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

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

Sharone Green

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


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

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

Sharone Green

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


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

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

Dissertations & Theses in Veterinary and Biomedical Science

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


Suppression Of Systemic Autoimmunity By The Innate Immune Adaptor Sting, Shrutie Sharma, Allison M. Campbell, Jennie Chan, Stefan A. Schattgen, Gregory M. Orlowski, Ribhu Nayar, Annie H. Huyler, Kerstin Nundel, Chandra Mohan, Leslie J. Berg, Mark J. Shlomchik, Ann Marshak-Rothstein, Katherine A. Fitzgerald 2017 University of Massachusetts Medical School

Suppression Of Systemic Autoimmunity By The Innate Immune Adaptor Sting, Shrutie Sharma, Allison M. Campbell, Jennie Chan, Stefan A. Schattgen, Gregory M. Orlowski, Ribhu Nayar, Annie H. Huyler, Kerstin Nundel, Chandra Mohan, Leslie J. Berg, Mark J. Shlomchik, Ann Marshak-Rothstein, Katherine A. Fitzgerald

Katherine A. Fitzgerald

Cytosolic DNA-sensing pathways that signal via Stimulator of interferon genes (STING) mediate immunity to pathogens and also promote autoimmune pathology in DNaseII- and DNaseIII-deficient mice. In contrast, we report here that STING potently suppresses inflammation in a model of systemic lupus erythematosus (SLE). Lymphoid hypertrophy, autoantibody production, serum cytokine levels, and other indicators of immune activation were markedly increased in STING-deficient autoimmune-prone mice compared with STING-sufficient littermates. As a result, STING-deficient autoimmune-prone mice had significantly shorter lifespans than controls. Importantly, Toll-like receptor (TLR)-dependent systemic inflammation during 2,6,10,14-tetramethylpentadecane (TMPD)-mediated peritonitis was similarly aggravated in STING-deficient mice ...


Pathways Involved In Recognition And Induction Of Trained Innate Immunity By Plasmodium Falciparum, Jacob E. Schrum 2017 University of Massachusetts Medical School

Pathways Involved In Recognition And Induction Of Trained Innate Immunity By Plasmodium Falciparum, Jacob E. Schrum

GSBS Dissertations and Theses

Malarial infection in naïve individuals induces a robust innate immune response, but our understanding of the mechanisms by which the innate immune system recognizes malaria and regulates its response remain incomplete. Our group previously showed that stimulation of macrophages with Plasmodium falciparum genomic DNA (gDNA) and AT-rich oligodeoxynucleotides (ODNs) derived from this gDNA induces the production of type I interferons (IFN-I) through a STING/TBK1/IRF3-dependent pathway; however, the identity of the upstream cytosolic DNA receptor remained elusive. Here, we demonstrate that this IFN-I response is dependent on cyclic GMP-AMP synthase (cGAS). cGAS produced the cyclic dinucleotide 2’3’-cGAMP ...


Finding A Link Between Circadian Rhythms And The Immune System Of Captive Zebra Finches (Taeniopygia Guttata), Amber Bishop 2017 Western Kentucky University

Finding A Link Between Circadian Rhythms And The Immune System Of Captive Zebra Finches (Taeniopygia Guttata), Amber Bishop

Honors College Capstone Experience/Thesis Projects

Circadian rhythms are commonplace in organisms and are normally controlled by a master clock. More recent evidence suggests that autonomous clocks operate in various systems in the body, including the immune system. This study looks for such a connection between the circadian rhythm and the immune system. In this study, captive zebra finches (Taeniopygia guttata) were exposed to different light and dark cycles and blood samples were taken every six hours. Birds were exposed to 12 hours of light and then 12 hours of darkness (LD), 24 hours of darkness (DD), or 48 hours of DD. After collecting whole blood ...


