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Immunology and Infectious Disease

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Articles 1 - 30 of 5653

Full-Text Articles in Life Sciences

Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Ejemel Monir, Chelsea A. Rapp, William D. Thomas Jr., Eric J. Sundberg, Zhiping Weng, Yan Wang Jun 2019

Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Ejemel Monir, Chelsea A. Rapp, William D. Thomas Jr., Eric J. Sundberg, Zhiping Weng, Yan Wang

Kurt Piepenbrink

Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as ...


Parasitic Dinoflagellate Hematodinium Perezi Prevalence In Larval And Juvenile Blue Crabs Callinectes Sapidus From Coastal Bays Of Virginia, Hj Small, Jp Huchin-Mian, Ks Reece, Km Pagenkopp Lohan, Mj Butler Iv, Jd Shields Jun 2019

Parasitic Dinoflagellate Hematodinium Perezi Prevalence In Larval And Juvenile Blue Crabs Callinectes Sapidus From Coastal Bays Of Virginia, Hj Small, Jp Huchin-Mian, Ks Reece, Km Pagenkopp Lohan, Mj Butler Iv, Jd Shields

VIMS Articles

The parasitic dinoflagellate Hematodinium perezi infects the American blue crab Callinectes sapidus and other decapods along the Eastern seaboard and Gulf of Mexico coast of the USA. Large juvenile and adult blue crabs experience high mortality during seasonal outbreaks of H. perezi, but less is known about its presence in the early life history stages of this host. We determined the prevalence of H. perezi in megalopae and early benthic juvenile crabs from multiple locations along the Virginia portion of the Delmarva Peninsula. The DNA of H. perezi was not detected in any megalopae collected from several locations within the ...


Regulation Of The Drosophila Imd Pathway By Signaling Amyloids, Anni Kleino, Neal S. Silverman Jun 2019

Regulation Of The Drosophila Imd Pathway By Signaling Amyloids, Anni Kleino, Neal S. Silverman

Neal Silverman

Fruit flies elicit effective defense responses against numerous microbes. The responses against Gram-negative bacteria are mediated by the Imd pathway, an evolutionarily conserved NF-kappaB pathway recognizing meso-diaminopimelic acid (DAP)-type peptidoglycan from bacterial cell walls. Several reviews already provide a detailed view of ligand recognition and signal transduction during Imd signaling, but the formation and regulation of the signaling complex immediately downstream of the peptidoglycan-sensing receptors is still elusive. In this review, we focus on the formation of the Imd amyloidal signaling center and post-translational modifications in the assembly and disassembly of the Imd signaling complex.


Nf-Κb In Biomphalaria Glabrata: A Genetic Fluke?, Paige Stocker May 2019

Nf-Κb In Biomphalaria Glabrata: A Genetic Fluke?, Paige Stocker

Lawrence University Honors Projects

Biomphalaria glabrata is the intermediate host to the disease causing parasitic worm, Schistosoma mansoni. Previous work has identified homologs of NF-κB, a known immune related transcription factor, in B. glabrata and work has also been done to establish putative κB sites. It has also been observed that the p65 homologous subunit has an extended N-terminal region not present in other homologs. The goal of the present study is twofold: investigate DNA binding affinity of two NF-κB subunits, Bg-p65 and Bg-p50, and characterize the nature of the N-terminal extension of Bg-p65. In the current work, it is shown through the use ...


Understanding The Role Of Macrophages In Lung Inflammation Through Mathematical Modeling, Sarah B. Minucci May 2019

Understanding The Role Of Macrophages In Lung Inflammation Through Mathematical Modeling, Sarah B. Minucci

Biology and Medicine Through Mathematics Conference

No abstract provided.


Development Of Enteric Neurons And Muscularis Macrophages, Marina Avetisyan May 2019

Development Of Enteric Neurons And Muscularis Macrophages, Marina Avetisyan

Arts & Sciences Electronic Theses and Dissertations

The enteric nervous system (ENS) is a complex interconnected network of neurons and glia in the bowel wall that regulates intestinal motility, blood flow, and epithelial function. The ENS also controls aspects of inflammatory signaling within the bowel. To perform these tasks, there are at least 20 types of enteric neuron and four types of enteric glia. Although much is known about early events in ENS development, signals governing the development of specific neuronal subtypes and communication with neighboring cell types within the bowel remain poorly understood. One fundamental hypothesis is that diverse trophic factors support distinct neuronal populations in ...


