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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 ...


New Gorilla Adenovirus Vaccine Vectors Induce Potent Immune Responses And Protection In A Mouse Malaria Model, Keith Limbach, Ann M. Moormann, Joseph T. Bruder 2018 Naval Medical Research Center

New Gorilla Adenovirus Vaccine Vectors Induce Potent Immune Responses And Protection In A Mouse Malaria Model, Keith Limbach, Ann M. Moormann, Joseph T. Bruder

Ann M. Moormann

BACKGROUND: A DNA-human Ad5 (HuAd5) prime-boost malaria vaccine has been shown to protect volunteers against a controlled human malaria infection. The potency of this vaccine, however, appeared to be affected by the presence of pre-existing immunity against the HuAd5 vector. Since HuAd5 seroprevalence is very high in malaria-endemic areas of the world, HuAd5 may not be the most appropriate malaria vaccine vector. This report describes the evaluation of the seroprevalence, immunogenicity and efficacy of three newly identified gorilla adenoviruses, GC44, GC45 and GC46, as potential malaria vaccine vectors.

RESULTS: The seroprevalence of GC44, GC45 and GC46 is very low, and ...


Immunoglobulin Therapy And Primary Immunodeficient Patients' Health-Related Quality Of Life And Well-Being, Niedre Heckman 2018 Walden University

Immunoglobulin Therapy And Primary Immunodeficient Patients' Health-Related Quality Of Life And Well-Being, Niedre Heckman

Walden Dissertations and Doctoral Studies

Individuals born with primary immune deficiency diseases (PIDD) have a dysfunctional immune system, and many are treated by lifelong injections of immunoglobulin therapy. Studies have shown that these patients have low health-related quality of life (HRQOL) and well-being (WB) and that these outcomes might be improved by the availability of therapy innovated according to preferences for fewer needle sticks or a shorter infusion time. Regulators at the U.S. Food and Drug Administration (FDA) have approved therapies innovated per these preferences. However, there is limited data demonstrating how these innovations impact HRQOL and WB. Using the biopsychosocial model, the purpose ...


Mozambique: Hiv/Aids, Camila Davila 2018 Augustana College, Rock Island Illinois

Mozambique: Hiv/Aids, Camila Davila

Global Public Health

Mozambique is a country located in Southeastern Africa near the Mozambique Channel and the Indian Ocean. The president of this nation is Filipe Jacinto Nyusi. The total population is 26, 573, 706 which is composed of mostly 99.68% Africans and other minorities. Its national language is Portuguese although most of the population speaks Emarkhuwa. Most of the population is Catholic and a few others include Muslims and Zionist Christians. Mozambique faces several challenges with malaria, poverty, malnutrition, HIV/AIDS, and illicit drugs. HIV/AIDS is a common health problem that targets the immune system and is transmitted through bodily ...


Discovery Of Novel, Orally Bioavailable, Antileishmanial Compounds Using Phenotypic Screening, Diana Ortiz, W. Armand Guiguemde, Jared T. Hammill, Angela K. Carrillo, Yizhe Chen, Michele Connelly, Kayla Stalheim, Carolyn Elya, Alex Johnson, Jaeki Min, Anang Shelat, David C. Smithson, Lei Yang, Fangyi Zhu, Rodney K. Guy, Scott M. Landfear 2017 Oregon Health & Science University

Discovery Of Novel, Orally Bioavailable, Antileishmanial Compounds Using Phenotypic Screening, Diana Ortiz, W. Armand Guiguemde, Jared T. Hammill, Angela K. Carrillo, Yizhe Chen, Michele Connelly, Kayla Stalheim, Carolyn Elya, Alex Johnson, Jaeki Min, Anang Shelat, David C. Smithson, Lei Yang, Fangyi Zhu, Rodney K. Guy, Scott M. Landfear

Pharmaceutical Sciences Faculty Publications

Leishmaniasis is a parasitic infection that afflicts approximately 12 million people worldwide. There are several limitations to the approved drug therapies for leishmaniasis, including moderate to severe toxicity, growing drug resistance, and the need for extended dosing. Moreover, miltefosine is currently the only orally available drug therapy for this infection. We addressed the pressing need for new therapies by pursuing a two-step phenotypic screen to discover novel, potent, and orally bioavailable antileishmanials. First, we conducted a high-throughput screen (HTS) of roughly 600,000 small molecules for growth inhibition against the promastigote form of the parasite life cycle using the nucleic ...


