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Immunology and Infectious Disease

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Articles 1 - 30 of 5470

Full-Text Articles in Life Sciences

Mrub_3019 Casa Gene Is An Ortholog To E. Coli B2760, Kelsey Heiland, Dr. Lori Scott Feb 2019

Mrub_3019 Casa Gene Is An Ortholog To E. Coli B2760, Kelsey Heiland, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This research is part of the Meiothermus ruber genome annotation project which aims to predict gene function with various bioinformatics tools. We investigated the function of Mrub_3019, which encodes the CasA protein involved in the multi-subunit effector complex for the CRISPR-Cas immunity system and predicted it to be an ortholog of E. coli K12 MG1655 b2760 (casA). We predicted that Mrub_3019 encodes the protein CasA, which is involved in PAM recognition of CRISPR interference pathway. Foreign DNA will bind to CasA, which signals Cas3 for helicase-mediated DNA degradation. Our hypothesis is supported by low E-values for pairwise alignment in NCBI ...


Multiple Variables At The Leukocyte Cell Surface Impact Fc Γ Receptor-Dependent Mechanisms, Kashyap R. Patel, Jacob T. Roberts, Adam W. Barb Feb 2019

Multiple Variables At The Leukocyte Cell Surface Impact Fc Γ Receptor-Dependent Mechanisms, Kashyap R. Patel, Jacob T. Roberts, Adam W. Barb

Biochemistry, Biophysics and Molecular Biology Publications

Fc γ receptors (FcγR) expressed on the surface of human leukocytes bind clusters of immunoglobulin G (IgG) to induce a variety of responses. Many therapeutic antibodies and vaccine-elicited antibodies prevent or treat infectious diseases, cancers and autoimmune disorders by binding FcγRs, thus there is a need to fully define the variables that impact antibody-induced mechanisms to properly evaluate candidate therapies and design new intervention strategies. A multitude of factors influence the IgG-FcγR interaction; one well-described factor is the differential affinity of the six distinct FcγRs for the four human IgG subclasses. However, there are several other recently described factors that ...


Non-Invasive Analysis Of The Sputum Transcriptome Discriminates Clinical Phenotypes Of Asthma, Xiting Yan Jan 2019

Non-Invasive Analysis Of The Sputum Transcriptome Discriminates Clinical Phenotypes Of Asthma, Xiting Yan

Yale Day of Data

Whole transcriptome wide gene expression profiles in the sputum and circulation from 100 asthma patients were measured using the Affymetrix HuGene 1.0ST arrays. Unsupervised clustering analysis based on pathways from KEGG were used to identify TEA clusters of patients from the sputum gene expression profiles. The identified TEA clusters have significantly different pre-bronchodilator FEV1, bronchodilator responsiveness, exhaled nitric oxide levels, history of hospitalization for asthma and history of intubation. Evaluation of TEA clusters in children from Asthma BRIDGE cohort confirmed the identified differences in intubation and hospitalization. Furthermore, evaluation of the TH2 gene signatures suggested a much lower prevalence ...


How Do Teachers Use Comics To Promote Engagement, Equity, And Diversity In Science Classrooms?, Camilla Matuk, Talia Hurwich, Amy Spiegel, Judy Diamond Jan 2019

How Do Teachers Use Comics To Promote Engagement, Equity, And Diversity In Science Classrooms?, Camilla Matuk, Talia Hurwich, Amy Spiegel, Judy Diamond

World of Viruses

Equitable learning opportunities are critical to the goals of science education. However, major curriculum standards are vague on how to achieve equity goals, and educators must often develop their own resources and strategies to achieve equity goals. This study examines how educators used a comic book series designed to interest youth in virology as a way to make science more broadly appealing to their diverse students. We begin with the notion of Pedagogical Design Capacity, which describes a dynamic relationship between teachers and their tools and the ability for teachers to perceive and leverage affordances of artifacts as tools in ...