The Antiviral Rna Interference Response Provides Resistance To Lethal Arbovirus Infection And Vertical Transmission In Caenorhabditis Elegans, Don B. Gammon, Takao Ishidate, Lichao Li, Weifeng Gu, Neal S. Silverman, Craig C. Mello 2017 University of Massachusetts Medical School

The Antiviral Rna Interference Response Provides Resistance To Lethal Arbovirus Infection And Vertical Transmission In Caenorhabditis Elegans, Don B. Gammon, Takao Ishidate, Lichao Li, Weifeng Gu, Neal S. Silverman, Craig C. Mello

Neal Silverman

The recent discovery of the positive-sense single-stranded RNA (ssRNA) Orsay virus (OV) as a natural pathogen of the nematode Caenorhabditis elegans has stimulated interest in exploring virus-nematode interactions. However, OV infection is restricted to a small number of intestinal cells, even in nematodes defective in their antiviral RNA interference (RNAi) response, and is neither lethal nor vertically transmitted. Using a fluorescent reporter strain of the negative-sense ssRNA vesicular stomatitis virus (VSV), we show that microinjection of VSV particles leads to a dose-dependent, muscle tissue-tropic, lethal infection in C. elegans. Furthermore, we find nematodes deficient for components of the antiviral RNAi ...


B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips 2017 Seton Hall University

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory ...


Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte 2017 University of Connecticut - Storrs

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen is ...


Developing Novel Approaches To Improve Response To T Cell Based Cancer Immunotherapy, Rina M. Mbofung 2017 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Developing Novel Approaches To Improve Response To T Cell Based Cancer Immunotherapy, Rina M. Mbofung

UT GSBS Dissertations and Theses (Open Access)

Recently, T cell based immunotherapies have moved to the forefront of cancer immunotherapy with the success of Adoptive T cell therapy (ACT) and Immune checkpoint blockade.ACT, where patients are treated with tumour infiltrating T cells (TILs), conferred a clinical response rate of ~50%. Treatment with anti-CTLA4 and anti –PD1 therapy, conferred response rates of up to 50%, greatly improving the overall survival of patients with advanced melanoma amongst other cancer types. Despite the encouraging outcomes, there are relatively low response rates coupled with the delay of weeks to months before tumour shrinkage can be appreciated. Thus, understanding what tumour ...


Characterization Of Murine Breast Cancer Cell Lines For Anti-Cancer Vaccine, Haven N. Frazier 2017 University of Arkansas, Fayetteville

Characterization Of Murine Breast Cancer Cell Lines For Anti-Cancer Vaccine, Haven N. Frazier

Biological Sciences Undergraduate Honors Theses

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer death among women in the United States (1). While treatments involving radiation and chemotherapy currently exist, disease must be detected early in order for the treatments to be somewhat effective, and there is no effective treatment after metastasis occurs (2). Additionally, current therapies do not mitigate tumor immunosuppression. Decreasing the tumor-associated immunosuppressive conditions while activating antitumor immunity could prevent recurrence and metastasis, possibly leading to an effective treatment for cancer (3). Tumor cell vaccines could possibly address this issue and have become a ...


Allele-Selective Suppression Of Mutant Huntingtin In Primary Human Blood Cells, James R. C. Miller, Edith L. Pfister, Wanzhao Liu, Ralph Andre, Ulrike Trager, Lori A. Kennington, Kimberly Lo, Sipke Dijkstra, Douglas Macdonald, Gary R. Ostroff, Neil Aronin, Sarah J. Tabrizi 2017 University College London

Allele-Selective Suppression Of Mutant Huntingtin In Primary Human Blood Cells, James R. C. Miller, Edith L. Pfister, Wanzhao Liu, Ralph Andre, Ulrike Trager, Lori A. Kennington, Kimberly Lo, Sipke Dijkstra, Douglas Macdonald, Gary R. Ostroff, Neil Aronin, Sarah J. Tabrizi

Open Access Articles

Post-transcriptional gene silencing is a promising therapy for the monogenic, autosomal dominant, Huntington's disease (HD). However, wild-type huntingtin (HTT) has important cellular functions, so the ideal strategy would selectively lower mutant HTT while sparing wild-type. HD patients were genotyped for heterozygosity at three SNP sites, before phasing each SNP allele to wild-type or mutant HTT. Primary ex vivo myeloid cells were isolated from heterozygous patients and transfected with SNP-targeted siRNA, using glucan particles taken up by phagocytosis. Highly selective mRNA knockdown was achieved when targeting each allele of rs362331 in exon 50 of the HTT transcript; this selectivity was ...


Binding Of A Monoclonal Antibody To B Virus Gd Linear Epitope On A Whole Virus Antigen Is Only After Antigen Denaturation, Jingyao Deng 2017 Georgia State University

Binding Of A Monoclonal Antibody To B Virus Gd Linear Epitope On A Whole Virus Antigen Is Only After Antigen Denaturation, Jingyao Deng

Georgia State Undergraduate Research Conference

No abstract provided.


