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Efficacy Of A Respiratory Syncytial Virus Vaccine Candidate In A Maternal Immunization Model, Jorge C. G. Blanco, Lioubov M. Pletneva, Lori McGinnes Cullen, Raymonde O. Otoa, Mira C. Patel, Lurds R. Fernando, Marina S. Boukhvalova, Trudy G. Morrison 2018 Sigmovir Biosystems Inc.

Efficacy Of A Respiratory Syncytial Virus Vaccine Candidate In A Maternal Immunization Model, Jorge C. G. Blanco, Lioubov M. Pletneva, Lori Mcginnes Cullen, Raymonde O. Otoa, Mira C. Patel, Lurds R. Fernando, Marina S. Boukhvalova, Trudy G. Morrison

Open Access Articles

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Maternal immunization is an option to increase maternal antibody levels and protect infants from infection. Here we assess the efficacy of virus-like particle (VLP) vaccine candidates containing stabilized pre-fusion (pre-F) or post-fusion (post-F) conformations of the RSV F protein and the attachment RSV G protein in a maternal immunization model using cotton rats. VLP vaccines containing RSV F and G proteins strongly boost pre-existing RSV immunity in dams preventing their perinatal drop in immunity. Boosting is stronger for the pre-F VLP than for the post-F VLP or ...


Ebola: Africa, James Goodwin 2018 Augustana College, Rock Island Illinois

Ebola: Africa, James Goodwin

Global Issues in Public Health

In this paper, I talk about the Ebola Hemorrhagic Fever. Ebola is a rare virus that spreads through the immune system and can be fatal. Ebola is a pathogen from Africa, specifically West Africa. There has been almost 32,000 cases since 1976. Symptoms include, Fever, Headache, Muscle pain, Fatigue, Diarrhea, Vomiting, Stomach pain, and Bleeding/Bruising. Transmission happens during close or direct contact. World Health Organization has been making efforts to handle outbreaks such as the outbreak in 2014. World Health Organization mobilized and set up relief efforts. Education is a key idea for my thoughts on how we ...


Conservation And Divergence In Modules Of The Transcriptional Programs Of The Human And Mouse Immune Systems, Tal Shay, Vladimir Jojic, Broad Institute of MIT and Harvard, Harvard Medical School, Stanford University, ImmGen Consortium, Kavitha Narayan, Katelyn E. Sylvia, Joonso Kang 2018 Broad Institute of MIT and Harvard

Conservation And Divergence In Modules Of The Transcriptional Programs Of The Human And Mouse Immune Systems, Tal Shay, Vladimir Jojic, Broad Institute Of Mit And Harvard, Harvard Medical School, Stanford University, Immgen Consortium, Kavitha Narayan, Katelyn E. Sylvia, Joonso Kang

University of Massachusetts Medical School Faculty Publications

Studies in mouse have shed important light on human hematopoietic differentiation and disease. However, substantial differences between the two species often limit the translation of findings from mouse to human. Here, we compare modules of co-expressed genes in human and mouse immune cells based on compendia of genome-wide profiles. We show that the overall modular organization of the transcriptional program is conserved. We highlight modules of co-expressed genes in one species that dissolve or split in the other species. Many of the associated regulatory mechanisms - as reflected by computationally inferred trans regulators, or enriched cis-regulatory elements - are conserved between the ...


The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha 2018 University of Connecticut

The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha

Honors Scholar Theses

Immunotherapy as a form of cancer treatment has become increasingly popular in the past few decades. Researchers have worked to figure out how to best use the body’s natural defense mechanism, the immune system, to fight off and destroy cancer cells. In particular, the goal has been to manipulate checkpoint blockades such as CTLA-4 and PD-1 in order to take the breaks off of the immune system, allowing for a prolonged immune response to the cancer. This work has led to the development of human versions of anti-CTLA4 antibodies (ipilimumab, tremelimumab) and anti-PD1 antibodies (pembrolizumab and Nivolumab) that are ...


