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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 ...


Endoplasmic Reticulum Stress-Induced Hepatocellular Death Pathways Mediate Liver Injury And Fibrosis Via Stimulator Of Interferon Genes., Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyongyosi, Abhishek Satishchandran, Patrick Lowe, Karen Kodys, Donna Catalano, Charles D. Calenda, Evelyn A. Kurt-Jones, Kate A. Fitzgerald, Gyongyi Szabo 2016 University of Massachusetts Medical School

Endoplasmic Reticulum Stress-Induced Hepatocellular Death Pathways Mediate Liver Injury And Fibrosis Via Stimulator Of Interferon Genes., Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyongyosi, Abhishek Satishchandran, Patrick Lowe, Karen Kodys, Donna Catalano, Charles D. Calenda, Evelyn A. Kurt-Jones, Kate A. Fitzgerald, Gyongyi Szabo

Katherine A. Fitzgerald

Fibrosis, driven by inflammation, marks the transition from benign to progressive stages of chronic liver diseases. Although inflammation promotes fibrogenesis, it is not known whether other events, such as hepatocyte death, are required for the development of fibrosis. Interferon Regulatory Factor 3 (IRF3) regulates hepatocyte apoptosis and production of Type-I interferons (IFNs). In the liver, IRF3 is activated via Toll-like receptor 4 (TLR4) signaling or the ER adapter, Stimulator of Interferon Genes (STING). We hypothesized that IRF3-mediated hepatocyte death is an independent determinant of chemically-induced liver fibrogenesis. To test this, we performed acute or chronic carbontetrachloride (CCl4) administration to WT ...


Endoplasmic Reticulum Stress-Induced Hepatocellular Death Pathways Mediate Liver Injury And Fibrosis Via Stimulator Of Interferon Genes., Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyongyosi, Abhishek Satishchandran, Patrick Lowe, Karen Kodys, Donna Catalano, Charles D. Calenda, Evelyn A. Kurt-Jones, Kate A. Fitzgerald, Gyongyi Szabo 2016 University of Massachusetts Medical School

Endoplasmic Reticulum Stress-Induced Hepatocellular Death Pathways Mediate Liver Injury And Fibrosis Via Stimulator Of Interferon Genes., Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyongyosi, Abhishek Satishchandran, Patrick Lowe, Karen Kodys, Donna Catalano, Charles D. Calenda, Evelyn A. Kurt-Jones, Kate A. Fitzgerald, Gyongyi Szabo

Gyongyi Szabo

Fibrosis, driven by inflammation, marks the transition from benign to progressive stages of chronic liver diseases. Although inflammation promotes fibrogenesis, it is not known whether other events, such as hepatocyte death, are required for the development of fibrosis. Interferon Regulatory Factor 3 (IRF3) regulates hepatocyte apoptosis and production of Type-I interferons (IFNs). In the liver, IRF3 is activated via Toll-like receptor 4 (TLR4) signaling or the ER adapter, Stimulator of Interferon Genes (STING). We hypothesized that IRF3-mediated hepatocyte death is an independent determinant of chemically-induced liver fibrogenesis. To test this, we performed acute or chronic carbontetrachloride (CCl4) administration to WT ...


Endoplasmic Reticulum Stress-Induced Hepatocellular Death Pathways Mediate Liver Injury And Fibrosis Via Stimulator Of Interferon Genes., Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyongyosi, Abhishek Satishchandran, Patrick Lowe, Karen Kodys, Donna Catalano, Charles D. Calenda, Evelyn A. Kurt-Jones, Kate A. Fitzgerald, Gyongyi Szabo 2016 University of Massachusetts Medical School

Endoplasmic Reticulum Stress-Induced Hepatocellular Death Pathways Mediate Liver Injury And Fibrosis Via Stimulator Of Interferon Genes., Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyongyosi, Abhishek Satishchandran, Patrick Lowe, Karen Kodys, Donna Catalano, Charles D. Calenda, Evelyn A. Kurt-Jones, Kate A. Fitzgerald, Gyongyi Szabo

Arvin Iracheta-Vellve

Fibrosis, driven by inflammation, marks the transition from benign to progressive stages of chronic liver diseases. Although inflammation promotes fibrogenesis, it is not known whether other events, such as hepatocyte death, are required for the development of fibrosis. Interferon Regulatory Factor 3 (IRF3) regulates hepatocyte apoptosis and production of Type-I interferons (IFNs). In the liver, IRF3 is activated via Toll-like receptor 4 (TLR4) signaling or the ER adapter, Stimulator of Interferon Genes (STING). We hypothesized that IRF3-mediated hepatocyte death is an independent determinant of chemically-induced liver fibrogenesis. To test this, we performed acute or chronic carbontetrachloride (CCl4) administration to WT ...


