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Regulation Of Innate Immunity In The C. Elegans Intestine By Olfactory Neurons, Kyle J. Foster 2020 University of Massachusetts Medical School

Regulation Of Innate Immunity In The C. Elegans Intestine By Olfactory Neurons, Kyle J. Foster

GSBS Dissertations and Theses

The intestinal epithelium represents one of the first lines of defense against pathogenic bacteria. Immune regulation at this critical barrier is necessary to maintain organismal fitness, and mis-regulation here has been linked to numerous debilitating diseases. Functional relationships between the nervous system and immune system have been found to be critical in the proper coordination of immune defenses at barrier surfaces, however the precise mechanisms underlying theses interactions remains unclear.

Through conducting a forward genetic screen utilizing the model organism Caenorhabditis elegans, we uncovered a surprising requirement for the olfactory neuron gene olrn-1 in the regulation of intestinal epithelial immunity ...


The Kinetics Of Influenza A (A/California/4/2009-H1n1) And B (B/Phuket/3073/2013 (Byam), B/Brisbane/60/2008 (Bvic)) Virus Infection In Ferrets, Demi L. Erickson 2020 University of South Dakota

The Kinetics Of Influenza A (A/California/4/2009-H1n1) And B (B/Phuket/3073/2013 (Byam), B/Brisbane/60/2008 (Bvic)) Virus Infection In Ferrets, Demi L. Erickson

Honors Thesis

Influenza is a persistent threat to individual and global health. Seasonal influenza kills nearly 500,000 people globally each year. Influenza viruses have circulated within the human population, causing a significant disease burden. In order to create the most effective antiviral therapies, knowledge concerning all lineages of influenza must be studied accurately and thoroughly. The influenza virus itself is not always responsible for these mortalities, rather, the secondary bacterial infections associated with death. In order to protect the population and examine the secondary infections that arise, the kinetics of influenza must be studied entirely. To understand the kinetics, researchers are ...


Sars-Coronavirus-2 Nucleocapsid Protein Measured In Blood Using A Simoa Ultra-Sensitive Immunoassay Differentiates Covid-19 Infection With High Clinical Sensitivity., Dandan Shan, Eicke Latz, Andrew J. Ball 2020 Quanterix Corporation

Sars-Coronavirus-2 Nucleocapsid Protein Measured In Blood Using A Simoa Ultra-Sensitive Immunoassay Differentiates Covid-19 Infection With High Clinical Sensitivity., Dandan Shan, Eicke Latz, Andrew J. Ball

University of Massachusetts Medical School Faculty Publications

The COVID-19 pandemic continues to have an unprecedented impact on societies and economies worldwide. Despite rapid advances in diagnostic test development and scale-up, there remains an ongoing need for SARS-CoV-2 tests which are highly sensitive, specific, minimally invasive, cost-effective and scalable for broad testing and surveillance. Here we report development of a highly sensitive single molecule array (Simoa) immunoassay on the automated HD-X platform for the detection of SARS-CoV-2 Nucleocapsid protein (N-protein) in venous and capillary blood (fingerstick). In pre-pandemic and clinical sample sets, the assay has 100% specificity and 97.4% sensitivity for serum / plasma samples. The limit of ...


Nano-Vesicle (Mis)Communication In Senescence-Related Pathologies, Sherin Saheera, Ajay Godwin Potnuri, Prasanna Krishnamurthy 2020 University of Massachusetts Medical School

Nano-Vesicle (Mis)Communication In Senescence-Related Pathologies, Sherin Saheera, Ajay Godwin Potnuri, Prasanna Krishnamurthy

COVID-19 Publications by UMMS Authors

Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising of exosomes, apoptotic bodies, and microvesicles. Of the extracellular vesicles, exosomes are the most widely sorted and extensively explored for their contents and function. The size of the nanovesicular structures (exosomes) range from 30 to 140 nm and are present in various biological fluids such as saliva, plasma, urine etc. These cargo-laden extracellular vesicles arise from endosome-derived multivesicular bodies and are known to carry proteins and nucleic acids. Exosomes are involved in multiple physiological and pathological processes, including cellular senescence. Exosomes mediate signaling crosstalk and play a critical role ...


