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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 ...


Genomic Insights Into The Ixodes Scapularis Tick Vector Of Lyme Disease, Monika Gulia-Nuss,, Daniel R. Caffrey, Neal S. Silverman, Adam R. Wespiser, Catherine A. Hill 2016 Purdue University

Genomic Insights Into The Ixodes Scapularis Tick Vector Of Lyme Disease, Monika Gulia-Nuss,, Daniel R. Caffrey, Neal S. Silverman, Adam R. Wespiser, Catherine A. Hill

Neal Silverman

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing approximately 57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing ...


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 ...


Channa Striatus Tnfr-1: Molecular Cloning, Characterization And Gene Expression, Rajesh Palanisamy 2016 SRM Institute of Science and Technology

Channa Striatus Tnfr-1: Molecular Cloning, Characterization And Gene Expression, Rajesh Palanisamy

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.


Gene Expression Of Interleukin 8 In Liver Of Japanese Flounder Paralichthys Olivaceus Infected With Edwardsiella Tarda, Osamu Kurata, Shinpei Wada 2016 Nippon Veterinary and Life Science University

Gene Expression Of Interleukin 8 In Liver Of Japanese Flounder Paralichthys Olivaceus Infected With Edwardsiella Tarda, Osamu Kurata, Shinpei Wada

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.


Il-2 And Il-6 Cooperate To Enhance The Generation Of Influenza-Specific Cd8 T Cells Responding To Live Influenza Virus In Aged Mice And Humans, Xin Zhou, Jacob W. Hopkins, Chongkai Wang, Vinayak Brahmakshatriya, Susan L. Swain, George A. Kuchel, Laura Haynes, Janet E. McElhaney 2016 University of ConnecticutSchool of Medicine

Il-2 And Il-6 Cooperate To Enhance The Generation Of Influenza-Specific Cd8 T Cells Responding To Live Influenza Virus In Aged Mice And Humans, Xin Zhou, Jacob W. Hopkins, Chongkai Wang, Vinayak Brahmakshatriya, Susan L. Swain, George A. Kuchel, Laura Haynes, Janet E. Mcelhaney

Open Access Articles

An age-related decline in cytolytic activity has been described in CD8+ T cells and we have previously shown that the poor CD8+ effector T cell responses to influenza A/H3N2 challenge result from a decline in the proportion and function of these cytolytic T lymphocytes (CTL). Here, we describe that addition of exogenous cytokines to influenza-stimulated PBMC from both aged mice and humans, enhances the generation of influenza specific CD8 CTL by increasing their proliferation and survival. Our data show that the addition of IL-2 and IL-6 to splenocytes from mice previously infected with influenza virus restores the aged CD8 ...


Reassessing The Role Of The Nlrp3 Inflammasome During Pathogenic Influenza A Virus Infection Via Temporal Inhibition, Michelle D. Tate, James D.H. Ong, Jennifer K. Dowling, Julie L. McAuley, Avril B. Robertson, Eicke Latz, Grant R. Drummond, Matthew A. Cooper, Paul J. Hertzog, Ashley Mansell 2016 Monash University

Reassessing The Role Of The Nlrp3 Inflammasome During Pathogenic Influenza A Virus Infection Via Temporal Inhibition, Michelle D. Tate, James D.H. Ong, Jennifer K. Dowling, Julie L. Mcauley, Avril B. Robertson, Eicke Latz, Grant R. Drummond, Matthew A. Cooper, Paul J. Hertzog, Ashley Mansell

Open Access Articles

The inflammasome NLRP3 is activated by pathogen associated molecular patterns (PAMPs) during infection, including RNA and proteins from influenza A virus (IAV). However, chronic activation by danger associated molecular patterns (DAMPs) can be deleterious to the host. We show that blocking NLRP3 activation can be either protective or detrimental at different stages of lethal influenza A virus (IAV). Administration of the specific NLRP3 inhibitor MCC950 to mice from one day following IAV challenge resulted in hypersusceptibility to lethality. In contrast, delaying treatment with MCC950 until the height of disease (a more likely clinical scenario) significantly protected mice from severe and ...