Endoplasmic Reticulum Stress-Induced Hepatocellular Death Pathways Mediate Liver Injury And Fibrosis Via Stimulator Of Interferon Genes., Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyongyosi, Abhishek Satishchandran, Patrick Lowe, Karen Kodys, Donna Catalano, Charles D. Calenda, Evelyn A. Kurt-Jones, Kate A. Fitzgerald, Gyongyi Szabo 2016 University of Massachusetts Medical School

Endoplasmic Reticulum Stress-Induced Hepatocellular Death Pathways Mediate Liver Injury And Fibrosis Via Stimulator Of Interferon Genes., Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyongyosi, Abhishek Satishchandran, Patrick Lowe, Karen Kodys, Donna Catalano, Charles D. Calenda, Evelyn A. Kurt-Jones, Kate A. Fitzgerald, Gyongyi Szabo

GSBS Student Publications

Fibrosis, driven by inflammation, marks the transition from benign to progressive stages of chronic liver diseases. Although inflammation promotes fibrogenesis, it is not known whether other events, such as hepatocyte death, are required for the development of fibrosis. Interferon Regulatory Factor 3 (IRF3) regulates hepatocyte apoptosis and production of Type-I interferons (IFNs). In the liver, IRF3 is activated via Toll-like receptor 4 (TLR4) signaling or the ER adapter, Stimulator of Interferon Genes (STING). We hypothesized that IRF3-mediated hepatocyte death is an independent determinant of chemically-induced liver fibrogenesis. To test this, we performed acute or chronic carbontetrachloride (CCl4) administration to WT ...


Novel Mutation Of Interferon-Γ Receptor 1 Gene Presenting As Early Life Mycobacterial Bronchial Disease, Maria J. Gutierrez, Neelu Kaira, Alexandra Horwitz, Gustavo Nino 2016 George Washington University

Novel Mutation Of Interferon-Γ Receptor 1 Gene Presenting As Early Life Mycobacterial Bronchial Disease, Maria J. Gutierrez, Neelu Kaira, Alexandra Horwitz, Gustavo Nino

Pediatrics Faculty Publications

Mendelian susceptibility to mycobacterial diseases (MSMD) are a spectrum of inherited disorders characterized by localized or disseminated infections caused by atypical mycobacteria. Interferon-γ receptor 1 (IFNGR1) deficiency was the first identified genetic disorder recognized as MSMD. Mutations in the genes encoding IFNGR1 can be recessive or dominant and cause complete or partial receptor deficiency. We present the case of a 2½-year-old boy with a history of recurrent wheezing, diagnosed with endobronchial mycobacterial infection. Immunological workup revealed a homozygous nonsense mutation in the IFNGR1 gene, a novel mutation predicted in silico to cause complete IFNGR1 deficiency. This case demonstrates that (a ...


Distinct Differences On Neointima Formation In Immunodeficient And Humanized Mice After Carotid Or Femoral Arterial Injury, Jill Moser, Joris van Ark, Marcory C. van Dijk, Dale L. Greiner, Leonard D. Shultz, Harry van Goor, Jan-Luuk Hillebrands 2016 University of Groningen

Distinct Differences On Neointima Formation In Immunodeficient And Humanized Mice After Carotid Or Femoral Arterial Injury, Jill Moser, Joris Van Ark, Marcory C. Van Dijk, Dale L. Greiner, Leonard D. Shultz, Harry Van Goor, Jan-Luuk Hillebrands

Open Access Articles

Percutaneous coronary intervention is widely adopted to treat patients with coronary artery disease. However, restenosis remains an unsolved clinical problem after vascular interventions. The role of the systemic and local immune response in the development of restenosis is not fully understood. Hence, the aim of the current study was to investigate the role of the human immune system on subsequent neointima formation elicited by vascular injury in a humanized mouse model. Immunodeficient NOD.Cg-PrkdcscidIL2rgtm1Wjl(NSG) mice were reconstituted with human (h)PBMCs immediately after both carotid wire and femoral cuff injury were induced in order to identify how differences in ...


