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Taking Control: Reorganization Of The Host Cytoskeleton By Chlamydia., Jordan Wesolowski, Fabienne Paumet 2017 Thomas Jefferson University

Taking Control: Reorganization Of The Host Cytoskeleton By Chlamydia., Jordan Wesolowski, Fabienne Paumet

Department of Microbiology and Immunology Faculty Papers

Both actin and microtubules are major cytoskeletal elements in eukaryotic cells that participate in many cellular processes, including cell division and motility, vesicle and organelle movement, and the maintenance of cell shape. Inside its host cell, the human pathogen Chlamydia trachomatis manipulates the cytoskeleton to promote its survival and enhance its pathogenicity. In particular, Chlamydia induces the drastic rearrangement of both actin and microtubules, which is vital for its entry, inclusion structure and development, and host cell exit. As significant progress in Chlamydia genetics has greatly enhanced our understanding of how this pathogen co-opts the host cytoskeleton, we will discuss ...


Suppression Of Mrnas Encoding Cd63 Family Tetraspanins From The Carcinogenic Liver Fluke Opisthorchis Viverrini Results In Distinct Tegument Phenotypes., Sujittra Chaiyadet, Watchara Krueajampa, Wiphawi Hipkaeo, Yada Plosan, Supawadee Piratae, Javier Sotillo, Michael Smout, Banchob Sripa, Paul J Brindley, Alex Loukas, Thewarach Laha 2017 George Washington University

Suppression Of Mrnas Encoding Cd63 Family Tetraspanins From The Carcinogenic Liver Fluke Opisthorchis Viverrini Results In Distinct Tegument Phenotypes., Sujittra Chaiyadet, Watchara Krueajampa, Wiphawi Hipkaeo, Yada Plosan, Supawadee Piratae, Javier Sotillo, Michael Smout, Banchob Sripa, Paul J Brindley, Alex Loukas, Thewarach Laha

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The liver fluke Opisthorchis viverrini infects 10 million people in Southeast Asia and causes cholangiocarcinoma (CCA). Fluke secreted and tegumental proteins contribute to the generation of a tumorigenic environment and are targets for drug and vaccine-based control measures. Herein, we identified two tetraspanins belonging to the CD63 family (Ov-TSP-2 and Ov-TSP-3) that are abundantly expressed in the tegument proteome of O. viverrini. Ov-tsp-2 and tsp-3 transcripts were detected in all developmental stages of O. viverrini. Protein fragments corresponding to the large extracellular loop (LEL) of each TSP were produced in recombinant form and antibodies were raised in rabbits. Ov-TSP-2 and ...


Induction Of Peripheral Tolerance In Ongoing Autoimmune Inflammation Requires Interleukin 27 Signaling In Dendritic Cells, Rodolfo Thome, Jason N. Moore, Elisabeth R. Mari, Javad Rasouli 2017 Thomas Jefferson University

Induction Of Peripheral Tolerance In Ongoing Autoimmune Inflammation Requires Interleukin 27 Signaling In Dendritic Cells, Rodolfo Thome, Jason N. Moore, Elisabeth R. Mari, Javad Rasouli

Department of Neurology Faculty Papers

Peripheral tolerance to autoantigens is induced via suppression of self-reactive lymphocytes, stimulation of tolerogenic dendritic cells (DCs) and regulatory T (Treg) cells. Interleukin (IL)-27 induces tolerogenic DCs and Treg cells; however, it is not known whether IL-27 is important for tolerance induction. We immunized wild-type (WT) and IL-27 receptor (WSX-1) knockout mice with MOG35-55 for induction of experimental autoimmune encephalomyelitis and intravenously (i.v.) injected them with MOG35-55 after onset of disease to induce i.v. tolerance. i.v. administration of MOG35-55 reduced disease severity in WT mice, but was ineffective in Wsx-/- mice. IL-27 signaling ...


Human Herpesvirus 8 Infects And Replicates In Langerhans Cells And Interstitial Dermal Dendritic Cells And Impairs Their Function., Giovanna Rappocciolo, Mariel Jais, Paolo A Piazza, Diana C DeLucia, Frank J Jenkins, Charles R Rinaldo 2017 George Washington University

Human Herpesvirus 8 Infects And Replicates In Langerhans Cells And Interstitial Dermal Dendritic Cells And Impairs Their Function., Giovanna Rappocciolo, Mariel Jais, Paolo A Piazza, Diana C Delucia, Frank J Jenkins, Charles R Rinaldo

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The predominant types of dendritic cells (DC) in the skin and mucosa are Langerhans cells (LC) and interstitial dermal DC (iDDC). LC and iDDC process cutaneous antigens and migrate out of the skin and mucosa to the draining lymph nodes to present antigens to T and B cells. Because of the strategic location of LC and iDDC and the ability of these cells to capture and process pathogens, we hypothesized that they could be infected with human herpesvirus 8 (HHV-8) (Kaposi's sarcoma [KS]-associated herpesvirus) and have an important role in the development of KS. We have previously shown ...


