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Transcriptional Regulation Of Effector And Memory Responses During Acute And Chronic Lymphocytic Choriomeningitis Virus (Lcmv) Infection, Elizabeth A. Olesin 2018 University of Massachusetts Medical School

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 ...


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 2018 Second Military Medical University

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 2018 Dstl Porton Down

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 ...


A Mathematical Model Of The Inflammatory Response To Pathogen Challenge, Lester Caudill, Fiona Lynch 2018 University of Richmond

A Mathematical Model Of The Inflammatory Response To Pathogen Challenge, Lester Caudill, Fiona Lynch

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Simulating Antibiotic Resistance In The Computer Lab And Biology Lab: Ideas For Undergraduate Projects, Anne E. Yust 2018 The New School

Simulating Antibiotic Resistance In The Computer Lab And Biology Lab: Ideas For Undergraduate Projects, Anne E. Yust

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Cd105 Deficiency In Mouse Aorta-Derived Progenitor Cells Promotes An Enhanced Inflammatory Response To Lipopolysaccharide, Joseph Granata, Hugo Sanchez, Phillip Loeschinger, Jodi F. Evans Ph.D. 2018 Molloy College

Cd105 Deficiency In Mouse Aorta-Derived Progenitor Cells Promotes An Enhanced Inflammatory Response To Lipopolysaccharide, Joseph Granata, Hugo Sanchez, Phillip Loeschinger, Jodi F. Evans Ph.D.

Jodi Evans

Mesenchymal progenitor cells are widely studied for their ability to regulate macrophage cell responses and can be suppressive or supportive during an inflammatory response. Mouse aorta-derived progenitors (mAo) support the macrophage inflammatory response and highly express CD105, also known as endoglin. Elevated CD105 expression is consistently associated with inflammatory disease. Therefore, we hypothesized that suppression of CD105 will reduce the immunosupportive capacity of mAo mesenchymal progenitors. We used siRNA to reduce expression of CD105 in mAo cells. We subsequently examined the effect of this deficiency in their response to both lipopolysaccharide (LPS) and their ability to support the macrophage inflammatory ...


Interleukin-1 Receptor-Associated Kinase 4 (Irak4) Plays A Dual Role In Myddosome Formation And Toll-Like Receptor Signaling, Dominic De Nardo, Katherine R. Balka, Yamel Cardona Gloria, Vikram R. Rao, Eicke Latz, Seth L. Masters 2018 University of Melbourne

Interleukin-1 Receptor-Associated Kinase 4 (Irak4) Plays A Dual Role In Myddosome Formation And Toll-Like Receptor Signaling, Dominic De Nardo, Katherine R. Balka, Yamel Cardona Gloria, Vikram R. Rao, Eicke Latz, Seth L. Masters

Open Access Articles

Toll-like receptors (TLRs) form part of the host innate immune system, in which they act as sensors of microbial and endogenous danger signals. Upon TLR activation, the intracellular Toll/interleukin-1 receptor domains of TLR dimers initiate oligomerization of a multiprotein signaling platform comprising myeloid differentiation primary response 88 (MyD88) and members of the interleukin-1 receptor-associated kinase (IRAK) family. Formation of this myddosome complex initiates signal transduction pathways, leading to the activation of transcription factors and the production of inflammatory cytokines. To date, little is known about the assembly and disassembly of the myddosome and about the mechanisms by which these ...


Tolerating The Unwelcome Guest; How The Host Withstands Persistent Mycobacterium Tuberculosis, Andrew J. Olive, Christopher M. Sassetti 2018 Michigan State University

Tolerating The Unwelcome Guest; How The Host Withstands Persistent Mycobacterium Tuberculosis, Andrew J. Olive, Christopher M. Sassetti

Open Access Articles

Our understanding of the host response to infections has historically focused on "resistance" mechanisms that directly control pathogen replication. However, both pathogen effectors and antimicrobial immune pathways have the capacity to damage host tissue, and the ability to tolerate these insults can also be critical for host survival. These "tolerance" mechanisms may be equally as important as resistance to prevent disease in the context of a persistent infection, such as tuberculosis, when resistance mechanisms are ineffective and the pathogen persists in the tissue for long periods. Host tolerance encompasses a wide range of strategies, many of which involve regulation of ...


Characterization Of The Protective Role Of Th17 Cells In An Fc Receptor-Targeted Vaccine Strategy Against Fracisella Tularensis Infection, Kyle Devenney 2018 Seton Hall University

Characterization Of The Protective Role Of Th17 Cells In An Fc Receptor-Targeted Vaccine Strategy Against Fracisella Tularensis Infection, Kyle Devenney

Seton Hall University Dissertations and Theses (ETDs)

Using a murine model, we have previously showed that targeting an inactivated form of F.tularensis (iFt) bacteria to Fcg receptors by utilizing an IgG2a, anti-LPS monoclonal antibody (mAb) provides 100% protection against a lethal dose with the live vaccine strain (LVS). The binding of anti-LPS monoclonal antibodies and iFt create an immune complex (mAb-iFt) allowing the Fc-region of the antibody to target Fc receptors expressed on antigen presenting cells, leading to a more robust and effective processing and presentation of the bacterial antigens. Although the resulting protective response generated relies on both humoral and cell-mediated immunity, in our study ...