Hla-Do Modulates The Diversity Of The Mhc-Ii Self-Peptidome, Padma P. Nanaware, Mollie M. Jurewicz, John D. Leszyk, Scott A. Shaffer, Lawrence J. Stern Dec 2018

Hla-Do Modulates The Diversity Of The Mhc-Ii Self-Peptidome, Padma P. Nanaware, Mollie M. Jurewicz, John D. Leszyk, Scott A. Shaffer, Lawrence J. Stern

Open Access Articles

Presentation of antigenic peptides on MHC-II molecules is essential for tolerance to self and for initiation of immune responses against foreign antigens. DO (HLA-DO in humans, H2-O in mice) is a non-classical MHC-II protein that has been implicated in control of autoimmunity and regulation of neutralizing antibody responses to viruses. These effects likely are related to a role of DO in selecting MHC-II epitopes, but previous studies examining the effect of DO on presentation of selected CD4 T cell epitopes have been contradictory. To understand how DO modulates MHC-II antigen presentation, we characterized the full spectrum of peptides presented by ...


Protective Versus Pathologic Pre-Exposure Cytokine Profiles In Dengue Virus Infection, Heather Friberg, Coreen M. Beaumier, Sangshin Park, Pamela P. Pazoles, Timothy P. Endy, Anuja Mathew, Jeffrey R. Currier, Richard G. Jarman, Kathryn B. Anderson, Steven Hatch, Stephen J. Thomas, Alan L. Rothman Dec 2018

Protective Versus Pathologic Pre-Exposure Cytokine Profiles In Dengue Virus Infection, Heather Friberg, Coreen M. Beaumier, Sangshin Park, Pamela P. Pazoles, Timothy P. Endy, Anuja Mathew, Jeffrey R. Currier, Richard G. Jarman, Kathryn B. Anderson, Steven Hatch, Stephen J. Thomas, Alan L. Rothman

Open Access Articles

BACKGROUND: Hyperendemic circulation of all four types of dengue virus (DENV-1-4) has expanded globally, fueling concern for increased incidence of severe dengue. While the majority of DENV infections are subclinical, epidemiologic studies suggest that type-cross-reactive immunity can influence disease outcome in subsequent infections. The mechanisms controlling these differential clinical outcomes remain poorly defined.

METHODOLOGY/PRINCIPAL FINDINGS: Blood samples were collected from a cohort of school-aged Thai children who subsequently experienced a subclinical DENV infection or developed dengue illness. PBMC collected prior to infection were stimulated in vitro with DENV and the secretion of 30 cytokines was measured using a multiplexed ...


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 Dec 2018

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

Open Access Articles

HIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, 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. Here we show that the HIV-1 provirus activates innate immune signaling in isolated dendritic cells, macrophages, and CD4(+) T cells. Immune activation requires transcription from the HIV-1 provirus and expression of CRM1-dependent, Rev-dependent, RRE-containing, unspliced HIV-1 RNA. If rev is provided in trans, all HIV-1 coding sequences are dispensable for activation except those cis-acting sequences required ...


Peptidylarginine Deiminases 2 And 4 Modulate Innate And Adaptive Immune Responses In Tlr-7-Dependent Lupus., Yudong Liu, Yaíma L Lightfoot, Nickie Seto, Santanu Mondal, Padmavathy Nandha Premnath, Paul R. Thompson Dec 2018

Peptidylarginine Deiminases 2 And 4 Modulate Innate And Adaptive Immune Responses In Tlr-7-Dependent Lupus., Yudong Liu, Yaíma L Lightfoot, Nickie Seto, Santanu Mondal, Padmavathy Nandha Premnath, Paul R. Thompson

University of Massachusetts Medical School Publications

The peptidylarginine deiminases PAD2 and PAD4 are implicated in the pathogenesis of several autoimmune diseases. PAD4 may be pathogenic in systemic lupus erythematosus (SLE) through its role in neutrophil extracellular trap (NET) formation that promotes autoantigen externalization, immune dysregulation, and organ damage. The role of this enzyme in mouse models of autoimmunity remains unclear, as pan-PAD chemical inhibitors improve clinical phenotype, whereas PAD4-KO models have given conflicting results. The role of PAD2 in SLE has not been investigated. The differential roles of PAD2 and PAD4 in TLR-7-dependent lupus autoimmunity were examined. Padi4-/- displayed decreased autoantibodies, type I IFN responses, immune ...


Instances Of Influenza In The United States Visualized, Parth Patel Dec 2018

Instances Of Influenza In The United States Visualized, Parth Patel

Publications and Research

The Tycho Project collects large data sets related to healthcare and in particular, instances and geographical information of diseases. We look at the instance counts and locations of Influenza from 1919-1951 across the United States. We hope to find seasonal and geographical insight to the spread of the disease.