Evaluating A Preoperative Protocol That Includes Magnetic Resonance Imaging For Lymph Node Metastasis In The Cholangiocarcinoma Screening And Care Program (Cascap) In Thailand., Metha Songthamwat, Nittaya Chamadol, Narong Khuntikeo, Jadsada Thinkhamrop, Supinda Koonmee, Nathaphop Chaichaya, Jeffrey Bethony, Bandit Thinkhamrop 2017 George Washington University

Evaluating A Preoperative Protocol That Includes Magnetic Resonance Imaging For Lymph Node Metastasis In The Cholangiocarcinoma Screening And Care Program (Cascap) In Thailand., Metha Songthamwat, Nittaya Chamadol, Narong Khuntikeo, Jadsada Thinkhamrop, Supinda Koonmee, Nathaphop Chaichaya, Jeffrey Bethony, Bandit Thinkhamrop

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Treatment planning especially liver resection in cholangiocarcinoma (CCA) depends on the extension of tumor and lymph node metastasis which is included as a key criterion for operability. Magnetic resonance imaging (MRI) offers a rapid and powerful tool for the detection of lymph node metastasis (LNM) and in the current manuscript is assessed as a critical tool in the preoperative protocol for liver resection for treatment of CCA. However, the accuracy of MRI to detect LNM from CCA had yet to be comprehensively evaluated.

METHODS: The accuracy of MRI to detect LNM was assessed in a cohort of individuals with ...


T-Cell Responses Targeting Hiv Nef Uniquely Correlate With Infected Cell Frequencies After Long-Term Antiretroviral Therapy., Allison S Thomas, Kimberley L Jones, Rajesh T Gandhi, Deborah K McMahon, Joshua C Cyktor, Dora Chan, Szu-Han Huang, Ronald Truong, Alberto Bosque, Amanda B Macedo, Colin Kovacs, Erika Benko, Joseph J Eron, Ronald J Bosch, Christina M Lalama, Samuel Simmens, Bruce D Walker, John W Mellors, R Brad Jones 2017 George Washington University

T-Cell Responses Targeting Hiv Nef Uniquely Correlate With Infected Cell Frequencies After Long-Term Antiretroviral Therapy., Allison S Thomas, Kimberley L Jones, Rajesh T Gandhi, Deborah K Mcmahon, Joshua C Cyktor, Dora Chan, Szu-Han Huang, Ronald Truong, Alberto Bosque, Amanda B Macedo, Colin Kovacs, Erika Benko, Joseph J Eron, Ronald J Bosch, Christina M Lalama, Samuel Simmens, Bruce D Walker, John W Mellors, R Brad Jones

Microbiology, Immunology, and Tropical Medicine Faculty Publications

HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART), these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression. Using a primary cell model of ...


Interventions To Reduce Neonatal Mortality From Neonatal Tetanus In Low And Middle Income Countries - A Systematic Review, Adeel Ahmed Khan, Aysha Zahidie, F. Rabbani 2017 Aga Khan University

Interventions To Reduce Neonatal Mortality From Neonatal Tetanus In Low And Middle Income Countries - A Systematic Review, Adeel Ahmed Khan, Aysha Zahidie, F. Rabbani

Fauziah Rabbani

Background In 1988, WHO estimated around 787,000 newborns deaths due to neonatal tetanus. Despite few success stories majority of the Low and Middle Income Countries (LMICs) are still struggling to reduce neonatal mortality due to neonatal tetanus. We conducted a systematic review to understand the interventions that have had a substantial effect on reducing neonatal mortality rate due to neonatal tetanus in LMICs and come up with feasible recommendations for decreasing neonatal tetanus in the Pakistani setting. Methods We systemically reviewed the published literature (Pubmed and Pubget databases) to identify appropriate interventions for reducing tetanus related neonatal mortality. A ...


