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Hydrogen sulfide contributes to hypoxic inhibition of airway transepithelial sodium absorption
(2016)
We demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit ATP-dependent release of interleukin-1β from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nAChR). Interleukin-1β is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. Control of interleukin-1β release is vital as excessively high systemic levels cause life threatening inflammatory diseases. In spite of its structural similarity to acetylcholine, there are no other reports on interactions of phosphocholine with nAChR. In this study, we demonstrate that phosphocholine inhibits ion-channel function of ATP receptor P2X7 in monocytic cells via nAChR containing α9 and α10 subunits. In stark contrast to choline, phosphocholine does not evoke ion current responses in Xenopus laevis oocytes, which heterologously express functional homomeric nAChR composed of α9 subunits or heteromeric receptors containing α9 and α10 subunits. Preincubation of these oocytes with phosphocholine, however, attenuated choline-induced ion current changes, suggesting that phosphocholine may act as a silent agonist. We conclude that phophocholine activates immuno-modulatory nAChR expressed by monocytes but does not stimulate canonical ionotropic receptor functions.
Hydrogen sulfide (H2S) is a well-known environmental chemical threat with an unpleasant smell of rotten eggs. Aside from the established toxic effects of high-dose H2S, research over the past decade revealed that cells endogenously produce small amounts of H2S with physiological functions. H2S has therefore been classified as a gasotransmitter. A major challenge for cells and tissues is the maintenance of low physiological concentrations of H2S in order to prevent potential toxicity. Epithelia of the respiratory and gastrointestinal tract are especially faced with this problem, since these barriers are predominantly exposed to exogenous H2S from environmental sources or sulfur-metabolising microbiota. In this paper, we review the cellular mechanisms by which epithelial cells maintain physiological, endogenous H2S concentrations. Furthermore, we suggest a concept by which epithelia use their electrolyte and liquid transport machinery as defence mechanisms in order to eliminate exogenous sources for potentially harmful H2S concentrations.
An exploratory study: Analysis of Serbian tourism market and identification of major market segments
(2016)
Currently, there are a lot of research activities dealing with gamma titanium aluminide (γ-TiAl) alloys as new materials for low pressure turbine (LPT) blades. Even though the scatter in mechanical properties of such intermetallic alloys is more distinctive as in conventional metallic alloys, stochastic investigations on γ -TiAl alloys are very rare. For this reason, we analyzed the scatter in static and dynamic mechanical properties of the cast alloy Ti-48Al-2Cr-2Nb. It was found that this alloy shows a size effect in strength which is less pronounced than the size effect of brittle materials. A weakest-link approach is enhanced for describing a scalable size effect under multiaxial stress states and implemented in a post processing tool for reliability analysis of real components. The presented approach is a first applicable reliability model for semi-brittle materials. The developed reliability tool was integrated into a multidisciplinary optimization of the geometry of a LPT blade. Some processes of the optimization were distributed in a wide area network, so that specialized tools for each discipline could be employed. The optimization results show that it is possible to increase the aerodynamic efficiency and the structural mechanics reliability at the same time, while ensuring the blade can be manufactured in an investment casting process.