Micro Rnas From Dna Viruses Are Found Widely In Plasma In A Large Observational Human Population, Milka Koupenova-Zamor, Eric O. Mick, Heather A. Corkrey, Tianxiao Huan, Lauren Clancy, Ravi Shah, Emelia J. Benjamin, Daniel Levy, Evelyn A. Kurt-Jones, Kahraman Tanriverdi, Jane E. Freedman 2018 University of Massachusetts Medical School

Micro Rnas From Dna Viruses Are Found Widely In Plasma In A Large Observational Human Population, Milka Koupenova-Zamor, Eric O. Mick, Heather A. Corkrey, Tianxiao Huan, Lauren Clancy, Ravi Shah, Emelia J. Benjamin, Daniel Levy, Evelyn A. Kurt-Jones, Kahraman Tanriverdi, Jane E. Freedman

Open Access Articles

Viral infections associate with disease risk and select families of viruses encode miRNAs that control an efficient viral cycle. The association of viral miRNA expression with disease in a large human population has not been previously explored. We sequenced plasma RNA from 40 participants of the Framingham Heart Study (FHS, Offspring Cohort, Visit 8) and identified 3 viral miRNAs from 3 different human Herpesviridae. These miRNAs were mostly related to viral latency and have not been previously detected in human plasma. Viral miRNA expression was then screened in the plasma of 2763 participants of the remaining cohort utilizing high-throughput RT-qPCR ...


Exploiting Glycan Topography For Computational Design Of Env Glycoprotein Antigenicity, Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, Galit Alter 2018 Massachusetts Institute of Technology

Exploiting Glycan Topography For Computational Design Of Env Glycoprotein Antigenicity, Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, Galit Alter

Open Access Articles

Mounting evidence suggests that glycans, rather than merely serving as a "shield", contribute critically to antigenicity of the HIV envelope (Env) glycoprotein, representing critical antigenic determinants for many broadly neutralizing antibodies (bNAbs). While many studies have focused on defining the role of individual glycans or groups of proximal glycans in bNAb binding, little is known about the effects of changes in the overall glycan landscape in modulating antibody access and Env antigenicity. Here we developed a systems glycobiology approach to reverse engineer the complexity of HIV glycan heterogeneity to guide antigenicity-based de novo glycoprotein design. bNAb binding was assessed against ...


Immunodeficient R2g2 Mouse Strain Yields Spleens With Unusual Cytoarchitecture And Sympathetic Innervation, Nicholas Mason Britt, Madeleine Kate Miller, Donald B. Hoover Ph.D., John B. Schweitzer M.D. 2018 East Tennessee State University

Immunodeficient R2g2 Mouse Strain Yields Spleens With Unusual Cytoarchitecture And Sympathetic Innervation, Nicholas Mason Britt, Madeleine Kate Miller, Donald B. Hoover Ph.D., John B. Schweitzer M.D.

Appalachian Student Research Forum

The nervous system and immune system contact one another through two-way communication in order to establish and preserve homeostasis. The sympathetic neurotransmitter norepinephrine has an impact on how the immune system responds by affecting regional blood flow and activation of adrenergic receptors on leukocytes. Former studies showed that immune cells are capable of releasing nerve growth factor allowing for the establishment and continuation of sympathetic nerves in targeted tissues. From this gathered information, it was hypothesized that sympathetic nerves would prove to be less frequent in spleens from the immunodeficient R2G2 mouse strain (Envigo) when compared to 129P3/J (129 ...


Primate Immunodeficiency Virus Vpx And Vpr Counteract Transcriptional Repression Of Proviruses By The Hush Complex, Leonid Yurkovetskiy, Mehmet Hakan Guney, Kyusik Kim, Shih Lin Goh, Sean M. McCauley, Ann Dauphin, William E. Diehl, Jeremy Luban 2018 University of Massachusetts Medical School

Primate Immunodeficiency Virus Vpx And Vpr Counteract Transcriptional Repression Of Proviruses By The Hush Complex, Leonid Yurkovetskiy, Mehmet Hakan Guney, Kyusik Kim, Shih Lin Goh, Sean M. Mccauley, Ann Dauphin, William E. Diehl, Jeremy Luban

University of Massachusetts Medical School Faculty Publications

Drugs that inhibit HIV-1 replication and prevent progression to AIDS do not eliminate HIV-1 proviruses from the chromosomes of long-lived CD4+ memory T cells. To escape eradication by these antiviral drugs, or by the host immune system, HIV-1 exploits poorly defined host factors that silence provirus transcription. These same factors, though, must be overcome by all retroviruses, including HIV-1 and other primate immunodeficiency viruses, in order to activate provirus transcription and produce new virus. Here we show that Vpx and Vpr, proteins from a wide range of primate immunodeficiency viruses, activate provirus transcription in human CD4+ T cells. Provirus activation ...


