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The Global Economic And Health Burden Of Human Hookworm Infection., Sarah M Bartsch, Peter J. Hotez, Lindsey Asti, Kristina M Zapf, Maria Elena Bottazzi, David J. Diemert, Bruce Y Lee 2016 George Washington University

The Global Economic And Health Burden Of Human Hookworm Infection., Sarah M Bartsch, Peter J. Hotez, Lindsey Asti, Kristina M Zapf, Maria Elena Bottazzi, David J. Diemert, Bruce Y Lee

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Even though human hookworm infection is highly endemic in many countries throughout the world, its global economic and health impact is not well known. Without a better understanding of hookworm's economic burden worldwide, it is difficult for decision makers such as funders, policy makers, disease control officials, and intervention manufacturers to determine how much time, energy, and resources to invest in hookworm control.

METHODOLOGY/PRINCIPLE FINDINGS: We developed a computational simulation model to estimate the economic and health burden of hookworm infection in every country, WHO region, and globally, in 2016 from the societal perspective. Globally, hookworm infection ...


Nox2-Derived Oxidative Stress Results In Inefficacy Of Antibiotics Against Post-Influenza S. Aureus Pneumonia., Keer Sun, Vijaya Kumar Yajjala, Christopher Bauer, G. Talmon, Karl J. Fischer, Tammy Kielian, Dennis W. Metzger 2016 University of Nebraska Medical Center

Nox2-Derived Oxidative Stress Results In Inefficacy Of Antibiotics Against Post-Influenza S. Aureus Pneumonia., Keer Sun, Vijaya Kumar Yajjala, Christopher Bauer, G. Talmon, Karl J. Fischer, Tammy Kielian, Dennis W. Metzger

Journal Articles: Pathology and Microbiology

Clinical post-influenza Staphylococcus aureus pneumonia is characterized by extensive lung inflammation associated with severe morbidity and mortality even after appropriate antibiotic treatment. In this study, we show that antibiotics rescue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2)-deficient mice but fail to fully protect WT animals from influenza and S. aureus coinfection. Further experiments indicate that the inefficacy of antibiotics against coinfection is attributable to oxidative stress-associated inflammatory lung injury. However, Nox2-induced lung damage during coinfection was not associated with aggravated inflammatory cytokine response or cell infiltration but rather caused by reduced survival of myeloid cells. Specifically, oxidative stress ...


Blimp-1–Mediated Cd4 T Cell Exhaustion Causes Cd8 T Cell Dysfunction During Chronic Toxoplasmosis, Sujin Hwang, Dustin A. Cobb, Rajarshi Bhadra, Ben Youngblood, Imtiaz A. Khan 2016 George Washington University

Blimp-1–Mediated Cd4 T Cell Exhaustion Causes Cd8 T Cell Dysfunction During Chronic Toxoplasmosis, Sujin Hwang, Dustin A. Cobb, Rajarshi Bhadra, Ben Youngblood, Imtiaz A. Khan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

CD8, but not CD4, T cells are considered critical for control of chronic toxoplasmosis. Although CD8 exhaustion has been previously reported inToxoplasma encephalitis (TE)–susceptible model, our current work demonstrates that CD4 not only become exhausted during chronic toxoplasmosis but this dysfunction is more pronounced than CD8 T cells. Exhausted CD4 population expressed elevated levels of multiple inhibitory receptors concomitant with the reduced functionality and up-regulation of Blimp-1, a transcription factor. Our data demonstrates for the first time that Blimp-1 is a critical regulator for CD4 T cell exhaustion especially in the CD4 central memory cell subset. Using a ...


In Vivo Monitoring Of Therapeutic Efficacy And Virulence Profile By Bioluminescent Klebsiella Pneumoniae., Ramy Ameen Fodah 2016 University of Louisville

In Vivo Monitoring Of Therapeutic Efficacy And Virulence Profile By Bioluminescent Klebsiella Pneumoniae., Ramy Ameen Fodah

Electronic Theses and Dissertations

Klebsiella pneumoniae causes an acute respiratory infection in human with severe outcomes and high mortality rates even with antibiotic treatment. Even with its critical clinical importance, few virulence systems have been identified for K. pneumoniae limiting the development of new therapeutic strategies. Accordingly, we performed Next Generation sequencing for the strain ATCC 43816, a virulent strain in mouse respiratory disease models, and compared its genomic data with two previously sequenced strains NTUH-K2044 and MGH 78578 for the purpose of identifying genes required for colonizing host lungs. Furthermore, the virulence potential of the three K. pneumoniae strains were tested in a ...


