Host cell responses of Salmonella typhimurium infected human dendritic cells

Live attenuated Salmonella are attractive vaccine candidates for mucosal application because they induce both mucosal immune responses and systematic immune responses. After breaking the epithelium barrier, Salmonella typhimurium is found within dendritic cells (DC) in the Peyer's patches. Although there are abundant data on the interaction of S. typhimurium with murine epithelial cells, macrophages and DC, little is known about its interaction with human DC. Live attenuated S. typhimurium have recently been shown to efficiently infect human DC in vitro and induce production of cytokines. In this study, we have analysed the morphological consequences of infection of human DC by the attenuated S. typhimurium mutant strains designated PhoPc, AroA and SipB and the wild-type strains of the American Type Culture Collection (Manassas, VA, USA), ATCC 14028 and ATCC C53, by electron microscopy at 30 min, 3 h and 24 h after exposure. Our results show that genetic background of the strains profoundly influence DC morphology following infection. The changes included (i) membrane ruffling; (ii) formation of tight or spacious phagosomes; (iii) apoptosis; and (iv) spherical, pedunculated membrane-bound microvesicles that project from the plasma membrane. Despite the fact that membrane ruffling was much more pronounced with the two virulent strains, all mutants were taken up by the DC. The microvesicles were induced by all the attenuated strains, including SipB, which did not induce apoptosis in the host cell. These results suggest that Salmonella is internalized by human DC, inducing morphological changes in the DC that could explain immunogenicity of the attenuated strains.

Regulation of phosphoinositide 3-kinase expression in health and disease

Both the biology and the therapeutic potential of the phosphoinositide 3-kinase (PI3K) signalling axis have been the subject of intense investigation; however, little is known about the regulation of PI3K expression. Emerging evidence indicates that PI3K levels change in response to cellular stimulation with insulin and nuclear receptor ligands, and during various physiological and pathological processes including differentiation, regeneration, hypertension and cancer. Recently identified mechanisms that control PI3K production include increased gene copy number in cancer, and transcriptional regulation of the p110alpha PI3K gene by FOXO3a, NF-kappaB and p53, and of the PI3K regulatory subunits by STAT3, EBNA-2 and SREBP. In most instances, however, the impact of alterations in PI3K expression on PI3K signalling and disease remains to be established.

EChO

A dedicated mission to investigate exoplanetary atmospheres represents a major milestone in our quest to understand our place in the universe by placing our Solar System in context and by addressing the suitability of planets for the presence of life. EChO—the Exoplanet Characterisation Observatory—is a mission concept specifically geared for this purpose. EChO will provide simultaneous, multi-wavelength spectroscopic observations on a stable platform that will allow very long exposures. The use of passive cooling, few moving parts and well established technology gives a low-risk and potentially long-lived mission. EChO will build on observations by Hubble, Spitzer and ground-based telescopes, which discovered the first molecules and atoms in exoplanetary atmospheres. However, EChO’s configuration and specifications are designed to study a number of systems in a consistent manner that will eliminate the ambiguities affecting prior observations. EChO will simultaneously observe a broad enough spectral region—from the visible to the mid-infrared—to constrain from one single spectrum the temperature structure of the atmosphere, the abundances of the major carbon and oxygen bearing species, the expected photochemically-produced species and magnetospheric signatures. The spectral range and resolution are tailored to separate bands belonging to up to 30 molecules and retrieve the composition and temperature structure of planetary atmospheres. The target list for EChO includes planets ranging from Jupiter-sized with equilibrium temperatures T eq up to 2,000 K, to those of a few Earth masses, with T eq \u223c 300 K. The list will include planets with no Solar System analog, such as the recently discovered planets GJ1214b, whose density lies between that of terrestrial and gaseous planets, or the rocky-iron planet 55 Cnc e, with day-side temperature close to 3,000 K. As the number of detected exoplanets is growing rapidly each year, and the mass and radius of those detected steadily decreases, the target list will be constantly adjusted to include the most interesting systems. We have baselined a dispersive spectrograph design covering continuously the 0.4–16 μm spectral range in 6 channels (1 in the visible, 5 in the InfraRed), which allows the spectral resolution to be adapted from several tens to several hundreds, depending on the target brightness. The instrument will be mounted behind a 1.5 m class telescope, passively cooled to 50 K, with the instrument structure and optics passively cooled to \u223c45 K. EChO will be placed in a grand halo orbit around L2. This orbit, in combination with an optimised thermal shield design, provides a highly stable thermal environment and a high degree of visibility of the sky to observe repeatedly several tens of targets over the year. Both the baseline and alternative designs have been evaluated and no critical items with Technology Readiness Level (TRL) less than 4–5 have been identified. We have also undertaken a first-order cost and development plan analysis and find that EChO is easily compatible with the ESA M-class mission framework.

Sulfate and Nitrate Assimilation in Leaves of Quercus ilex and Quercus pubescens Grown Near Natural CO2 Springs in Central Italy

The effect of long-term exposure to elevated pCO2 concentrations on sulfate and nitrate assimilation was studied under field conditions using leaves from Quercus ilex and Quercus pubescens trees growing with ambient or elevated CO2 concentrations in the vicinity of three natural CO2 springs, Bossoleto, Laiatico and Sulfatara, in Tuscany, Italy. The activity of the key enzymes of sulfate assimilation, adenosine 5′-phosphosulfate reductase (APR) and nitrate assimilation, nitrate reductase (NR), were measured together with the levels of acid soluble thiols, and soluble non-proteinogenic nitrogen compounds. Whereas NR activity remained unaffected in Q. ilex or increased Q. pubescence, APR activity decreased in the area of CO2 springs. The latter changes were often accompanied by increased GSH concentrations, apparently synthesized from H2S and SO2 present in the gas mixture emitted from the CO2 springs. Thus, the diminished APR activity in leaves of Q. ilex and Q. pubescence from spring areas can best be explained by the exposure to gaseous sulfur compounds. Although the concentrations of H2S and SO2 in the gas mixture emitted from the vents at the CO2 springs were low at the Bossoleto and Laiatico spring, these sulfur gases pose physiological effects, which may override consequences of elevated pCO2.