Drug-Resistance And Population Structure Of Plasmodium Falciparum Across The Democratic Republic Of Congo Using High-Throughput Molecular Inversion Probes, Ozkan Aydemir, Nicholas J. Hathaway, Patrick W. Marsh, Alice Tran, Thomas Reimonn, Jeffrey A. Bailey 2018 University of Massachusetts Medical School

Drug-Resistance And Population Structure Of Plasmodium Falciparum Across The Democratic Republic Of Congo Using High-Throughput Molecular Inversion Probes, Ozkan Aydemir, Nicholas J. Hathaway, Patrick W. Marsh, Alice Tran, Thomas Reimonn, Jeffrey A. Bailey

Open Access Articles

A better understanding of the drivers of the spread of malaria parasites and drug resistance across space and time is needed. These drivers can be elucidated using genetic tools. Here, a novel molecular inversion probe (MIP) panel targeting all major drug-resistance mutations and a set of microsatellites was used to genotype Plasmodium falciparum infections of 552 children from the 2013-2014 Demographic and Health Survey conducted in the Democratic Republic of the Congo (DRC). Microsatellite-based analysis of population structure suggests that parasites within the DRC form a homogeneous population. In contrast, sulfadoxine-resistance markers in dihydropteroate synthase show marked spatial structure with ...


Assessment Of Melanocyte-Specific Primary And Memory Autoimmune Responses In Vitiligo-Prone Smyth And Vitiligo-Susceptible, Non-Expressing Brown Line Chickens, Daniel Morales Falcon 2018 University of Arkansas, Fayetteville

Assessment Of Melanocyte-Specific Primary And Memory Autoimmune Responses In Vitiligo-Prone Smyth And Vitiligo-Susceptible, Non-Expressing Brown Line Chickens, Daniel Morales Falcon

Theses and Dissertations

Vitiligo is an acquired de-pigmentation disorder characterized by the post-natal loss of epidermal melanocytes (pigment-producing cells) resulting in the appearance of white patches in the skin. The Smyth line of chicken is the only model for vitiligo that shares all the characteristics of the human condition including: spontaneous post-natal loss of melanocytes, interactions between genetic, environmental and immunological factors and associations with other autoimmune diseases. In addition, an avian model for vitiligo has the added benefit of an easily accessible target tissue (a growing feather) that allows for the repeated sampling of an individual and thus the continuous monitoring of ...


Immune Function And Metabolism Of Hibernating North American Bats With White-Nose Syndrome, Briana Nicole Anderson 2018 Missouri State University

Immune Function And Metabolism Of Hibernating North American Bats With White-Nose Syndrome, Briana Nicole Anderson

MSU Graduate Theses

White-nose syndrome (WNS) causes substantial mortality in certain species of hibernating North American bats. The responsible agent is Pseudogymnoascus destructans (Pd), a fungus which causes physiological complications such as increased arousals and energy depletion during the hibernation season. Tricolored bats (Perimyotis subflavus) and northern long-eared bats (Myotis septentrionalis) suffer extensive WNS mortality, while gray bats (Myotis grisescens) and big brown bats (Eptesicus fuscus) are infected, but mortality is rarely observed. It is hypothesized that there is a difference in immune responses and/or hibernation metabolism between these bat species, resulting in this interspecific variation in disease severity. To test these ...


Total Body Cd4+ T Cell Dynamics In Treated And Untreated Siv Infection Revealed By In Vivo Imaging, Michele Di Mascio, Sharat Srinivasula, Insook Kim, Gorka Duralde, Alexis St. Claire, Paula DeGrange, Marisa St. Claire, Keith A. Reimann, Erin E. Gabriel, Jorge Carrasquillo, Richard C. Reba, Chang Paik, Henry C. Lane 2018 National Institute of Allergy and Infectious Diseases

Total Body Cd4+ T Cell Dynamics In Treated And Untreated Siv Infection Revealed By In Vivo Imaging, Michele Di Mascio, Sharat Srinivasula, Insook Kim, Gorka Duralde, Alexis St. Claire, Paula Degrange, Marisa St. Claire, Keith A. Reimann, Erin E. Gabriel, Jorge Carrasquillo, Richard C. Reba, Chang Paik, Henry C. Lane

Open Access Articles

The peripheral blood represents only a small fraction of the total number of lymphocytes in the body. To develop a more thorough understanding of T cell dynamics, including the effects of SIV/SHIV/HIV infection on immune cell depletion and immune reconstitution following combination antiretroviral therapy (cART), one needs to utilize approaches that allow direct visualization of lymphoid tissues. In the present study, noninvasive in vivo imaging of the CD4+ T cell pool has revealed that the timing of the CD4+ T cell pool reconstitution following initiation of ART in SIV-infected nonhuman primates (NHPs) appears seemingly stochastic among clusters of ...


