles From The Human Filarial Parasite Brugia Malayi, Mostafa Zamanian, Lisa M. Fraser, Prince N. Agbedanu, Hiruni Harischandra, Andrew R. Moorhead, Tim A. Day, Lyric Bartholomay, Michael J. Kimber 2015 Iowa State University

Release Of Small Rna-Containing Exosome-Like Vesicles From The Human Filarial Parasite Brugia Malayi, Mostafa Zamanian, Lisa M. Fraser, Prince N. Agbedanu, Hiruni Harischandra, Andrew R. Moorhead, Tim A. Day, Lyric Bartholomay, Michael J. Kimber

Biomedical Sciences Publications

Lymphatic filariasis (LF) is a socio-economically devastating mosquito-borne Neglected Tropical Disease caused by parasitic filarial nematodes. The interaction between the parasite and host, both mosquito and human, during infection, development and persistence is dynamic and delicately balanced. Manipulation of this interface to the detriment of the parasite is a promising potential avenue to develop disease therapies but is prevented by our very limited understanding of the host-parasite relationship. Exosomes are bioactive small vesicles (30–120 nm) secreted by a wide range of cell types and involved in a wide range of physiological processes. Here, we report the identification and partial ...


The Right Tool For The Job: Detection Of Soil-Transmitted Helminths In Areas Co-Endemic For Other Helminths, Maria V. Periago, Renata C. Diniz, Simone A. Pinto, Anna Yakovleva, Rodrigo Correa-Oliveira, David J. Diemert, Jeffrey M. Bethony 2015 George Washington University

The Right Tool For The Job: Detection Of Soil-Transmitted Helminths In Areas Co-Endemic For Other Helminths, Maria V. Periago, Renata C. Diniz, Simone A. Pinto, Anna Yakovleva, Rodrigo Correa-Oliveira, David J. Diemert, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Due to the recent increased use of the McMaster (MM) fecal egg counting method for assessing benzimidazole drug efficacy for treating soil-transmitted helminth (STH) infections, the aim of the current study was to determine the operational value of including the MM method alongside the Kato-Katz (KK) fecal thick smear to increase the diagnostic sensitivity when STHs are co-endemic with trematode helminths (e.g., Schistosoma mansoni).

Methods

A cross-sectional study was conducted in school-aged children aged 4-18 years in the northeastern region of the State of Minas Gerais (Brazil), where Necator americanus, Ascaris lumbricoides, Trichuris trichiura, and S. mansoni are co-endemic ...


Lack Of Artemisinin Resistance In Plasmodium Falciparum In Uganda Based On Parasitological And Molecular Assays, Roland A. Cooper, Melissa D. Conrad, Quentin D. Watson, Stephanie J. Huezo, Harriet Ninsiima, Patrick Tumwebaze, Samuel L. Nsobya, Philip J. Rosenthal 2015 Department of Natural Sciences and Mathematics, Dominican University of California

Lack Of Artemisinin Resistance In Plasmodium Falciparum In Uganda Based On Parasitological And Molecular Assays, Roland A. Cooper, Melissa D. Conrad, Quentin D. Watson, Stephanie J. Huezo, Harriet Ninsiima, Patrick Tumwebaze, Samuel L. Nsobya, Philip J. Rosenthal

Collected Faculty and Staff Scholarship

We evaluated markers of artemisinin resistance in Plasmodium falciparum isolated in Kampala in 2014. By standard in vitro assays, all isolates were highly sensitive to dihydroartemisinin (DHA). By the ring-stage survival assay, after a 6-h DHA pulse, parasitemia was undetectable in 40 of 43 cultures at 72 h. Two of 53 isolates had nonsynonymous K13-propeller gene polymorphisms but did not have the mutations associated with resistance in Asia. Thus, we did not see evidence for artemisinin resistance in Uganda.


Levels Of 8-Oxodg Predict Hepatobiliary Pathology In Opisthorchis Viverrini Endemic Settings In Thailand., Prasert Saichua, Anna Yakovleva, Christine Kamamia, Amar R. Jariwala, Paul J. Brindley, Jeffrey M. Bethony, + 8 more 2015 Khon Kaen University School of Medicine, Khon Kaen, Thailand

Levels Of 8-Oxodg Predict Hepatobiliary Pathology In Opisthorchis Viverrini Endemic Settings In Thailand., Prasert Saichua, Anna Yakovleva, Christine Kamamia, Amar R. Jariwala, Paul J. Brindley, Jeffrey M. Bethony, + 8 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini is distinct among helminth infections as it drives a chronic inflammatory response in the intrahepatic bile duct that progresses from advanced periductal fibrosis (APF) to cholangiocarcinoma (CCA). Extensive research shows that oxidative stress (OS) plays a critical role in the transition from chronic O. viverrini infection to CCA. OS also results in the excision of a modified DNA lesion (8-oxodG) into urine, the levels of which can be detected by immunoassay. Herein, we measured concentrations of urine 8-oxodG by immunoassay from the following four groups in the Khon Kaen Cancer Cohort study: (1) O. viverrini negative individuals, (2 ...


