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Towards A Mechanism Of Action Of An Antischistosomal Drug: Measuring Granulocytic Activity, Samantha Sack 2018 University of Nebraska at Omaha

Towards A Mechanism Of Action Of An Antischistosomal Drug: Measuring Granulocytic Activity, Samantha Sack

Student Research and Creative Activity Fair

Schistosomiasis is a neglected tropical disease caused by a family of schistosome parasites which leads to vital organ damage. Praziquantel (PZ) is the only available treatment, but it is effective only against the adult worm. Partner labs have tested an antischistosomal drug which has been shown to have a higher efficacy against both juvenile and mature parasites in mice and monkeys compared to PZ. This effectiveness does not transfer to in vitro experiments; it kills the parasite outside of its host only at extremely high concentrations. This indicates that its efficacy is host-dependent, but the mechanism by which it functions ...


The Major Histocompatibility Complex In Song Sparrows: Immunity, Signals, And Mate Choice, Joel W.G. Slade 2018 The University of Western Ontario

The Major Histocompatibility Complex In Song Sparrows: Immunity, Signals, And Mate Choice, Joel W.G. Slade

Electronic Thesis and Dissertation Repository

In recent years, sexual selection theory has redefined genetic quality to consider not only additive genetic effects on fitness but also non-additive genetic effects, such as heterozygote advantage or disadvantage. In jawed vertebrates, the major histocompatibility complex (MHC) gene family has been shown to exhibit both additive and non-additive genetic effects on fitness. MHC gene products are involved in initiating adaptive immune responses, and MHC genotype determines the range of pathogens to which an individual can respond. Therefore, parasite-mediated selection at MHC may favour locally-adapted, rare, or particular combination of alleles. Because heterozygote advantage at MHC is widespread, sexual selection ...


Acinetobacter Bacteriophage Discovery In Soil, Michael Plaskett 2018 Rose-Hulman Institute of Technology

Acinetobacter Bacteriophage Discovery In Soil, Michael Plaskett

Rose-Hulman Undergraduate Research Publications

The Acinetobacter genus is home to a wide range of bacteria that are gram-negative, aerobic, non-motile, oxidase-negative, catalase positive, and coccobacilli with a G+C content of 39 to 47% (Bergogne-Berezin, 1996). These bacteria are universal as they reside in the soil, water, sewage, various surfaces; and are also able to infect humans; however, a majority of the infections are caused by the species Acinetobacter baumannii. This bacterium is the most prevalent etiological cause of the Acinetobacter infections due to it being a nosocomial infection or one that is acquired in a health care setting. The infections that occur in ...


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 ...


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 ...


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 ...


Granulin Secreted By The Food-Borne Liver Fluke, Brandon Haugen, Shannon E Karinshak, Victoria H Mann, Anastas Popratiloff, Alex Loukas, Paul J Brindley, Michael J Smout 2018 George Washington University

Granulin Secreted By The Food-Borne Liver Fluke, Brandon Haugen, Shannon E Karinshak, Victoria H Mann, Anastas Popratiloff, Alex Loukas, Paul J Brindley, Michael J Smout

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The liver fluke Opisthorchis viverrini is a food-borne, zoonotic pathogen endemic to Thailand and adjacent countries in Southeast Asia. The adult developmental stage of the O. viverrini parasite excretes and secretes numerous proteins within the biliary tract including the gall bladder. Lesions caused by the feeding activities of the liver fluke represent wounds that undergo protracted cycles of healing and re-injury during chronic infection, which can last for decades. Components of the excretory/secretory (ES) complement released by the worms capably drive proliferation of bile duct epithelial cells and are implicated in establishing the oncogenic milieu that leads to bile ...


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 ...


Screening Of Primary Gp120 Immunogens To Formulate The Next Generation Polyvalent Dna Prime-Protein Boost Hiv-1 Vaccines, Shixia Wang, Te-Hui Chou, Anthony Hackett, Veronica Efros, Yan Wang, Dong Han, Aaron Wallace, Yuxin Chen, Guangnan Hu, Shuying Liu, Paul R. Clapham, James Arthos, David Montefiori, Shan Lu 2017 University of Massachusetts Medical School

Screening Of Primary Gp120 Immunogens To Formulate The Next Generation Polyvalent Dna Prime-Protein Boost Hiv-1 Vaccines, Shixia Wang, Te-Hui Chou, Anthony Hackett, Veronica Efros, Yan Wang, Dong Han, Aaron Wallace, Yuxin Chen, Guangnan Hu, Shuying Liu, Paul R. Clapham, James Arthos, David Montefiori, Shan Lu

Open Access Articles

Our previous preclinical studies and a Phase I clinical trial DP6-001 have indicated that a polyvalent Env formulation was able to elicit broadly reactive antibody responses including low titer neutralizing antibody responses against viral isolates of subtypes A, B, C and AE. In the current report, a panel of 62 gp120 immunogens were screened in a rabbit model to identify gp120 immunogens that can elicit improved binding and neutralizing antibody responses and some of them can be included in the next polyvalent formulation. Only about 19% of gp120 immunogens in this panel were able to elicit neutralizing antibodies against greater ...


The Dynamics Of Immunoglobulin V-Gene Usage And Clonotype Expansion In Mice After Prime And Boost Immunizations As Analyzed By Ngs, Diego José Farfán Arribas, Shuying Liu, Shixia Wang, Shan Lu 2017 University of Massachusetts Medical School

The Dynamics Of Immunoglobulin V-Gene Usage And Clonotype Expansion In Mice After Prime And Boost Immunizations As Analyzed By Ngs, Diego José Farfán Arribas, Shuying Liu, Shixia Wang, Shan Lu

Open Access Articles

In the current study, an improved NGS approach was developed to study the B-cell repertoire evolution in a simple mouse immunization model including only two DNA immunizations. The combination of 5'RACE and Ion Torrent long reads enabled unbiased immunoglobulin repertoire analysis even from small amounts of peripheral mouse blood. The B-cell population expanded by the vaccine displayed a relatively strong clonality. Upon priming with the first vaccine dose, we observed a consistent pattern of V-segment gene and CDR3 usage (public specificities). Interestingly, this pattern diversified with the second dose of immunization -it was relatively different in individual mice in ...


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 ...


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 ...


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 ...


Planning An Innovation Marathon At An Infectious Disease Conference With Results From The International Meeting On Emerging Diseases And Surveillance 2016 Hackathon, John W. Ramatowski, Christopher Xiang Lee, Aikaterini Mantzavino, Joao Ribas, Winter Guerra, Nicholas D. Preston, Eva Schernhammer, Lawrence C. Madoff, Britta Lassmann 2017 International Society for Infectious Diseases

Planning An Innovation Marathon At An Infectious Disease Conference With Results From The International Meeting On Emerging Diseases And Surveillance 2016 Hackathon, John W. Ramatowski, Christopher Xiang Lee, Aikaterini Mantzavino, Joao Ribas, Winter Guerra, Nicholas D. Preston, Eva Schernhammer, Lawrence C. Madoff, Britta Lassmann

Open Access Articles

A hackathon is best described as an 'innovation marathon'. Derived from the words 'hacking' and 'marathon', it brings together multidisciplinary teams to collaborate intensely over a short period of time to define a problem, devise a solution, and design a working prototype. International scientific meetings are conducive to successful hackathons, providing an audience of expert professionals who describe challenges and ensure the proposed solutions address end-user needs. Collaborations with local organizations and academic centers are crucial to attracting complementary specialties such as IT advisors, engineers, and entrepreneurs to develop sustainable projects. The core process of first identifying and deconstructing a ...


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