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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 2017 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

Jiang Liu

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 ...


Capillaries, Old Age And Alzheimer’S Disease, Charles T. Ambrose 2017 University of Kentucky

Capillaries, Old Age And Alzheimer’S Disease, Charles T. Ambrose

Charles T. Ambrose

Many of the minor complaints of old age may have a common etiology and are grouped together here under the term ‘the lesser ailments of aging’ (LAA). This essay proposes that they are due in large part to an age-linked reduced microcirculation. Capillary density (CD) in the tissues is determined by levels of angiogenic growth factors (AGFs). Over 47 studies have reported a reduced CD and/or waning AGFs throughout the bodies of aging animals and people. More convincing than such a generalization are the 80 sets of data comparing these two parameters in adult vs. the aged. These data ...


Analysis Of The Local And Systemic Cytokine Response Profiles In Patients With Community-Acquired Pneumonia. Relationship With Disease Severity And Outcomes., Rafael Fernandez-Botran, Timothy Lee Wiemken, Robert R. Kelley, Paula Peyrani, Jose Bordon, Rodrigo Cavallazzi, Julio A. Ramirez 2017 University of Louisville

Analysis Of The Local And Systemic Cytokine Response Profiles In Patients With Community-Acquired Pneumonia. Relationship With Disease Severity And Outcomes., Rafael Fernandez-Botran, Timothy Lee Wiemken, Robert R. Kelley, Paula Peyrani, Jose Bordon, Rodrigo Cavallazzi, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

The goals of this study were to investigate the relationship of systemic and local cytokine responses with time to clinical stability (TCS) in patients with community-acquired pneumonia (CAP) and to develop a model to integrate multiple cytokine data into “cytokine response profiles” based on local vs. systemic and pro- vs. anti-inflammatory cytokine patterns in order to better understand their relationships with measures of CAP severity and outcomes. Forty hospitalized patients enrolled through the Community Acquired Pneumonia Inflammatory Study Group (CAPISG) were analyzed. Based on the ranked distribution of the levels of eight different pro-inflammatory cytokines and chemokines (IL-1b, IL-6, IL-8 ...


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

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

Microbiology, Immunology, and Tropical Medicine Faculty Publications

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


Safety And Immunogenicity Of The Na-Gst-1 Hookworm Vaccine In Brazilian And American Adults., David J Diemert, Janaína Freire, Vanderson Valente, Carlos Geraldo Fraga, Frederico Talles, Shannon Grahek, Doreen Campbell, Amar Jariwala, Maria Victoria Periago, Martin Enk, Maria Flávia Gazzinelli, Maria Elena Bottazzi, Robert Hamilton, Jill Brelsford, Anna Yakovleva, Guangzhao Li, Jin Peng, Rodrigo Correa-Oliveira, Peter Hotez, Jeffrey Bethony 2017 George Washington University

Safety And Immunogenicity Of The Na-Gst-1 Hookworm Vaccine In Brazilian And American Adults., David J Diemert, Janaína Freire, Vanderson Valente, Carlos Geraldo Fraga, Frederico Talles, Shannon Grahek, Doreen Campbell, Amar Jariwala, Maria Victoria Periago, Martin Enk, Maria Flávia Gazzinelli, Maria Elena Bottazzi, Robert Hamilton, Jill Brelsford, Anna Yakovleva, Guangzhao Li, Jin Peng, Rodrigo Correa-Oliveira, Peter Hotez, Jeffrey Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) plays a role in the digestion of host hemoglobin by adult N. americanus hookworms. Vaccination of laboratory animals with recombinant Na-GST-1 is associated with significant protection from challenge infection. Recombinant Na-GST-1 was expressed in Pichia pastoris and adsorbed to aluminum hydroxide adjuvant (Alhydrogel) according to current Good Manufacturing Practice. Two Phase 1 trials were conducted in 142 healthy adult volunteers in the United States and Brazil, first in hookworm-naïve individuals and then in residents of a N. americanus endemic area in Brazil. Volunteers received one of three doses of recombinant Na-GST-1 (10 ...