Phylogenetic Analysis Of Sars-Cov-2 In The Boston Area Highlights The Role Of Recurrent Importation And Superspreading Events, Jacob Lemieux, Katherine J. Siddle, Jeremy Luban, Glen R. Gallagher, Lawrence C. Madoff, Sandra Smole, Virginia M. Pierce, Eric Rosenberg, Pardis C. Sabeti, Daniel J. Park, Bronwyn L. MacInnis 2020 Broad Institute

Phylogenetic Analysis Of Sars-Cov-2 In The Boston Area Highlights The Role Of Recurrent Importation And Superspreading Events, Jacob Lemieux, Katherine J. Siddle, Jeremy Luban, Glen R. Gallagher, Lawrence C. Madoff, Sandra Smole, Virginia M. Pierce, Eric Rosenberg, Pardis C. Sabeti, Daniel J. Park, Bronwyn L. Macinnis

COVID-19 Publications by UMMS Authors

SARS-CoV-2 has caused a severe, ongoing outbreak of COVID-19 in Massachusetts with 111,070 confirmed cases and 8,433 deaths as of August 1, 2020. To investigate the introduction, spread, and epidemiology of COVID-19 in the Boston area, we sequenced and analyzed 772 complete SARS-CoV-2 genomes from the region, including nearly all confirmed cases within the first week of the epidemic and hundreds of cases from major outbreaks at a conference, a nursing facility, and among homeless shelter guests and staff. The data reveal over 80 introductions into the Boston area, predominantly from elsewhere in the United States and Europe ...


Host Immunity Increases Mycobacterium Tuberculosis Reliance On Cytochrome Bd Oxidase, Yi Cai, Eleni Jaecklein, Jared Mackenzie, Kadamba Papavinasasundaram, Michigan State University, Xinchun Chen, Africa Health Research Institute, Christopher M. Sassetti 2020 Shenzhen University

Host Immunity Increases Mycobacterium Tuberculosis Reliance On Cytochrome Bd Oxidase, Yi Cai, Eleni Jaecklein, Jared Mackenzie, Kadamba Papavinasasundaram, Michigan State University, Xinchun Chen, Africa Health Research Institute, Christopher M. Sassetti

University of Massachusetts Medical School Faculty Publications

In order to sustain a persistent infection, Mycobacterium tuberculosis (Mtb) must adapt to a changing environment that is shaped by the developing immune response. This necessity to adapt is evident in the flexibility of many aspects of Mtb metabolism, including a respiratory chain that consists of two distinct terminal cytochrome oxidase complexes. Under the conditions tested thus far, the bc1/aa3 complex appears to play a dominant role, while the alternative bd oxidase is largely redundant. However, presence of two terminal oxidases in this obligate pathogen implies that respiratory requirements might change during infection. We report that the ...


A Cross-Reactive Human Iga Monoclonal Antibody Blocks Sars-Cov-2 Spike-Ace2 Interaction, Ejemel Monir, Qi Li, Shurong Hou, Zachary Schiller, Aaron Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Jacqueline R. Toomey, Ryan Schneider, Anudeep S. Ramchetty, Chandrashekar Ganesa, Lisa Cavacini, Mark S. Klempner, Celia A. Schiffer, Yan Wang 2020 University of Massachusetts Medical School

A Cross-Reactive Human Iga Monoclonal Antibody Blocks Sars-Cov-2 Spike-Ace2 Interaction, Ejemel Monir, Qi Li, Shurong Hou, Zachary Schiller, Aaron Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Jacqueline R. Toomey, Ryan Schneider, Anudeep S. Ramchetty, Chandrashekar Ganesa, Lisa Cavacini, Mark S. Klempner, Celia A. Schiffer, Yan Wang

COVID-19 Publications by UMMS Authors

COVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity. No vaccine to boost mucosal immunity, or as a therapeutic, has yet been developed to SARS-CoV-2. In this study, we discover and characterize a cross-reactive human IgA monoclonal antibody, MAb362. MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 ...


Broad Host Range Of Sars-Cov-2 Predicted By Comparative And Structural Analysis Of Ace2 In Vertebrates, Joana Damas, Elinor K. Karlsson, Harris A. Lewin 2020 University of California, Davis

Broad Host Range Of Sars-Cov-2 Predicted By Comparative And Structural Analysis Of Ace2 In Vertebrates, Joana Damas, Elinor K. Karlsson, Harris A. Lewin

COVID-19 Publications by UMMS Authors

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19. The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike ...