Ticks, Ixodes Scapularis, Feed Repeatedly On White-Footed Mice Despite Strong Inflammatory Response: An Expanding Paradigm For Understanding Tick-Host Interactions, Jennifer M. Anderson, Ian N. Moore, Bianca M. Nagata, José M.C. Ribeiro, Jesus G. Valenzuela, Daniel E. Sonenshine 2017 Old Dominion University

Ticks, Ixodes Scapularis, Feed Repeatedly On White-Footed Mice Despite Strong Inflammatory Response: An Expanding Paradigm For Understanding Tick-Host Interactions, Jennifer M. Anderson, Ian N. Moore, Bianca M. Nagata, José M.C. Ribeiro, Jesus G. Valenzuela, Daniel E. Sonenshine

Biological Sciences Faculty Publications

Ticks transmit infectious agents including bacteria, viruses and protozoa. However, their transmission may be compromised by host resistance to repeated tick feeding. Increasing host resistance to repeated tick bites is well known in laboratory animals, including intense inflammation at the bite sites. However, it is not known whether this also occurs in wild rodents such as white-footed mice, Peromyscus leucopus, and other wildlife, or if it occurs at all. According to the "host immune incompetence" hypothesis, if these mice do not have a strong inflammatory response, they would not reject repeated tick bites by Ixodes scapularis. To test this hypothesis ...


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 ...


The Pul37 Tegument Protein Guides Alphaherpesvirus Retrograde Axonal Transport To Promote Neuroinvasion, Alexsia L. Richards, Patricia J. Sollars, Jared D. Pitts, Austin M. Stults, Ekaterina E. Heldwein, Gary E. Pickard, Gregory A. Smith 2017 The Whitehead Institute for Biomedical Research

The Pul37 Tegument Protein Guides Alphaherpesvirus Retrograde Axonal Transport To Promote Neuroinvasion, Alexsia L. Richards, Patricia J. Sollars, Jared D. Pitts, Austin M. Stults, Ekaterina E. Heldwein, Gary E. Pickard, Gregory A. Smith

Papers in Veterinary and Biomedical Science

A hallmark property of the neurotropic alpha-herpesvirinae is the dissemination of infection to sensory and autonomic ganglia of the peripheral nervous system following an initial exposure at mucosal surfaces. The peripheral ganglia serve as the latent virus reservoir and the source of recurrent infections such as cold sores (herpes simplex virus type I) and shingles (varicella zoster virus). However, the means by which these viruses routinely invade the nervous system is not fully understood. We report that an internal virion component, the pUL37 tegument protein, has a surface region that is an essential neuroinvasion effector. Mutation of this region rendered ...


Severity Of Acute Infectious Mononucleosis Correlates With Cross-Reactive Influenza Cd8 T-Cell Receptor Repertoires, Nuray Aslan, Levi B. Watkin, Anna Gil, Rabinarayan Mishra, Fransenio G. Clark, Raymond M. Welsh, Dario Ghersi, Katherine Luzuriaga, Liisa K. Selin 2017 University of Massachusetts Medical School

Severity Of Acute Infectious Mononucleosis Correlates With Cross-Reactive Influenza Cd8 T-Cell Receptor Repertoires, Nuray Aslan, Levi B. Watkin, Anna Gil, Rabinarayan Mishra, Fransenio G. Clark, Raymond M. Welsh, Dario Ghersi, Katherine Luzuriaga, Liisa K. Selin

UMass Center for Clinical and Translational Science Supported Publications

Fifty years after the discovery of Epstein-Barr virus (EBV), it remains unclear how primary infection with this virus leads to massive CD8 T-cell expansion and acute infectious mononucleosis (AIM) in young adults. AIM can vary greatly in severity, from a mild transient influenza-like illness to a prolonged severe syndrome. We questioned whether expansion of a unique HLA-A2.01-restricted, cross-reactive CD8 T-cell response between influenza virus A-M158 (IAV-M1) and EBV BMLF1280 (EBV-BM) could modulate the immune response to EBV and play a role in determining the severity of AIM in 32 college students. Only ex vivo total IAV-M1 and IAV-M1+EBV-BM ...


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 ...