A Constitutively Active G Protein-Coupled Acetylcholine Receptor Regulates Motility Of Larval Schistosoma Mansoni, Kevin MacDonald, Michael J. Kimber, Timothy A. Day, Paula Ribeiro 2015 McGill University

A Constitutively Active G Protein-Coupled Acetylcholine Receptor Regulates Motility Of Larval Schistosoma Mansoni, Kevin Macdonald, Michael J. Kimber, Timothy A. Day, Paula Ribeiro

Biomedical Sciences Publications

The neuromuscular system of helminths controls a variety of essential biological processes and therefore represents a good source of novel drug targets. The neuroactive substance, acetylcholine controls movement of Schistosoma mansoni but the mode of action is poorly understood. Here, we present first evidence of a functional G protein-coupled acetylcholine receptor in S. mansoni, which we have named SmGAR. A bioinformatics analysis indicated that SmGAR belongs to a clade of invertebrate GAR-like receptors and is related to vertebrate muscarinic acetylcholine receptors. Functional expression studies in yeast showed that SmGAR is constitutively active but can be further activated by acetylcholine and ...


Neurocysticercosis, Abigail Hill 2015 Otterbein University

Neurocysticercosis, Abigail Hill

Master of Science in Nursing (MSN) Student Scholarship

Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system in humans and is the most serious clinical manifestation of cysticercosis. NCC is caused by the ingestion of the larval form of the pork tapeworm Taenia solium. NCC is endemic in low income developing countries where pigs are commonly raised, including the countries of Central America, South America, and parts of Africa and Asia. (Naddaf, Seeger, & Stafstrom, 2014). The parasite Taenia solium encysts in the brain and can express a broad range of symptoms including seizures, headache, hydrocephalus, encephalitis, stroke and mental health and cognitive ...


Chagas Disease: Immigrating Into The United States, Angela Metzger 2015 Otterbein University

Chagas Disease: Immigrating Into The United States, Angela Metzger

Master of Science in Nursing (MSN) Student Scholarship

Chagas Disease is starting to make a profound entrance into our communities within the United States. The influx of the immigrant population is the principal cause of the accumulation in the number of reported cases. (Center for Disease Control and Prevention, 2014). The Trypanosoma cruzi is a parasite that causes Chagas disease. The triatomine blood sucking insect enjoys the mucosal membranes of their pray, both humans and animals. The most common regions of the penetrating bite are the conjunctiva of the eye or around the mouth. It is through the feces of the vector entering the inoculation site that initiates ...


Inhaled Nitric Oxide As An Adjunctive Treatment For Cerebral Malaria In Children: A Phase Ii Randomized Open-Label Clinical Trial, Juliet Mwanga-Amumpaire, Ryan W. Carroll, Elisabeth Baudin, Elisabeth Kemigisha, Dorah Nampijjah, Kenneth Mworozi, Data Santorino, Dan Nyehangane, Daniel I. Nathan, Pierre De Beaudrap, Jean-Francois Etard, Martin Feelish, Bernadette O. Fernandez, Annie Berssenbrugge, David Bangsberg, Kenneth D. Bloch, Yap Boum II, Warren M. Zapol 2015 Mbarara University of Science and Technology

Inhaled Nitric Oxide As An Adjunctive Treatment For Cerebral Malaria In Children: A Phase Ii Randomized Open-Label Clinical Trial, Juliet Mwanga-Amumpaire, Ryan W. Carroll, Elisabeth Baudin, Elisabeth Kemigisha, Dorah Nampijjah, Kenneth Mworozi, Data Santorino, Dan Nyehangane, Daniel I. Nathan, Pierre De Beaudrap, Jean-Francois Etard, Martin Feelish, Bernadette O. Fernandez, Annie Berssenbrugge, David Bangsberg, Kenneth D. Bloch, Yap Boum Ii, Warren M. Zapol

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background. Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM.

Methods. This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate.We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment.

Results. Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N2 for 48 or more hours. Plasma Ang-1 ...


Development Of A Biosensor-Based Rapid Urine Test For Detection Of Urogenital Schistosomiasis., Kathleen E Mach, Ruchika Mohan, Shailja Patel, Pak Kin Wong, Michael Hsieh, Joseph C Liao 2015 George Washington University

Development Of A Biosensor-Based Rapid Urine Test For Detection Of Urogenital Schistosomiasis., Kathleen E Mach, Ruchika Mohan, Shailja Patel, Pak Kin Wong, Michael Hsieh, Joseph C Liao

Urology Faculty Publications

No abstract provided.


Hemocyte Differentiation Mediates The Mosquito Late-Phase Immune Response Against Plasmodium In Anopheles Gambiae, Ryan C. Smith, Carolina Barillas-Mury, Marcelo Jacobs-Lorena 2015 Johns Hopkins Bloomberg School of Public Health

Hemocyte Differentiation Mediates The Mosquito Late-Phase Immune Response Against Plasmodium In Anopheles Gambiae, Ryan C. Smith, Carolina Barillas-Mury, Marcelo Jacobs-Lorena

Ryan C. Smith

Plasmodium parasites must complete development in the mosquito vector for transmission to occur. The mosquito innate immune response is remarkably efficient in limiting parasite numbers. Previous work has identified a LPS-induced TNFα transcription factor (LITAF)-like transcription factor, LITAF-like 3 (LL3), which significantly influences parasite numbers. Here, we demonstrate that LL3 does not influence invasion of the mosquito midgut epithelium or ookinete-to-oocyst differentiation but mediates a late-phase immune response that decreases oocyst survival. LL3 expression in the midgut and hemocytes is activated by ookinete midgut invasion and is independent of the mosquito microbiota, suggesting that LL3 may be a component ...


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