RESUMO
Human rhinoviruses (RVs) are positive-strand RNA viruses that cause respiratory tract disease in children and adults. Here we show that the innate immune signaling protein STING is required for efficient replication of members of two distinct RV species, RV-A and RV-C. The host factor activity of STING was identified in a genome-wide RNA interference (RNAi) screen and confirmed in primary human small airway epithelial cells. Replication of RV-A serotypes was strictly dependent on STING, whereas RV-B serotypes were notably less dependent. Subgenomic RV-A and RV-C RNA replicons failed to amplify in the absence of STING, revealing it to be required for a step in RNA replication. STING was expressed on phosphatidylinositol 4-phosphate (PI4P)-enriched membranes and was enriched in RV-A16 compared with RV-B14 replication organelles isolated in isopycnic gradients. The host factor activity of STING was species-specific, as murine STING (mSTING) did not rescue RV-A16 replication in STING-deficient cells. This species specificity mapped primarily to the cytoplasmic, ligand-binding domain of STING. Mouse-adaptive mutations in the RV-A16 2C protein allowed for robust replication in cells expressing mSTING, suggesting a role for 2C in recruiting STING to RV-A replication organelles. Palmitoylation of STING was not required for RV-A16 replication, nor was the C-terminal tail of STING that mediates IRF3 signaling. Despite co-opting STING to promote its replication, interferon signaling in response to STING agonists remained intact in RV-A16 infected cells. These data demonstrate a surprising requirement for a key host mediator of innate immunity to DNA viruses in the life cycle of a small pathogenic RNA virus.
Assuntos
Enterovirus/patogenicidade , Interações Hospedeiro-Patógeno/imunologia , Proteínas de Membrana/metabolismo , Replicação Viral/imunologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Resfriado Comum/imunologia , Resfriado Comum/virologia , Enterovirus/genética , Enterovirus/imunologia , Enterovirus/metabolismo , Células HeLa , Humanos , Imunidade Inata , Fator Regulador 3 de Interferon/metabolismo , Lipoilação , Proteínas de Membrana/agonistas , Mutação , Domínios Proteicos/genética , Transdução de Sinais , Especificidade da Espécie , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismoRESUMO
For the professional nephrology nurse, the interplay of certification, education, and professional association membership go hand-in-hand. The association provides the foundation, networking, and educational opportunities; certification validates skills and expertise; and education challenges and inspires the nurse to keep moving forward.
Assuntos
Mobilidade Ocupacional , Certificação , Enfermagem em Nefrologia/educação , Enfermagem em Nefrologia/normas , Humanos , Sociedades de Enfermagem , Estados UnidosRESUMO
Professional nephrology nurses are responsible for their ongoing education and competency in their area of practice. ANNA has an additional opportunity for education for nephrology nurses at the 47th National Symposium to be held May 1-4, 2016, in Louisville, Kentucky. The Janel Parker Memorial Opening Session keynote speaker for the meeting will be Suzanne Miyamoto, PhD, RN, Senior Director of Government Affairs and Health Policy with the American Association of Colleges of Nursing. Her topic will be "Are We Practicing to the Fullest Extent? Licensure, Certification, and Education?" This session will help address educational competence in nephrology nursing.
Assuntos
Certificação/normas , Competência Clínica/normas , Educação em Enfermagem/organização & administração , Licenciamento/normas , Enfermagem em Nefrologia/educação , Especialidades de Enfermagem/educação , Congressos como Assunto , Humanos , Kentucky , Objetivos OrganizacionaisAssuntos
Falência Renal Crônica/enfermagem , Enfermagem em Nefrologia/organização & administração , Enfermagem Pediátrica/organização & administração , Especialidades de Enfermagem/organização & administração , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Pediatric patients with end stage renal disease (ESRD) are not as prevalent as adults with ESRD, but the numbers are increasing each year. Medical management is the same for pediatric patients as it is with adults with ESRD: hemodialysis, peritoneal dialysis, no therapy, or transplantation. Among most pediatric nephrology centers, the goal for patients is to achieve transplantation.