Characterizing The Humoral Response To Flavivirus Infection, Estefania Fernandez May 2019

Characterizing The Humoral Response To Flavivirus Infection, Estefania Fernandez

Arts & Sciences Electronic Theses and Dissertations

Flaviviruses are positive (+) sense, single-stranded RNA viruses of the Flaviviridae family that are transmitted by mosquitoes. For our studies, we focused on Zika virus (ZIKV) and Japanese encephalitis virus (JEV). Most human infections with ZIKV historically resulted in a mild self-limiting febrile illness. However, since 2013, a worldwide spread and increase in ZIKV infections has been observed. Notably, ZIKV has been associated with autoimmune ascending paralysis (Guillain-Barré Syndrome) and ophthalmologic effects in adults and intrauterine growth restriction and microcephaly in developing fetuses. Current vaccine efforts utilize technologies implemented for related flaviviruses (yellow fever virus (YFV), Dengue virus (DENV), and JEV ...


Elucidating The Mechanism Of Action Of Experimental Compound Sw33 In Toxoplasma Gondii, Sean Watson May 2019

Elucidating The Mechanism Of Action Of Experimental Compound Sw33 In Toxoplasma Gondii, Sean Watson

Theses/Capstones/Creative Projects

In recent years, antimicrobial drug resistance has become widespread and thus triggered an ever-growing need for the development of new, efficacious drug treatments. As an antimicrobial drug is developed, its mechanism of action is often identified before it becomes a potential candidate for clinical use. One potential method for identifying mechanism of action is chemical mutagenesis, in which induction of drug-resistant populations is followed by whole-genome sequencing of several clonal isolates. The subsequent observation of identical point mutations in the same gene across multiple drug-resistant populations can indicate a likely molecular target. However, this technique lacks the capacity to facilitate ...


Regulation Of The Drosophila Imd Pathway By Signaling Amyloids, Anni Kleino, Neal S. Silverman May 2019

Regulation Of The Drosophila Imd Pathway By Signaling Amyloids, Anni Kleino, Neal S. Silverman

Open Access Articles

Fruit flies elicit effective defense responses against numerous microbes. The responses against Gram-negative bacteria are mediated by the Imd pathway, an evolutionarily conserved NF-kappaB pathway recognizing meso-diaminopimelic acid (DAP)-type peptidoglycan from bacterial cell walls. Several reviews already provide a detailed view of ligand recognition and signal transduction during Imd signaling, but the formation and regulation of the signaling complex immediately downstream of the peptidoglycan-sensing receptors is still elusive. In this review, we focus on the formation of the Imd amyloidal signaling center and post-translational modifications in the assembly and disassembly of the Imd signaling complex.


Seasonal Changes In Susceptibility To Chytridiomycosis In Columbia Spotted Frogs, Delaney Burrows Apr 2019

Seasonal Changes In Susceptibility To Chytridiomycosis In Columbia Spotted Frogs, Delaney Burrows

Carroll College Student Undergraduate Research Festival

Chytridiomycosis is a potentially deadly skin disease found in amphibian populations all over the world. Chytridiomycosis is caused by the fungus Batrachochytrium dendrobatidis (Bd) that grows on the skin of amphibians. The fungus can cause a disruption in the homeostatic functions of the amphibian skin and can lead to death. The relationship between an amphibian’s antimicrobial skin secretions, cutaneous microbial communities and environmental water quality can affect their resistance and susceptibility to Bd infection. Columbia spotted frogs (Lithobates luteiventris) are native to western Montana and have been affected by chytridiomycosis. Three lakes known to be positive for Bd were ...


Is Ndvi A Predictor Of C. Tarsalis In Eastern Montana, Patrick Oster Apr 2019

Is Ndvi A Predictor Of C. Tarsalis In Eastern Montana, Patrick Oster

Carroll College Student Undergraduate Research Festival

Culex Tarsalis, is a Mosquito species found throughout the Continental United States. With the outbreak of West Nile Virus (WNV) in the United States in the early 90’s, Tarsalis is the largest vector of WNV in Montana Tarsalis is mostly found in the Eastern portion of Montana and in the Mountain Valleys in Western Montana. This is due to a thought that Tarsalis does not like a lot of vegetation, specifically trees. Subsequently, a survey of using current Tarsalis data, and Normalized Difference Vegetation Index (NDVI) should allow a model to be made in Eastern Montana possible With collaboration ...


