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Characterization Of Interleukin (Il)-1Β Regulatory Elements And Chromatin Conformation In Macrophage Activation, Woohyun Cho 2018 The University of Western Ontario

Characterization Of Interleukin (Il)-1Β Regulatory Elements And Chromatin Conformation In Macrophage Activation, Woohyun Cho

Electronic Thesis and Dissertation Repository

IL-1β is a potent inflammatory cytokine promptly expressed in activated myeloid cells. PU.1 is a lineage-determining transcription factor that regulates myeloid-specific genes by activating distal enhancers. This study addresses the functional importance of a potential enhancer of IL-1β, and how PU.1 regulates its activity state. A putative enhancer RNA (eRNA) was transcribed from the enhancer, and eRNA knock-down with antisense oligonucleotides inhibited IL-1β production. Furthermore, enhancer-promoter interactions in stimulated macrophages were detected via chromatin conformation capture (3C) analysis. The role of PU.1 was examined in PU.1-overexpressed B16-BL6 cells, which responded to LPS and expressed IL-1β mRNA ...


Identification And Characterization Of Human Monoclonal Antibodies For Immunoprophylaxis Against Enterotoxigenic Escherichia Coli Infection, Serena Giuntini, Matteo Stoppato, Maja Sedic, Ejemel Monir, Jessica R. Pondish, Danielle Wisheart, Zachary Schiller, William D. Thomas Jr., Eileen M. Barry, Lisa Cavacini, mark S. klempner, Yan Wang 2018 University of Massachusetts Medical School

Identification And Characterization Of Human Monoclonal Antibodies For Immunoprophylaxis Against Enterotoxigenic Escherichia Coli Infection, Serena Giuntini, Matteo Stoppato, Maja Sedic, Ejemel Monir, Jessica R. Pondish, Danielle Wisheart, Zachary Schiller, William D. Thomas Jr., Eileen M. Barry, Lisa Cavacini, Mark S. Klempner, Yan Wang

Open Access Articles

Background. Enterotoxigenic Escherichia coli (ETEC) cause diarrheal illness in infants in the developing world and travelers to endemic countries including military personnel. ETEC infection of the host involves colonization of the small intestinal epithelium and toxin secretion leading to watery diarrhea. There is currently no vaccine licensed to prevent ETEC. CFA/I is one of the most common colonization factor antigens (CFAs). The CFA/I adhesin subunit, CfaE, is required for ETEC adhesion to host intestinal cells. Human antibodies against CfaE have potential to block colonization of ETEC and serve as an immunoprophylactic against ETEC-related diarrhea.

Methods. Mice transgenic for ...


Sodium Pyruvate Alters The Immune Response To Influenza A Virus Infection In Macrophages, Hazzar Abysalamah 2018 Missouri State University

Sodium Pyruvate Alters The Immune Response To Influenza A Virus Infection In Macrophages, Hazzar Abysalamah

MSU Graduate Theses

ABSTRACT

Pyruvate is the end product of glycolysis. It can either be transported into the mitochondria for use in the TCA cycle or be used to regenerate NAD+ during fermentation or aerobic glycolysis (also called the Warburg Effect). I recently discovered that addition of sodium pyruvate to the culture medium during infection of macrophages with influenza A virus affects the production of cytokines involved in immune signaling. While infection of macrophages with influenza A virus resulted in high levels of cytokines (IL-6, IL-1β, and TNF-α) in the absence of sodium pyruvate, the addition of sodium pyruvate significantly impaired cytokine production ...


From Olfaction To Immunity: Characterization Of Nasal Immunity In Bony Fish, Ali Sepahi 2018 University of New Mexico

From Olfaction To Immunity: Characterization Of Nasal Immunity In Bony Fish, Ali Sepahi

Biology ETDs

The olfactory system is a common route pathogen entry in vertebrates. As a consequence, the nasopharynx-associated lymphoid tissue (NALT) needs to rapidly clear infections without compromising the sense of olfaction. NALT is present in teleost fish but its cellular and molecular mechanisms of action have not been investigated to this date. This dissertation focuses on three aims: 1. investigating the role of CCL19-like as a primordial chemokine in vertebrate nasal immunity, 2. determining the presence of tissue microenvironments within the olfactory organ (OO) of rainbow trout, and 3. understanding the immune contributions of olfactory sensory neurons (OSNs) in teleosts against ...