Creation Of An Immunodeficient Hla-Transgenic Mouse (Humamice) And Functional Validation Of Human Immunity After Transfer Of Hla-Matched Human Cells, Yang Zeng, Bingrun Liu, Marie-Therese Rubio, Xinyue Wang, David M. Ojcius, Ruoping Tang, Antoine Durrbach, Zhitao Ru, Yusen Zhou, Yu-Chun Lone 2017 Beijing Institute of Microbiology and Epidemiology

Creation Of An Immunodeficient Hla-Transgenic Mouse (Humamice) And Functional Validation Of Human Immunity After Transfer Of Hla-Matched Human Cells, Yang Zeng, Bingrun Liu, Marie-Therese Rubio, Xinyue Wang, David M. Ojcius, Ruoping Tang, Antoine Durrbach, Zhitao Ru, Yusen Zhou, Yu-Chun Lone

Dugoni School of Dentistry Faculty Articles

Research on human immunology has been hindered by the lack of optimal small animal models, given that the protective immune responses of human and non-human species show significant differences. However, due to ethical constraints[1] and the high cost of clinical trials, it is urgent to improve the current animal models that can mimic faithfully human physiology, particularly the human immune system (HIS). HIS mice had been generated recently by engrafting human hematopoietic stem cells (hHSCs) or human peripheral mononuclear cells (hPBMCs) into highly immuno-deficient mice such as NSG, NOG or NRG mice. However, a major experimental drawback for studies ...


The Antiviral Rna Interference Response Provides Resistance To Lethal Arbovirus Infection And Vertical Transmission In Caenorhabditis Elegans, Don B. Gammon, Takao Ishidate, Lichao Li, Weifeng Gu, Neal S. Silverman, Craig C. Mello 2017 University of Massachusetts Medical School

The Antiviral Rna Interference Response Provides Resistance To Lethal Arbovirus Infection And Vertical Transmission In Caenorhabditis Elegans, Don B. Gammon, Takao Ishidate, Lichao Li, Weifeng Gu, Neal S. Silverman, Craig C. Mello

University of Massachusetts Medical School Faculty Publications

The recent discovery of the positive-sense single-stranded RNA (ssRNA) Orsay virus (OV) as a natural pathogen of the nematode Caenorhabditis elegans has stimulated interest in exploring virus-nematode interactions. However, OV infection is restricted to a small number of intestinal cells, even in nematodes defective in their antiviral RNA interference (RNAi) response, and is neither lethal nor vertically transmitted. Using a fluorescent reporter strain of the negative-sense ssRNA vesicular stomatitis virus (VSV), we show that microinjection of VSV particles leads to a dose-dependent, muscle tissue-tropic, lethal infection in C. elegans. Furthermore, we find nematodes deficient for components of the antiviral RNAi ...


P23. Elucidation Of The Signaling Pathway Of Mertk, Kyle Taruc 2017 Western University

P23. Elucidation Of The Signaling Pathway Of Mertk, Kyle Taruc

Western Research Forum

Background

Mer Tyrosine Kinase (MERTK) is a receptor which mediates efferocytosis – removal of apoptotic cells by phagocytes such as macrophages. MERTK plays a critical role in homeostasis, with mutations in MERTK associated with the development and progression of atherosclerosis, the buildup of cholesterol-laden plaque in the sub-arterial space. Indeed, one MERTK allele is associated with 66% (heterozygous) to 75% (homozygous) protection from atherosclerosis, while other alleles and SNP’s pre-dispose to atherosclerosis and autoimmunity. Complications resulting from atherosclerosis, including heart attack and stroke, are currently the second leading cause of mortality in Canada. Despite the importance of MERTK in atherosclerosis ...


Thermal Biology Of Insect Immunity And Host-Microbe Interactions, Laura V. Ferguson 2017 The University of Western Ontario

Thermal Biology Of Insect Immunity And Host-Microbe Interactions, Laura V. Ferguson

Electronic Thesis and Dissertation Repository

The influence of temperature on interactions with pathogenic or symbiotic microbes is a driving force behind the survival of insects under climate change. However, we know little of how insects physiologically respond to these pressures. In temperate climates, winter dominates the thermal landscape; thus, I am particularly interested in how cold interacts with insect responses to microbes. Here I explore the thermal biology of the insect immune system and the impacts of cold on host-microbe interactions. First, I demonstrate that acute exposure to cold activates selective components of immunity in Drosophila melanogaster, as a compensatory response to trade-offs or injury ...