The Effects Of The Increasing Immunization Schedule On Children In The United States And Its Influence On The Anti-Vaccination Movement, Clara J. Welhouse Apr 2019

The Effects Of The Increasing Immunization Schedule On Children In The United States And Its Influence On The Anti-Vaccination Movement, Clara J. Welhouse

Huskies Showcase

Best Our Husky Compact Reflection for "Integrate Existing and Evolving Technologies".

Abstract

In recent decades, the immunization schedule required for children in the United States has increased significantly because new vaccinations are being formulated. In this research paper I will investigate and explore the possible effects of this increase. My analysis will also focus on the emerging trends of blame that fall to the vaccinations administered to children; these criticisms lead to patterns of noncompliance to mandated immunization schedules. Medicine is constantly changing, this holds true for vaccinations. Currently the Centers for Disease Control and Prevention recommends the administration of ...


A Highly Expressed Intestinal Cysteine Protease Of Ancylostoma Ceylanicum Protects Vaccinated Hamsters From Hookworm Infection, Jason B. Noon, Erich M. Schwarz, Gary R. Ostroff, Raffi V. Aroian Apr 2019

A Highly Expressed Intestinal Cysteine Protease Of Ancylostoma Ceylanicum Protects Vaccinated Hamsters From Hookworm Infection, Jason B. Noon, Erich M. Schwarz, Gary R. Ostroff, Raffi V. Aroian

Open Access Articles

BACKGROUND: Human hookworms (Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum) are intestinal blood-feeding parasites that infect ~500 million people worldwide and are among the leading causes of iron-deficiency anemia in the developing world. Drugs are useful against hookworm infections, but hookworms rapidly reinfect people, and the parasites can develop drug resistance. Therefore, having a hookworm vaccine would be of tremendous benefit.

METHODOLOGY/PRINCIPAL FINDINGS: We investigated the vaccine efficacy in outbred Syrian hamsters of three A. ceylanicum hookworm antigen candidates from two classes of proteins previously identified as promising vaccine candidates. These include two intestinally-enriched, putatively secreted cathepsin B cysteine ...


The Role Of Platelets In Mediating A Response To Human Influenza Infection, Milka Koupenova-Zamor, Heather A. Corkrey, Olga Vitseva, Giorgia Manni, Catherine J. Pang, Lauren Clancy, Chen Yao, Jeffrey J. Rade, Daniel Levy, Jennifer P. Wang, Robert W. Finberg, Evelyn A. Kurt-Jones, Jane E. Freedman Apr 2019

The Role Of Platelets In Mediating A Response To Human Influenza Infection, Milka Koupenova-Zamor, Heather A. Corkrey, Olga Vitseva, Giorgia Manni, Catherine J. Pang, Lauren Clancy, Chen Yao, Jeffrey J. Rade, Daniel Levy, Jennifer P. Wang, Robert W. Finberg, Evelyn A. Kurt-Jones, Jane E. Freedman

Open Access Articles

Influenza infection increases the incidence of myocardial infarction but the reason is unknown. Platelets mediate vascular occlusion through thrombotic functions but are also recognized to have immunomodulatory activity. To determine if platelet processes are activated during influenza infection, we collected blood from 18 patients with acute influenza infection. Microscopy reveals activated platelets, many containing viral particles and extracellular-DNA associated with platelets. To understand the mechanism, we isolate human platelets and treat them with influenza A virus. Viral-engulfment leads to C3 release from platelets as a function of TLR7 and C3 leads to neutrophil-DNA release and aggregation. TLR7 specificity is confirmed ...


Lipoarabinomannan From Mycobacterium Smegmatis Stimulates An Inflammatory Response In Raw 264.7 Murine Macrophages, Aysha Zaman Apr 2019

Lipoarabinomannan From Mycobacterium Smegmatis Stimulates An Inflammatory Response In Raw 264.7 Murine Macrophages, Aysha Zaman

Student Scholar Showcase

Macrophages are a key leukocyte in defense against Mycobacterium tuberculosis infection. The precise mechanism by which M. tuberculosis evades host macrophage defenses remains unknown, so understanding how macrophages interact with cell wall components of mycobacteria is critical. Lipoarabinomannan (LAM) is a glycolipid Toll-like receptor-2 (TLR-2) ligand found on the cell wall of mycobacteria, and is thought to contribute to the cell wall structural integrity. When LAM binds to TLR on host leukocytes, this activates cellular responses and phagocytosis by host macrophages. Nitric oxide production can be used as a measure of inflammatory response and can be evaluated via nitrite response ...


