Conductive hydrogels are a class of stretchable conductive materials that are important for various applications. However, water-based conductive hydrogels inevitably lose elasticity and conductivity at subzero temperatures, which severely limits their applications at low temperatures. Herein we report anti-freezing conductive organohydrogels by using an H O/ethylene glycol binary solvent as dispersion medium. Owing to the freezing tolerance of the binary solvent, our organohydrogels exhibit stable flexibility and strain-sensitivity in the temperature range from -55.0 to 44.6 °C. Meanwhile, the solvent molecules could form hydrogen bonds with polyvinyl alcohol (PVA) chains and induce the crystallization of PVA, greatly improving the mechanical strength of the organohydrogels. Furthermore, the non-covalent crosslinks endow the conductive organohydrogels with intriguing remoldability and self-healing capability, which are important for practical applications.

BCL-2 is a 26-kDa integral membrane protein that represses apoptosis by an unknown menism. Recent findings indicate that Ca+ release from the endoplasmic reticulum (ER) mediates apoptosis in mouse lymphoma cells. In view of growing evidence that BCL-2 localizes to the ER, as well as mitochondria and the perinuclear membrane, we investigated the possibility that BCL-2 represses apoptosis by regulating CaW+ fluxes through the ER membrane. A cDNA encoding BCL-2 was introduced into WEHI7.2 cells and two subclones, W.Hb12 and W.Hbl3, which express high and low levels ofBCL-2 mRNA and protein, respectively, were isolated.

As rapid progress has been achieved in emerging thin film solar cell technology, organic–inorganic hybrid perovskite solar cells (PVSCs) have aroused many concerns with several desired properties for photovoltaic applications, including large absorption coefficients, excellent carrier mobility, long charge carrier diffusion lengths, low‐cost, and unbelievable progress. Power conversion efficiencies increased from 3.8% in 2009 up to the current world record of 22.1%. However, poor long‐term stability of PVSCs limits the future commercial application. Here, the degradation mechanisms for unstable perovskite materials and their corresponding solar cells are discussed. The strategies for enhancing the stability of perovskite materials and PVSCs are also summarized. This review is expected to provide helpful insights for further enhancing the stability of perovskite materials and PVSCs in this exciting field.

Many biological organisms with exceptional freezing tolerance can resist the damages to cells from extra-/intracellular ice crystals and thus maintain their mechanical stability at subzero temperatures. Inspired by the freezing tolerance mechanisms found in nature, here we report a strategy of combining hydrophilic/oleophilic heteronetworks to produce self-adaptive, freeze-tolerant and mechanically stable organohydrogels. The organohydrogels can simultaneously use water and oil as a dispersion medium, and quickly switch between hydrogel- and organogel-like behaviours in response to the nature of the surrounding phase. Accordingly, their surfaces display unusual adaptive dual superlyophobic in oil/water system (that is, they are superhydrophobic under oil and superoleophobic under water). Moreover, the organogel component can inhibit the ice crystallization of the hydrogel component, thus enhancing the mechanical stability of organohydrogel over a wide temperature range (−78 to 80 °C). The organohydrogels may have promising applications in complex and harsh environments.

The pore-forming ␣-subunits of large conductance calcium-and voltage-activated potassium (BK) channels are encoded by a single gene that undergoes extensive alternative pre-mRNA splicing. However, the extent to which differential exon usage at a single site of splicing may confer functionally distinct properties on BK channels is largely unknown. Here we demonstrated that alternative splicing at site of splicing C2 in the mouse BK channel C terminus generates five distinct splice variants: ZERO, e20, e21(STREX), e22, and a novel variant ⌬e23. Splice variants display distinct patterns of tissue distribution with e21(STREX) expressed at the highest levels in adult endocrine tissues and e22 at embryonic stages of mouse development. ⌬e23 is not functionally expressed at the cell surface and acts as a dominant negative of cell surface expression by trapping other BK channel splice variant ␣-subunits in the endoplasmic reticulum and perinuclear compartments. Splice variants display a range of biophysical properties. e21(STREX) and e22 variants display a significant left shift (>20 mV at 1 M [Ca 2؉ ] i ) in half-maximal voltage of activation compared with ZERO and e20 as well as considerably slower rates of deactivation. Splice variants are differentially sensitive to phosphorylation by endogenous cAMP-dependent protein kinase; ZERO, e20, and e22 variants are all activated, whereas e21 (STREX) is the only variant that is inhibited. Thus alternative pre-mRNA splicing from a single site of splicing provides a mechanism to generate a physiologically diverse complement of BK channel ␣-subunits that differ dramatically in their tissue distribution, trafficking, and regulation.Large conductance calcium-and voltage-activated potassium (BK) 3 channels are uniquely regulated by changes in both transmembrane potential as well as intracellular free calcium levels (1). They are widely expressed and thus play an important role in the modulation of cellular excitability in many tissues. Hence, they control diverse physiological processes, including regulation of vascular tone (2-4), micturition (5), neuronal excitability (6, 7), neurotransmitter release (8, 9), endocrine function (10 -12), innate immunity (13), and hearing (14, 15).BK channels in native tissues display a physiologically diverse array of phenotypes. Even neighboring cells (16, 17), or compartments within cells (18,19), may express BK channels with differences in their functional properties. Furthermore, these properties can be modified temporally, for example, during development (20 -22) or following a physiological challenge (23-27).At least two major post-transcriptional mechanisms are involved in generating such functional diversity as follows: alternative pre-mRNA splicing of BK channel pore-forming ␣-subunits and assembly of ␣-subunits with a family of transmembrane modulatory ␤-subunits. Although ␣-subunits are encoded by a single gene (1, 28 -30) (KCNMA1, also referred to as Slo), ␤-subunits are encoded by four distinct genes (KCNMB1-4) (31-34).Several sites o...