An Investigation Of The Levels Of Pro-Inflammation Cytokines In The Brain Of Autoimmune Lewis Rats, Han Yang 2017 University of the Incarnate Word

An Investigation Of The Levels Of Pro-Inflammation Cytokines In The Brain Of Autoimmune Lewis Rats, Han Yang

Theses & Dissertations

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which can cause cartilage and bone damage, as well as disability. A reported symptom of RA includes tissue inflammation disease and cognitive dysfunction. This study aimed to compare the concentration of selected cytokines in the cerebral cortex, hippocampus, hypothalamus, amygdala, and cerebellum of Lewis rats. Age and sex-matched Lewis rats were separated into two groups: control and adjuvant-induced RA. Twenty-eight days after the adjuvant injection, groups were sacrificed and brains dissected using the stereotaxic atlas of Paximos and Watson as a guide. Pro-inflammatory cytokines IL-1β, IL-6, and IL-23, plus the anti-inflammatory ...


Type Ix Secretion System : Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru 2017 University of Louisville

Type Ix Secretion System : Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru

Electronic Theses and Dissertations

Porphyromonas gingivalis and Tannerella forsythia are two of the primary pathogens that are associated in the etiology and progression of chronic periodontitis. In T. forsythia, KLIKK proteases are the recently identified group of proteolytic enzymes that are secreted through Type IX secretion system (T9SS). Among, these KLIKK proteases a synergistic relationship was observed between karilysin and mirolysin in invading the host complement system for the survival of the bacteria. Since, karilysin has been already characterized, in this study we propose to study about mirolysin through structural, biochemical and biological characterization. The obtained results from the experiments has shown the propensity ...


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 ...


Age-Structured And Vaccination Models Of Devil Facial Tumor Disease, Christopher D. Bruno, Timothy Comar, Megan O. Powell, Adjo Tameklo 2017 University of St. Francis

Age-Structured And Vaccination Models Of Devil Facial Tumor Disease, Christopher D. Bruno, Timothy Comar, Megan O. Powell, Adjo Tameklo

Spora: A Journal of Biomathematics

Tasmanian devil populations have been devastated by devil facial tumor disease (DFTD) since its first appearance in 1996. The average lifespan of a devil has decreased from six years to three years. We present an age-structured model to represent how the disease has affected the age and breeding structures of the population. We show that with the recent increase in the breeding of juvenile devils, the overall devil population will increase but not nearly to pre-DFTD levels. The basic reproductive number may be increased with the influx of young breeding devils. In addition, our model shows that the release of ...


Molecular Evolution Of Dengue Type 2 Virus In Thailand, Rebeca Rico-Hesse, Lisa M. Harrison, Ananda Nisalak, David W. Vaughn, Siripen Kalayanarooj, Sharone Green, Alan L. Rothman, Francis A. Ennis 2017 Yale University School of Medicine

Molecular Evolution Of Dengue Type 2 Virus In Thailand, Rebeca Rico-Hesse, Lisa M. Harrison, Ananda Nisalak, David W. Vaughn, Siripen Kalayanarooj, Sharone Green, Alan L. Rothman, Francis A. Ennis

Sharone Green

Dengue is a mosquito-borne viral infection that in recent years has become a major international public health concern. Dengue hemorrhagic fever (DHF), first recognized in Southeast Asia in the 1950s, is today a leading cause of childhood death in many countries. The pathogenesis of this illness is poorly understood, mainly because there are no laboratory or animal models of disease. We have studied the genetic relationships of dengue viruses of serotype 2, one of four antigenically distinct dengue virus groups, to determine if viruses obtained from cases of less severe dengue fever (DF) have distinct evolutionary origins from those obtained ...


Rapid Diagnosis Of Dengue Viremia By Reverse Transcriptase-Polymerase Chain Reaction Using 3'-Noncoding Region Universal Primers, T. Mirawati Sudiro, Hiroaki Ishiko, Sharone Green, Ananda Nisalak, David W. Vaughn, Siripen Kalayanarooj, Alan L. Rothman, Boonyos Raengsakulrach, Jurand Janus, Ichiro Kurane, Francis A. Ennis 2017 University of Massachusetts Medical School

Rapid Diagnosis Of Dengue Viremia By Reverse Transcriptase-Polymerase Chain Reaction Using 3'-Noncoding Region Universal Primers, T. Mirawati Sudiro, Hiroaki Ishiko, Sharone Green, Ananda Nisalak, David W. Vaughn, Siripen Kalayanarooj, Alan L. Rothman, Boonyos Raengsakulrach, Jurand Janus, Ichiro Kurane, Francis A. Ennis