Interrogating Plant Cell Culture Library For Novel Antimicrobial Agents, John Solitro, Yong Zhang, Vanessa Bartolo, Alexander Popchuk, Sergey Savinov, Lin-Jun Ma, Jennifer Normanly, Tristram Seidler, Elizabeth Vierling 2016 University of Massachusetts Amherst

Interrogating Plant Cell Culture Library For Novel Antimicrobial Agents, John Solitro, Yong Zhang, Vanessa Bartolo, Alexander Popchuk, Sergey Savinov, Lin-Jun Ma, Jennifer Normanly, Tristram Seidler, Elizabeth Vierling

UMass Center for Clinical and Translational Science Research Retreat

The Plant Cell Culture Library (PCCL) at UMass Amherst contains more than 2,200 live plant cell cultures, representing diverse plant species from around the world. The availability of this collection offers a rich resource for us to discover bioactive phytochemicals and uncover their mechanisms of action. Using data-mining surveys of bioactive plant extracts, I have organized subsets of PCCL cell lines that are likely to possess antifungal, antibacterial, antiviral, anthelmintic, anti-trypanosomal, or anticancer properties, which prove to be useful when deciding which species to screen first against a specific pathogen. Another distinct advantage of using the live plant cells ...


Rapid Diagnostics For Infectious Disease Using Noble Metal Nanoparticles, Chun-Wan Yen, Helena de Puig, Justina Tam, José Gómez-Márquez, Irene Bosch, Lee Gehrke, Kimberly Hamad-Schifferli 2016 Massachusetts Institute of Technology

Rapid Diagnostics For Infectious Disease Using Noble Metal Nanoparticles, Chun-Wan Yen, Helena De Puig, Justina Tam, José Gómez-Márquez, Irene Bosch, Lee Gehrke, Kimberly Hamad-Schifferli

UMass Center for Clinical and Translational Science Research Retreat

Rapid point-of-care (POC) diagnostic devices are needed for field-forward screening of severe acute systemic febrile illnesses such as dengue, Ebola, chikungunya, and others. Multiplexed rapid lateral flow diagnostics have the potential to distinguish among multiple pathogens, thereby facilitating diagnosis and improving patient care. We present a platform for multiplexed pathogen detection which uses gold or silver nanoparticles conjugated to antibodies to sense the presence of biomarkers for different infectious diseases. We exploit the size-dependent optical properties of Ag NPs to construct a multiplexed paperfluidic lateral flow POC sensor. AgNPs of different sizes were conjugated to antibodies that bind to specific ...


Microfluidic Platforms To Study Host-Microbiome Interactions, Abhinav Sharma, Neil Forbes, Jungwoo Lee 2016 University of Massachusetts Amherst

Microfluidic Platforms To Study Host-Microbiome Interactions, Abhinav Sharma, Neil Forbes, Jungwoo Lee

UMass Center for Clinical and Translational Science Research Retreat

About three-quarters of human body surface is exposed to dense microbial population along the gastro-intestinal tract (GIT) that accommodates around 80% of immune cells. The GIT is one of the most critical sites for metabolic and immunologic homeostasis in the body. While large-scale genomic analysis and germ-free mice have been widely used, they are limited to capture the dynamic functional interaction between host-microbiome in a humanized setting. in-vitro recapitulation of GIT physiology can be a powerful alternative for hypothesis testing in diseases like IBD and cancer.

As a first step, we developed a simple transwell assembly to closely emulate GIT ...


Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez 2016 Augustana College, Rock Island Illinois

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 ...