Viral Prevalence Among Social Bees In Different Landscapes, Tugce Karacoban Dec 2018

Viral Prevalence Among Social Bees In Different Landscapes, Tugce Karacoban

Dissertations and Student Research in Entomology

Honey bees and wild bees provide important pollination services to numerous crops and native plants. In recent years, declines in bee populations have highlighted the importance of the ecological services they provide and the need for more research into the reasons for their decline. Currently, many conservation efforts to mitigate bee losses include increasing forage and habitat, however, there is growing concern over the role interspecific pathogen transmission plays in bee decline. Viruses commonly found in honey bees may be transmitted and pose a threat to other bee species when bees come together at foraging sites. To elucidate the impact ...


Development And Application Of A Reverse Genetics System For Zika Virus, Jordan C. Frank Dec 2018

Development And Application Of A Reverse Genetics System For Zika Virus, Jordan C. Frank

All Graduate Theses and Dissertations

Zika virus (ZIKV) has emerged in many regions of the world, with infection outcomes spanning from no apparent illness to crippling nervous system disease. ZIKV and its close relatives, West Nile virus, Japanese encephalitis virus, dengue virus, and yellow fever virus are primarily transmitted by mosquitoes. Three ZIKVs were selected: MR-766 (Uganda, 1947), P6-740 (Malaysia, 1966), and PRVABC-59 (Puerto Rico, 2015), whose place of origin and time of isolation differ substantially. Stable, complementary DNA (cDNA) copies of the three ZIKV RNA genomes were cloned to examine the significance of viral and host genetic variations in directing ZIKV infection outcomes. Using ...


Cd11b Regulation Of B Cell Receptor Signaling In Health And Systemic Lupus Erythematosus., Paul Lorenzo Dascani Dec 2018

Cd11b Regulation Of B Cell Receptor Signaling In Health And Systemic Lupus Erythematosus., Paul Lorenzo Dascani

Electronic Theses and Dissertations

Loss of function mutation in CD11b has been associated with incidence of systemic lupus erythematosus (SLE), a disease driven by B cell production of pathogenic autoimmune antibody. Our previous work has revealed the ability of CD11b to regulate B cell receptor (BCR) signaling and control autoimmune disease in mice. However, how CD11b regulates the immune response under normal conditions remains unknown. Through the use of a CD11b knockout model, we demonstrated that CD11b-deficient mice have an elevated antigen-specific humoral response in a Th2 type immunization. Deletion of CD11b resulted in elevated serum IgM and IgG antibody, increases in antigen-specific germinal ...


Cryptococcus Neoformans Cda1 And Its Chitin Deacetylase Activity Are Required For Fungal Pathogenesis, Rajendra Upadhya, Lorina G. Baker, Woei C. Lam, Charles A. Specht, Maureen J. Donlin, Jennifer K. Lodge Nov 2018

Cryptococcus Neoformans Cda1 And Its Chitin Deacetylase Activity Are Required For Fungal Pathogenesis, Rajendra Upadhya, Lorina G. Baker, Woei C. Lam, Charles A. Specht, Maureen J. Donlin, Jennifer K. Lodge

Open Access Articles

Chitin is an essential component of the cell wall of Cryptococcus neoformans conferring structural rigidity and integrity under diverse environmental conditions. Chitin deacetylase genes encode the enyzmes (chitin deacetylases [Cdas]) that deacetylate chitin, converting it to chitosan. The functional role of chitosan in the fungal cell wall is not well defined, but it is an important virulence determinant of C. neoformans Mutant strains deficient in chitosan are completely avirulent in a mouse pulmonary infection model. C. neoformans carries genes that encode three Cdas (Cda1, Cda2, and Cda3) that appear to be functionally redundant in cells grown under vegetative conditions. Here ...


The Nf-Kappab Factor Relish Regulates Atg1 Expression And Controls Autophagy, Anubhab Nandy, Lin Lin, Panagiotis D. Velentzas, Louisa P. Wu, Eric H. Baehrecke, Neal S. Silverman Nov 2018

The Nf-Kappab Factor Relish Regulates Atg1 Expression And Controls Autophagy, Anubhab Nandy, Lin Lin, Panagiotis D. Velentzas, Louisa P. Wu, Eric H. Baehrecke, Neal S. Silverman

Open Access Articles

Macroautophagy and cell death both contribute to innate immunity, but little is known about how these processes integrate. Drosophila larval salivary glands require autophagy for developmentally programmed cell death, and innate immune signaling factors increase in these dying cells. Here, we show that the nuclear factor kappaB (NF-kappaB) factor Relish, a component of the immune deficiency (Imd) pathway, is required for salivary gland degradation. Surprisingly, of the classic Imd pathway components, only Relish and the PGRP receptors were involved in salivary gland degradation. Significantly, Relish controls salivary gland degradation by regulating autophagy but not caspases. In addition, expression of either ...