Anti-Herv-K (Hml-2) Capsid Antibody Responses In Hiv Elite Controllers., Miguel de Mulder, Devi SenGupta, Steven G Deeks, Jeffrey N Martin, Christopher D Pilcher, Frederick M Hecht, Jonah B Sacha, Douglas F Nixon, Henri-Alexandre Michaud 2017 George Washington University

Anti-Herv-K (Hml-2) Capsid Antibody Responses In Hiv Elite Controllers., Miguel De Mulder, Devi Sengupta, Steven G Deeks, Jeffrey N Martin, Christopher D Pilcher, Frederick M Hecht, Jonah B Sacha, Douglas F Nixon, Henri-Alexandre Michaud

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection.

Results

We developed an ELISA assay using either recombinant protein or 164 redundant “15mer” HERV-K (HML-2) Gag peptides to test sera for antibody reactivity. We identified a total of eight potential HERV-K (HML-2) Gag immunogenic domains: two on ...


Differential Live Mycobacterium Tuberculosis- , M. Bovis Bcg-, Recombinant Esat6-, And Culture Filtrate Protein 10-Induced Immunity In Tuberculosis, Zahra Hasan, Bushra Jamil, Mussarat Ashraf, Muniba Islam, Maqboola Dojki, Muhammad Irfan, Rabia Hussain 2017 Aga Khan University

Differential Live Mycobacterium Tuberculosis- , M. Bovis Bcg-, Recombinant Esat6-, And Culture Filtrate Protein 10-Induced Immunity In Tuberculosis, Zahra Hasan, Bushra Jamil, Mussarat Ashraf, Muniba Islam, Maqboola Dojki, Muhammad Irfan, Rabia Hussain

Bushra Jamil

The high prevalence of Mycobacterium tuberculosis makes it imperative that immune responses to evaluate could be predictive of infection. We investigated live Mycobacterium- and recombinant antigen-induced cytokine and chemokine responses in patients with active tuberculosis (TB) compared with those of healthy controls from an area where TB is endemic (ECs). M. tuberculosis-, M. bovis BCG-, ESAT6-, and culture filtrate protein 10 (CFP10)-induced responses were determined in peripheral blood mononuclear cells from patients with pulmonary TB (n = 38) and ECs (n = 39). The levels of the cytokines gamma interferon (IFN-γ) and interleukin-10 (IL-10) and the chemokines CCL2, CCL3, and CXCL9 ...


Multiple Myeloma Baseline Immunoglobulin G Level And Pneumococcal Vaccination Antibody Response, Michael A. Thompson, Martin K. Oaks, Maharaj Singh, Karen M. Michel, Michael P. Mullane, Husam S. Tarawneh, Angi Kraut, Kayla J. Hamm 2017 Aurora Research Institute / Aurora Cancer Care, Aurora Health Care

Multiple Myeloma Baseline Immunoglobulin G Level And Pneumococcal Vaccination Antibody Response, Michael A. Thompson, Martin K. Oaks, Maharaj Singh, Karen M. Michel, Michael P. Mullane, Husam S. Tarawneh, Angi Kraut, Kayla J. Hamm

Journal of Patient-Centered Research and Reviews

Infections are a major cause of morbidity and mortality in multiple myeloma (MM), a cancer of the immune system. Vaccination clinical efficacy endpoints have not been demonstrated, and there are limited data on surrogate markers of efficacy. This pilot study evaluated sequential immunologic markers after standard pneumococcal vaccination (PV) in patients with MM and non-MM controls. Vaccination was standard for PV (PCV13 or PPV23), with laboratory testing at baseline and at 2, 4, 12 and 24 weeks after vaccination. Immunoglobulin G (IgG) antibodies to pneumococcal antigens were detected by ELISA. Prevaccination total IgG levels and IgG subclass levels were also ...


Forgiveness: How It Manifests In Our Health, Well-Being, And Longevity, Kathi Norman 2017 University of Pennsylvania

Forgiveness: How It Manifests In Our Health, Well-Being, And Longevity, Kathi Norman

Master of Applied Positive Psychology (MAPP) Capstone Projects

Forgiveness is a character strength and process that, when practiced, is associated with improved psychological well-being, physical health outcomes, and longevity. Forgiveness can serve as a protective factor that buffers against poor health and psychological consequences. Common misconceptions about forgiveness can serve as barriers to the desire to cultivate this protective strength, as forgiveness is often conflated with permissiveness, and perceived as permission for a transgressor to engage in hurtful conduct. The benefits of forgiveness, however, are most significant for the individual who has been transgressed, rather than the transgressor. Failing to forgive, or unforgiveness, is the practice of engaging ...