Hla Class I Supertype Associations With Clinical Outcome Of Secondary Dengue Virus Infections In Ethnic Thais, Sasijit Vejbaesya, Rungrot Thongpradit, Siripen Kalayanarooj, Komon Luangtrakool, Panpimon Luangtrakool, Robert V. Gibbons, Duangporn Srinak, Somporn Ngammthaworn, Kusuma Apisawes, In-Kyu Yoon, Stephen J. Thomas, Richard G. Jarman, Anon Srikiatkhachorn, Sharone Green, Dasnayanee Chandanayingyong, Sangshin Park, Jennifer Friedman, Alan L. Rothman, Henry A.F. Stephens 2016 Mahidol University

Hla Class I Supertype Associations With Clinical Outcome Of Secondary Dengue Virus Infections In Ethnic Thais, Sasijit Vejbaesya, Rungrot Thongpradit, Siripen Kalayanarooj, Komon Luangtrakool, Panpimon Luangtrakool, Robert V. Gibbons, Duangporn Srinak, Somporn Ngammthaworn, Kusuma Apisawes, In-Kyu Yoon, Stephen J. Thomas, Richard G. Jarman, Anon Srikiatkhachorn, Sharone Green, Dasnayanee Chandanayingyong, Sangshin Park, Jennifer Friedman, Alan L. Rothman, Henry A.F. Stephens

Sharone Green

BACKGROUND: Human leukocyte antigen (HLA) supertypes are groups of functionally related alleles that present structurally similar antigens to the immune system.

OBJECTIVES: To analyze HLA class I supertype associations with clinical outcome in hospitalized Thai children with acute dengue illness.

METHODS: Seven hundred sixty-two patients and population-matched controls recruited predominantly in Bangkok were HLA-A and -B typed. HLA supertype frequencies were compared and tested for significant dengue disease associations using logistic regression analyses. Multivariable models were built by conducting forward stepwise selection procedures.

RESULTS: In the final logistic regression model, the HLA-B44 supertype was protective against dengue hemorrhagic fever (DHF ...


Comparison Of Anti-Pneumococcal Functions Of Native And Modified Forms Of C-Reactive Protein, Donald Neba Ngwa 2016 East Tennessee State Universtiy

Comparison Of Anti-Pneumococcal Functions Of Native And Modified Forms Of C-Reactive Protein, Donald Neba Ngwa

Electronic Theses and Dissertations

The anti-pneumococcal function of native C-reactive protein (CRP) involves its binding to phosphocholine molecules present on Streptococcus pneumoniae and subsequent activation of the complement system. However, when pneumococci recruit complement inhibitory protein factor H on their surface, they escape complement attack. Non-native forms of CRP have been shown to bind immobilized factor H. Accordingly, we hypothesized that modified CRP would bind to factor H on pneumococci, masking its complement inhibitory activity, allowing native CRP to exert its anti-pneumococcal function. As reported previously, native CRP protected mice from lethal pneumococcal infection when injected 30 minutes before infection but not when injected ...


Immune Complex-Induced, Nitric Oxide-Mediated Vascular Endothelial Cell Death By Phagocytes Is Prevented With Decoy Fcyreceptors, Ramanjaneya V. R. Mula, Deepa Machiah, Lauren Holland, Xinyu Wang, Harish Parihar, Avadhesh Sharma, Periasamy Selvaraj, Rangaiah Shashidharamurthy 2016 Philadelphia College of Osteopathic Medicine

Immune Complex-Induced, Nitric Oxide-Mediated Vascular Endothelial Cell Death By Phagocytes Is Prevented With Decoy Fcyreceptors, Ramanjaneya V. R. Mula, Deepa Machiah, Lauren Holland, Xinyu Wang, Harish Parihar, Avadhesh Sharma, Periasamy Selvaraj, Rangaiah Shashidharamurthy

Avadhesh C. Sharma

Autoimmune vasculitis is an endothelial inflammatory disease that results from the deposition of immune-complexes (ICs) in blood vessels. The interaction between Fcgamma receptors (FcyRs) expressed on inflammatory cells with ICs is known to cause blood vessel damage. Hence, blocking the interaction of ICs and inflammatory cells is essential to prevent the IC-mediated blood vessel damage. Thus we tested if uncoupling the interaction of FcyRs and ICs prevents endothelium damage. Herein, we demonstrate that dimeric FcyR-Igs prevented nitric oxide (NO) mediated apoptosis of human umbilical vein endothelial cells (HUVECs) in an in vitro vasculitis model. Dimeric FcyR-Igs significantly inhibited the IC-induced ...