The Validity Of Medicare Claims-Based Codes To Identify Nontuberculous Mycobacterial Infection In Patients With Bronchiectasis, Jennifer Ku Apr 2019

The Validity Of Medicare Claims-Based Codes To Identify Nontuberculous Mycobacterial Infection In Patients With Bronchiectasis, Jennifer Ku

OHSU-PSU School of Public Health Annual Conference

Background: Nontuberculous mycobacteria (NTM) is a disease of increasing incidence, causing permanent airway damage leading to destructive pulmonary disease. Medicare claims-based codes have been used to identify NTM infection and to evaluate trends in diagnosis and disease outcomes. However, claims-based codes to identify NTM infection have not been validated.

Methods: We linked patients with a bronchiectasis diagnosis (ICD-9-CM 494.0 or 494.1) excluding cystic fibrosis from the national 2006-2014 Centers for Medicare and Medicaid (Medicare) data to the U.S. Bronchiectasis Research Registry (BRR). The BRR is a national prospective cohort of patients with bronchiectasis, that collects detailed clinical ...


Or14i1 Is A Receptor For The Human Cytomegalovirus Pentameric Complex And Defines Viral Epithelial Cell Tropism, Xiaofei E, Paul Meraner, Ping Lu, Jill M. Perreira, Aaron M. Aker, William M. Mcdougall, Ronghua Zhuge, Gary C. Chan, Rachel M. Gerstein, Patrizia Caposio, Andrew D. Yurochko, Abraham L. Brass, Timothy F. Kowalik Apr 2019

Or14i1 Is A Receptor For The Human Cytomegalovirus Pentameric Complex And Defines Viral Epithelial Cell Tropism, Xiaofei E, Paul Meraner, Ping Lu, Jill M. Perreira, Aaron M. Aker, William M. Mcdougall, Ronghua Zhuge, Gary C. Chan, Rachel M. Gerstein, Patrizia Caposio, Andrew D. Yurochko, Abraham L. Brass, Timothy F. Kowalik

Open Access Articles

A human cytomegalovirus (HCMV) pentameric glycoprotein complex (PC), gH-gL-UL128-UL130-UL131A, is necessary for viral infection of clinically relevant cell types, including epithelial cells, which are important for interhost transmission and disease. We performed genome-wide CRISPR/Cas9 screens of different cell types in parallel to identify host genes specifically required for HCMV infection of epithelial cells. This effort identified a multipass membrane protein, OR14I1, as a receptor for HCMV infection. This olfactory receptor family member is required for HCMV attachment, entry, and infection of epithelial cells and is dependent on the presence of viral PC. OR14I1 is required for AKT activation and ...


The Life Of An Unknown Assassin: Leon Czolgosz And The Death Of William Mckinley, Cary Federman Apr 2019

The Life Of An Unknown Assassin: Leon Czolgosz And The Death Of William Mckinley, Cary Federman

Cary Federman

The purpose of this essay is to examine the discourses that surrounded the life of Leon Czolgosz, the assassin of President William McKinley. The gaps in Czolgosz’s life, his peculiar silences, his poor health and the ambiguity and thinness of his confession, rather than taken as instances of mental and physical distress, have, instead, been understood as signs of a revolutionary anarchistic assassin. Czolgosz is an expression of a cultural tradition in somatic form. I argue that the discursive construction of criminality, already present in the late nineteenth century within the medical and human sciences, is what shaped Czolgosz ...


The Ecological Niche Of Echinococcus Multilocularis In North America: Understanding Biotic And Abiotic Determinants Of Parasite Distribution With New Records In New Mexico And Maryland, United States, Sebastian Botero-Cañola, Altangerel Tsogtsaikhan Dursahinhan, Sara E. Rácz, Parker V. Lowe, John E. Ubelaker, Scott Lyell Gardner Apr 2019

The Ecological Niche Of Echinococcus Multilocularis In North America: Understanding Biotic And Abiotic Determinants Of Parasite Distribution With New Records In New Mexico And Maryland, United States, Sebastian Botero-Cañola, Altangerel Tsogtsaikhan Dursahinhan, Sara E. Rácz, Parker V. Lowe, John E. Ubelaker, Scott Lyell Gardner