Hitchhiker's Guide To Migration: Effects Of Experimental Parasitic Infection And Other Immune Challenges On Migratory Traits Of Sparrows, Tosha R. Kelly Nov 2018

Hitchhiker's Guide To Migration: Effects Of Experimental Parasitic Infection And Other Immune Challenges On Migratory Traits Of Sparrows, Tosha R. Kelly

Electronic Thesis and Dissertation Repository

Seasonal migration exposes animals to a variety of habitats and parasites, and if infected migratory birds migrate successfully there is great potential for birds to transport infectious diseases long distances. Our current understanding of whether birds contribute to the spread of disease relies upon observational field studies that are limited in their ability to discern cause from effect. Using captive and field-based experiments for my doctoral research, I answered three research questions: (1) are nocturnal migratory restlessness (Zugunruhe) and body condition affected by mounting an acute phase immune response during migration; (2) what are the impacts of parasitic infection on ...


Characterization Of The Caspase-3 Cleavage Motif Of The Salmonella Typhimurium Effector Protein Sifa And Its Role In Pathogenesis, Samir Patel Nov 2018

Characterization Of The Caspase-3 Cleavage Motif Of The Salmonella Typhimurium Effector Protein Sifa And Its Role In Pathogenesis, Samir Patel

GSBS Dissertations and Theses

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative facultative anaerobe that induces severe inflammation resulting in gastroenteritis. In the case of S. Typhimurium infection, induction of an inflammatory response has been linked to its primary virulence mechanism, the type III secretion system (T3SS). The T3SS secretes protein effectors that exploit the host’s cell biology to facilitate bacterial entry and intracellular survival, and to modulate the host immune response.

One such effector, SifA, is a bi-functional T3SS effector protein that plays an important role in Salmonella virulence. The N-terminal domain of SifA binds SifA-Kinesin-Interacting-Protein (SKIP), and via an interaction ...


Deciphering The Molecular Basis Of Mycobacteria And Lipoglycan Recognition By The C-Type Lectin Dectin-2, Alexiane Decout, Devinder Kaur, Jerome Nigou Nov 2018

Deciphering The Molecular Basis Of Mycobacteria And Lipoglycan Recognition By The C-Type Lectin Dectin-2, Alexiane Decout, Devinder Kaur, Jerome Nigou

Open Access Articles

Dectin-2 is a C-type lectin involved in the recognition of several pathogens such as Aspergillus fumigatus, Candida albicans, Schistosoma mansonii, and Mycobacterium tuberculosis that triggers Th17 immune responses. Identifying pathogen ligands and understanding the molecular basis of their recognition is one of the current challenges. Purified M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) was shown to induce signaling via Dectin-2, an activity that requires the (alpha1 --> 2)-linked mannosides forming the caps. Here, using isogenic M. tuberculosis mutant strains, we demonstrate that ManLAM is a bona fide and actually the sole ligand mediating bacilli recognition by Dectin-2, although M. tuberculosis produces a ...


Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater Nov 2018

Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater

Posters-at-the-Capitol

Immunotherapy strategies are very promising treatments for cancer patients. Specifically, Immune checkpoint inhibitor therapy focusing on the PD-1/PD-L1 pathway shows long-lasting positive results in many cancer patients. Unfortunately, not all the patients can benefit from this highly effective treatment. Hence, there is a great need for predictive biomarkers. Immunohistochemical (IHC) staining has been used as a way of predicting patient response, yet shows many problems. For example, IHC utilizes an invasive biopsy and sample fixing, which creates an incomplete and delayed picture of the patient’s biochemistry and the tumor microenvironment, consequently ignoring metastases.

The purpose of this study ...