Large conductance calcium-and voltage-gated potassium (BK) channels are important regulators of physiological homeostasis and their function is potently modulated by protein kinase A (PKA) phosphorylation. PKA regulates the channel through phosphorylation of residues within the intracellular C terminus of the poreforming ␣-subunits. However, the molecular mechanism(s) by which phosphorylation of the ␣-subunit effects changes in channel activity are unknown. Inhibition of BK channels by PKA depends on phosphorylation of only a single ␣-subunit in the channel tetramer containing an alternatively spliced insert (STREX) suggesting that phosphorylation results in major conformational rearrangements of the C terminus. Here, we define the mechanism of PKA inhibition of BK channels and demonstrate that this regulation is conditional on the palmitoylation status of the channel. We show that the cytosolic C terminus of the STREX BK channel uniquely interacts with the plasma membrane via palmitoylation of evolutionarily conserved cysteine residues in the STREX insert. PKA phosphorylation of the serine residue immediately upstream of the conserved palmitoylated cysteine residues within STREX dissociates the C terminus from the plasma membrane, inhibiting STREX channel activity. Abolition of STREX palmitoylation by site-directed mutagenesis or pharmacological inhibition of palmitoyl transferases prevents PKA-mediated inhibition of BK channels. Thus, palmitoylation gates BK channel regulation by PKA phosphorylation. Palmitoylation and phosphorylation are both dynamically regulated; thus, cross-talk between these 2 major posttranslational signaling cascades provides a mechanism for conditional regulation of BK channels. Interplay of these distinct signaling cascades has important implications for the dynamic regulation of BK channels and physiological homeostasis.L arge conductance calcium-and voltage-gated potassium (BK) channels are potently regulated by protein phosphorylation (1) and are important determinants of neuronal, cardiovascular, endocrine, and epithelial function where channel dysfunction may lead to major disorders such as hypertension (2, 3), ataxia (4), epilepsy (5, 6), and incontinence (7). BK channels are potently regulated by phosphorylation, and several putative phosphorylation motifs on the pore-forming ␣-subunit have been identified (8-12). However, as for other potassium channels, the molecular basis through which phosphorylation of the ␣-subunit effects changes in BK channel activity is essentially unknown.BK channel pore-forming ␣-subunits are encoded by a single gene, KCNMA1 (13), and native BK channels show functional heterogeneity in their response to protein kinase A (PKA)-mediated phosphorylation. This diversity results, in large part, from the extensive alternative pre-mRNA splicing of the pore-forming ␣-subunits (10, 12). Previous studies have demonstrated that PKA phosphorylation of a conserved C-terminal phosphorylation motif. RQPS 899 results in BK channel activation (9,10,14). Inclusion of ...

Non-technical summaryOur ability to respond to stress is critically dependent upon the release of the stress hormone adrenocorticotrophic hormone (ACTH) from corticotroph cells of the anterior pituitary gland. ACTH release is controlled by the electrical properties of corticotrophs that are determined by the movement of ions through channel pores in the plasma membrane. We show that a calcium-activated potassium ion channel called SK4 is expressed in corticotrophs and regulates ACTH release. We provide evidence of how SK4 channels control corticotroph function, which is essential for understanding homeostasis and for treating stress-related disorders.AbstractThe anterior pituitary corticotroph is a major control point for the regulation of the hypothalamic–pituitary–adrenal (HPA) axis and the neuroendocrine response to stress. Although corticotrophs are known to be electrically excitable, ion channels controlling the electrical properties of corticotrophs are poorly understood. Here, we exploited a lentiviral transduction system to allow the unequivocal identification of live murine corticotrophs in culture. We demonstrate that corticotrophs display highly heterogeneous spontaneous action-potential firing patterns and their resting membrane potential is modulated by a background sodium conductance. Physiological concentrations of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) cause a depolarization of corticotrophs, leading to a sustained increase in action potential firing. A major component of the outward potassium conductance was mediated via intermediate conductance calcium-activated (SK4) potassium channels. Inhibition of SK4 channels with TRAM-34 resulted in an increase in corticotroph excitability and exaggerated CRH/AVP-stimulated ACTH secretion in vitro. In accordance with a physiological role for SK4 channels in vivo, restraint stress-induced plasma ACTH and corticosterone concentrations were significantly enhanced in gene-targeted mice lacking SK4 channels (Kcnn4−/−). In addition, Kcnn4−/− mutant mice displayed enhanced hypothalamic c-fos and nur77 mRNA expression following restraint, suggesting increased neuronal activation. Thus, stress hyperresponsiveness observed in Kcnn4−/− mice results from enhanced secretagogue-induced ACTH output from anterior pituitary corticotrophs and may also involve increased hypothalamic drive, thereby suggesting an important role for SK4 channels in HPA axis function.

Conductive hydrogels are a class of stretchable conductive materials that are important for various applications. However, water‐based conductive hydrogels inevitably lose elasticity and conductivity at subzero temperatures, which severely limits their applications at low temperatures. Herein we report anti‐freezing conductive organohydrogels by using an H2O/ethylene glycol binary solvent as dispersion medium. Owing to the freezing tolerance of the binary solvent, our organohydrogels exhibit stable flexibility and strain‐sensitivity in the temperature range from −55.0 to 44.6 °C. Meanwhile, the solvent molecules could form hydrogen bonds with polyvinyl alcohol (PVA) chains and induce the crystallization of PVA, greatly improving the mechanical strength of the organohydrogels. Furthermore, the non‐covalent crosslinks endow the conductive organohydrogels with intriguing remoldability and self‐healing capability, which are important for practical applications.