A Test Of The Effects Of Androgens On Immunity: No Relationship Between 11-Keto Testosterone And Immune Performance In Bluegill Sunfish (Lepomis Macrochirus), John W. Loggie 2016 The University of Western Ontario

A Test Of The Effects Of Androgens On Immunity: No Relationship Between 11-Keto Testosterone And Immune Performance In Bluegill Sunfish (Lepomis Macrochirus), John W. Loggie

Electronic Thesis and Dissertation Repository

The posited immunosuppressive effects of androgens are a key component of the immunocompetence handicap hypothesis (ICHH). My thesis uses bluegill sunfish (Lepomis macrochirus) to test two predictions arising from this hypothesis: (1) natural concentrations of the androgen 11-keto testosterone (11-KT) will be negatively related with immunity, and (2) an immunochallenge will lower 11-KT concentration. I found no evidence for a relationship between natural 11-KT concentration and measures of immunity (leukocyte counts, respiratory burst, cytokine gene expression), and an immunochallenge with Vibrio vaccine did not affect 11-KT concentration. I performed a meta-analysis of immunochallenge studies to help interpret my results, and ...


Surveillance Immunity: An Emerging Paradigm Of Innate Defense Activation In Caenorhabditis Elegans, Read Pukkila-Worley 2016 University of Massachusetts Medical School

Surveillance Immunity: An Emerging Paradigm Of Innate Defense Activation In Caenorhabditis Elegans, Read Pukkila-Worley

Open Access Articles

No abstract provided.


A Model To Explain How The Bacille Calmette Guerin (Bcg) Vaccine Drives Interleukin-12 Production In Neonates, Chido Loveness Kathivu, Daniel H. Libraty 2016 University of Massachusetts Medical School

A Model To Explain How The Bacille Calmette Guerin (Bcg) Vaccine Drives Interleukin-12 Production In Neonates, Chido Loveness Kathivu, Daniel H. Libraty

Open Access Articles

The Bacille Calmette Guerin (BCG) vaccine is the only routine vaccination at birth that effectively induces neonatal T-helper 1 (Th1)-polarized immune responses. The primary cytokine that drives CD4+ T-cell Th1 differentiation is interleukin (IL)-12 p70, a heterodimeric cytokine composed of the IL-12 p35 and IL-12 p40 subunits. We therefore examined the mechanisms involved in BCG vaccine stimulation of IL-12 p35 and p40 production from human umbilical cord (neonatal) cells. We found that BCG bacilli did not upregulate IL-12 p35 mRNA production, but upregulated IL-12 p40 mRNA production in a Toll-like receptor (TLR)2-dependent manner, in human neonatal monocyte-derived ...


Dynamic Host-Pathogen Interactions Result In Fungal Epitope Unmasking, Alex Hopke 2016 University of Maine

Dynamic Host-Pathogen Interactions Result In Fungal Epitope Unmasking, Alex Hopke

Electronic Theses and Dissertations

Molecular camouflage is used by a diverse set of pathogens to disguise their identity and avoid recognition by protective host receptors. The opportunistic fungal pathogen Candida albicans is a good example, as it masks the inflammatory component β-glucan in its cell wall to evade detection by the immune receptor Dectin-1. Interestingly, it has been seen that β-glucan becomes unmasked during infection in vivo, though the underlying mechanisms remained unclear. Exposure levels of this epitope may be important, as Dectin-1 mediates protection from some strains of C. albicans and alterations in the organization and composition of the Candida cell wall can ...


A Fluorescent Reporter Mouse For Inflammasome Assembly Demonstrates An Important Role For Cell-Bound And Free Asc Specks During In Vivo Infection, Te-Chen Tzeng, Stefan A. Schattgen, Brian G. Monks, Donghai Wang, Anna M. Cerny, Eicke Latz, Katherine A. Fitzgerald, Douglas T. Golenbock 2016 University of Massachusetts Medical School

A Fluorescent Reporter Mouse For Inflammasome Assembly Demonstrates An Important Role For Cell-Bound And Free Asc Specks During In Vivo Infection, Te-Chen Tzeng, Stefan A. Schattgen, Brian G. Monks, Donghai Wang, Anna M. Cerny, Eicke Latz, Katherine A. Fitzgerald, Douglas T. Golenbock

Katherine A. Fitzgerald

Inflammasome activation is associated with numerous diseases. However, in vivo detection of the activated inflammasome complex has been limited by a dearth of tools. We have developed transgenic mice that ectopically express the fluorescent adaptor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and characterized the formation of assembled inflammasome complexes ("specks") in primary cells and tissues. In addition to hematopoietic cells, we have found that a stromal population in the lung tissues formed specks during the early phase of influenza infection, whereas myeloid cells showed speck formation after 2 days. In a peritonitis and group B streptococcus ...