Sharone Green

A reverse transcriptase-polymerase chain reaction (RT-PCR) method was developed as a rapid diagnostic test of dengue viremia. To detect dengue viruses in serum or plasma specimens, a pair of universal primers was designed for use in the RT-PCR. Using these primers, the 3'-noncoding region of dengue virus types 1, 2, 3, and 4 could be amplified, but not those of other flaviviruses, such as West Nile virus, Japanese encephalitis virus, and yellow fever virus, or the alphavirus Sindbis virus. The sensitivity of the RT-PCR assay was similar to that of a quantitative fluorescent focus assay of dengue viruses in ...


Effectiveness Of Composting As A Biosecure Disposal Method For Porcine Epidemic Diarrhea Virus (Pedv)-Infected Pig Carcasses, Sarah Vitosh-Sillman, John Dustin Loy, Bruce Brodersen, Clayton Kelling, Kent Eskridge, Amy Millmier Schmidt 2017 University of Nebraska-Lincoln

Effectiveness Of Composting As A Biosecure Disposal Method For Porcine Epidemic Diarrhea Virus (Pedv)-Infected Pig Carcasses, Sarah Vitosh-Sillman, John Dustin Loy, Bruce Brodersen, Clayton Kelling, Kent Eskridge, Amy Millmier Schmidt

Papers in Veterinary and Biomedical Science

Porcine epidemic diarrhea virus (PEDV) is an enteric disease of swine that has emerged as a worldwide threat to swine herd health and production. Substantial research has been conducted to assess viability of the virus on surfaces of vehicles and equipment, in feed and water, and on production building surfaces, but little is known about the persistence in PEDV-infected carcasses and effective disposal methods thereof. This study was conducted to quantify the persistence of PEDV RNA via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) at various time-temperature combinations and in infected piglet carcasses subjected to composting. Although this method ...


Cytoplasmic Proteins As Autoantigens In The Development Of Inflammatory Heart Disease, Bharathi Yalaka 2017 University of Nebraska-Lincoln

Cytoplasmic Proteins As Autoantigens In The Development Of Inflammatory Heart Disease, Bharathi Yalaka

Dissertations & Theses in Veterinary and Biomedical Science

Inflammatory heart disease can result from infectious or non-infectious etiologies. When infectious causes are involved, autoimmune responses are commonly suspected to explain persistence of inflammation, leading to the suggestion that pathogens primarily affecting the target organs can lead to a secondary generation of autoimmune responses. In addressing this hypothesis, we had previously reported that Coxsackievirus B3 (CVB) infection accompanies the generation of cardiac myosin-specific T cells, which can transfer disease to naïve mice. This work led us to propose that the postinfectious phase of CVB infection involves the generation of autoreactive T cells with multiple antigen specificities. To this end ...


Role Of Granulocyte-Macrophage Colony-Stimulating Factor Production By T Cells During Mycobacterium Tuberculosis Infection, Britni L. Stowell, Girija Goyal, Claudio Nunes-Alves, Qianting Yang, Kadamba Papavinasasundaram, Christopher M. Sassetti, Glenn Dranoff, Xinchun Chen, Jinhee Lee, Samuel M. Behar 2017 Harvard Medical School

Role Of Granulocyte-Macrophage Colony-Stimulating Factor Production By T Cells During Mycobacterium Tuberculosis Infection, Britni L. Stowell, Girija Goyal, Claudio Nunes-Alves, Qianting Yang, Kadamba Papavinasasundaram, Christopher M. Sassetti, Glenn Dranoff, Xinchun Chen, Jinhee Lee, Samuel M. Behar

UMass Metabolic Network Publications

Mice deficient for granulocyte-macrophage colony-stimulating factor (GM-CSF(-/-)) are highly susceptible to infection with Mycobacterium tuberculosis, and clinical data have shown that anti-GM-CSF neutralizing antibodies can lead to increased susceptibility to tuberculosis in otherwise healthy people. GM-CSF activates human and murine macrophages to inhibit intracellular M. tuberculosis growth. We have previously shown that GM-CSF produced by iNKT cells inhibits growth of M. tuberculosis However, the more general role of T cell-derived GM-CSF during infection has not been defined and how GM-CSF activates macrophages to inhibit bacterial growth is unknown. Here we demonstrate that, in addition to nonconventional T cells, conventional T ...


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