Scott Gardner Publications & Papers

English: Understanding the factors shaping the niche of parasites and its expression over geographical space and through time continues to be a modern scientific challenge with the results of research in this area directly influencing both theoretical and applied biology. This is especially important for proactive management of zoonotic parasites such as Echinococcus multilocularis, the etiologic agent of alveolar echinococcosis. Echinococcus multilocularis has a Holarctic distribution; with its geographic range and prevalence increasing recently in areas of the western Palearctic, while its distribution dynamics are poorly understood in the Nearctic. In this paper, we use an ecological niche modeling (ENM ...


Constitutive Interferon Signaling Maintains Critical Threshold Of Mlkl Expression To License Necroptosis, Joseph Sarhan, Beiyun C. Liu, Hayley I. Muendlein, Chi G. Weindel, Irina Smirnova, Amy Y. Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A. Fitzgerald, Alexander Poltorak Mar 2019

Constitutive Interferon Signaling Maintains Critical Threshold Of Mlkl Expression To License Necroptosis, Joseph Sarhan, Beiyun C. Liu, Hayley I. Muendlein, Chi G. Weindel, Irina Smirnova, Amy Y. Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A. Fitzgerald, Alexander Poltorak

Katherine A. Fitzgerald

Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein. We found that the pre-established IFN status of the cell, instead of LPS-induced IFN, is critical for the early initiation of necroptosis in macrophages. This pre-established IFN signature stems from cytosolic DNA sensing via cGAS ...


Impact Of Intrinsic Physiological Factors In The Population Recovery Of Myotis Lucifugus (Little Brown Myotis) From White-Nose Syndrome, Caroline Burke, Caitlin Looney, Alissah Sillah, Christopher Richardson Mar 2019

Impact Of Intrinsic Physiological Factors In The Population Recovery Of Myotis Lucifugus (Little Brown Myotis) From White-Nose Syndrome, Caroline Burke, Caitlin Looney, Alissah Sillah, Christopher Richardson

Lesley University Community of Scholars Day

White-nose Syndrome (WNS) has decimated populations of hibernating bats in the US. In particular, Myotis lucifugus (little brown myotis) has been one of the most affected. We investigated the energetic cost of innate immune response and Pseudogymnoascus destructans (Pd) fungal activity on post-hibernating little brown myotis and the link with the recovery of local populations in New England from WNS. We captured bats at one of each of 4 colonies in Eastern Massachusetts and Southern New Hampshire, consecutively, every 14 days to minimize disturbance to the colony. Blood samples were collected from each bat. Respirometry trials were performed on each ...


Streptolysin O Induces The Ubiquitination And Degradation Of Pro-Il-1beta, Dora Hancz, Elsa Westerlund, Christine Valfridsson, Getachew Melkamu Aemero, Benedicte Bastiat-Sempe, M. Pontus A. Orning, Egil Lien, Michael R. Wessels, Jenny J. Persson Mar 2019

Streptolysin O Induces The Ubiquitination And Degradation Of Pro-Il-1beta, Dora Hancz, Elsa Westerlund, Christine Valfridsson, Getachew Melkamu Aemero, Benedicte Bastiat-Sempe, M. Pontus A. Orning, Egil Lien, Michael R. Wessels, Jenny J. Persson

Open Access Articles

Group A Streptococcus (GAS) is a common and versatile human pathogen causing a variety of diseases. One of the many virulence factors of GAS is the secreted pore-forming cytotoxin streptolysin O (SLO), which has been ascribed multiple properties, including inflammasome activation leading to release of the potent inflammatory cytokine IL-1beta from infected macrophages. IL-1beta is synthesized as an inactive pro-form, which is activated intracellularly through proteolytic cleavage. Here, we use a macrophage infection model to show that SLO specifically induces ubiquitination and degradation of pro-IL-1beta. Ubiquitination was dependent on SLO being released from the infecting bacterium, and pore formation by ...