Long-Term Activation Of The Innate Immune System In Atherosclerosis, Anette Christ, Siroon Bekkering, Eicke Latz, Niels P. Riksen 2016 University of Massachusetts Medical School

Long-Term Activation Of The Innate Immune System In Atherosclerosis, Anette Christ, Siroon Bekkering, Eicke Latz, Niels P. Riksen

Open Access Articles

Efforts to reverse the pathologic consequences of vulnerable plaques are often stymied by the complex treatment resistant pro-inflammatory environment within the plaque. This suggests that pro-atherogenic stimuli, such as LDL cholesterol and high fat diets may impart longer lived signals on (innate) immune cells that persist even after reversing the pro-atherogenic stimuli. Recently, a series of studies challenged the traditional immunological paradigm that innate immune cells cannot display memory characteristics. Epigenetic reprogramming in these myeloid cell subsets, after exposure to certain stimuli, has been shown to alter the expression of genes upon re-exposure. This phenomenon has been termed trained innate ...


A Fluorescent Reporter Mouse For Inflammasome Assembly Demonstrates An Important Role For Cell-Bound And Free Asc Specks During In Vivo Infection, Te-Chen Tzeng, Stefan A. Schattgen, Brian G. Monks, Donghai Wang, Anna M. Cerny, Eicke Latz, Katherine A. Fitzgerald, Douglas T. Golenbock 2016 University of Massachusetts Medical School

A Fluorescent Reporter Mouse For Inflammasome Assembly Demonstrates An Important Role For Cell-Bound And Free Asc Specks During In Vivo Infection, Te-Chen Tzeng, Stefan A. Schattgen, Brian G. Monks, Donghai Wang, Anna M. Cerny, Eicke Latz, Katherine A. Fitzgerald, Douglas T. Golenbock

Open Access Articles

Inflammasome activation is associated with numerous diseases. However, in vivo detection of the activated inflammasome complex has been limited by a dearth of tools. We have developed transgenic mice that ectopically express the fluorescent adaptor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and characterized the formation of assembled inflammasome complexes ("specks") in primary cells and tissues. In addition to hematopoietic cells, we have found that a stromal population in the lung tissues formed specks during the early phase of influenza infection, whereas myeloid cells showed speck formation after 2 days. In a peritonitis and group B streptococcus ...


Chronic Saline Exposures Interfere With Basal And Induced Immunity In Striped Catfish (Pangasianodon Hypophthalmus, Sauvage) Exposed To Virulent Strain Of Edwardsiella Ictaluri., Mélodie Schmitz 2016 University of Namur

Chronic Saline Exposures Interfere With Basal And Induced Immunity In Striped Catfish (Pangasianodon Hypophthalmus, Sauvage) Exposed To Virulent Strain Of Edwardsiella Ictaluri., Mélodie Schmitz

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.


Constitutively Overexpressed Type I Interferon Transgenic Medaka Fish Down-Regulate The Antiviral Response, Shun Maekawa 2016 Institute of Biotechnology, National Cheng Kung University,Taiwan

Constitutively Overexpressed Type I Interferon Transgenic Medaka Fish Down-Regulate The Antiviral Response, Shun Maekawa

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.


Membrane Disruption Antimicrobial Mechanism Of Channa Striatus Lysozyme-Derived Antimicrobial Peptide, Venkatesh Kumaresan 2016 SRM University

Membrane Disruption Antimicrobial Mechanism Of Channa Striatus Lysozyme-Derived Antimicrobial Peptide, Venkatesh Kumaresan

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.


Functional Characterization Of Recombinant Interleukin (Il)-17a/F1 In The Japanese Pufferfish (Takifugu Rubripes), Jun-ichi Hikima Dr., Koshin Mihara, Shun Maekawa, Han-Ching Wang, Takashi Aoki, Tomoya Kono, Masahiro Sakai 2016 University of Miyazaki, Faculty of Agriculture

Functional Characterization Of Recombinant Interleukin (Il)-17a/F1 In The Japanese Pufferfish (Takifugu Rubripes), Jun-Ichi Hikima Dr., Koshin Mihara, Shun Maekawa, Han-Ching Wang, Takashi Aoki, Tomoya Kono, Masahiro Sakai

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.


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