Chemical And Structural Characterization Of A Model Post-Termination Complex (Potc) For The Ribosome Recycling Reaction: Evidence For The Release Of The Mrna By Rrf And Ef-G., Nobuhiro Iwakura, Takeshi Yokoyama, Fabio Quaglia, Kaoru Mitsuoka, Kazuhiro Mio, Hideki Shigematsu, Mikako Shirouzu, Akira Kaji, Hideko Kaji 2017 Thomas Jefferson University

Chemical And Structural Characterization Of A Model Post-Termination Complex (Potc) For The Ribosome Recycling Reaction: Evidence For The Release Of The Mrna By Rrf And Ef-G., Nobuhiro Iwakura, Takeshi Yokoyama, Fabio Quaglia, Kaoru Mitsuoka, Kazuhiro Mio, Hideki Shigematsu, Mikako Shirouzu, Akira Kaji, Hideko Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

A model Post-Termination Complex (PoTC) used for the discovery of Ribosome Recycling Factor (RRF) was purified and characterized by cryo-electron microscopic analysis and biochemical methods. We established that the model PoTC has mostly one tRNA, at the P/E or P/P position, together with one mRNA. The structural studies were supported by the biochemical measurement of bound tRNA and mRNA. Using this substrate, we establish that the release of tRNA, release of mRNA and splitting of ribosomal subunits occur during the recycling reaction. Order of these events is tRNA release first followed by mRNA release and splitting almost simultaneously ...


The Effect Of Photoactivated Tmp On Burkholderia Cepacia Biofilms, Reyna G. Osorio, Chandra N. Swiech, Tracy L. Collins 2017 Cedarville University

The Effect Of Photoactivated Tmp On Burkholderia Cepacia Biofilms, Reyna G. Osorio, Chandra N. Swiech, Tracy L. Collins

The Research and Scholarship Symposium

Burkholderia cepacia is an opportunistic pathogen that causes infections in immunocompromised individuals such as cystic fibrosis patients. B. cepacia infections are typically characterized by the formation of complex communities of cells known as biofilms. Because B. cepacia biofilms are difficult to eradicate using antibiotics, it is important to pursue alternative treatment methods. Photodynamic therapy (PDT) is a type of therapy that uses light, a photosensitizer, and oxygen to elicit cell death through the production of reactive oxygen species. PDT has been shown in previous studies to be successful in killing both Pseudomonas aeruginosa and Staphylococcus aureus. In this study, we ...


Broadly Neutralizing Antibodies As Treatment: Effects On Virus And Immune System., Jinal N Bhiman, Rebecca M Lynch 2017 George Washington University

Broadly Neutralizing Antibodies As Treatment: Effects On Virus And Immune System., Jinal N Bhiman, Rebecca M Lynch

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Purpose of Review

The purpose of this study is to summarize recent advances in the use of broadly neutralizing antibodies (bNAbs) as therapeutics in human clinical trials and in non-human primate (NHP) models. We seek to highlight lessons from these studies with an emphasis on consequences to the virus and immune system.

Recent Findings

In the past 10 years, advances in HIV-1 trimer structure and B cell isolation methods have precipitated the identification of “new-generation” anti-HIV antibodies with broad and potent neutralization. In the past 2 years, the concept of using these bNAbs as therapeutic tools has moved from NHP ...


Dynamic Transcriptomes Identify Biogenic Amines And Insect-Like Hormonal Regulation For Mediating Reproduction In Schistosoma Japonicum., Jipeng Wang, Ying Yu, Haimo Shen, Tao Qing, Yuanting Zheng, Qing Li, Xiaojin Mo, Shuqi Wang, Nana Li, Riyi Chai, Bin Xu, Mu Liu, Paul J Brindley, Donald P McManus, Zheng Feng, Leming Shi, Wei Hu 2017 George Washington University

Dynamic Transcriptomes Identify Biogenic Amines And Insect-Like Hormonal Regulation For Mediating Reproduction In Schistosoma Japonicum., Jipeng Wang, Ying Yu, Haimo Shen, Tao Qing, Yuanting Zheng, Qing Li, Xiaojin Mo, Shuqi Wang, Nana Li, Riyi Chai, Bin Xu, Mu Liu, Paul J Brindley, Donald P Mcmanus, Zheng Feng, Leming Shi, Wei Hu

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Eggs produced by the mature female parasite are responsible for the pathogenesis and transmission of schistosomiasis. Female schistosomes rely on a unique male-induced strategy to accomplish reproductive development, a process that is incompletely understood. Here we map detailed transcriptomic profiles of male and female Schistosoma japonicum across eight time points throughout the sexual developmental process from pairing to maturation. The dynamic gene expression pattern data reveal clear sex-related characteristics, indicative of an unambiguous functional division between males and females during their interplay. Cluster analysis, in situ hybridization and RNAi assays indicate that males likely use biogenic amine neurotransmitters through the ...