Assuntos
Falência Renal Crônica/terapia , Transplante de Rim/normas , Doadores Vivos , Enfermagem em Nefrologia/normas , Seleção de Pacientes , Enfermagem Pediátrica/normas , Guias de Prática Clínica como Assunto , Adolescente , Criança , Pré-Escolar , Educação Continuada em Enfermagem , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estados UnidosRESUMO
Children with end stage renal disease (ESRD) frequently miss great amounts of school due to hospitalizations and three-times-a week hemodialysis (if that is their modality); thus, they miss opportunities to be with their peers and learn normal social interactions with other students. Because of this lack of normal socialization, many children with ESRD are behind in development in contrast to their peers and need opportunities to enhance their growth and development. One way this can occur for children with ESRD is by providing them opportunities to attend age-appropriate and disease-appropriate camps.
Assuntos
Acampamento , Falência Renal Crônica/psicologia , Falência Renal Crônica/terapia , Pacientes/psicologia , Terapia Recreacional/métodos , Estresse Psicológico/prevenção & controle , Estresse Psicológico/terapia , Adolescente , Atitude Frente a Saúde , Criança , Pré-Escolar , Educação Continuada em Enfermagem , Feminino , Humanos , Relações Interpessoais , Masculino , Enfermagem em Nefrologia/métodos , Enfermagem Pediátrica/métodos , Grupo Associado , Adulto JovemAssuntos
Educação Continuada em Enfermagem/organização & administração , Enfermagem em Nefrologia/educação , Recursos Humanos de Enfermagem Hospitalar/educação , Sociedades de Enfermagem/organização & administração , Competência Clínica , Humanos , Objetivos Organizacionais , Segurança do Paciente , Qualidade da Assistência à Saúde , Estados UnidosRESUMO
One way to speed up the TB drug discovery process is to search for antitubercular activity among compound series that already possess some of the key properties needed in anti-infective drug discovery, such as whole-cell activity and oral absorption. Here, we present MGIs, a new series of Mycobacterium tuberculosis gyrase inhibitors, which stem from the long-term efforts GSK has dedicated to the discovery and development of novel bacterial topoisomerase inhibitors (NBTIs). The compounds identified were found to be devoid of fluoroquinolone (FQ) cross-resistance and seem to operate through a mechanism similar to that of the previously described NBTI GSK antibacterial drug candidate. The remarkable in vitro and in vivo antitubercular profiles showed by the hits has prompted us to further advance the MGI project to full lead optimization.
Assuntos
Antituberculosos/farmacologia , Inibidores Enzimáticos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/enzimologia , Animais , Descoberta de Drogas , Feminino , Fluoroquinolonas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Modelos Moleculares , Mycobacterium bovis/efeitos dos fármacos , Inibidores da Topoisomerase I/farmacologia , Tuberculose/tratamento farmacológico , Tuberculose/microbiologiaRESUMO
With over 101,000 people currently on the waiting list for a kidney transplant, innovative solutions are needed to expand the number of available donor organs. This article describes the experience of one transplant center in using living donor paired exchanges and donor swaps to result in a chain of 28 kidney transplant recipients in the past year.
Assuntos
Nefropatias/cirurgia , Transplante de Rim/estatística & dados numéricos , Doadores Vivos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Transplantados/estatística & dados numéricos , Educação Continuada em Enfermagem , Humanos , Estudos de Casos Organizacionais , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Estados UnidosRESUMO
We developed a homogenous microtiter based assay using the cationic dye 3, 3'-Diethyloxacarbocyanine iodide, DiOC2(3), to measure the effect of compounds on membrane potential in Staphylococcus aureus. In a screen of 372 compounds from a synthetic compound collection with anti-Escherichia coli activity due to unknown modes of action at least 17% demonstrated potent membrane activity, enabling rapid discrimination of nuisance compounds.