Biliary Microbiota, Gallstone Disease And Infection With Opisthorchis Felineus., Irina V. Saltykova, Vjacheslav A Petrov, Maria D Logacheva, Polina G Ivanova, Nikolay V Merzlikin, Alexey E Sazonov, Ludmila M Ogorodova, Paul J. Brindley 2016 George Washington University

Biliary Microbiota, Gallstone Disease And Infection With Opisthorchis Felineus., Irina V. Saltykova, Vjacheslav A Petrov, Maria D Logacheva, Polina G Ivanova, Nikolay V Merzlikin, Alexey E Sazonov, Ludmila M Ogorodova, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: There is increasing interest in the microbiome of the hepatobiliary system. This study investigated the influence of infection with the fish-borne liver fluke, Opisthorchis felineus on the biliary microbiome of residents of the Tomsk region of western Siberia.

METHODOLOGY/PRINCIPAL FINDINGS: Samples of bile were provided by 56 study participants, half of who were infected with O. felineus, and all of who were diagnosed with gallstone disease. The microbiota of the bile was investigated using high throughput, Illumina-based sequencing targeting the prokaryotic 16S rRNA gene. About 2,797, discrete phylotypes of prokaryotes were detected. At the level of phylum ...


Inversion Of The Vδ1 To Vδ2 Γδ T Cell Ratio In Cvid Is Not Restored By Ivig And Is Associated With Immune Activation And Exhaustion., Dominic Paquin-Proulx, Nathália Silveira Barsotti, Bianca A N Santos, Ana Karolina B B Marinho, Cristina M Kokron, Karina I Carvalho, Myrthes T Barros, Jorge Kalil, Douglas F. Nixon, Esper G Kallas 2016 George Washington University

Inversion Of The Vδ1 To Vδ2 Γδ T Cell Ratio In Cvid Is Not Restored By Ivig And Is Associated With Immune Activation And Exhaustion., Dominic Paquin-Proulx, Nathália Silveira Barsotti, Bianca A N Santos, Ana Karolina B B Marinho, Cristina M Kokron, Karina I Carvalho, Myrthes T Barros, Jorge Kalil, Douglas F. Nixon, Esper G Kallas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Common variable immunodeficiency (CVID) is defined by low levels of IgG and IgA, but perturbations in T cells are also commonly found. However, there is limited information on γδ T cells in CVID patients. Newly diagnosed CVID patients (n = 15) were enrolled before and after intravenous IgG (IVIg) replacement therapy. Cryopreserved peripheral blood mononuclear cells were then used to study γδ T cells and CVID patients were compared to healthy controls (n = 22). The frequency and absolute count of Vδ1 γδ T cells was found to be increased in CVID (median 0.60% vs 2.64%, P <0.01 and 7.5 vs 39, P <0.01 respectively), while they were decreased for Vδ2 γδ T cells (median, 2.36% vs 0.74%,P <0.01 and 37.8 vs 13.9, P ...


Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro MD 2016 Marshall University

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Zijian Xie

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice ...


Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro MD 2016 Marshall University

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Joseph I Shapiro MD

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice ...


Antioxidants Condition Pleiotropic Vascular Responses To Exogenous H2o2: Role Of Modulation Of Vascular Tp Receptors And The Heme Oxygenase System, Nitin Puri, Fan Zhang, Sumit R. Monu, Komal R. Sodhi, Lars Bellner, Brian D. Lamon, Yilun Zhang, Nader G. Abraham, Alberto Nasjletti 2016 Marshall University

Antioxidants Condition Pleiotropic Vascular Responses To Exogenous H2o2: Role Of Modulation Of Vascular Tp Receptors And The Heme Oxygenase System, Nitin Puri, Fan Zhang, Sumit R. Monu, Komal R. Sodhi, Lars Bellner, Brian D. Lamon, Yilun Zhang, Nader G. Abraham, Alberto Nasjletti

Komal Sodhi

Aims: Hydrogen peroxide (H(2)O(2)), a nonradical oxidant, is employed to ascertain the role of redox mechanisms in regulation of vascular tone. Where both dilation and constriction have been reported, we examined the hypothesis that the ability of H(2)O(2) to effect vasoconstriction or dilation is conditioned by redox mechanisms and may be modulated by antioxidants.

