Glucocorticoids: mechanisms of action and anti-inflammatory potential in asthma.

GLUCOCORTICOIDS are potent inhibitors of inflammatory processes and are widely used in the treatment of asthma. The anti-inflammatory effects are mediated either by direct binding of the glucocorticoid/glucocorticoid receptor complex to glucocorticoid responsive elements in the promoter region of genes, or by an interaction of this complex with other transcription factors, in particular activating protein-1 or nuclear factor-kappaB. Glucocorticoids inhibit many inflammation-associated molecules such as cytokines, chemokines, arachidonic acid metabolites, and adhesion molecules. In contrast, anti-inflammatory mediators often are up-regulated by glucocorticoids. In vivo studies have shown that treatment of asthmatic patients with inhaled glucocorticoids inhibits the bronchial inflammation and simultaneously improves their lung function. In this review, our current knowledge of the mechanism of action of glucocorticoids and their anti-inflammatory potential in asthma is described. Since bronchial epithelial cells may be important targets for glucocorticoid therapy in asthma, the effects of glucocorticoids on epithelial expressed inflammatory genes will be emphasized

Kinetic simulation of an extreme ultraviolet radiation driven plasma near a multilayer mirror

Future generation lithog. tools will use extreme UV radiation to enable the printing of sub-50 nm features on silicon wafers. The extreme UV radiation, coming from a pulsed discharge, photoionizes the low pressure background gas in the tool. A weakly ionized plasma is formed, which will be in contact with the optical components of the lithog. device. In the plasma sheath region ions will be accelerated towards the surfaces of multilayer mirrors. A self-consistent kinetic particle-in-cell model has been applied to describe a radiation driven plasma. The simulations predict the plasma parameters and notably the energy at which ions impact on the plasma boundaries. We have studied the influence of photoelectron emission from the mirror on the sheath dynamics and on the ion impact energy. Furthermore, the ion impact energy distribution has been convoluted with the formula of Yamamura and Tawara [At. Data Nucl. Data Tables 62, 149 (1996)] for the sputter yield to obtain the rate of phys. sputtering. The model predicts that the sputter rate is dominated by the presence of doubly ionized argon ions. [on SciFinder (R)

An Overview of the TROPICS NASA Earth Venture Mission

The Time-Resolved Observations of Precipitation structure and storm Intensity with a Constellation of Smallsats (TROPICS) mission was selected by NASA as part of the Earth Venture-Instrument (EVI-3) program. The overarching goal for TROPICS is to provide nearly all-weather observations of 3D temperature and humidity, as well as cloud ice and precipitation horizontal structure, at high temporal resolution to conduct high-value science investigations of tropical cyclones. TROPICS will provide rapid-refresh microwave measurements (median refresh rate better than 60 min for the baseline mission) which can be used to observe the thermodynamics of the troposphere and precipitation structure for storm systems at the mesoscale and synoptic scale over the entire storm life cycle. TROPICS comprises six Cube-Sats in three low-Earth orbital planes. Each CubeSat will host a high-performance radiometer to provide temperature profiles using seven channels near the 118.75 GHz oxygen absorption line, water vapour profiles using three channels near the 183 GHz water vapour absorption line, imagery in a single channel near 90 GHz for precipitation measurements (when combined with higher-resolution water vapour channels), and a single channel near 205 GHz which is more sensitive to precipitation-sized ice particles. This observing system offers an unprecedented combination of horizontal and temporal resolution to measure environmental and inner-core conditions for tropical cyclones on a nearly global scale and is a major leap forward in the temporal resolution of several key parameters needed for assimilation into advanced data assimilation systems capable of utilizing rapid-update radiance or retrieval data.Launch readiness is currently projected for late 2019

Interstellar abundances in the neutral and ionized gas of NGC604

We present FUSE spectra of the giant HII region NGC604 in the spiral galaxy M33. Chemical abundances are derived from far-UV absorption lines and are compared to those derived from optical emission lines. We derived the column densities of HI, NI, OI, SiII, PII, ArI, and FeII, fitting the line profiles with either a single component or several components. Our net results, assuming a single component, show that N, O, Si, and Ar are apparently underabundant in the neutral phase by a factor of 10 or more with respect to the ionized phase, while Fe is the same. However, we discuss the possibility that the absorption lines are made of individual unresolved components, and find that only PII, ArI, and FeII lines should not be affected by the presence of hidden saturated components, while NI, OI, and SiII might be much more affected. If N, O, and Si are actually underabundant in the neutral gas of NGC604 with respect to the ionized gas, this would confirm earlier results obtained for the blue compact dwarfs. However, a deeper analysis focused on P, Ar, and Fe mitigates the above conclusion and indicates that the neutral gas and ionized gas could have similar abundances.Comment: Accepted for publication in A&

Protein kinase C α and ε phosphorylation of troponin and myosin binding protein C reduce Ca2+ sensitivity in human myocardium

Previous studies indicated that the increase in protein kinase C (PKC)-mediated myofilament protein phosphorylation observed in failing myocardium might be detrimental for contractile function. This study was designed to reveal and compare the effects of PKCα- and PKCε-mediated phosphorylation on myofilament function in human myocardium. Isometric force was measured at different [Ca2+] in single permeabilized cardiomyocytes from failing human left ventricular tissue. Activated PKCα and PKCε equally reduced Ca2+ sensitivity in failing cardiomyocytes (ΔpCa50 = 0.08 ± 0.01). Both PKC isoforms increased phosphorylation of troponin I- (cTnI) and myosin binding protein C (cMyBP-C) in failing cardiomyocytes. Subsequent incubation of failing cardiomyocytes with the catalytic subunit of protein kinase A (PKA) resulted in a further reduction in Ca2+ sensitivity, indicating that the effects of both PKC isoforms were not caused by cross-phosphorylation of PKA sites. Both isozymes showed no effects on maximal force and only PKCα resulted in a modest significant reduction in passive force. Effects of PKCα were only minor in donor cardiomyocytes, presumably because of already saturated cTnI and cMyBP-C phosphorylation levels. Donor tissue could therefore be used as a tool to reveal the functional effects of troponin T (cTnT) phosphorylation by PKCα. Massive dephosphorylation of cTnT with alkaline phosphatase increased Ca2+ sensitivity. Subsequently, PKCα treatment of donor cardiomyocytes reduced Ca2+ sensitivity (ΔpCa50 = 0.08 ± 0.02) and solely increased phosphorylation of cTnT, but did not affect maximal and passive force. PKCα- and PKCε-mediated phosphorylation of cMyBP-C and cTnI as well as cTnT decrease myofilament Ca2+ sensitivity and may thereby reduce contractility and enhance relaxation of human myocardium

The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis

Acknowledgements We wish to thank Jorge Galán, Gregory Pazour, Derek Toomre, Giuliano Callaini, Joel Rosenbaum, Alessandra Boletta and Francesco Blasi for generously providing reagents and for productive discussions, and Sonia Grassini for technical assistance. The work was carried out with the financial support of Telethon (GGP11021) and AIRC.Peer reviewedPostprin