The Tlr4 Adaptor Tram Controls The Phagocytosis Of Gram-Negative Bacteria By Interacting With The Rab11-Family Interacting Protein 2, Astrid Skjesol, Douglas T. Golenbock, Harald Husebye Mar 2019

The Tlr4 Adaptor Tram Controls The Phagocytosis Of Gram-Negative Bacteria By Interacting With The Rab11-Family Interacting Protein 2, Astrid Skjesol, Douglas T. Golenbock, Harald Husebye

Open Access Articles

Phagocytosis is a complex process that eliminates microbes and is performed by specialised cells such as macrophages. Toll-like receptor 4 (TLR4) is expressed on the surface of macrophages and recognizes Gram-negative bacteria. Moreover, TLR4 has been suggested to play a role in the phagocytosis of Gram-negative bacteria, but the mechanisms remain unclear. Here we have used primary human macrophages and engineered THP-1 monocytes to show that the TLR4 sorting adapter, TRAM, is instrumental for phagocytosis of Escherichia coli as well as Staphylococcus aureus. We find that TRAM forms a complex with Rab11 family interacting protein 2 (FIP2) that is recruited ...


The Immune Checkpoint Molecules Pd-1, Pd-L1, Tim-3 And Lag-3 In Diffuse Large B-Cell Lymphoma, Benjamin J. Chen, Ravi Dashnamoorthy, Pallavi Galera, Vladislav Makarenko, Hong Chang, Srimoyee Ghosh, Andrew M. Evens Mar 2019

The Immune Checkpoint Molecules Pd-1, Pd-L1, Tim-3 And Lag-3 In Diffuse Large B-Cell Lymphoma, Benjamin J. Chen, Ravi Dashnamoorthy, Pallavi Galera, Vladislav Makarenko, Hong Chang, Srimoyee Ghosh, Andrew M. Evens

Open Access Articles

Signaling through immune checkpoint receptors may lead to T-cell exhaustion and function as immune escape mechanisms in cancer. For diffuse large B-cell lymphoma (DLBCL), the mechanistic and prognostic importance of these markers on tumor cells and the tumor microenvironment remains unclear. We determined the immunohistochemical expression of PD-1, PD-L1, TIM-3, and LAG-3 on tumor cells and on tumor infiltrating lymphocytes (TILs) among 123 DLBCL patients. TIM-3 showed positive staining on tumor cells in 39% of DLBCL cases and PD-L1 expression was noted in 15% of cases. Both PD-1 and LAG-3 were positive on tumor cells in a minority of DLBCL ...


Genome-Wide Prediction Of Synthetic Rescue Mediators Of Resistance To Targeted And Immunotherapy, Avinash Das Sahu, Olga Ponomarova, Eytan Ruppin Mar 2019

Genome-Wide Prediction Of Synthetic Rescue Mediators Of Resistance To Targeted And Immunotherapy, Avinash Das Sahu, Olga Ponomarova, Eytan Ruppin

Open Access Articles

Most patients with advanced cancer eventually acquire resistance to targeted therapies, spurring extensive efforts to identify molecular events mediating therapy resistance. Many of these events involve synthetic rescue (SR) interactions, where the reduction in cancer cell viability caused by targeted gene inactivation is rescued by an adaptive alteration of another gene (the rescuer). Here, we perform a genome-wide in silico prediction of SR rescuer genes by analyzing tumor transcriptomics and survival data of 10,000 TCGA cancer patients. Predicted SR interactions are validated in new experimental screens. We show that SR interactions can successfully predict cancer patients' response and emerging ...


Anti-Drug Antibody Responses Impair Prophylaxis Mediated By Aav-Delivered Hiv-1 Broadly Neutralizing Antibodies, Matthew R. Gardner, Ina Fetzer, Lisa M. Kattenhorn, Meredith E. Davis-Gardner, Amber S. Zhou, Barnett Alfant, Jesse A. Weber, Hema R. Kondur, Jose M. Martinez-Navio, Sebastian P. Fuchs, Ronald C. Desrosiers, Guangping Gao, Jeffrey D. Lifson, Michael Farzan Mar 2019

Anti-Drug Antibody Responses Impair Prophylaxis Mediated By Aav-Delivered Hiv-1 Broadly Neutralizing Antibodies, Matthew R. Gardner, Ina Fetzer, Lisa M. Kattenhorn, Meredith E. Davis-Gardner, Amber S. Zhou, Barnett Alfant, Jesse A. Weber, Hema R. Kondur, Jose M. Martinez-Navio, Sebastian P. Fuchs, Ronald C. Desrosiers, Guangping Gao, Jeffrey D. Lifson, Michael Farzan

Open Access Articles

Adeno-associated virus (AAV) delivery of potent and broadly neutralizing antibodies (bNAbs is a promising approach for the prevention of HIV-1 infection. The immunoglobulin G (IgG)1 subtype is usually selected for this application, because it efficiently mediates antibody effector functions and has a somewhat longer half-life. However, the use of IgG1-Fc has been associated with the generation of anti-drug antibodies (ADAs) that correlate with loss of antibody expression. In contrast, we have shown that expression of the antibody-like molecule eCD4-Ig bearing a rhesus IgG2-Fc domain showed reduced immunogenicity and completely protected rhesus macaques from simian-HIV (SHIV)-AD8 challenges. To directly ...