Exploiting The Immunomodulatory Potentials Of Inkt Cells In Sepsis And Cancer., Joshua Choi 2020 The University of Western Ontario

Exploiting The Immunomodulatory Potentials Of Inkt Cells In Sepsis And Cancer., Joshua Choi

Electronic Thesis and Dissertation Repository

Invariant natural killer T (iNKT) cells are a unique unconventional T cell subset that recognize glycolipids presented by CD1d expressing cells. The prototypical glycolipid agonist of iNKT cells, α-Galactosylceramide (α-GalCer), can induce the rapid release of an arsenal of cytotoxic effector molecules and enormous amounts of immunomodulatory cytokines as early as two hours after activation. In addition to α-GalCer, various glycolipid agonists are available that allow for specific, in vivo targeting of iNKT cells, and can exert divergent T-helper (TH)1 and/or TH2 immune responses. Therefore, the type of response instigated by iNKT cells can profoundly ...


A Genome-Wide Screen In Macrophages Identifies New Regulators Of Ifnγ-Inducible Mhcii That Contribute To T Cell Activation, Michael C. Kiritsy, Michigan State University, Audrey E. Lord, M. Pontus A. Orning, Roland Elling, Katherine A. Fitzgerald 2020 University of Massachusetts Medical School

A Genome-Wide Screen In Macrophages Identifies New Regulators Of Ifnγ-Inducible Mhcii That Contribute To T Cell Activation, Michael C. Kiritsy, Michigan State University, Audrey E. Lord, M. Pontus A. Orning, Roland Elling, Katherine A. Fitzgerald

University of Massachusetts Medical School Faculty Publications

Cytokine-mediated activation of host immunity is central to the control of pathogens. A key cytokine in protective immunity is interferon-gamma (IFNγ), which is a potent activator of antimicrobial and immunomodulatory effectors within the host. A major role of IFNγ is to induce major histocompatibility complex class II molecules (MHCII) on the surface of cells, which is required for CD4+ T cell activation. Despite its central role in host immunity, the complex and dynamic regulation of IFNγ-induced MHCII is not well understood. Here, we integrated functional genomics and transcriptomics to comprehensively define the genetic control of IFNγ-mediated MHCII surface expression in ...


Seroprevalence Of Sars-Cov-2-Specific Igg Antibodies Among Adults Living In Connecticut Between March 1 And June 1, 2020: Post-Infection Prevalence (Pip) Study, Shiwani Mahajan, Lokinendi V. Rao, Harlan M. Krumholz 2020 Yale University

Seroprevalence Of Sars-Cov-2-Specific Igg Antibodies Among Adults Living In Connecticut Between March 1 And June 1, 2020: Post-Infection Prevalence (Pip) Study, Shiwani Mahajan, Lokinendi V. Rao, Harlan M. Krumholz

University of Massachusetts Medical School Faculty Publications

Importance: A seroprevalence study can estimate the percentage of people with SARS-CoV-2 antibodies in the general population. Most existing reports have used a convenience sample, which may bias their estimates.

Objective: To estimate the seroprevalence of antibodies against SARS-CoV-2 based on a random sample of adults living in Connecticut between March 1 and June 1, 2020.

Design: Cross-sectional. Setting: We sought a representative sample of Connecticut residents who completed a survey between June 4 and June 23, 2020 and underwent serology testing for SARS-CoV-2-specific IgG antibodies between June 10 and July 6, 2020.

Participants: 505 respondents, aged ≥18 years, residing ...


The Dhodh Inhibitor Ptc299 Arrests Sars-Cov-2 Replication And Suppresses Induction Of Inflammatory Cytokines, Jeremy Luban, Caterina Strambio De Castilla, Yetao Wang, Allan Jacobson, Stuart Peltz 2020 University of Massachusetts Medical School

The Dhodh Inhibitor Ptc299 Arrests Sars-Cov-2 Replication And Suppresses Induction Of Inflammatory Cytokines, Jeremy Luban, Caterina Strambio De Castilla, Yetao Wang, Allan Jacobson, Stuart Peltz

University of Massachusetts Medical School Faculty Publications

The coronavirus disease 2019 (COVID-19) pandemic has created an urgent need for therapeutics that inhibit the SARS-CoV-2 virus and suppress the fulminant inflammation characteristic of advanced illness. Here, we describe the anti-COVID-19 potential of PTC299, an orally available compound that is a potent inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme of the de novo pyrimidine biosynthesis pathway. In tissue culture, PTC299 manifests robust, dose-dependent, and DHODH-dependent inhibition of SARS CoV-2 replication (EC50 range, 2.0 to 31.6 nM) with a selectivity index >3,800. PTC299 also blocked replication of other RNA viruses, including Ebola virus. Consistent with known ...


