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Within this work, a fluorescence microscopy approach for the investigation of the distribution of polymer additives in polypropylene is presented. The fluorescent whitening agent 2,5-bis-(5-tert-butyl-benzoxazol-2-yl)-thiophene was used as a model compound representing other groups of polymer additives. So far, methods reported in the literature such as UV and IR microscopy offer a high spatial resolution, however, suffer from poor sensitivities, thus not allowing them to analyze samples with low additive concentrations typically used in engineering materials. Using the fluorescence microscopy technique, it was shown that independent from the applied concentrations (0.1–1.7 wt%), additives are distributed on a spherulitic scale with the majority being found at the spherulite boundary and only traces in the center. Furthermore, it could be demonstrated that the additive distribution is affected not only by the spherulite sizes but also by the cooling rate of the polymer melt leading to more or less...

Calcium (Ca(2+)) entry into non-excitable cells is mainly carried by store-operated channels (SOCs), which serve essential functions ranging from regulation of transcription to cell growth. The best-characterized store-operated current, I(CRAC), is the calcium release-activated calcium (CRAC) current initially discovered in T-lymphocytes and mast cells. The search for the molecular components of the CRAC channel lasted over 20 years. Recently STIM1 has been identified as the Ca(2+) sensor in the endoplasmic reticulum (ER) that accumulates into punctae close to the plasma-membrane following store-depletion. The identification of STIM1 has been closely followed by the discovery of Orai1 as the CRAC channel pore in human T-cells. Upon punctae formation STIM1 activates Ca(2+) influx via Orai1 channels. This review covers functional details concerning the activation cascade of the STIM1/Orai1 complex from ER Ca(2+) sensing to Ca(2+) influx through Orai1. Furthermore, functional domains within STIM1 and Orai1 in comparison to their structural homologs STIM2 as well as Orai2 and Orai3, respectively, are displayed together with recent findings on the pore architecture and selectivity filter of Orai channels. A broad tissue expression of STIM and Orai proteins together with substantial effects in STIM1/Orai1 knock-out mice suggests an essential physiological role in store-operated Ca(2+) signalling in human health and disease.

Let me first take the opportunity to thank all the authors for their excellent contributions to this special issue dedicated to the relatively young field of “STIM/Orai” research. I would also like to express my sincere thanks to the Channels Editor-in-Chief, Gerald Zamponi, who approached me more than a year ago with this project and the extraordinary dedicated Channels staff, in particular, Harmony Zambrano, who successfully helped to get this issue wrapped up. The concept of store-operated channels (SOCs) was first introduced by James Putney, almost 30 years ago, suggesting that the depletion of an intracellular Ca2+ store leads to the activation of Ca2+ entry, the extent of which is regulated by the filling state of the endoplasmic reticulum. The prototypic SOC is represented by the Ca2+ release-activated Ca2+ (CRAC) current which has been initially characterized by electrophysiological experiments in mast cells and T-lyphocytes. In 2005 and 2006, the molecular key components of CRAC channels have been identified as STIM1 and Orai, respectively. The latest breakthrough, providing structural resolution, has been obtained in 2012 by the crystallization of active entities of both STIM1 and Orai. In the time period between the identification of these key components and their structural resolution, substantial progress has been achieved in understanding the mechanism of STIM/Orai coupling culminating in CRAC channel activation. Moreover, additional proteins have emerged that modulate STIM-Orai communication. Even store-independent activation has been identified by arachidonate- (ARC) or leukotrieneC4- regulated Ca2+-channels involving STIM1/Orai. All of these findings have meanwhile paved the way for elucidation of the (patho)physiological role of STIM and Orai proteins in native Ca2+ signaling pathways, for instance in regulating gene expression or immunity and their involvement in pathogenesis of various diseases. Particularly with respect to the latter, molecular pharmacology on the STIM/Orai system has just started in an attempt to provide tissue- and disease-specific drugs for therapeutic interventions. The purpose of this special issue of Channels is to cover the above aspects in a manner that provides students or scientists interested in the field with up-to-date information on the current concepts and developments in the STIM/Orai research, which we expect to gain increasing importance as molecular structures and mechanisms will be linked to (patho)physiological processes.