Results: Exogenous H(2)O(2) (0.1-10.0 μM), dose-dependently reduced the internal diameter of rat renal interlobular and 3rd-order mesenteric arteries (p<0.05). This response was obliterated in arteries pretreated with antioxidants, including tempol, pegylated superoxide dismutase (PEG-SOD), butylated hydroxytoluene (BHT), and biliverdin (BV). However, as opposed to tempol or PEG-SOD, BHT & BV, antioxidants targeting radicals downstream of H(2)O(2), also uncovered vasodilation.

Innovations: Redox-dependent vasoconstriction to H(2)O(2) was blocked by inhibitors of cyclooxygenase (COX) (indomethacin-10 ...


Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro MD 2016 Marshall University

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Komal Sodhi

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice ...


Antioxidants Condition Pleiotropic Vascular Responses To Exogenous H2o2: Role Of Modulation Of Vascular Tp Receptors And The Heme Oxygenase System, Nitin Puri, Fan Zhang, Sumit R. Monu, Komal R. Sodhi, Lars Bellner, Brian D. Lamon, Yilun Zhang, Nader G. Abraham, Alberto Nasjletti 2016 Marshall University

Antioxidants Condition Pleiotropic Vascular Responses To Exogenous H2o2: Role Of Modulation Of Vascular Tp Receptors And The Heme Oxygenase System, Nitin Puri, Fan Zhang, Sumit R. Monu, Komal R. Sodhi, Lars Bellner, Brian D. Lamon, Yilun Zhang, Nader G. Abraham, Alberto Nasjletti

Nader G. Abraham

Aims: Hydrogen peroxide (H(2)O(2)), a nonradical oxidant, is employed to ascertain the role of redox mechanisms in regulation of vascular tone. Where both dilation and constriction have been reported, we examined the hypothesis that the ability of H(2)O(2) to effect vasoconstriction or dilation is conditioned by redox mechanisms and may be modulated by antioxidants. Results: Exogenous H(2)O(2) (0.1-10.0 μM), dose-dependently reduced the internal diameter of rat renal interlobular and 3rd-order mesenteric arteries (p<0.05). This response was obliterated in arteries pretreated with antioxidants, including tempol, pegylated superoxide dismutase ...


Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro MD 2016 Marshall University

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Nader G. Abraham

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice ...


Traveling With Stowaways: The Human Microbiome And Travel, Alisha N. Hughes 2016 University of Washington - Tacoma Campus

Traveling With Stowaways: The Human Microbiome And Travel, Alisha N. Hughes

Global Honors Theses

The human microbiome is a research field that is fairly new and thus, not yet fully understood. However, past research has revealed that the human host and the microorganisms interact with each other. To comprehend how influential the connection between host and its stowaways is, the following text will first offer general information on the human microbiome, before moving on to a pilot case study proposal. With the use of similar case studies, this proposal aims to investigate how the human microbiome changes when the host travels and analyzes the changes and their affects on the individual’s health. The ...


Dysglycemia Induces Abnormal Circadian Blood Pressure Variability, Sivarajan Kumarasamy, Kathirvel Gopalakrishnan, Dong Hyun Kim, Nader G. Abraham, William D. Johnson, Bina Joe, Alok K. Gupta 2016 Marshall University

Dysglycemia Induces Abnormal Circadian Blood Pressure Variability, Sivarajan Kumarasamy, Kathirvel Gopalakrishnan, Dong Hyun Kim, Nader G. Abraham, William D. Johnson, Bina Joe, Alok K. Gupta

Nader G. Abraham

Background: Prediabetes (PreDM) in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV).

Hypothesis: Systemic inflammation and glycemia influence circadian blood pressure variability.

Methods: Dahl salt-sensitive (S) rats (n = 19) after weaning were fed either an American (AD) or a standard (SD) diet. The AD (high-glycemic-index, high-fat) simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat) mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG), adipokines (leptin and adiponectin), and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1) and ...


Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez 2016 Augustana College, Rock Island Illinois

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 ...


Yy1 Is Required For Germinal Center B Cell Development., Anupam Banerjee, Vishal Sindhava, Raja Vuyyuru, Vibha Jha, Suchita Hodewadekar, Tim Manser, Michael L Atchison 2016 Department of Biomedical Sciences, University of Pennsylvania, School of Veterinary Medicine

Yy1 Is Required For Germinal Center B Cell Development., Anupam Banerjee, Vishal Sindhava, Raja Vuyyuru, Vibha Jha, Suchita Hodewadekar, Tim Manser, Michael L Atchison

Department of Microbiology and Immunology Faculty Papers

YY1 has been implicated as a master regulator of germinal center B cell development as YY1 binding sites are frequently present in promoters of germinal center-expressed genes. YY1 is known to be important for other stages of B cell development including the pro-B and pre-B cells stages. To determine if YY1 plays a critical role in germinal center development, we evaluated YY1 expression during B cell development, and used a YY1 conditional knock-out approach for deletion of YY1 in germinal center B cells (CRE driven by the immunoglobulin heavy chain γ1 switch region promoter; γ1-CRE). We found that YY1 is ...


