HSV-1 exploits the innate immune scavenger receptor MARCO to enhance epithelial adsorption and infection

HSV-1 is an important epithelial pathogen and has the potential for significant morbidity in humans. Here we demonstrate that a cell surface scavenger receptor, macrophage receptor with collagenous structure (MARCO), previously thought to enhance antiviral defense by enabling nucleic acid recognition, is usurped by HSV-1 and functions together with heparan sulfate proteoglycans to mediate adsorption to epithelial cells. Ligands of MARCO dramatically inhibit HSV-1 adsorption and infection of human keratinocytes and protect mice against infection. HSV-1 glycoprotein C (gC) closely co-localizes with MARCO at the cell surface, and gC binds directly to purified MARCO with high affinity. Increasing MARCO expression enhances HSV-1 infection while MARCO-/- mice have reduced susceptibility to infection by HSV-1. These findings demonstrate that HSV-1 binds to MARCO to enhance its capacity for disease, and suggests a new therapeutic target to alter pathogenicity of HSV-1 in skin infection

The relative resistance of children to sepsis mortality: from pathways to drug candidates

Attempts to develop drugs that address sepsis based on leads developed in animal models have failed. We sought to identify leads based on human data by exploiting a natural experiment: the relative resistance of children to mortality from severe infections and sepsis. Using public datasets, we identified key differences in pathway activity (Pathprint) in blood transcriptome profiles of septic adults and children. To find drugs that could promote beneficial (child) pathways or inhibit harmful (adult) ones, we built an in silico pathway drug network (PDN) using expression correlation between drug, disease, and pathway gene signatures across 58,475 microarrays. Specific pathway clusters from children or adults were assessed for correlation with drug-based signatures. Validation by literature curation and by direct testing in an endotoxemia model of murine sepsis of the most correlated drug candidates demonstrated that the Pathprint-PDN methodology is more effective at generating positive drug leads than gene-level methods (e.g., CMap). Pathway-centric Pathprint-PDN is a powerful new way to identify drug candidates for intervention against sepsis and provides direct insight into pathways that may determine survival

The Ergogenic Potential of Arginine

Arginine is a conditionally essential amino acid that is involved in protein synthesis, the detoxification of ammonia, and its conversion to glucose as well as being catabolized to produce energy. In addition to these physiological functions, arginine has been purported to have ergogenic potential. Athletes have taken arginine for three main reasons: 1) its role in the secretion of endogenous growth hormone; 2) its involvement in the synthesis of creatine; 3) its role in augmenting nitric oxide. These aspects of arginine supplementation will be discussed as well as a review of clinical investigations involving exercise performance and arginine ingestion

Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants

AbstractBackgroundRespiratory syncytial virus (RSV) is the global leading cause of lower respiratory tract infection in infants. Nearly 30% of all infected infants develop severe disease including bronchiolitis, but susceptibility mechanisms remain unclear.MethodsWe infected a panel of 30 inbred strains of mice with RSV and measured changes in lung disease parameters 1 and 5days post-infection and they were used in genome-wide association (GWA) studies to identify quantitative trait loci (QTL) and susceptibility gene candidates.FindingsGWA identified QTLs for RSV disease phenotypes, and the innate immunity scavenger receptor Marco was a candidate susceptibility gene; targeted deletion of Marco worsened murine RSV disease. We characterized a human MARCO promoter SNP that caused loss of gene expression, increased in vitro cellular response to RSV infection, and associated with increased risk of disease severity in two independent populations of children infected with RSV.InterpretationTranslational integration of a genetic animal model and in vitro human studies identified a role for MARCO in human RSV disease severity. Because no RSV vaccines are approved for clinical use, genetic studies have implications for diagnosing individuals who are at risk for severe RSV disease, and disease prevention strategies (e.g. RSV antibodies)

A Consensus Definitive Classification of Scavenger Receptors and Their Roles in Health and Disease

Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a diverse variety of ligands including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by theUnited StatesNational Institute of Allergy and Infectious Diseases, National Institutes of Health, to help develop a clear definition of scavenger receptors and a standardized nomenclature based on that definition. Fifteen experts in the scavenger receptor field attended the workshop and, after extensive discussion, reached a consensus regarding the definition of scavenger receptors and a proposed scavenger receptor nomenclature. Scavenger receptors were defined as cell surface receptors that typically bind multiple ligands and promote the removal of nonself or altered-self targets. They often function by mechanisms that include endocytosis, phagocytosis, adhesion, and signaling that ultimately lead to the elimination of degraded or harmful substances. Based on this definition, nomenclature and classification of these receptors into 10 classes were proposed. This classification was discussed at three national meetings and input from participants at these meetings was requested. The following manuscript is a consensus statement that combines the recommendations of the initial workshop and incorporates the input received from the participants at the three national meetings

Uso de morteros catalíticos sobre paneles, para el análisis de la reducción de partículas contaminantes en el aire

Trabajo de Investigación TecnológicaEste proyecto de grado se enfoca en la contaminación del aire y el uso de las nuevas tecnologías en la construcción para combatir este problema que genera afectaciones no solo ambientales, sino en la salud humana, en la flora y la fauna. La nanotecnología, es una rama que se desprende de las nuevas tecnologías y que se ha abierto paso en la industria de la construcción, por medio de la implementación de materiales y aditivos te tamaño nanométrico que mejoran y generan nuevas propiedades en los materiales comunes de construcción como el acero, concretos, morteros, pinturas, etc. En este proyecto se elaboró un concreto y mortero adicionando el Dióxido de titanio (TiO2), el cual actúa como un catalizador al combinarse con el cemento y los rayos ultra violeta, y su función principal es oxidar las partículas contaminantes suspendidas en el aire, por lo cual se categoriza como un descontaminante. Adicionalmente, el TiO2 puede mejorar las propiedades del concreto. Para comprobar el efecto del TiO2 en el concreto, se elaboraron cuatro cilindros de concreto común y de concreto adicionado, los cuales se fallaron en las edades típicas de falla y se compararon los resultados obtenidos. De igual manera, se fabricó un mortero adicionado, el cual se colocó sobre paneles y se dejó expuesto ocho días en un área de monitoreo de aire, y con los datos obtenidos se realizó el análisis correspondiente.1 INTRODUCCIÓN 2 ANTECEDENTES 3 PLANTEAMIENTO DEL PROBLEMA 4 OBJETIVOS 5 JUSTIFICACIÓN 6 DELIMITACIONES 7 MARCO DE REFERENCIA 8 METODOLOGÍA 9 DISEÑO METODOLÓGICO. 10 CONCLUSIONES 11 RECOMENDACIONES BIBLIOGRAFÍAPregradoIngeniero Civi