Bringing Til Therapy Beyond Melanoma: Advancing The Treatment Of Advanced Pancreatic And Ovarian Cancers, Donald Sakellariou-Thompson 2020 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Bringing Til Therapy Beyond Melanoma: Advancing The Treatment Of Advanced Pancreatic And Ovarian Cancers, Donald Sakellariou-Thompson

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

The success of checkpoint blockade immunotherapy (CBI) has reinvigorated the cancer therapy field, particularly for advanced melanoma which has doubled the survival rates compared to 20 years ago. However, there are many solid tumor types that are yet to receive substantial benefit from this groundbreaking therapy, two of which are pancreatic cancer (PDAC) and ovarian cancer (OvCa). As such, the 5-year survival rate for PDAC and OvCa stand at 9% and 28% respectively. Despite the lack of efficacy of CBI so far, there is still evidence for the role of immune control in these cancers as evidenced by presence of ...


Performance Of Abbott Architect, Ortho Vitros, And Euroimmun Assays In Detecting Prior Sars-Cov-2 Infection, Shiwani Mahajan, Carrie A. Redlich, Adam V. Wisnewski, Louis E. Fazen, Lokinendi V. Rao, Karthik Kuppusamy, Albert I. Ko, Harlan M. Krumholz 2020 Yale University

Performance Of Abbott Architect, Ortho Vitros, And Euroimmun Assays In Detecting Prior Sars-Cov-2 Infection, Shiwani Mahajan, Carrie A. Redlich, Adam V. Wisnewski, Louis E. Fazen, Lokinendi V. Rao, Karthik Kuppusamy, Albert I. Ko, Harlan M. Krumholz

University of Massachusetts Medical School Faculty Publications

Background: Several serological assays have been developed to detect anti-SARS-CoV-2 IgG antibodies, but evidence about their comparative performance is limited. We sought to assess the sensitivity of four anti-SARS-CoV-2 IgG enzyme-linked immunosorbent assays (ELISA) in individuals with evidence of prior SARS-CoV-2 infection.

Methods: We obtained sera from 36 individuals with PCR-confirmed SARS-CoV-2 infection between March and May 2020. We evaluated samples collected at around 21 days (±14 days) after their initial PCR test using 3 commercially available ELISA assays, two anti-spike (Ortho-Clinical Diagnostics Vitros, and Euroimmun) and one anti-nucleocapsid (Abbott Architect), and a Yale-developed anti-spike ELISA test. We determined the ...


Mycobacterium Tuberculosis Evasion Of Guanylate Binding Protein-Mediated Host Defense In Mice Requires The Esx1 Secretion System, Andrew J. Olive, Clare M. Smith, Christina E. Baer, Jörn Coers, Christopher M. Sassetti 2020 Michigan State University

Mycobacterium Tuberculosis Evasion Of Guanylate Binding Protein-Mediated Host Defense In Mice Requires The Esx1 Secretion System, Andrew J. Olive, Clare M. Smith, Christina E. Baer, Jörn Coers, Christopher M. Sassetti

University of Massachusetts Medical School Faculty Publications

Cell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis (Mtb) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent inducer of cell-autonomous immunity is the lymphocyte-derived cytokine IFNγ. While the production of IFNγ by T cells is essential to protect against Mtb, it is not capable of fully eradicating Mtb infection. This suggests that Mtb evades a subset of IFNγ-mediated antimicrobial responses, yet what mechanisms Mtb resists remains unclear. The IFNγ-inducible Guanylate binding proteins (GBPs) are key host defense proteins able to control infections with intracellular pathogens. GBPs were previously shown ...


Infectious Disease Outbreaks Among Forcibly Displaced Persons: An Analysis Of Promed Reports 1996-2016, Angel N. Desai, John W. Ramatowski, Nina Marano, Lawrence C. Madoff, Britta Lassmann 2020 International Society for Infectious Diseases

Infectious Disease Outbreaks Among Forcibly Displaced Persons: An Analysis Of Promed Reports 1996-2016, Angel N. Desai, John W. Ramatowski, Nina Marano, Lawrence C. Madoff, Britta Lassmann

Open Access Articles

Background: The United Nations Refugee Agency (UNHCR) estimates the number of forcibly displaced people increased from 22.7 million people in 1996 to 67.7 million people in 2016. Human mobility is associated with the introduction of infectious disease pathogens. The aim of this study was to describe the range of pathogens in forcibly displaced populations over time using an informal event monitoring system.

Methods: We conducted a retrospective analysis of ProMED, a digital disease monitoring system, to identify reports of outbreak events involving forcibly displaced populations between 1996 and 2016. Number of outbreak events per year was tabulated. Each ...