A Conserved Dna Repeat Promotes Selection Of A Diverse Repertoire Of Trypanosoma Brucei Surface Antigens From The Genomic Archive., Galadriel Hovel-Miner, Monica R. Mugnier, Benjamin Goldwater, George A. M. Cross, F. Nina Papavasiliou 2016 George Washington University

A Conserved Dna Repeat Promotes Selection Of A Diverse Repertoire Of Trypanosoma Brucei Surface Antigens From The Genomic Archive., Galadriel Hovel-Miner, Monica R. Mugnier, Benjamin Goldwater, George A. M. Cross, F. Nina Papavasiliou

Microbiology, Immunology, and Tropical Medicine Faculty Publications

African trypanosomes are mammalian pathogens that must regularly change their protein coat to survive in the host bloodstream. Chronic trypanosome infections are potentiated by their ability to access a deep genomic repertoire of Variant Surface Glycoprotein (VSG) genes and switch from the expression of one VSG to another. Switching VSG expression is largely based in DNA recombination events that result in chromosome translocations between an acceptor site, which houses the actively transcribed VSG, and a donor gene, drawn from an archive of more than 2,000 silent VSGs. One element implicated in these duplicative gene conversion events is a DNA ...


Examination Of Cd133 And Cd147 As Cancer Stem Cell Markers, Christopher McMahon 2016 Northern Michigan University

Examination Of Cd133 And Cd147 As Cancer Stem Cell Markers, Christopher Mcmahon

All NMU Master's Theses

To date, as many as 14,000 patients in the United States per year are diagnosed with glioblastoma, the most common and most malignant primary brain tumor. Glioblastomas are characterized by their ability to evade treatment on many fronts, thus a novel approach to curative therapies is imperative. A population of cells with stem cell-like properties are found within glioblastoma tumors and drive their initiation and progression. Identification of extracellular markers on these tumor stem cells is thus paramount. The cell surface glycoproteins CD133 and CD147 were examined as potential markers of cancer stem cells found in glioblastoma. Here we ...


Redesigning Gfp Reporter System For Utilization In Clostridium Difficile, Laura E. Fitzgerald 2016 University of Arkansas, Fayetteville

Redesigning Gfp Reporter System For Utilization In Clostridium Difficile, Laura E. Fitzgerald

Biological Sciences Undergraduate Honors Theses

Clostridium difficile (C. difficile) is a gram-positive bacterium that comprises part of the healthy human gut microbiome. When it gains sufficient access to peptides, C. difficile flourishes and releases tissue-damaging toxins, which cause inflammation of the colon that can develop into a Clostridium difficile Infection (CDI).10 The Ivey Laboratory believes that the best tactic in preventing CDIs is stopping peptide ingestion, which theoretically could be accomplished by manipulating the oligopeptide permease (App) system.7 In order to verify that altering the App system would successfully impede peptide uptake, first the expression of the app Promoter Region (appProR) of ...


Porphyromonas Gingivalis Gingipains Induce A Pro-Inflammatory Extracellular Microenvironment : The Role Of Par-2 And Fibronectin., Jeffrey S. Marschall 2016 University of Louisville

Porphyromonas Gingivalis Gingipains Induce A Pro-Inflammatory Extracellular Microenvironment : The Role Of Par-2 And Fibronectin., Jeffrey S. Marschall

Electronic Theses and Dissertations

Periodontitis is a chronic inflammatory disease that is characterized by severe tissue destruction of the gingiva and other tooth supporting structures; if left untreated, tooth loss and disintegration of the alveolar bone occurs. This chronic inflammatory state has been linked to other systemic diseases such as cardiovascular disease, diabetes, rheumatoid arthritis, and Alzheimer’s disease. Porphyromonas gingivalis is the major pathogenic microbe in periodontitis. The main virulence factors of P. gingivalis are the Arg-aa and Lys-aa gingipains, which are proteolytic enzymes implicated in a plethora of activities that allow P. gingivalis to subvert the human immune system in the oral ...


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