Production Of A Candidate Recombinant Protein Vaccine For Mannheimia Haemolytica In Lettuce And Tobacco Chloroplasts, Coby K. Martin 2018 The University of Western Ontario

Production Of A Candidate Recombinant Protein Vaccine For Mannheimia Haemolytica In Lettuce And Tobacco Chloroplasts, Coby K. Martin

Electronic Thesis and Dissertation Repository

The cattle industry worldwide is ravaged by bovine respiratory disease (BRD), a bacterial disease caused by Mannheimia haemolytica. Recent efforts to design vaccines against M. haemolytica focus on a virulence factor, leukotoxin, in addition to surface lipoproteins. Plant-based protein production is a safe and inexpensive alternative to traditional methods. Edible vaccines deliver antigens to pharyngeal tissues, which can provide local immunization against M. haemolytica prior to its progression into the lungs. In this project, a chimeric protein containing M. haemolytica antigens was produced in tobacco chloroplasts as a candidate edible vaccine for BRD. Attempts were made to transform lettuce chloroplasts ...


Fas Ligand Promotes An Inducible Tlr-Dependent Model Of Cutaneous Lupus-Like Inflammation, Purvi Mande, Bahar Zirak, Wei-Che Ko, Keyon Taravati, Karen L. Bride, Tia Bumpus Brodeur, April C. Deng, Karen A. Dresser, Zhaozhao Jiang, Rachel Ettinger, Katherine A. Fitzgerald, Michael D. Rosenblum, John E. Harris, Ann Marshak-Rothstein 2018 University of Massachusetts Medical School

Fas Ligand Promotes An Inducible Tlr-Dependent Model Of Cutaneous Lupus-Like Inflammation, Purvi Mande, Bahar Zirak, Wei-Che Ko, Keyon Taravati, Karen L. Bride, Tia Bumpus Brodeur, April C. Deng, Karen A. Dresser, Zhaozhao Jiang, Rachel Ettinger, Katherine A. Fitzgerald, Michael D. Rosenblum, John E. Harris, Ann Marshak-Rothstein

University of Massachusetts Medical School Faculty Publications

Toll-like receptors TLR7 and TLR9 are both implicated in the activation of autoreactive B cells and other cell types associated with systemic lupus erythematosus (SLE) pathogenesis. However, Tlr9-/- autoimmune-prone strains paradoxically develop more severe disease. We have now leveraged the negative regulatory role of TLR9 to develop an inducible rapid-onset murine model of systemic autoimmunity that depends on T cell detection of a membrane-bound OVA fusion protein expressed by MHC class II+ cells, expression of TLR7, expression of the type I IFN receptor, and loss of expression of TLR9. These mice are distinguished by a high frequency of OVA-specific Tbet ...


P38b And Jak-Stat Signaling Protect Against Invertebrate Iridescent Virus 6 Infection In Drosophila, Cara C. West, Neal S. Silverman 2018 University of Massachusetts Medical School

P38b And Jak-Stat Signaling Protect Against Invertebrate Iridescent Virus 6 Infection In Drosophila, Cara C. West, Neal S. Silverman

Open Access Articles

The fruit fly Drosophila melanogaster is a powerful model system for the study of innate immunity in vector insects as well as mammals. For vector insects, it is particularly important to understand all aspects of their antiviral immune defenses, which could eventually be harnessed to control the transmission of human pathogenic viruses. The immune responses controlling RNA viruses in insects have been extensively studied, but the response to DNA virus infections is poorly characterized. Here, we report that infection of Drosophila with the DNA virus Invertebrate iridescent Virus 6 (IIV-6) triggers JAK-STAT signaling and the robust expression of the Turandots ...


Enhanced Production Of Pro-Il-1Βeta Contributes To Immunopathology During The Coinfection Of Influenza A Virus And Streptococcus Pneumoniae, Angeline E. Rodriguez 2018 Missouri State University

Enhanced Production Of Pro-Il-1Βeta Contributes To Immunopathology During The Coinfection Of Influenza A Virus And Streptococcus Pneumoniae, Angeline E. Rodriguez

MSU Graduate Theses

Viral bacterial coinfections are known to cause severe pneumonia, especially in the elderly and in pediatric patients. Antibiotics like β-Lactams kill the bacteria but fail to improve symptoms suggesting a faulty immune system may play an important role in the disease. Interleukin-1β (IL-1β) is an important immune signaling cytokine responsible for inflammation. It exists as an inactive precursor that can be activated by caspase-1 containing inflammasomes (multi-protein complex). Influenza A virus (IAV) and Streptococcus pneumoniae (S. pneumoniae) activate the inflammasome through the NOD-like receptor protein NLRP3 and/or AIM2. Previous reports in mice indicate that IL-1β levels are dramatically elevated ...


