The complete genome sequence of Chromobacterium violaceum reveals remarkable and exploitable bacterial adaptability

Chromobacterium violaceum is one of millions of species of free-living microorganisms that populate the soil and water in the extant areas of tropical biodiversity around the world. Its complete genome sequence reveals (i) extensive alternative pathways for energy generation, (ii) ≈500 ORFs for transport-related proteins, (iii) complex and extensive systems for stress adaptation and motility, and (iv) wide-spread utilization of quorum sensing for control of inducible systems, all of which underpin the versatility and adaptability of the organism. The genome also contains extensive but incomplete arrays of ORFs coding for proteins associated with mammalian pathogenicity, possibly involved in the occasional but often fatal cases of human C. violaceum infection. There is, in addition, a series of previously unknown but important enzymes and secondary metabolites including paraquat-inducible proteins, drug and heavy-metal-resistance proteins, multiple chitinases, and proteins for the detoxification of xenobiotics that may have biotechnological applications

Pharmacologic inhibition of hypoxia-inducible factor (HIF)-hydroxylases ameliorates allergic contact dermatitis

Background When an immune cell migrates from the bloodstream to a site of chronic inflammation, it experiences a profound decrease in microenvironmental oxygen levels leading to a state of cellular hypoxia. The hypoxia‐inducible factor‐1α (HIF‐1α) promotes an adaptive transcriptional response to hypoxia and as such is a major regulator of immune cell survival and function. HIF hydroxylases are the family of oxygen‐sensing enzymes primarily responsible for conferring oxygen dependence upon the HIF pathway. Methods Using a mouse model of allergic contact dermatitis (ACD), we tested the effects of treatment with the pharmacologic hydroxylase inhibitor DMOG, which mimics hypoxia, on disease development. Results Re‐exposure of sensitized mice to 2,4‐dinitrofluorobenzene (DNFB) elicited inflammation, edema, chemokine synthesis (including CXCL1 and CCL5) and the recruitment of neutrophils and eosinophils. Intraperitoneal or topical application of the pharmacologic hydroxylase inhibitors dymethyloxalylglycine (DMOG) or JNJ1935 attenuated this inflammatory response. Reduced inflammation was associated with diminished recruitment of neutrophils and eosinophils but not lymphocytes. Finally, hydroxylase inhibition reduced cytokine‐induced chemokine production in cultured primary keratinocytes through attenuation of the JNK pathway. Conclusion These data demonstrate that hydroxylase inhibition attenuates the recruitment of neutrophils to inflamed skin through reduction of chemokine production and increased neutrophilic apoptosis. Thus, pharmacologic inhibition of HIF hydroxylases may be an effective new therapeutic approach in allergic skin inflammation.This work was funded by Science Foundation Ireland grants to Cormac Taylor and Martin Steinhoff and a grant from the European Union (ERACoSYSMed) to Cormac Taylor and Martin Schneider. Moritz Strowitzki receives funding from the German Research Foundation (DFG; STR 1570/1-1) and the Braun Foundation (Braun; BBSTD18/00018).Scopu

IL-22 modulates IL-17A production and controls inflammation and tissue damage in experimental dengue infection

Dengue virus (DENV), a mosquito-borne flavivirus, is a public health problem in many tropical countries. IL-22 and IL-17A are key cytokines in several infectious and inflammatory diseases. We have assessed the contribution of IL-22 and IL-17A in the pathogenesis of experimental dengue infection using a mouse-adapted DENV serotype 2 strain (P23085) that causes a disease that resembles severe dengue in humans. We show that IL-22 and IL-17A are produced upon DENV-2 infection in immune-competent mice. Infected IL-22−/− mice had increased lethality, neutrophil accumulation and pro-inflammatory cytokines in tissues, notably IL-17A. Viral load was increased in spleen and liver of infected IL-22−/− mice. There was also more severe liver injury, as seen by increased transaminases levels and tissue histopathology. γδ T cells and NK cells are sources of IL-17A and IL-22, respectively, in liver and spleen. We also show that DENV-infected HepG2 cells treated with rhIL-22 had reduced cell death and decreased IL-6 production. IL-17RA−/− mice were protected upon infection and IL-17A-neutralizing-Ab-treatment partially reversed the phenotype observed in IL-22−/−-infected mice. We suggest that disrupting the balance between IL-22 and IL-17A levels may represent an important strategy to reduce inflammation and tissue injury associated with severe dengue infection

Acúmulo de forragem em pastos de Brachiaria decumbens adubados com nitrogênio Biomass of the forage in Brachiaria decumbens pastures fertilized with nitrogen

A dinâmica de crescimento de plantas forrageiras tem sido foco de estudo nos últimos anos, visando aprimorar o conhecimento do processo de produção de forragem em pastagens. O objetivo deste trabalho foi avaliar o acúmulo de forragem em pastos de Brachiaria decumbens Stapf. adubados com nitrogênio e submetidos a uma mesma intensidade de pastejo. Os tratamentos consistiram de 75, 150, 225 e 300 kg ha-1 ano-1 de N, aplicados antes do início das avaliações experimentais, as quais foram realizadas durante as estações de verão, outono, inverno e primavera de 2002. O delineamento experimental utilizado foi o de blocos completos casualizados com duas repetições. O capim-braquiária apresentou incremento de produção de matéria seca proporcional às doses de nitrogênio. Observaram-se maiores valores de taxa de acúmulo de folha, colmo e forragem nas estações primavera-verão e valores menores no inverno. As variações nas condições climáticas com as estações do ano alteraram as taxas de acúmulo de folha e colmo, senescência e de produção de forragem em Brachiaria decumbens.<br>In the last years, the growth dynamics of forage plants has been focused, in order to improve the knowledge of forage yield and distribution process in pasture. The objective of this work was to evaluate the effect of nitrogen fertilization on accumulation of the forage in Brachiaria decumbens Stapf. pastures submitted to the same stocking rate. Treatments consisted of 75, 150, 225 and 300 kg ha-1 yr-1 N applied before the beginning of experimental evaluations, which were performed during summer, autumn, winter and spring of 2002. A randomized block experimental design was used with two replicates. Brachiaria grass showed an increase in the dry matter yield proportionally to nitrogen doses, with higher rates for daily accumulation of leaves, stems and forage yield in summer-spring seasons, while lower rates were shown in the winter. The variation of climatic conditions within yearly seasons changed the rates of leaf accumulation, senescence, and forage yield in the Brachiaria decumbens pasture