No abstract

STIM1 and Orai represent the key components of Ca2+ release-activated Ca2+ channels. Activation of Orai channels requires coupling of the C terminus of STIM1 to the N and C termini of Orai. Although the latter appears to be central in the interaction with STIM1, the role of the N terminus and particularly of the conserved region close to the first transmembrane sequence is less well understood. Here, we investigated in detail the functional role of this conserved region in Orai3 by stepwise deletions. Molecular determinants were mapped for the two modes of Orai3 activation via STIM1 or 2-aminoethoxydiphenyl borate (2-APB) and for current gating characteristics. Increasing N-terminal truncations revealed a progressive decrease of the specific fast inactivation of Orai3 concomitant with diminished binding to calmodulin. STIM1-dependent activation of Orai3 was maintained as long as the second half of this conserved N-terminal domain was present. Further truncations abolished it, whereas Orai3 stimulation via 2-APB was partially retained. In aggregate, the N-terminal conserved region plays a multifaceted role in Orai3 current gating with distinct structural requirements for STIM1- and 2-APB-stimulated activation.

We report on the synthesis and properties of 6,6′-dithienylindigo (DTI) and poly(DTI). Redox chemistry and ambipolar charge transport with μh = 0.11 cm2 V−1 s−1 and μe = 0.08 cm2 V−1 s−1 and excellent air stability are shown.

There exists a tremendous interest in metallic polymers as they combine facile processing, high conductivity and transparency. However, to date no straightforward method has been found to engineer a system that unites high doping and high order. [1][2][3][4][5][6] The apparent conflict lies in the nature of doping of a conducting polymer, which occurs through a distinct mechanism compared to inorganic semiconductors. Severe lattice distortions arise in the doping of conducting polymers as a result of the penetration of ions into the system. Consequently, the solid-state order becomes disrupted-it transforms from a former homogeneous organic vander-Waals crystal into a disordered salt. To form a substantial degree of order, growth methods have to consider the effect of ion penetration. [7][8][9][10][11][12][13][14][15][16] Small molecular systems have the advantage that they can be dissolved in polar solvents. Thus they can be grown in the doped form as a salt dissolved from Conductive polymers represent a rare case in which free-carrier absorption is shifted to the far-infrared-an attractive advantage in light of the requirement of highly transparent conductors across the visible and near-infrared. Unfortunately, prior approaches to doping these polymers-imperative for high conductance-have consistently led to strong localization arising from fluctuating band alignment among polymer chains. Here, this study overcomes this problem of doping-induced Anderson localization for the first time in polymers by developing a new conductive polymer synthesis strategy. This study achieves polymerization and doping simultaneously, thereby using an alternative nonmetal oxidant and thereby avoiding the introduction of excess energy that normally arises from exergonic polymerization. The resulting conductive polymer is the first to provide electron coherence in a metallic polymer thin film. The conductivity reaches a remarkable 3300 S cm −1 at 1.8 K and the mean electron scattering length a record 330 Å. This enhancement drives the glassy metal transition in the vicinity of the Mott-Ioffe-Regel (MIR) limit. The new metallic polymer achieves 10 −2 Ω −1 figure of merit, making it a contender for transparent conductive contacts previously only accessible using inorganics. The new material offers a uniquely broad transparency window spanning the UV to the mid-infrared. The ORCID identification number(s) for the author(s) of this article can be found under http://dx

ScopeKnown pharmacological activities of guava (Psidium guajava) include modulation of blood glucose levels. However, mechanistic details remain unclear in many cases.Methods and resultsThis study investigated the effects of different guava leaf and fruit extracts on intestinal glucose transport in vitro and on postprandial glucose levels in vivo. Substantial dose‐ and time‐dependent glucose transport inhibition (up to 80%) was observed for both guava fruit and leaf extracts, at conceivable physiological concentrations in Caco‐2 cells. Using sodium‐containing (both glucose transporters, sodium‐dependent glucose transporter 1 [SGLT1] and glucose transporter 2 [GLUT2], are active) and sodium‐free (only GLUT2 is active) conditions, we show that inhibition of GLUT2 was greater than that of SGLT1. Inhibitory properties of guava extracts also remained stable after digestive juice treatment, indicating a good chemical stability of the active substances. Furthermore, we could unequivocally show that guava extracts significantly reduced blood glucose levels (≈fourfold reduction) in a time‐dependent manner in vivo (C57BL/6N mice). Extracts were characterized with respect to their main putative bioactive compounds (polyphenols) using HPLC and LC‐MS.ConclusionThe data demonstrated that guava leaf and fruit extracts can potentially contribute to the regulation of blood glucose levels.