Revisiting Neutrophil Responses To Toll-Like Receptor 4 : Influence Of Ligand Structures And Cellular Environments., Shuvasree Sengupta 2017 University of Louisville

Revisiting Neutrophil Responses To Toll-Like Receptor 4 : Influence Of Ligand Structures And Cellular Environments., Shuvasree Sengupta

Electronic Theses and Dissertations

Neutrophils respond to bacterial LPS through Toll-like receptor 4 (TLR4), which activates or potentiates immune defensive functions and prolongs cell survival. Activation of TLR4 signaling in neutrophils is beneficial for effective clearance of LPS-bearing Gram-negative bacteria, but may also drive aberrant inflammation if not stringently regulated. The regulatory processes by which neutrophil functions are calibrated to respond appropriately to different LPS-bearing bacteria are incompletely understood. Described here are investigations that reveal an unexpected sensitivity of TLR4 in neutrophils to small changes in LPS structure typical of various Gram-negative bacteria, including those that are dangerously virulent (Escherichia coli and Salmonella enterica ...


Modulation Of Let-7 Mirnas Controls The Differentiation Of Effector Cd8 T Cells, Alexandria C. Wells, Keith A. Daniels, Constance C. Angelou, Eric Fagerberg, Amy S. Burnside, Michele Markstein, Dominique Alfandari, Raymond M. Welsh, Elena L. Pobezinskaya, Leonid A. Pobezinsky 2017 University of Massachusetts Amherst

Modulation Of Let-7 Mirnas Controls The Differentiation Of Effector Cd8 T Cells, Alexandria C. Wells, Keith A. Daniels, Constance C. Angelou, Eric Fagerberg, Amy S. Burnside, Michele Markstein, Dominique Alfandari, Raymond M. Welsh, Elena L. Pobezinskaya, Leonid A. Pobezinsky

Open Access Articles

The differentiation of naive CD8 T cells into effector cytotoxic T lymphocytes upon antigen stimulation is necessary for successful antiviral, and antitumor immune responses. Here, using a mouse model, we describe a dual role for the let-7 microRNAs in the regulation of CD8 T cell responses, where maintenance of the naive phenotype in CD8 T cells requires high levels of let-7 expression, while generation of cytotoxic T lymphocytes depends upon T cell receptor-mediated let-7 downregulation. Decrease of let-7 expression in activated T cells enhances clonal expansion and the acquisition of effector function through derepression of the let-7 targets, including Myc ...


Helminth Infection-Induced Malignancy., Paul J Brindley, Alex Loukas 2017 George Washington University

Helminth Infection-Induced Malignancy., Paul J Brindley, Alex Loukas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infectious diseases cause more than 20% of cancers in the developing world [1]. About a dozen pathogens including Epstein-Barr virus and human T cell lymphocytotropic virus 1 are among the well-known examples. In addition, infection with several trematodes, which are eukaryotes, can cause malignancy. The International Agency for Research on Cancer categorizes infection with the fish-borne trematodes Opisthorchis viverrini and Clonorchis sinensis and the blood fluke Schistosoma haematobium as Group 1 biological carcinogens [2]. In addition to parasitism directly damaging development, health, and prosperity of infected populations, infection with these helminths leads to cholangiocarcinoma (CCA) (bile duct cancer) and squamous ...


Parasite Microbiome Project: Systematic Investigation Of Microbiome Dynamics Within And Across Parasite-Host Interactions., Nolwenn M Dheilly, Daniel Bolnick, Seth Bordenstein, Paul J Brindley, Cédric Figuères, Edward C Holmes, Joaquín Martínez Martínez, Anna J Phillips, Robert Poulin, Karyna Rosario 2017 George Washington University

Parasite Microbiome Project: Systematic Investigation Of Microbiome Dynamics Within And Across Parasite-Host Interactions., Nolwenn M Dheilly, Daniel Bolnick, Seth Bordenstein, Paul J Brindley, Cédric Figuères, Edward C Holmes, Joaquín Martínez Martínez, Anna J Phillips, Robert Poulin, Karyna Rosario

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Understanding how microbiomes affect host resistance, parasite virulence, and parasite-associated diseases requires a collaborative effort between parasitologists, microbial ecologists, virologists, and immunologists. We hereby propose the Parasite Microbiome Project to bring together researchers with complementary expertise and to study the role of microbes in host-parasite interactions. Data from the Parasite Microbiome Project will help identify the mechanisms driving microbiome variation in parasites and infected hosts and how that variation is associated with the ecology and evolution of parasites and their disease outcomes. This is a call to arms to prevent fragmented research endeavors, encourage best practices in experimental approaches, and ...