Application Of Area Scaling Analysis To Identify Natural Killer Cell And Monocyte Involvement In The Grantoxilux Antibody Dependent Cell-Mediated Cytotoxicity Assay, Justin Pollara, Chiara Orlandi, Charles Beck, R Whitney Edwards, Yi Hu, Shuying Liu, Shixia Wang, Richard A. Koup, Thomas N. Denny, Shan Lu, Georgia D. Tomaras, Anthony DeVico, George K. Lewis, Guido Ferrari 2018 Duke University

Application Of Area Scaling Analysis To Identify Natural Killer Cell And Monocyte Involvement In The Grantoxilux Antibody Dependent Cell-Mediated Cytotoxicity Assay, Justin Pollara, Chiara Orlandi, Charles Beck, R Whitney Edwards, Yi Hu, Shuying Liu, Shixia Wang, Richard A. Koup, Thomas N. Denny, Shan Lu, Georgia D. Tomaras, Anthony Devico, George K. Lewis, Guido Ferrari

Open Access Articles

Several different assay methodologies have been described for the evaluation of HIV or SIV-specific antibody-dependent cell-mediated cytotoxicity (ADCC). Commonly used assays measure ADCC by evaluating effector cell functions, or by detecting elimination of target cells. Signaling through Fc receptors, cellular activation, cytotoxic granule exocytosis, or accumulation of cytolytic and immune signaling factors have been used to evaluate ADCC at the level of the effector cells. Alternatively, assays that measure killing or loss of target cells provide a direct assessment of the specific killing activity of antibodies capable of ADCC. Thus, each of these two distinct types of assays provides information ...


Autologous/Allogeneic Hematopoietic Cell Transplantation Versus Tandem Autologous Transplantation For Multiple Myeloma: Comparison Of Long-Term Postrelapse Survival, Myo Htut, Muthalagu Ramanathan, Parameswaran Hari 2018 City of Hope Medical Center

Autologous/Allogeneic Hematopoietic Cell Transplantation Versus Tandem Autologous Transplantation For Multiple Myeloma: Comparison Of Long-Term Postrelapse Survival, Myo Htut, Muthalagu Ramanathan, Parameswaran Hari

Open Access Articles

We compared postrelapse overall survival (OS) after autologous/allogeneic (auto/allo) versus tandem autologous (auto/auto) hematopoietic cell transplantation (HCT) in patients with multiple myeloma (MM). Postrelapse survival of patients receiving an auto/auto or auto/allo HCT for MM and prospectively reported to the Center for International Blood and Marrow Transplant Research between 2000 and 2010 were analyzed. Relapse occurred in 404 patients (72.4%) in the auto/auto group and in 178 patients (67.4%) in the auto/allo group after a median follow-up of 8.5 years. Relapse occurred before 6 months after a second HCT in ...


Emergence Of The Erythroid Lineage From Multipotent Hematopoiesis, Betsabeh K. Tusi, Samuel L. Wolock, Caleb Weinreb, Yung Hwang, Daniel Hidalgo, Rapolas Zilionis, Ari Waisman, Jun R. Huh, Allon M. Klein, Merav Socolovsky 2018 University of Massachusetts Medical School

Emergence Of The Erythroid Lineage From Multipotent Hematopoiesis, Betsabeh K. Tusi, Samuel L. Wolock, Caleb Weinreb, Yung Hwang, Daniel Hidalgo, Rapolas Zilionis, Ari Waisman, Jun R. Huh, Allon M. Klein, Merav Socolovsky

University of Massachusetts Medical School Faculty Publications

Red cell formation begins with the hematopoietic stem cell, but the manner by which it gives rise to erythroid progenitors, and their subsequent developmental path, remain unclear. Here we combined single-cell transcriptomics of murine hematopoietic tissues with fate potential assays to infer a continuous yet hierarchical structure for the hematopoietic network. We define the erythroid differentiation trajectory as it emerges from multipotency and diverges from 6 other blood lineages. With the aid of a new flow-cytometric sorting strategy, we validated predicted cell fate potentials at the single cell level, revealing a coupling between erythroid and basophil/mast cell fates. We ...