Genetic Models Reveal Cis And Trans Immune-Regulatory Activities For Lincrna-Cox2, Roland Elling, Zhaozhao Jiang, Shiuli Agarwal, Mona Motwani, Jennie Chan, Shrutie Sharma, Katherine A. Fitzgerald, Susan Carpenter Nov 2018

Genetic Models Reveal Cis And Trans Immune-Regulatory Activities For Lincrna-Cox2, Roland Elling, Zhaozhao Jiang, Shiuli Agarwal, Mona Motwani, Jennie Chan, Shrutie Sharma, Katherine A. Fitzgerald, Susan Carpenter

Open Access Articles

An inducible gene expression program is a hallmark of the host inflammatory response. Recently, long intergenic non-coding RNAs (lincRNAs) have been shown to regulate the magnitude, duration, and resolution of these responses. Among these is lincRNA-Cox2, a dynamically regulated gene that broadly controls immune gene expression. To evaluate the in vivo functions of this lincRNA, we characterized multiple models of lincRNA-Cox2-deficient mice. LincRNA-Cox2-deficient macrophages and murine tissues had altered expression of inflammatory genes. Transcriptomic studies from various tissues revealed that deletion of the lincRNA-Cox2 locus also strongly impaired the basal and inducible expression of the neighboring gene prostaglandin-endoperoxide synthase (Ptgs2 ...


Thymic Epithelial Cell Reprogramming And Co-Culture With T-Cell Progenitors, Isabelle Riddle Nov 2018

Thymic Epithelial Cell Reprogramming And Co-Culture With T-Cell Progenitors, Isabelle Riddle

Georgia Undergraduate Research Conference (GURC)

The thymus is a lymphoid organ found in the neck region of vertebrates that produces T-cells critical for the adaptive immune system. However, thymus involution relatively early in the aging process leads to a deterioration in immune function. Models in regenerative medicine have the prospect of replacing lost cells and combating the problem. This experiment is a preliminary step geared towards achieving the overarching goal of boosting long-term maintenance of adaptive immunity over the typical aging process or following therapeutic immune depletion. Specifically, the objective is to show that disparate cell lineages can be reprogrammed—both morphologically and physiologically—using ...


21 - Cigarette Smoke Exposure Upregulation Of Pge₂ Expression In The Bladder, Jessica Nix Nov 2018

21 - Cigarette Smoke Exposure Upregulation Of Pge₂ Expression In The Bladder, Jessica Nix

Georgia Undergraduate Research Conference (GURC)

CIGARETTE SMOKE EXPOSURE UPREGULATION OF PGE₂ EXPRESSION IN THE BLADDER

Jessica Nix, Jane McHowat, Shannon Kispert

Cigarette smoking remains the leading cause of preventable death and disease in the United States. Despite known risks, 42.1 million Americans continue to smoke, making research into tobacco-related pathologies relevant and necessary. We previously discovered that cigarette smoke exposure leads to tumor progression in the breast via platelet activating factor (PAF) and other phospholipase A₂ (PLA₂) metabolic pathways. These results led us to examine the PLA2 metabolite, prostaglandin E₂ (PGE₂). We observed the expression of PGE₂ in mouse bladder and human heart ...


Museum Metabarcoding: A Novel Method Revealing Gut Helminth Communities Of Small Mammals Across Space And Time, Stephen E. Greiman, Joseph A. Cook, Vasyl V. Tkach, Eric P. Hoberg, Damian M. Menning, Andrew G. Hope, Sarah A. Sonsthagen, Sandra L. Talbot Nov 2018

Museum Metabarcoding: A Novel Method Revealing Gut Helminth Communities Of Small Mammals Across Space And Time, Stephen E. Greiman, Joseph A. Cook, Vasyl V. Tkach, Eric P. Hoberg, Damian M. Menning, Andrew G. Hope, Sarah A. Sonsthagen, Sandra L. Talbot

Faculty Publications from the Harold W. Manter Laboratory of Parasitology

Natural history collections spanning multiple decades provide fundamental historical baselines to measure and understand changing biodiversity. New technologies such as next generation DNA sequencing have considerably increased the potential of museum specimens to address significant questions regarding the impact of environmental changes on host and parasite/pathogen dynamics. We developed a new technique to identify intestinal helminth parasites and applied it to shrews (Eulipotyphla: Soricidae) because they are ubiquitous, occupy diverse habitats, and host a diverse and abundant parasite fauna. Notably, we included museum specimens preserved in various ways to explore the efficacy of using metabarcoding analyses that may enable ...


