Phosphorylcholine Allows for Evasion of Bactericidal Antibody by Haemophilus influenzae

The human pathogen Haemophilus influenzae has the ability to quickly adapt to different host environments through phase variation of multiple structures on its lipooligosaccharide (LPS), including phosphorylcholine (ChoP). During colonization with H. influenzae, there is a selection for ChoP+ phase variants. In a murine model of nasopharyngeal colonization, this selection is lost in the absence of adaptive immunity. Based on previous data highlighting the importance of natural antibody in limiting H. influenzae colonization, the effect of ChoP expression on antibody binding and its bactericidal activity was investigated. Flow cytometric analysis revealed that ChoP+ phase variants had decreased binding of antibody to LPS epitopes compared to ChoP− phase variants. This difference in antibody binding correlated with increased survival of ChoP+ phase variants in the presence of antibody-dependent, complement-mediated killing. ChoP+ phase variants were also more resistant to trypsin digestion, suggesting a general effect on the physical properties of the outer membrane. Moreover, ChoP-mediated protection against antibody binding correlated with increased resilience of outer membrane integrity. Collectively, these data suggest that ChoP expression provides a selective advantage during colonization through ChoP-mediated effects on the accessibility of bactericidal antibody to the cell surface

Redox signal integration: from stimulus to networks and genes

Dietz K-J. Redox signal integration: from stimulus to networks and genes. PHYSIOLOGIA PLANTARUM. 2008;133(3):459-468.Recent research has established redox-dependent thiol modification of proteins as a major regulatory layer superimposed on most cell functional categories in plants. Modern proteomics and forward as well as reverse genetics approaches have enabled the identification of a high number of novel targets of redox regulation. Redox-controlled processes range from metabolism to transport, transcription and translation. Gene activity regulation by transcription factors such as TGA, Athb-9 and RAP2 directly or indirectly is controlled by the redox state. Knowledge on putative redox sensors such as the peroxiredoxins, on redox transmitters including thioredoxins and glutaredoxins and biochemical mechanisms of their linkage to the metabolic redox environment has emerged as the framework of a functional redox regulatory network. Its basic principle is similar in eukaryotic cells and particularly complex in the photosynthesizing chloroplast. Methods and knowledge are now at hand to develop a quantitative understanding of redox signalling and the redox regulatory network in the eukaryotic cell

Adaptação de instrumento para dimensionar horas diárias de assistência de enfermagem residencial Adaptacion de instrumento para medir horas diarias de atención de enfermería domiciliaria Adaptation of an instrument for the measurement of daily hours for nursing care at patient's home

O Therapeutic Intervention Scoring System Intermediate: TISS-Intermediário foi traduzido para a língua portuguesa e adaptado para estabelecer horas diárias de assistência domiciliar. O processo de modificação do instrumento, desenvolvido através da Técnica Delphi, teve como participantes 16 enfermeiros, que atuam em empresas de assistência domiciliar e determinam horas diárias de assistência de enfermagem para pacientes na residência, após a hospitalização. Ao término do estudo obteve-se um instrumento com 104 itens, para ser no futuro validado clinicamente. Tal instrumento ajudará enfermeiros a estender cuidados de enfermagem a pacientes em casa, após a alta hospitalar, especialmente na tomada de decisões relativas à avaliação dos pacientes.<br>El Therapeutic Intervention Scoring System Intermediate: TISS-Intermedio, fue traducido para el idioma portugués y adaptado para establecer las horas diarias de asistencia en el domicilio. Dieciséis enfermeros participaron del proceso de modificación del instrumento desarrollado a través de la Técnica Delphi. Esos enfermeros actúan en empresas de atención a domicilio y determinan las horas diarias de atención de enfermería a los pacientes en su domicilio después del alta. Al término del estudio se obtuvo un instrumento con 104 items para ser validado clínicamente.Tal instrumento ayudará a los enfermeros a extender sus cuidados de enfermería a pacientes que se encuentran en casa, después del alta hospitalario, especialmente en la toma de decisiones relacionadas con la evaluación de los pacientes.<br>The Therapeutic Intervention Scoring System Intermediate: TISS-Intermediate, was translated into Portuguese and adapted to establish the number of hours daily of home care. The adaptation process of the instrument, developed with the Delphi Technique, used 16 nurses, who work in home care service providers and helped in calculating the number of nursing care hours for patients at their home after a period of hospitalization. At the end of the study, a 104 item-instrument was obtained for future clinical validation. This instrument will help nurses to extend nursing care to patients in their homes after they are discharged from hospitals, especially in regard to their decision-making concerning patient assessment

N6-isopentenyladenosine dual targeting of AMPK and Rab7 prenylation inhibits melanoma growth through the impairment of autophagic flux

Targeting the autophagic process is considered a promising therapeutic strategy in cancer since a great number of tumors, including melanoma, show high basal levels of protective autophagy that contributes to tumor progression and chemoresistance. Here, exploiting both in vitro and in vivo approaches, we identified N6-isopentenyladenosine (iPA), an end product of the mevalonate pathway, as a novel autophagy inhibitor with an interesting anti-melanoma activity. iPA, after being phosphorylated by adenosine kinase into 5'-iPA-monophosphate, induces autophagosome accumulation through AMPK activation, measured by increased fluorescent GFP-LC3 puncta and enhanced conversion into the lipidated autophagosome-associated LC3-II. However, at a later stage iPA blocks the autophagic flux monitored by p62 accumulation, Luciferase reporter-based assay for LC3 turnover in living cells and fluorescence of a tandem RFP-GFP-LC3 construct. Impaired autophagic flux is due to the block of autophagosome-lysosome fusion through the defective localization and function of Rab7, whose prenylation is inhibited by iPA, resulting in a net inhibition of autophagy completion that finally leads to melanoma apoptotic cell death. AMPK silencing prevents apoptosis upon iPA treatment, whereas basal autophagosome turnover is still inhibited due to unprenylated Rab7. These results strongly support the advantage of targeting autophagy for therapeutic gain in melanoma and provide the preclinical rational to further investigate the antitumor action of iPA, able to coordinately induce autophagosome accumulation and inhibit the autophagic flux, independently targeting AMPK and Rab7 prenylation. This property may be particularly useful for the selective killing of tumors, like melanoma, that frequently develop chemotherapy resistance due to protective autophagy activation.Cell Death and Differentiation advance online publication, 13 October 2017; doi:10.1038/cdd.2017.165

Comparison of the genomes of two Xanthomonas pathogens with differing host specificities

The genus Xanthomonas is a diverse and economically important group of bacterial phytopathogens, belonging to the gamma-subdivision of the Proteobacteria. Xanthomonas axonopodis pv. citri (Xac) causes citrus canker, which affects most commercial citrus cultivars, resulting in significant losses worldwide. Symptoms include canker lesions, leading to abscission of fruit and leaves and general tree decline(1). Xanthomonas campestris pv. campestris (Xcc) causes black rot, which affects crucifers such as Brassica and Arabidopsis. Symptoms include marginal leaf chlorosis and darkening of vascular tissue, accompanied by extensive wilting and necrosis(2). Xanthomonas campestris pv. campestris is grown commercially to produce the exopolysaccharide xanthan gum, which is used as a viscosifying and stabilizing agent in many industries(3). Here we report and compare the complete genome sequences of Xac and Xcc. Their distinct disease phenotypes and host ranges belie a high degree of similarity at the genomic level. More than 80% of genes are shared, and gene order is conserved along most of their respective chromosomes. We identified several groups of strain-specific genes, and on the basis of these groups we propose mechanisms that may explain the differing host specificities and pathogenic processes.417688745946