The Final (Oral Ebola) Vaccine Trial On Captive Chimpanzees?, Peter D. Walsh, Drishya Kurup, Dana L. Hasselschwert, Christoph Wirblich, Jason E. Goetzmann, Matthias J. Schnell 2017 University of Cambridge

The Final (Oral Ebola) Vaccine Trial On Captive Chimpanzees?, Peter D. Walsh, Drishya Kurup, Dana L. Hasselschwert, Christoph Wirblich, Jason E. Goetzmann, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Could new oral vaccine technologies protect endangered wildlife against a rising tide of infectious disease? We used captive chimpanzees to test oral delivery of a rabies virus (RABV) vectored vaccine against Ebola virus (EBOV), a major threat to wild chimpanzees and gorillas. EBOV GP and RABV GP-specific antibody titers increased exponentially during the trial, with rates of increase for six orally vaccinated chimpanzees very similar to four intramuscularly vaccinated controls. Chimpanzee sera also showed robust neutralizing activity against RABV and pseudo-typed EBOV. Vaccination did not induce serious health complications. Blood chemistry, hematologic, and body mass correlates of psychological stress suggested ...


Capillaries, Old Age And Alzheimer’S Disease, Charles T. Ambrose 2017 University of Kentucky

Capillaries, Old Age And Alzheimer’S Disease, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Many of the minor complaints of old age may have a common etiology and are grouped together here under the term ‘the lesser ailments of aging’ (LAA). This essay proposes that they are due in large part to an age-linked reduced microcirculation. Capillary density (CD) in the tissues is determined by levels of angiogenic growth factors (AGFs). Over 47 studies have reported a reduced CD and/or waning AGFs throughout the bodies of aging animals and people. More convincing than such a generalization are the 80 sets of data comparing these two parameters in adult vs. the aged. These data ...


The Host Microbiome Regulates And Maintains Human Health: A Primer And Perspective For Non-Microbiologists, Sunil Thomas, Jacques Izard, Emily Walsh, Kristen Batich, Pakawat Chongsathidkiet, Gerard Clarke, David A. Sela, Alexander J. Muller, James M. Mullin, Korin Albert, John P. Gilligan, Katherine DiGuilio, Rima Dilbarova, Walker Alexander, George P. Prendergast 2017 Lankenau Institute for Medical Research, Wynnewood, Pennsylvania

The Host Microbiome Regulates And Maintains Human Health: A Primer And Perspective For Non-Microbiologists, Sunil Thomas, Jacques Izard, Emily Walsh, Kristen Batich, Pakawat Chongsathidkiet, Gerard Clarke, David A. Sela, Alexander J. Muller, James M. Mullin, Korin Albert, John P. Gilligan, Katherine Diguilio, Rima Dilbarova, Walker Alexander, George P. Prendergast

Faculty Publications in Food Science and Technology

Humans consider themselves discrete autonomous organisms, but recent research is rapidly strengthening the appreciation that associated microorganisms make essential contributions to human health and well being. Each person is inhabited and also surrounded by his/her own signature microbial cloud. A low diversity of microorganisms is associated with a plethora of diseases, including allergy, diabetes, obesity, arthritis, inflammatory bowel diseases, and even neuropsychiatric disorders. Thus, an interaction of microorganisms with the host immune system is required for a healthy body. Exposure to microorganisms from the moment we are born and appropriate microbiome assembly during childhood are essential for establishing an ...


