The Youngest Victims Of The Opioid Epidemic, 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, 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, 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, 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, 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, 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, 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 ...
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
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 ...
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 ...
Bone Marrow Derived Progenitor Cells And Their Contributions To The Thymic Stroma, 2018 CUNY City College
Bone Marrow Derived Progenitor Cells And Their Contributions To The Thymic Stroma, Mohammed Hoque
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, 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 ...
Emerging Infectious Disease And The Imperiled Relict Leopard Frog, 2017 University of Nevada, Las Vegas
Emerging Infectious Disease And The Imperiled Relict Leopard Frog, Anthony Wayne Waddle
UNLV Theses, Dissertations, Professional Papers, and Capstones
The disease chytridiomycosis, caused by the aquatic fungal pathogen Batrachochytrium dendrobatidis (Bd), has emerged as a major contributing factor for worldwide amphibian declines. Although relatively recently described, the impacts from the disease this pathogen causes have been definitively tied to amphibian declines, including some that occurred decades ago. In some cases, declines of individual species occurred with little documentation and are thus poorly understood. The relict leopard frog (Rana onca = Lithobates onca) has experienced such a decline and by the latter part of the 20th century only occurred in two general areas in southern Nevada. Recent research has found Bd ...
Molecular Evolution Of Dengue Type 2 Virus In Thailand, 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
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, 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
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, 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, 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 ...
Discovery Of Pf-06928215 As A High Affinity Inhibitor Of Cgas Enabled By A Novel Fluorescence Polarization Assay, Justin Hall, Douglas T. Golenbock, Eicke Latz
Open Access Articles
Cyclic GMP-AMP synthase (cGAS) initiates the innate immune system in response to cytosolic dsDNA. After binding and activation from dsDNA, cGAS uses ATP and GTP to synthesize 2', 3' -cGAMP (cGAMP), a cyclic dinucleotide second messenger with mixed 2'-5' and 3'-5' phosphodiester bonds. Inappropriate stimulation of cGAS has been implicated in autoimmune disease such as systemic lupus erythematosus, thus inhibition of cGAS may be of therapeutic benefit in some diseases; however, the size and polarity of the cGAS active site makes it a challenging target for the development of conventional substrate-competitive inhibitors. We report here the development of ...
Evaluation Of Il2 And Hla On The Homeostasis And Function Of Human Cd4 And Cd8 T Cells, 2017 University of Massachusetts Medical School
Evaluation Of Il2 And Hla On The Homeostasis And Function Of Human Cd4 And Cd8 T Cells, Philip A. Durost
GSBS Dissertations and Theses
Homeostasis of human T cells is regulated by many factors that control proliferation, differentiation of effector cells and generation of memory. Our current knowledge of the mechanisms controlling human T cell homeostasis in vivo is based on experiments in small animal models. However many differences exist between immune systems of mice and humans, including cell composition, function, and gene expression. Humanized mouse models have shown great value in the study of human immunobiology. I have used novel humanized mouse models to examine the role of human MHC (HLA) and human IL2 in CD8 T cell and CD4 regulatory T cell ...
Different Journeys, Same Destination: Exploring The Role Of A Pyhin Protein And Involvement Of Caspase-8 In The Regulation And Activation Of Inflammasomes, 2017 University of Massachusetts Medical School
Different Journeys, Same Destination: Exploring The Role Of A Pyhin Protein And Involvement Of Caspase-8 In The Regulation And Activation Of Inflammasomes, Sreya Ghosh
GSBS Dissertations and Theses
Interferon-inducible PYHIN protein family includes the DNA-binding proteins, AIM2 and IFI16, which form ASC-caspase 1 dependent inflammasomes, important in immunity against cytosolic bacteria, DNA viruses and HIV. The role of other members of this family in the recognition of DNA and/or regulation of immune responses is unclear. We identified an immune regulatory function of p205, another member of the PYHIN family, in the transcriptional control of immune genes. Knockdown of p205 in macrophages revealed that inflammasome activation due to dsDNA and ligands that engage the NLRP3 inflammasome were severely compromised. Detailed mechanistic analysis showed that loss of p205 was ...
Alloimmune Responses Of Humanized Mice To Human Pluripotent Stem Cell Therapeutics, 2017 Stanford University
Alloimmune Responses Of Humanized Mice To Human Pluripotent Stem Cell Therapeutics, Nigel G. Kooreman, Michael A. Brehm, Dale L. Greiner, Leonard D. Shultz, Joseph C. Wu
Open Access Articles
There is growing interest in using embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an "allogenized" mouse model, we show the feasibility of reconstituting immunodeficient mice with ...