Immune Complex-Induced, Nitric Oxide-Mediated Vascular Endothelial Cell Death By Phagocytes Is Prevented With Decoy Fcyreceptors, Ramanjaneya V. R. Mula, Deepa Machiah, Lauren Holland, Xinyu Wang, Harish Parihar, Avadhesh Sharma, Periasamy Selvaraj, Rangaiah Shashidharamurthy 2016 Philadelphia College of Osteopathic Medicine

Immune Complex-Induced, Nitric Oxide-Mediated Vascular Endothelial Cell Death By Phagocytes Is Prevented With Decoy Fcyreceptors, Ramanjaneya V. R. Mula, Deepa Machiah, Lauren Holland, Xinyu Wang, Harish Parihar, Avadhesh Sharma, Periasamy Selvaraj, Rangaiah Shashidharamurthy

Harish S. Parihar

Autoimmune vasculitis is an endothelial inflammatory disease that results from the deposition of immune-complexes (ICs) in blood vessels. The interaction between Fcgamma receptors (FcyRs) expressed on inflammatory cells with ICs is known to cause blood vessel damage. Hence, blocking the interaction of ICs and inflammatory cells is essential to prevent the IC-mediated blood vessel damage. Thus we tested if uncoupling the interaction of FcyRs and ICs prevents endothelium damage. Herein, we demonstrate that dimeric FcyR-Igs prevented nitric oxide (NO) mediated apoptosis of human umbilical vein endothelial cells (HUVECs) in an in vitro vasculitis model. Dimeric FcyR-Igs significantly inhibited the IC-induced ...


Immune Complex-Induced, Nitric Oxide-Mediated Vascular Endothelial Cell Death By Phagocytes Is Prevented With Decoy Fcyreceptors, Ramanjaneya V. R. Mula, Deepa Machiah, Lauren Holland, Xinyu Wang, Harish Parihar, Avadhesh Sharma, Periasamy Selvaraj, Rangaiah Shashidharamurthy 2016 Philadelphia College of Osteopathic Medicine

Immune Complex-Induced, Nitric Oxide-Mediated Vascular Endothelial Cell Death By Phagocytes Is Prevented With Decoy Fcyreceptors, Ramanjaneya V. R. Mula, Deepa Machiah, Lauren Holland, Xinyu Wang, Harish Parihar, Avadhesh Sharma, Periasamy Selvaraj, Rangaiah Shashidharamurthy

Rangaiah Shashidharamurthy

Autoimmune vasculitis is an endothelial inflammatory disease that results from the deposition of immune-complexes (ICs) in blood vessels. The interaction between Fcgamma receptors (FcyRs) expressed on inflammatory cells with ICs is known to cause blood vessel damage. Hence, blocking the interaction of ICs and inflammatory cells is essential to prevent the IC-mediated blood vessel damage. Thus we tested if uncoupling the interaction of FcyRs and ICs prevents endothelium damage. Herein, we demonstrate that dimeric FcyR-Igs prevented nitric oxide (NO) mediated apoptosis of human umbilical vein endothelial cells (HUVECs) in an in vitro vasculitis model. Dimeric FcyR-Igs significantly inhibited the IC-induced ...


Optimization Of Fluorescent Phagocytic Assay Using Apoptotic Cells, Jacob L. Brown, Jason R. Leigh, Ryan Marquardt, Cambria R. Puffenberger, Daniel J. Stank, Kaleb M. Pauley 2016 Cedarville University

Optimization Of Fluorescent Phagocytic Assay Using Apoptotic Cells, Jacob L. Brown, Jason R. Leigh, Ryan Marquardt, Cambria R. Puffenberger, Daniel J. Stank, Kaleb M. Pauley

The Research and Scholarship Symposium

Sjögren’s Syndrome is a systemic autoimmune disease that primarily affects the exocrine glands and is characterized by severe dry eyes and mouth. Previous studies have shown that there are elevated levels of the microRNA miR-146a in Sjögren’s patients. Mir-146a is a microRNA that has been found to be involved in down regulating inflammation. Yet, in patients with Sjögren’s Syndrome, there is a large upregulation of miR-146a that exists alongside chronic inflammation. This led us to investigate the role of miR-146a in Sjögren’s Syndrome. We found that miR-146a upregulates phagocytosis of E. coli by human macrophages. Therefore ...