The Role Of Estradiol Metabolism In Urogenital Schistosomiasis-Induced Bladder Cancer, Nuno Vale, Maria Gouveia, Gabriel Rinaldi, Julio Santos, Lucio Lara Santos, Paul J. Brindley, Jose Correia da Costa 2017 George Washington University

The Role Of Estradiol Metabolism In Urogenital Schistosomiasis-Induced Bladder Cancer, Nuno Vale, Maria Gouveia, Gabriel Rinaldi, Julio Santos, Lucio Lara Santos, Paul J. Brindley, Jose Correia Da Costa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Urogenital schistosomiasis is a neglected tropical disease that can lead to bladder cancer. How urogenital schistosomiasis induces carcinogenesis remains unclear, although there is evidence that the human blood fluke Schistosoma haematobium, the infectious agent of urogenital schistosomiasis, releases estradiol-like metabolites. These kind of compounds have been implicated in other cancers. Aiming for enhanced understanding of the pathogenesis of the urogenital schistosomiasisinduced bladder cancer, here we review, interpret, and discuss findings of estradiol-like metabolites detected in both the parasite and in the human urine during urogenital schistosomiasis. Moreover, we predict pathways and enzymes that are involved in the production of these ...


Elevated Prevalence Of Helicobacter Species And Virulence Factors In Opisthorchiasis And Associated Hepatobiliary Disease., Raksawan Deenonpoe, Eimorn Mairiang, Pisaln Mairiang, Chawalit Pairojkul, Yaovalux Chamgramol, Gabriel Rinaldi, Alex Loukas, Paul J. Brindley, Banchob Sripa 2017 George Washington University

Elevated Prevalence Of Helicobacter Species And Virulence Factors In Opisthorchiasis And Associated Hepatobiliary Disease., Raksawan Deenonpoe, Eimorn Mairiang, Pisaln Mairiang, Chawalit Pairojkul, Yaovalux Chamgramol, Gabriel Rinaldi, Alex Loukas, Paul J. Brindley, Banchob Sripa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Recent reports suggest that Opisthorchis viverrini serves as a reservoir of Helicobacter and implicate Helicobacter in pathogenesis of opisthorchiasis-associated cholangiocarcinoma (CCA). Here, 553 age-sex matched cases and controls, 293 and 260 positive and negative for liver fluke O. viverrini eggs, of residents in Northeastern Thailand were investigated for associations among infection with liver fluke, Helicobacter and hepatobiliary fibrosis. The prevalence of H. pylori infection was higher in O. viverrini-infected than uninfected participants. H. pylori bacterial load correlated positively with intensity of O. viverrini infection, and participants with opisthorchiasis exhibited higher frequency of virulent cagA-positive H. pylori than those free of ...


Advances In Neglected Tropical Disease Vaccines: Developing Relative Potency And Functional Assays For The Na-Gst-1/Alhydrogel Hookworm Vaccine., Jill B. Brelsford, Jordan L Plieskatt, Anna Yakovleva, Amar Jariwala, Brian P Keegan, Jin Peng, Pengjun Xia, Guangzhao Li, Doreen Campbell, Maria Victoria Periago, Rodrigo Correa-Oliveira, Maria Elena Bottazzi, Peter J. Hotez, David Diemert, Jeffrey M. Bethony 2017 George Washington University

Advances In Neglected Tropical Disease Vaccines: Developing Relative Potency And Functional Assays For The Na-Gst-1/Alhydrogel Hookworm Vaccine., Jill B. Brelsford, Jordan L Plieskatt, Anna Yakovleva, Amar Jariwala, Brian P Keegan, Jin Peng, Pengjun Xia, Guangzhao Li, Doreen Campbell, Maria Victoria Periago, Rodrigo Correa-Oliveira, Maria Elena Bottazzi, Peter J. Hotez, David Diemert, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

A new generation of vaccines for the neglected tropical diseases (NTDs) have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. The current manuscript focuses on the often overlooked critical aspects of NTD vaccine product development, more specifically, vaccine stability testing programs. A key measure of vaccine stability testing is "relative potency" or the immunogenicity of the vaccine during storage. As with most NTD vaccines, the Na-GST-1/Alhydrogel Hookworm Vaccine was not developed by attenuation or inactivation of the pathogen (Necator americanus), so conventional methods for measuring relative ...