The Youngest Victims Of The Opioid Epidemic, Katelyn E. MIller, Abby Reed 2018 Cedarville University

The Youngest Victims Of The Opioid Epidemic, Katelyn E. Miller, Abby Reed

The Research and Scholarship Symposium

When babies are born to opioid-addicted mothers, they often develop Neonatal Abstinence Syndrome (NAS). NAS is characterized by symptoms associated with abrupt opioid withdrawal (“Neonatal Abstinence”, 2015). By preventing NAS in babies before they are born and properly caring for a baby with NAS after birth, we will aim to decrease the incidence of this condition and as its harmful effects in the lives of babies. In Ohio, there are many neonates suffering from NAS. The rates for babies born with NAS have quadrupled since 2011 when 2.2 out of every 1000 babies had NAS to 2015, where 12 ...


Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. McCauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban 2018 University of Massachusetts Medical School

Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. Mccauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban

Program in Molecular Medicine Publications and Presentations

HIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, these individuals have chronic inflammation associated with heightened risk of cardiovascular pathology. HIV-1 establishes proviruses in long-lived CD4+ memory T cells, and perhaps other cell types, that preclude elimination of the virus even after years of continuous antiviral therapy. Though the majority of proviruses that persist during antiviral therapy are defective for production of infectious virions, many are expressed, raising the possibility that the HIV-1 provirus or its transcripts contribute to ongoing inflammation. Here we found that the HIV-1 provirus activated innate immune ...


Down-Regulation Of Microrna-203-3p Initiates Type 2 Pathology During Schistosome Infection Via Elevation Of Interleukin-33, Xing He, Jun Xie, Yange Wang, Xiaobin Fan, Qin Su, Yue Sun, Nanhang Lei, Dongmei Zhang, Guangping Gao, Weiqing Pan 2018 Second Military Medical University

Down-Regulation Of Microrna-203-3p Initiates Type 2 Pathology During Schistosome Infection Via Elevation Of Interleukin-33, Xing He, Jun Xie, Yange Wang, Xiaobin Fan, Qin Su, Yue Sun, Nanhang Lei, Dongmei Zhang, Guangping Gao, Weiqing Pan

Open Access Articles

The type 2 immune response is the central mechanism of disease progression in schistosomiasis, but the signals that induce it after infection remain elusive. Aberrant microRNA (miRNA) expression is a hallmark of human diseases including schistosomiasis, and targeting the deregulated miRNA can mitigate disease outcomes. Here, we demonstrate that efficient and sustained elevation of miR-203-3p in liver tissues, using the highly hepatotropic recombinant adeno-associated virus serotype 8 (rAAV8), protects mice against lethal schistosome infection by alleviating hepatic fibrosis. We show that miR-203-3p targets interleukin-33 (IL-33), an inducer of type 2 immunity, in hepatic stellate cells to regulate the expansion and ...


Serum Tumour Necrosis Factor Alpha In Osteopenic And Osteoporotic Postmenopausal Females: A Cross-Sectional Study In Pakistan, Rafat Murad, Zahra Shezad, Saara Ahmed, Mussarat Ashraf, Murad Qadir, Rehana Rehman 2018 Bahria University Medical & Dental College

Serum Tumour Necrosis Factor Alpha In Osteopenic And Osteoporotic Postmenopausal Females: A Cross-Sectional Study In Pakistan, Rafat Murad, Zahra Shezad, Saara Ahmed, Mussarat Ashraf, Murad Qadir, Rehana Rehman

Department of Biological & Biomedical Sciences

Objective: To compare biochemical parameters serum tumour necrosis factor alpha, calcium, magnesium, bone-specific alkaline phosphatase and vitamin D in postmenopausal women.
Methods: This cross-sectional study was carried out from June 2015 to July 2016 at Jinnah Medical and Dental College, Karachi, and comprised postmenopausal women. Bone mineral density done by dual energy X-ray absorptiometryscan categorised subjects by World Health Organisation classification into normal (T score > -1) osteopenic (T score between -1 and -2.5) and osteoporotic (T score < -2.5). Biochemical parameters like tumour necrosis alpha, calcium, magnesium, bone-specific alkaline phosphatase and vitamin D were measured by solid phase enzyme amplified sensitivity immunoassay method. SPSS 16 was used to analyse the data.
Results: Of the 146 women, 34(23%) were normal, 93(67%) were osteopenic and 19(13%) were osteoporotic. There was significant difference ...