Transporters Mrp1 And Mrp2 Regulate Opposing Inflammatory Signals To Control Transepithelial Neutrophil Migration During Streptococcus Pneumoniae Lung Infection, Andrew Zukauskas, Randall J. Mrsny, Paula Cortes Barrantes, Jerrold R. Turner, John M. Leong, Beth A. McCormick 2018 University of Massachusetts Medical School

Transporters Mrp1 And Mrp2 Regulate Opposing Inflammatory Signals To Control Transepithelial Neutrophil Migration During Streptococcus Pneumoniae Lung Infection, Andrew Zukauskas, Randall J. Mrsny, Paula Cortes Barrantes, Jerrold R. Turner, John M. Leong, Beth A. Mccormick

Open Access Articles

Streptococcus pneumoniae remains a source of morbidity and mortality in both developed and underdeveloped nations of the world. Disease can manifest as pneumonia, bacteremia, and meningitis, depending on the localization of infection. Interestingly, there is a correlation in experimental murine infections between the development of bacteremia and influx of neutrophils into the pulmonary lumen. Reduction of this neutrophil influx has been shown to improve survivability during infection. In this study, we use in vitro biotinylation and neutrophil transmigration and in vivo murine infection to identify a system in which two epithelium-localized ATP-binding cassette transporters, MRP1 and MRP2, have inverse activities ...


The Role Of Eukaryotic Abc-Transporters In Eliciting Neutrophil Infiltration During Streptococcus Pneumoniae Infection, Andrew Zukauskas 2018 University of Massachusetts Medical School

The Role Of Eukaryotic Abc-Transporters In Eliciting Neutrophil Infiltration During Streptococcus Pneumoniae Infection, Andrew Zukauskas

GSBS Dissertations and Theses

Streptococcus pneumoniae (S. pneumoniae) is a Gram-positive, encapsulated bacterium capable of causing significant morbidity and mortality throughout the world. A hallmark of S. pneumoniae infection is infiltration of neutrophils (PMNs) that assist in controlling the spread infection but may also contribute to pathology. Paradoxically, studies have shown that limiting PMN infiltration into the lumen of the lung during infection actually betters clinical outcome in experimental S. pneumoniae infection. The final step in PMN luminal trafficking is a Hepoxilin A3 (HXA3)-dependent migration across the pulmonary epithelium. HXA3 is a PMN chemoattractant that forms gradients along the polarized epithelial ...


Avoiding Death Like The Plague: Wound Care In The Roman Army, Gwendolyn E. Dougherty 2018 Nazareth College of Rochester

Avoiding Death Like The Plague: Wound Care In The Roman Army, Gwendolyn E. Dougherty

#History: A Journal of Student Research

At its peak, Roman Empire controlled over two million square miles of territory. To conquer and control that much land, Rome produced a highly skilled army. Casualties and deaths were to be expected, but ancient medical sources about caring for the wounded in the Roman army point to treatments considered advanced for the time period. Galen of Pergamum was an important contributor to this field. The use of food products and natural resources helped combat infections, healing the wounded soldiers and returning them to their military units. This paper identifies and analyzes what those specific products for wound care were ...


Investigating Present-Day Health Issues Of The American Lobster (Homarus Americanus), Deborah A. Bouchard 2018 University of Maine

Investigating Present-Day Health Issues Of The American Lobster (Homarus Americanus), Deborah A. Bouchard

Electronic Theses and Dissertations

The American lobster, Homarus americanus, H. Milne Edwards, 1837, supports the most economically valuable fishery along the North Atlantic coast of North America. A collapse in lobster populations in Southern New England (SNE) has coincided with increasing ocean temperatures and emerging diseases. This research investigated the etiologies of limp lobster disease (LLD) and epizootic shell disease (ESD), two diseases that continue to cause significant mortality in natural lobster populations. Mortality from LLD is associated with the bacteria Photobacterium indicum and is more intense in impounded lobsters. To more clearly define the community ecology of this suspected opportunistic pathogen, the microbial ...


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

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

Open Access Articles

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


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

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

MSU Graduate Theses

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


Investigation Into The Causes And Severity Of The 1918 Influenza Pandemic, Alex T. Freedenberg 2018 St. John Fisher College

Investigation Into The Causes And Severity Of The 1918 Influenza Pandemic, Alex T. Freedenberg

The Review: A Journal of Undergraduate Student Research

The 1918 Influenza outbreak is regarded as one of the worst pandemics in human history due to its widespread effects across the globe and its high death rate. This death rate was unusual among influenza infections as most strains do not cause the amount of death that is seen in this outbreak, with 20 million dead as a conservative estimate and 100 million by other estimations. This pandemic was not very well contained for a plethora of reasons. Two main reasons are that it came at a time when understanding viral mechanics still escaped medical professionals, and due to the ...


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