Host Immunity And The Colon Microbiota Of Mice Infected With Citrobacter Rodentium Are Beneficially Modulated By Lipid-Soluble Extract From Late-Cutting Alfalfa In The Early Stages Of Infection, Krysten Fries-Craft, Justin M. Anast, Stephan Schmitz-Esser, Elizabeth A. Bobeck 2020 Iowa State University

Host Immunity And The Colon Microbiota Of Mice Infected With Citrobacter Rodentium Are Beneficially Modulated By Lipid-Soluble Extract From Late-Cutting Alfalfa In The Early Stages Of Infection, Krysten Fries-Craft, Justin M. Anast, Stephan Schmitz-Esser, Elizabeth A. Bobeck

Animal Science Publications

Alfalfa is a forage legume commonly associated with ruminant livestock production that may be a potential source of health-promoting phytochemicals. Anecdotal evidence from producers suggests that later cuttings of alfalfa may be more beneficial to non-ruminants; however, published literature varies greatly in measured outcomes, supplement form, and cutting. The objective of this study was to measure body weight, average daily feed intake, host immunity, and the colon microbiota composition in mice fed hay, aqueous, and chloroform extracts of early (1st) and late (5th) cutting alfalfa before and after challenge with Citrobacter rodentium. Prior to inoculation, alfalfa supplementation did not have ...


Convalescent Plasma Therapy In Coronavirus Disease 2019 (Covid-19) Patients: A Brief Review, Muhammad Arif Khan, Ikram Ullah 2020 The University of Haripur

Convalescent Plasma Therapy In Coronavirus Disease 2019 (Covid-19) Patients: A Brief Review, Muhammad Arif Khan, Ikram Ullah

The University of Louisville Journal of Respiratory Infections

The recent outbreak of the COVID-19 pandemic has reevaluated effectiveness of the convalescent plasma therapy (CPT). This review was carried out to assess the usefulness of CPT in critically COVID-19 patients, based on the published data to date. To the best of our knowledge, this is the second review of the usefulness of CPT in COVID-19 patients. PubMed, Google Scholar, Medline and EMBASE databases were searched for the relevant reports up to June 21, 2020. All the records of the published data were analyzed according to eligibility criteria protocols. Five different studies on CPT for COVID-19 critically ill patients were ...


Sexual Dimorphism In Host Innate Response To Staphylococcus Aureus: Mechanisms Driving Sex Differences In Immune Cell Function And Host-Directed Interventions, Srijana Pokhrel 2020 University of New Mexico

Sexual Dimorphism In Host Innate Response To Staphylococcus Aureus: Mechanisms Driving Sex Differences In Immune Cell Function And Host-Directed Interventions, Srijana Pokhrel

Biomedical Sciences ETDs

With the emerging antibiotic resistance, Staphylococcus aureus, primary causative agent of skin and soft tissue infections (SSTIs) as well as other life-threatening conditions has become a global health concern. While factors contributing to host defense against S. aureus SSTIs has been well studied, impact of sex as a variable has not been reported. In Chapter 2, we uncover the sex-specific differences in host response to S. aureus SSTIs and the contribution of female sex hormone, estrogen (E2) in providing protection in females. In Chapter 3, we identify mechanisms of innate differences in neutrophils bactericidal efficacy between sexes and in Chapter ...


Modeling Type 1 Diabetes In Vitro Using Human Pluripotent Stem Cells, Nayara C. Leite, Elad Sintov, Torsten B. Meissner, Michael A. Brehm, Dale L. Greiner, David M. Harlan, Douglas A. Melton 2020 Harvard University

Modeling Type 1 Diabetes In Vitro Using Human Pluripotent Stem Cells, Nayara C. Leite, Elad Sintov, Torsten B. Meissner, Michael A. Brehm, Dale L. Greiner, David M. Harlan, Douglas A. Melton

Open Access Articles

Understanding the root causes of autoimmune diseases is hampered by the inability to access relevant human tissues and identify the time of disease onset. To examine the interaction of immune cells and their cellular targets in type 1 diabetes, we differentiated human induced pluripotent stem cells into pancreatic endocrine cells, including beta cells. Here, we describe an in vitro platform that models features of human type 1 diabetes using stress-induced patient-derived endocrine cells and autologous immune cells. We demonstrate a cell-type-specific response by autologous immune cells against induced pluripotent stem cell-derived beta cells, along with a reduced effect on alpha ...


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