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

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

Electronic Thesis and Dissertation Repository

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


Ischemia Augments Alloimmune Injury Through Il-6-Driven Cd4(+) Alloreactivity, Mayuko Uehara, Zhabiz Solhjou, Naima Banouni, Vivek Kasinath, Ye Xiaqun, Li Dai, Osman Yilmam, Mine Yilmaz, Takaharu Ichimura, Paolo Fiorina, Paulo N.A. Martins, Shunsuke Ohori, Indira Guleria, Omar H. Maarouf, Stefan G. Tullius, Martina M. McGrath, Reza Abdi 2018 Harvard Medical School

Ischemia Augments Alloimmune Injury Through Il-6-Driven Cd4(+) Alloreactivity, Mayuko Uehara, Zhabiz Solhjou, Naima Banouni, Vivek Kasinath, Ye Xiaqun, Li Dai, Osman Yilmam, Mine Yilmaz, Takaharu Ichimura, Paolo Fiorina, Paulo N.A. Martins, Shunsuke Ohori, Indira Guleria, Omar H. Maarouf, Stefan G. Tullius, Martina M. Mcgrath, Reza Abdi

Open Access Articles

Ischemia reperfusion injuries (IRI) are unavoidable in solid organ transplantation. IRI augments alloimmunity but the mechanisms involved are poorly understood. Herein, we examined the effect of IRI on antigen specific alloimmunity. We demonstrate that ischemia promotes alloimmune activation, leading to more severe histological features of rejection, and increased CD4(+) and CD8(+) T cell graft infiltration, with a predominantly CD8(+) IFNgamma(+) infiltrate. This process is dependent on the presence of alloreactive CD4(+) T cells, where depletion prevented infiltration of ischemic grafts by CD8(+) IFNgamma(+) T cells. IL-6 is a known driver of ischemia-induced rejection. Herein, depletion of donor antigen-presenting cells reduced ...


Pilot Study Of Delayed Icos/Icos-L Blockade With Alphacd40 To Modulate Pathogenic Alloimmunity In A Primate Cardiac Allograft Model, Natalie A. O'Neill, Tianshu Zhang, Gheorghe Braileanu, Xiangfei Cheng, Alena Hershfeld, Wenji Sun, Keith A. Reimann, Sia Dahi, Natalia Kubicki, Wessam Hassanein, Christopher Laird, Arielle Cimeno, Agnes M. Azimzadeh, Richard N. Pierson 2018 University of Maryland at Baltimore

Pilot Study Of Delayed Icos/Icos-L Blockade With Alphacd40 To Modulate Pathogenic Alloimmunity In A Primate Cardiac Allograft Model, Natalie A. O'Neill, Tianshu Zhang, Gheorghe Braileanu, Xiangfei Cheng, Alena Hershfeld, Wenji Sun, Keith A. Reimann, Sia Dahi, Natalia Kubicki, Wessam Hassanein, Christopher Laird, Arielle Cimeno, Agnes M. Azimzadeh, Richard N. Pierson

Open Access Articles

Background: Inducible costimulator (ICOS) is rapidly upregulated with T-cell stimulation and may represent an escape pathway for T-cell costimulation in the setting of CD40/CD154 costimulation blockade. Induction treatment exhibited no efficacy in a primate renal allograft model, but rodent transplant models suggest that the addition of delayed ICOS/ICOS-L blockade may prolong allograft survival and prevent chronic rejection. Here, we ask whether ICOS-Ig treatment, timed to anticipate ICOS upregulation, prolongs NHP cardiac allograft survival or attenuates pathogenic alloimmunity.

Methods: Cynomolgus monkey heterotopic cardiac allograft recipients were treated with alphaCD40 (2C10R4, d0-90) either alone or with the addition of delayed ...


Hiv-1 Unmasks The Plasticity Of Innate Lymphoid Cells, Yetao Wang, Kyle Gellatly, Alan G. Derr, Smita Jaiswal, Alper Kucukural, Patrick McDonel, Thomas C. Greenough, JeanMarie Houghton, Manuel Garber, Jeremy Luban 2018 University of Massachusetts Medical School

Hiv-1 Unmasks The Plasticity Of Innate Lymphoid Cells, Yetao Wang, Kyle Gellatly, Alan G. Derr, Smita Jaiswal, Alper Kucukural, Patrick Mcdonel, Thomas C. Greenough, Jeanmarie Houghton, Manuel Garber, Jeremy Luban

University of Massachusetts Medical School Faculty Publications

Pharmaceuticals that suppress HIV-1 viremia preserve CD4+ T cells and prevent AIDS. Nonetheless, HIV-1 infected people taking these drugs have chronic inflammation attributable to persistent disruption of intestinal barrier function with increased rates of cardiovascular mortality. To better understand the etiology of this inflammation we examined the effect of HIV-1 infection on innate lymphoid cells (ILCs). These innate immune counterparts of T cells lack clonotypic antigen receptors, classify according to signature transcription factors and cytokines, and maintain homeostasis in inflamed tissues. ILCs have been defined, in part, by the IL-7Rα, CD127. Here we report that the vast majority of type ...