Biology Of Platelet Purinergic Receptors And Implications For Platelet Heterogeneity, Milka Koupenova-Zamor, Katya Ravid 2018 University of Massachusetts Medical School

Biology Of Platelet Purinergic Receptors And Implications For Platelet Heterogeneity, Milka Koupenova-Zamor, Katya Ravid

Open Access Articles

Platelets are small anucleated cells present only in mammals. Platelets mediate intravascular hemostatic balance, prevent interstitial bleeding, and have a major role in thrombosis. Activation of platelet purinergic receptors is instrumental in initiation of hemostasis and formation of the hemostatic plug, although this activation process becomes problematic in pathological settings of thrombosis. This review briefly outlines the roles and function of currently known platelet purinergic receptors (P1 and P2) in the setting of hemostasis and thrombosis. Additionally, we discuss recent novel studies on purinergic receptor distribution according to heterogeneous platelet size, and the possible implication of this distribution on hemostatic ...


Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack 2018 CUNY City College

Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack

Master's Theses

Thymic epithelial cells (TEC) are essential for a proper adaptive immune response by regulating thymocyte development and establishing central tolerance. In the thymus, TECs differentially express Wnt proteins, which activate canonical and non-canonical Wnt signaling pathways. Wnt signaling is thought to regulate cell survival, proliferation, and development although the direct molecular mechanisms in TECs have yet to be elucidated. The inducible inhibition of canonical Wnt signaling with Dkk1 leads to a rapid loss of TEC progenitors as well as a decline in mature Aire-expressing mTECs. Therefore, we explore the role of Wnt ligands potentially responsible for stimulating and/or regulating ...


Dermatologist And Patient Preferences In Choosing Treatments For Moderate To Severe Psoriasis, Matthew Alcusky, Seina Lee, Gordon Lau, Gretchen R. Chiu, Nandini Hadker, Aparna Deshpande, Stephen Fleming, Nicola Vance, Steve Fakharzadeh 2017 University of Massachusetts Medical School

Dermatologist And Patient Preferences In Choosing Treatments For Moderate To Severe Psoriasis, Matthew Alcusky, Seina Lee, Gordon Lau, Gretchen R. Chiu, Nandini Hadker, Aparna Deshpande, Stephen Fleming, Nicola Vance, Steve Fakharzadeh

Open Access Articles

INTRODUCTION: The objective of the study was to determine the relative importance (RI) of treatment attributes psoriasis patients and physicians consider when choosing between biologic therapies based on psoriasis severity.

METHODS: A discrete choice experiment (DCE) weighting preference for eight sets of hypothetical treatments for moderate or severe psoriasis was conducted. DCE hypothetical treatments were defined and varied on combinations of efficacy, safety, and dosing attributes [frequency/setting/route of administration (ROA)].

RESULTS: When assuming moderate psoriasis in the patient DCE, ROA (RI 29%) and efficacy (RI 27%) drive treatment choices. When assuming severe disease in the DCE, patients preferred ...


Improving Type And Screen Specimen Collection Prior To Elective Surgery, NorDx Blood Bank Staff, Haley Pelletier, Suneela Nayak, Stephen Tyzik, Ruth Hanselman 2017 Maine Medical Center

Improving Type And Screen Specimen Collection Prior To Elective Surgery, Nordx Blood Bank Staff, Haley Pelletier, Suneela Nayak, Stephen Tyzik, Ruth Hanselman

Maine Medical Center

To avoid delays in the availability of compatible blood for elective surgery patients requiring transfusion, a type and screen specimen should be completed at least 24 hours prior to surgery. Baseline metrics in an acute care inpatient blood bank demonstrated a significant number of cases with no type or screen completed.

The objective of this KPI was to prevent any delays in providing compatible blood products to scheduled surgical patients. Several internal and external system issues were identified as a result of a root cause analysis and a number of actions were initiated.

Outcomes have been positive. Data collection post ...


Stromal Cell Subsets Directing Neonatal Spleen Regeneration, Jonathan K H Tan, Takeshi Watanabe 2017 Bond University

Stromal Cell Subsets Directing Neonatal Spleen Regeneration, Jonathan K H Tan, Takeshi Watanabe

Faculty of Health Sciences & Medicine Publications

Development of lymphoid tissue is determined by interactions between stromal lymphoid tissue organiser (LTo) and hematopoietic lymphoid tissue inducer (LTi) cells. A failure for LTo to receive appropriate activating signals during embryogenesis through lymphotoxin engagement leads to a complete cessation of lymph node (LN) and Peyer's patch development, identifying LTo as a key stromal population for lymphoid tissue organogenesis. However, little is known about the equivalent stromal cells that induce spleen development. Here, by dissociating neonatal murine spleen stromal tissue for re-aggregation and transplant into adult mouse recipients, we have identified a MAdCAM-1(+)CD31(+)CD201(+) spleen stromal organizer cell-type ...