Targeted Therapy For The Future: The Use Of Novel Antimicrobial Peptides Against P. Aeurginosa, Matthew Froid Mar 2019

Targeted Therapy For The Future: The Use Of Novel Antimicrobial Peptides Against P. Aeurginosa, Matthew Froid

Student Research and Creative Activity Fair

Pathogenic bacteria, such as the gram-negative bacterium Pseudomonas aeruginosa, are becoming resistant to our current arsenal of antibiotics at an alarming rate. P. aeruginosa is a leading cause of nosocomial acquired infections and is a primary co-morbidity in patients with compromised immune systems. One potential source of new antibiotic agents is antimicrobial peptides. Antimicrobial peptides (AMPs) are small proteins, and some have shown a high degree of efficacy and broad-spectrum activity against both Gram-positive and Gram-negative bacteria. An experimental AMP that has been developed by Dr. Wang at UNMC, DASamp2, has shown to be effective against virulent bacteria, including P ...


Large Scale Dynamical Model Of Macrophage/Hiv Interactions, Matthew M. Froid Mar 2019

Large Scale Dynamical Model Of Macrophage/Hiv Interactions, Matthew M. Froid

Student Research and Creative Activity Fair

Properties emerge from the dynamics of large-scale molecular networks that are not discernible at the individual gene or protein level. Mathematical models - such as probabilistic Boolean networks - of molecular systems offer a deeper insight into how these emergent properties arise. Here, we introduce a non-linear, deterministic Boolean model of protein, gene, and chemical interactions in human macrophage cells during HIV infection. Our model is composed of 713 nodes with 1583 interactions between nodes and is responsive to 38 different inputs including signaling molecules, bacteria, viruses, and HIV viral particles. Additionally, the model accurately simulates the dynamics of over 50 different ...


Antimicrobial Resistance In Neisseria Gonorrhoeae: Proceedings Of The Star Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting, Anthony D. Cristillo, Peter A. Rice Mar 2019

Antimicrobial Resistance In Neisseria Gonorrhoeae: Proceedings Of The Star Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting, Anthony D. Cristillo, Peter A. Rice

Open Access Articles

The goal of the Sexually Transmitted Infection Clinical Trial Group's Antimicrobial Resistance (AMR) in Neisseria gonorrhoeae (NG) meeting was to assemble experts from academia, government, nonprofit and industry to discuss the current state of research, gaps and challenges in research and technology and priorities and new directions to address the continued emergence of multidrug-resistant NG infections. Topics discussed at the meeting, which will be the focus of this article, include AMR NG global surveillance initiatives, the use of whole genome sequencing and bioinformatics to understand mutations associated with AMR, mechanisms of AMR, and novel antibiotics, vaccines and other methods ...


Targeting Lipooligosaccharide (Los) For A Gonococcal Vaccine, Sunita Gulati, Jutamas Shaughnessy, Sanjay Ram, Peter A. Rice Feb 2019

Targeting Lipooligosaccharide (Los) For A Gonococcal Vaccine, Sunita Gulati, Jutamas Shaughnessy, Sanjay Ram, Peter A. Rice

Open Access Articles

The increasing incidence of gonorrhea worldwide and the global spread of multidrug-resistant strains of Neisseria gonorrhoeae, constitute a public health emergency. With dwindling antibiotic treatment options, there is an urgent need to develop safe and effective vaccines. Gonococcal lipooligosaccharides (LOSs) are potential vaccine candidates because they are densely represented on the bacterial surface and are readily accessible as targets of adaptive immunity. Less well-understood is whether LOSs evoke protective immune responses. Although gonococcal LOS-derived oligosaccharides (OSs) are major immune targets, often they undergo phase variation, a feature that seemingly makes LOS less desirable as a vaccine candidate. However, the identification ...