Antiviral Immune Responses To Invertebrate Iridescent Virus 6 In Drosophila, Cara C. West 2018 University of Massachusetts Medical School

Antiviral Immune Responses To Invertebrate Iridescent Virus 6 In Drosophila, Cara C. West

GSBS Dissertations and Theses

The innate immune system is a critical first line of defense against invading pathogens. Innate immunity directly detects pathogens, sets up an appropriate adaptive response, and can directly kill pathogens.

Drosophila may lack an adaptive immune response, but have a robust innate immune system with a variety of defense effector mechanisms. While the responses to bacteria, fungi, and RNA viruses have been well characterized, not much is known about the response to DNA viruses. My studies have set out to characterize the Drosophila immune response to a DNA virus, utilizing the large dsDNA virus, Invertebrate Iridescent Virus 6 (IIV-6). IIV-6 ...


In Sickness And In Health: Understanding The Interactive Effects Of Immune Challenge And Foraging Behavior On Parental Investment In A Monogamous Seabird, Zachary Garrett 2018 The University of Akron

In Sickness And In Health: Understanding The Interactive Effects Of Immune Challenge And Foraging Behavior On Parental Investment In A Monogamous Seabird, Zachary Garrett

Honors Research Projects

Abstract

Carotenoid ornamentation is quite common in many species of birds, and often serves as an honest indicator of their fitness. The honesty of carotenoid ornamentation in the brown booby (Sula leucogaster brewsteri), a monogamous seabird, is likely driven by rarity of carotenoids in the diet but may also be regulated through additional pathways. For example, the trade-off hypothesis states that carotenoid pigments used in ornaments may also be required for the immune system as an antioxidant, thereby allowing only the healthiest birds to afford the carotenoid ornamentation. To test the trade-off hypothesis, I took advantage of a previously conducted ...


Bone Marrow Derived Progenitor Cells And Their Contributions To The Thymic Stroma, Mohammed Hoque 2018 CUNY City College

Bone Marrow Derived Progenitor Cells And Their Contributions To The Thymic Stroma, Mohammed Hoque

Master's Theses

The thymus serves as the primary lymphoid organ responsible for the development and selection of a self-tolerant T cell repertoire. In paradox to its critical functions for the adaptive immune response, the thymus undergoes a profound age associated decline beginning in early adult life resulting in significant decline in T-cell function.Thymic epithelial cells (TECs) are the most critical component of the thymic microenvironment and undergo rapid turn-over, so understanding the cellular mechanisms responsible for the maintenance of TEC number and organization will be critical in counteracting age associated involution, particularly in cancer patients, due to enhanced degeneration in response ...


Severity Of Acute Infectious Mononucleosis Correlates With Cross-Reactive Influenza Cd8 T-Cell Receptor Repertoires, Nuray Aslan, Levi B. Watkin, Anna Gil, Rabinarayan Mishra, Fransenio G. Clark, Raymond M. Welsh, Dario Ghersi, Katherine Luzuriaga, Liisa K. Selin 2017 University of Massachusetts Medical School

Severity Of Acute Infectious Mononucleosis Correlates With Cross-Reactive Influenza Cd8 T-Cell Receptor Repertoires, Nuray Aslan, Levi B. Watkin, Anna Gil, Rabinarayan Mishra, Fransenio G. Clark, Raymond M. Welsh, Dario Ghersi, Katherine Luzuriaga, Liisa K. Selin

UMass Center for Clinical and Translational Science Supported Publications

Fifty years after the discovery of Epstein-Barr virus (EBV), it remains unclear how primary infection with this virus leads to massive CD8 T-cell expansion and acute infectious mononucleosis (AIM) in young adults. AIM can vary greatly in severity, from a mild transient influenza-like illness to a prolonged severe syndrome. We questioned whether expansion of a unique HLA-A2.01-restricted, cross-reactive CD8 T-cell response between influenza virus A-M158 (IAV-M1) and EBV BMLF1280 (EBV-BM) could modulate the immune response to EBV and play a role in determining the severity of AIM in 32 college students. Only ex vivo total IAV-M1 and IAV-M1+EBV-BM ...


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