Namibia : Hiv As A National Issue, Elisabeth Vlasak 2017 Augustana College, Rock Island Illinois

Namibia : Hiv As A National Issue, Elisabeth Vlasak

Global Public Health

Namibia is located on the southwestern coast of Africa, bordering Angola, Botswana, Zambia, South Africa, and the Atlantic Ocean. Namibia has a population of 2,265,000, as of 2016. Namibia has many challenges, including food insecurity and malnutrition, access to health services, unequal distribution of wealth, but HIV/AIDS is one of the country’s leading challenges. It is estimated that the overall adult infection rate of HIV/AIDS is 15.4% and it is the leading cause of death in Namibia. Adults ages 18-24 are the most at-risk for the disease. Some of the major risk factors are ...


Diverse Human Extracellular Rnas Are Widely Detected In Human Plasma, Jane E. Freedman, Eric Mick, Lea M. Beaulieu, Selim E. Tanriverdi, Milka Koupenova-Zamor, Ekaterina Mikhalev, Kahraman Tanriverdi 2016 University of Massachusetts Medical School

Diverse Human Extracellular Rnas Are Widely Detected In Human Plasma, Jane E. Freedman, Eric Mick, Lea M. Beaulieu, Selim E. Tanriverdi, Milka Koupenova-Zamor, Ekaterina Mikhalev, Kahraman Tanriverdi

Open Access Articles

There is growing appreciation for the importance of non-protein-coding genes in development and disease. Although much is known about microRNAs, limitations in bioinformatic analyses of RNA sequencing have precluded broad assessment of other forms of small-RNAs in humans. By analysing sequencing data from plasma-derived RNA from 40 individuals, here we identified over a thousand human extracellular RNAs including microRNAs, piwi-interacting RNA (piRNA), and small nucleolar RNAs. Using a targeted quantitative PCR with reverse transcription approach in an additional 2,763 individuals, we characterized almost 500 of the most abundant extracellular transcripts including microRNAs, piRNAs and small nucleolar RNAs. The presence ...


Thymic Involution Perturbs Negative Selection And Leads To Chronic Inflammation, Brandon D. Coder B.S. 2015 University of North Texas Health Science Center at Fort Worth

Thymic Involution Perturbs Negative Selection And Leads To Chronic Inflammation, Brandon D. Coder B.S.

Theses and Dissertations

The ubiquitous presence of chronic low-level pro-inflammatory factors in elderly individuals (termed inflammaging) is a significant risk factor for morbidity and mortality. The etiology of inflammaging is largely unknown. Recent evidence has identified the persistent activation of immune cells, thought to arise from latent viral infections, as key contributors towards the development of a chronic inflammatory environment. However, the contribution of autoreactive T cells towards the development of inflammaging has yet to be investigated. Another pervasive feature of the aging process is the age-related involution of the thymus gland, which has been linked with a predisposition toward developing autoimmunity. In ...


Specific Inflammatory Stimuli Lead To Distinct Platelet Responses In Mice And Humans, Lea M. Beaulieu, Lauren Clancy, Kahraman Tanriverdi, Emelia J. Benjamin, Carolyn D. Kramer, Ellen O. Weinberg, Xianbao He, Samrawit Mekasha, Eric O. Mick, Robin R. Ingalls, Caroline A. Genco, Jane E. Freedman 2015 University of Massachusetts Medical School

Specific Inflammatory Stimuli Lead To Distinct Platelet Responses In Mice And Humans, Lea M. Beaulieu, Lauren Clancy, Kahraman Tanriverdi, Emelia J. Benjamin, Carolyn D. Kramer, Ellen O. Weinberg, Xianbao He, Samrawit Mekasha, Eric O. Mick, Robin R. Ingalls, Caroline A. Genco, Jane E. Freedman

Open Access Articles

INTRODUCTION: Diverse and multi-factorial processes contribute to the progression of cardiovascular disease. These processes affect cells involved in the development of this disease in varying ways, ultimately leading to atherothrombosis. The goal of our study was to compare the differential effects of specific stimuli - two bacterial infections and a Western diet - on platelet responses in ApoE-/- mice, specifically examining inflammatory function and gene expression. Results from murine studies were verified using platelets from participants of the Framingham Heart Study (FHS; n = 1819 participants).

METHODS: Blood and spleen samples were collected at weeks 1 and 9 from ApoE-/- mice infected with ...


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