Characterization Of Tick Organic Anion Transporting Polypeptides (Oatps) Upon Bacterial And Viral Infections, Vikas Taank, Wenshou Zhou, Xuran Zhuang, John F. Anderson, Utpal Pal, Hameeda Sultana, Girish Neelakanta Nov 2018

Characterization Of Tick Organic Anion Transporting Polypeptides (Oatps) Upon Bacterial And Viral Infections, Vikas Taank, Wenshou Zhou, Xuran Zhuang, John F. Anderson, Utpal Pal, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Background: Ixodes scapularis organic anion transporting polypeptides (OATPs) play important roles in tickrickettsial pathogen interactions. In this report, we characterized the role of these conserved molecules in ticks infected with either Lyme disease agent Borrelia burgdorferi or tick-borne Langat virus (LGTV), a pathogen closely related to tick-borne encephalitis virus (TBEV).

Results: Quantitative real-time polymerase chain reaction analysis revealed no significant changes in oatps gene expression upon infection with B. burgdorferi in unfed ticks. Synchronous infection of unfed nymphal ticks with LGTV in vitro revealed no significant changes in oatps gene expression. However, expression of specific oatps was significantly downregulated upon ...


Immunization With Recombinant Myelin Oligodendrocyte Glycoprotein Identifies Autoreactive T Cells As A Limiting Factor In Autoreactive Germinal Center Maintenance, Rajiv William Jain Oct 2018

Immunization With Recombinant Myelin Oligodendrocyte Glycoprotein Identifies Autoreactive T Cells As A Limiting Factor In Autoreactive Germinal Center Maintenance, Rajiv William Jain

Electronic Thesis and Dissertation Repository

Germinal center (GC) responses are responsible for the protection provided by immunizations but can also drive autoimmunity. B and T cells collaborate in the GC to target the same antigen (Ag) to inform B cell differentiation; however, the properties of Ags differ substantially in autoimmunity and foreign-Ag driven immunity. Currently, it is not well understood how properties of the Ag itself influence the initiation or progression of GC responses, limiting our ability to develop effective vaccinations and predict the progression of autoimmune responses. The purpose of this thesis is to assess how GC responses initiate and progress when immunizing with ...


Generation And Characterization Of Monoclonal Antibodies That Recognize Human And Murine Supervillin Protein Isoforms, Tara C. Smith, Richard G. Saul, Elisabeth R. Barton, Elizabeth J. Luna Oct 2018

Generation And Characterization Of Monoclonal Antibodies That Recognize Human And Murine Supervillin Protein Isoforms, Tara C. Smith, Richard G. Saul, Elisabeth R. Barton, Elizabeth J. Luna

Open Access Articles

Supervillin isoforms have been implicated in cell proliferation, actin filament-based motile processes, vesicle trafficking, and signal transduction. However, an understanding of the roles of these proteins in cancer metastasis and physiological processes has been limited by the difficulty of obtaining specific antibodies against these highly conserved membrane-associated proteins. To facilitate research into the biological functions of supervillin, monoclonal antibodies were generated against the bacterially expressed human supervillin N-terminus. Two chimeric monoclonal antibodies with rabbit Fc domains (clones 1E2/CPTC-SVIL-1; 4A8/CPTC-SVIL-2) and two mouse monoclonal antibodies (clones 5A8/CPTC-SVIL-3; 5G3/CPTC-SVIL-4) were characterized with respect to their binding sites, affinities ...


Transcriptional Regulation Of Effector And Memory Responses During Acute And Chronic Lymphocytic Choriomeningitis Virus (Lcmv) Infection, Elizabeth A. Olesin Oct 2018

Transcriptional Regulation Of Effector And Memory Responses During Acute And Chronic Lymphocytic Choriomeningitis Virus (Lcmv) Infection, Elizabeth A. Olesin

GSBS Dissertations and Theses

Transcriptional regulation of CD8+ T cell differentiation during acute and chronic viral infections is an intricate web made up of many of transcription factors. While several transcription factors have been elucidated in this process, there are still many more that remain elusive. In this work, we look into the role of two transcription factors, IRF4 and Runx2, and their role in CD8+ T cell terminal effector cells and memory precursor cells during acute LCMV-Armstrong infection. We found that IRF4 expression was regulated by TCR signal strength during infection, and that IRF4 expression levels directly correlated with the magnitude of the ...