Mhc Class Iiβ Diversity As A Correlate Of Neutral-Locus Similarity And Diversity, And A Predictor Of Overwinter Return, In Song Sparrows (Melospiza Melodia), Matthew J. Watson 2017 The University of Western Ontario

Mhc Class Iiβ Diversity As A Correlate Of Neutral-Locus Similarity And Diversity, And A Predictor Of Overwinter Return, In Song Sparrows (Melospiza Melodia), Matthew J. Watson

Electronic Thesis and Dissertation Repository

Abstract

The major histocompatibility complex (MHC) is a family of genes involved with recognizing pathogens and mounting an immune response. Parasite-mediated selection often favours heterozygosity at MHC because MHC-diverse individuals recognize a wider range of pathogens. Because migratory birds encounter many pathogens, I hypothesized that MHC diversity predicts overwinter and juvenile survivorship in song sparrows (Melospiza melodia). I found no correlation between MHC diversity and neutral-locus (microsatellite) heterozygosity, suggesting that measures of neutral and adaptive genetic diversity provide complementary rather than redundant information. However, pairwise similarity at MHC predicted pairwise similarity at microsatellite loci. In contrast to my hypothesis, MHC ...


Soluble Uric Acid Activates The Nlrp3 Inflammasome, Tarcio Teodoro Braga, Maria Fernanda Forni, Matheus Correa-Costa, Rodrigo Nalio Ramos, Jose Alexandre Barbuto, Paola Branco, Angela Castoldi, Meire Ioshie Hiyane, Mariana Rodrigues Davanso, Eicke Latz, Bernardo S. Franklin, Alicia J. Kowaltowski, Niels Olsen Saraiva Camara 2017 University of São Paulo

Soluble Uric Acid Activates The Nlrp3 Inflammasome, Tarcio Teodoro Braga, Maria Fernanda Forni, Matheus Correa-Costa, Rodrigo Nalio Ramos, Jose Alexandre Barbuto, Paola Branco, Angela Castoldi, Meire Ioshie Hiyane, Mariana Rodrigues Davanso, Eicke Latz, Bernardo S. Franklin, Alicia J. Kowaltowski, Niels Olsen Saraiva Camara

Open Access Articles

Uric acid is a damage-associated molecular pattern (DAMP), released from ischemic tissues and dying cells which, when crystalized, is able to activate the NLRP3 inflammasome. Soluble uric acid (sUA) is found in high concentrations in the serum of great apes, and even higher in some diseases, before the appearance of crystals. In the present study, we sought to investigate whether uric acid, in the soluble form, could also activate the NLRP3 inflammasome and induce the production of IL-1beta. We monitored ROS, mitochondrial area and respiratory parameters from macrophages following sUA stimulus. We observed that sUA is released in a hypoxic ...


Isolation, Culture And Characterization Of Hirsutella Sinensis Mycelium From Caterpillar Fungus Fruiting Body, Yun-Fei Komi, Jian-Ching Liau, Chien-Sheng Lee, Chen-Yaw Chiu, Jan Martel, Chuan-Sheng Lin, Shan-Fu Tseng, David M. Ojcius, Chia-Chen Lu, Hsin-Chih Lai, John Ding-E. Young 2017 Chang Gung Biotechnology Corporation

Isolation, Culture And Characterization Of Hirsutella Sinensis Mycelium From Caterpillar Fungus Fruiting Body, Yun-Fei Komi, Jian-Ching Liau, Chien-Sheng Lee, Chen-Yaw Chiu, Jan Martel, Chuan-Sheng Lin, Shan-Fu Tseng, David M. Ojcius, Chia-Chen Lu, Hsin-Chih Lai, John Ding-E. Young

Dugoni School of Dentistry Faculty Articles

The caterpillar fungus Ophiocordyceps sinensis (previously called Cordyceps sinensis) has been used for centuries in Asia as a tonic to improve health and longevity. Recent studies show that O. sinensis produces a wide range of biological effects on cells, laboratory animals and humans, including anti-fatigue, anti-infection, anti-inflammatory, antioxidant, and anti-tumor activities. In view of the rarity of O. sinensis fruiting bodies in nature, cultivation of its anamorph mycelium represents a useful alternative for large-scale production. However, O. sinensis fruiting bodies harvested in nature harbor several fungal contaminants, a phenomenon that led to the isolation and characterization of a large number ...


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