Isolated Candida Infection Of The Lung, Yousef Shweihat MD, James Perry, Darshana T. Shah PhD 2017 Marshall University

Isolated Candida Infection Of The Lung, Yousef Shweihat Md, James Perry, Darshana T. Shah Phd

Darshana Shah

Candida pneumonia is a rare infection of the lungs, with the majority of cases occurring secondary to hematological dissemination of Candida organisms from a distant site, usually the gastrointestinal tract or skin. We report a case of a 77-year-old male who is life-long smoker with a history of rheumatoid arthritis and polymyalgia rheumatica, but did not take immunosuppressants for those conditions. Here, we present an extremely rare case of isolated pulmonary parenchymal Candida infection in the form pulmonary nodules without evidence of systemic disease which has only been described in a few previous reports.


Isolated Candida Infection Of The Lung, Yousef Shweihat MD, James Perry, Darshana T. Shah PhD 2017 Marshall University

Isolated Candida Infection Of The Lung, Yousef Shweihat Md, James Perry, Darshana T. Shah Phd

Yousef R. Shweihat

Candida pneumonia is a rare infection of the lungs, with the majority of cases occurring secondary to hematological dissemination of Candida organisms from a distant site, usually the gastrointestinal tract or skin. We report a case of a 77-year-old male who is life-long smoker with a history of rheumatoid arthritis and polymyalgia rheumatica, but did not take immunosuppressants for those conditions. Here, we present an extremely rare case of isolated pulmonary parenchymal Candida infection in the form pulmonary nodules without evidence of systemic disease which has only been described in a few previous reports.


Chemical Modulation Of Cancer Cells To Enhance Tumor Immunity, Florisela Herrejon Chavez 2017 Portland State University

Chemical Modulation Of Cancer Cells To Enhance Tumor Immunity, Florisela Herrejon Chavez

PSU McNair Scholars Online Journal

Breakthroughs in immunotherapy have led to cancer therapeutics that activate the immune system by blocking inhibitory mechanisms. This class of therapeutics has resulted in longer survival rates for cancer patients, some living over 10 years after being diagnosed as terminally ill. However, only a small fraction of patients who receive immunotherapy drugs respond favorably.Recent studies suggest that certain anticancer agents (both cytotoxic chemotherapeutics and targeted drugs) stimulate immune recognition of cancers. Identification of such immunomodulatory anticancer agents would make ideal partners for current immunotherapy treatments, thus increasing the proportion of the treated patients who benefit from immunotherapy. This study ...


Subsets Of Inflammatory Cytokine Gene Polymorphisms Are Associated With Risk Of Carcinogenic Liver Fluke Opisthorchis Viverrini-Associated Advanced Periductal Fibrosis And Cholangiocarcinoma., Arpa Surapaitoon, Sutas Suttiprapa, Eimorn Mairiang, Narong Khuntikeo, Chawalit Pairojkul, Jeffrey Bethony, Paul J Brindley, Banchob Sripa 2017 George Washington University

Subsets Of Inflammatory Cytokine Gene Polymorphisms Are Associated With Risk Of Carcinogenic Liver Fluke Opisthorchis Viverrini-Associated Advanced Periductal Fibrosis And Cholangiocarcinoma., Arpa Surapaitoon, Sutas Suttiprapa, Eimorn Mairiang, Narong Khuntikeo, Chawalit Pairojkul, Jeffrey Bethony, Paul J Brindley, Banchob Sripa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF−, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-1β ...


The Effect Of Group 1 Cd1-Restricted T Cells On Atherosclerosis, Shon Thomas, Sreya Bagchi 2017 Northwestern University

The Effect Of Group 1 Cd1-Restricted T Cells On Atherosclerosis, Shon Thomas, Sreya Bagchi

Undergraduate Research and Arts Exposition

Approximately 1 in 3 deaths in the US is caused by cardiovascular diseases, among them atherosclerosis. Atherosclerosis occurs through excessive cholesterol deposition (hyperlipidemia) along the inner layer of the artery called the intima, resulting in plaque formation that blocks arterial blood flow and could lead to heart attacks and strokes. It has recently been recognized that inflammation plays an important role in plaque formation. Specifically, T cell activation can affect the progression of atherosclerosis through interaction with antigen presenting cells (APCs) in a hyperlipidemic environment. APCs ingest foreign objects and present digested remnants on antigen presenting molecules at the cell ...


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