Cutting Edge: The Heat Shock Protein Gp96 Activates Inflammasome-Signaling Platforms In Apcs, Yifei Wang, Abigail L. Sedlacek, Sudesh Pawaria, Haiyan Xu, Melanie J. Scott, Robert J. Binder Oct 2018

Cutting Edge: The Heat Shock Protein Gp96 Activates Inflammasome-Signaling Platforms In Apcs, Yifei Wang, Abigail L. Sedlacek, Sudesh Pawaria, Haiyan Xu, Melanie J. Scott, Robert J. Binder

Open Access Articles

Several heat shock proteins (HSPs) prime immune responses, which are, in part, a result of activation of APCs. APCs respond to these immunogenic HSPs by upregulating costimulatory molecules and secreting cytokines, including IL-1beta. These HSP-mediated responses are central mediators in pathological conditions ranging from cancer, sterile inflammation associated with trauma, and rheumatoid arthritis. We tested in this study the requirement of inflammasomes in the release of IL-1beta by one immunogenic HSP, gp96. Our results show that murine APCs activate NLRP3 inflammasomes in response to gp96 by K(+) efflux. This is shown to initiate inflammatory conditions in vivo in the absence ...


Microrna-96 Promotes Schistosomiasis Hepatic Fibrosis In Mice By Suppressing Smad7, Xufeng Luo, Dongmei Zhang, Jun Xie, Qin Su, Xing He, Ruipu Bai, Guangping Gao, Weiqing Pan Oct 2018

Microrna-96 Promotes Schistosomiasis Hepatic Fibrosis In Mice By Suppressing Smad7, Xufeng Luo, Dongmei Zhang, Jun Xie, Qin Su, Xing He, Ruipu Bai, Guangping Gao, Weiqing Pan

UMass Center for Clinical and Translational Science Supported Publications

Infection with Schistosoma causes aberrant expression of host microRNAs (miRNAs), and normalizing the levels of dysregulated miRNAs can attenuate pathology. Here, we show that the host miRNA, miR-96, is markedly upregulated during the progression of hepatic schistosomiasis. We demonstrate that elevation of miR-96 induces hepatic fibrosis in infected mice by suppressing the expression of its target gene, Smad7. We show that infection with Schistosoma induces the expression of transforming growth factor beta1 (TGF-beta1), which in turn upregulates the expression of miR-96 through SMAD2/3-DROSHA-mediated post-transcriptional regulation. Furthermore, inhibition of miR-96 with recombinant adeno-associated virus 8 (rAAV8)-mediated delivery of Tough ...


Protection Induced By A Francisella Tularensis Subunit Vaccine Delivered By Glucan Particles, Adam O. Whelan, Helen C. Flick-Smith, Jane Homan, Zu T. Shen, Zoe Carpenter, Payam Khoshkenar, Ambily Abraham, Nicola J. Walker, Stuart M. Levitz, Gary R. Ostroff, Petra C. F. Oyston Oct 2018

Protection Induced By A Francisella Tularensis Subunit Vaccine Delivered By Glucan Particles, Adam O. Whelan, Helen C. Flick-Smith, Jane Homan, Zu T. Shen, Zoe Carpenter, Payam Khoshkenar, Ambily Abraham, Nicola J. Walker, Stuart M. Levitz, Gary R. Ostroff, Petra C. F. Oyston

Open Access Articles

Francisella tularensis is an intracellular pathogen causing the disease tularemia, and an organism of concern to biodefence. There is no licensed vaccine available. Subunit approaches have failed to induce protection, which requires both humoral and cellular immune memory responses, and have been hampered by a lack of understanding as to which antigens are immunoprotective. We undertook a preliminary in silico analysis to identify candidate protein antigens. These antigens were then recombinantly expressed and encapsulated into glucan particles (GPs), purified Saccharomyces cerevisiae cell walls composed primarily of beta-1,3-glucans. Immunological profiling in the mouse was used to down-selection to seven lead ...


The Effect Of Demographic Variability, Environmental Variability, And Periodic Fluctuations On Stochastic Epidemic Models, Kaniz Fatema Nipa, Linda J. Allen Oct 2018

The Effect Of Demographic Variability, Environmental Variability, And Periodic Fluctuations On Stochastic Epidemic Models, Kaniz Fatema Nipa, Linda J. Allen

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.