Parasite Infection, Carcinogenesis And Human Malignancy., Hoang van Tong, Paul J. Brindley, Christian G Meyer, Thirumalaisamy P Velavan 2017 George Washington University

Parasite Infection, Carcinogenesis And Human Malignancy., Hoang Van Tong, Paul J. Brindley, Christian G Meyer, Thirumalaisamy P Velavan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in ...


Yeast Help Identify Cytopathic Factors Of Zika Virus, Michael I. Bukrinsky 2017 George Washington University

Yeast Help Identify Cytopathic Factors Of Zika Virus, Michael I. Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Accumulating evidence implicates Zika virus (ZIKV) in pathogenesis of microcephaly in newborns and Guillain-Barré syndrome in adults. However, it remains unclear which viral proteins are responsible for these effects and what are the underlying mechanisms of their pathogenic activity. A recent paper by Drs. Zhao and Gallo, and their colleagues at University of Maryland in Baltimore used fission yeast for genome-wide analysis of ZIKV proteins. They demonstrated cytopathogenic activity for seven ZIKV proteins, anaC, C, prM, M, E, NS2B and NS4A. This activity was shown to be dependent on oxidative stress, and for NS4A they demonstrated involvement of the TOR ...


Freshwater Fungal Infections, Dennis J. Baumgardner 2017 Aurora UW Medical Group, Aurora Health Care

Freshwater Fungal Infections, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

Fungal infections as a result of freshwater exposure or trauma are fortunately rare. Etiologic agents are varied, but commonly include filamentous fungi and Candida. This narrative review describes various sources of potential freshwater fungal exposure and the diseases that may result, including fungal keratitis, acute otitis externa and tinea pedis, as well as rare deep soft tissue or bone infections and pulmonary or central nervous system infections following traumatic freshwater exposure during natural disasters or near-drowning episodes. Fungal etiology should be suspected in appropriate scenarios when bacterial cultures or molecular tests are normal or when the infection worsens or fails ...


A Comparison Of The Quality Of Informed Consent For Clinical Trials Of An Experimental Hookworm Vaccine Conducted In Developed And Developing Countries., David J. Diemert, Lucas Lobato, Ashley Styczynski, Maria Zumer, Amanda Soares, Maria Flávia Gazzinelli 2017 George Washington University

A Comparison Of The Quality Of Informed Consent For Clinical Trials Of An Experimental Hookworm Vaccine Conducted In Developed And Developing Countries., David J. Diemert, Lucas Lobato, Ashley Styczynski, Maria Zumer, Amanda Soares, Maria Flávia Gazzinelli

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Informed consent is one of the principal ethical requirements of conducting clinical research, regardless of the study setting. Breaches in the quality of the informed consent process are frequently described in reference to clinical trials conducted in developing countries, due to low levels of formal education, a lack of familiarity with biomedical research, and limited access to health services in these countries. However, few studies have directly compared the quality of the informed consent process in developed and developing countries using the same tool and in similar clinical trials. This study was conducted to compare the quality of the informed ...


Novel Long-Chain Compounds With Both Immunomodulatory And Mena Inhibitory Activities Against Staphylococcus Aureus And Its Biofilm., Seoung-Ryoung Choi, Joel Frandsen, Prabagaran Narayanasamy 2017 University of Nebraska Medical Center

Novel Long-Chain Compounds With Both Immunomodulatory And Mena Inhibitory Activities Against Staphylococcus Aureus And Its Biofilm., Seoung-Ryoung Choi, Joel Frandsen, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Menaquinone (MK) biosynthesis pathway is a potential target for evaluating antimicrobials in gram-positive bacteria. Here, 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) was targeted to reduce methicillin-resistant Staphylococcus aureus (MRSA) growth. MenA inhibiting, long chain-based compounds were designed, synthesized and evaluated against MRSA and menaquinone utilizing bacteria in aerobic conditions. The results showed that these bacteria were susceptible to most of the compounds. Menaquinone (MK-4) supplementation rescued MRSA growth, suggesting these compounds inhibit MK biosynthesis. 3a and 7c exhibited promising inhibitory activities with MICs ranging 1-8 μg/mL against MRSA strains. The compounds did not facilitate small colony variant formation. These compounds also ...


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