Investigating The Effects Of Increasing Anti-Ama1, Anti-Msp1, And Anti-Msp2 In Preventing Malaria Incidence, April Skipper 2016 Southeastern University - Lakeland

Investigating The Effects Of Increasing Anti-Ama1, Anti-Msp1, And Anti-Msp2 In Preventing Malaria Incidence, April Skipper

Selected Honors Theses

Malaria is a life-threatening illness that 3.2 billion people, half of the world's population, are at risk of contracting. In 2015, there were 214 million malaria cases and 438,000 deaths caused by the disease. It is caused by Plasmodium parasites which infect humans through the bite of the Anopheles mosquito. The four species of Plasmodium that are known to cause malaria are P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. The symptoms of malaria greatly resemble symptoms of a common cold, so accurate diagnosis can be a challenge. Symptoms commonly include fever, headache, vomiting ...


Investigating The Efficacy And Anti-Resistance Activity Of Fexinidazole In Conjunction With Eflornithine Against Trypanosoma Brucei For Treatment Of Human African Trypanosomiasis, Mercy Toma 2016 Southeastern University - Lakeland

Investigating The Efficacy And Anti-Resistance Activity Of Fexinidazole In Conjunction With Eflornithine Against Trypanosoma Brucei For Treatment Of Human African Trypanosomiasis, Mercy Toma

Selected Honors Theses

Human African Trypanosomiasis (HAT) is one of 17 neglected tropical disease prioritized by the World Health Organization (WHO). Neglected tropical diseases are diseases which affect poor or developing countries and which do not get as much as attention as the ‘big three’: malaria, tuberculosis and HIV/AIDS. HAT specifically affects coutries in Sub-Saharan Africa and is caused by a parasitic protozoa, Trypanosoma brucei. There are two stages of HAT: the early haemolymphatic and late meningo-encephalitic stages. There are also two subtypes of the disease caused by either T. b. gambiense or T.b rhodesiense forms of the parasite. There are ...


Interaction Of A Dengue Virus Ns1-Derived Peptide With The Inhibitory Receptor Kir3dl1 On Natural Killer Cells, Elizabeth Townsley, G. O'Connor, C. Cosgrove, Marcia Woda, Mary Dawn T. Co, S. J. Thomas, Siripen Kalayanarooj, In-Kyu Yoon, Ananda Nisalak, Anon Srikiatkhachorn, Sharone Green, H. A. F. Stephens, Emma Gostick, David A. Price, M. Carrington, Galit Alter, D. W. McVicar, Alan L. Rothman, Anuja Mathew 2016 University of Massachusetts Medical School

Interaction Of A Dengue Virus Ns1-Derived Peptide With The Inhibitory Receptor Kir3dl1 On Natural Killer Cells, Elizabeth Townsley, G. O'Connor, C. Cosgrove, Marcia Woda, Mary Dawn T. Co, S. J. Thomas, Siripen Kalayanarooj, In-Kyu Yoon, Ananda Nisalak, Anon Srikiatkhachorn, Sharone Green, H. A. F. Stephens, Emma Gostick, David A. Price, M. Carrington, Galit Alter, D. W. Mcvicar, Alan L. Rothman, Anuja Mathew

University of Massachusetts Medical School Faculty Publications

Killer immunoglobulin-like receptors (KIRs) interact with human leucocyte antigen (HLA) class I ligands and play a key role in the regulation and activation of NK cells. The functional importance of KIR-HLA interactions has been demonstrated for a number of chronic viral infections, but to date only a few studies have been performed in the context of acute self-limited viral infections. During our investigation of CD8(+) T cell responses to a conserved HLA-B57-restricted epitope derived from dengue virus (DENV) non-structural protein-1 (NS1), we observed substantial binding of the tetrameric complex to non-T/non-B lymphocytes in peripheral blood mononuclear cells (PBMC) from ...


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