The mechanism by which inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5, 6)P4) regulates chloride (Cl-) secretion was evaluated in the colonic epithelial cell line T84 using whole cell voltage clamp techniques. Our studies focused on the calcium-dependent chloride conductance (gClCa) that was activated either by mobilizing intracellular calcium (Cai) stores with thapsigargin or by introduction of the autonomous, autophosphorylated calmodulin-dependent protein kinase II (CaMKII) into the cell via the patch pipette. Basal concentrations of Ins(3,4,5,6)P4 (1 microM) present in the pipette solution had no significant effect on Cl- current; however, as the concentration of the polyphosphate was increased there was a corresponding reduction in anion current, with near complete inhibition at 8-10 microM Ins(3,4,5,6)P4. Corresponding levels are found in cells after sustained receptor-dependent activation of phospholipase C. The Ins(3,4,5, 6)P4-induced inhibition of gClCa was isomer specific; neither Ins(1, 3,4,5)P4, Ins(1,3,4,6)P4, Ins(1,4,5,6)P4, nor Ins(1,3,4,5,6)P5 induced current inhibition at concentrations of up to 100 microM. Annexin IV also plays an inhibitory role in modulating gClCa in T84 cells. When 2 microM annexin IV was present in the pipette solution, a concentration that by itself has no effect on gClCa, the potency of Ins(3,4,5,6)P4 was approximately doubled. The combination of Ins(3,4,5,6)P4 and annexin IV did not alter the in vitro activity of CaMKII. These data demonstrate that Ins(3,4,5,6)P4 is an additional cellular signal that participates in the control of salt and fluid secretion, pH balance, osmoregulation, and other physiological activities that depend upon gClCa activation. Ins(3,4,5,6)P4 metabolism and action should also be taken into account when designing treatment strategies for cystic fibrosis.

The cystic fibrosis gene encodes a cyclic AMP-gated chloride channel (CFTR) that mediates electrolyte transport across the luminal surfaces of a variety of epithelial cells. The molecular mechanisms that modulate CFTR activity in epithelial tissues are poorly understood. Here we show that CFTR is regulated by an epithelially expressed syntaxin (syntaxin 1A), a membrane protein that also modulates neurosecretion and calcium-channel gating in brain. Syntaxin 1A physically interacts with CFTR chloride channels and regulates CFTR-mediated currents both in Xenopus oocytes and in epithelial cells that normally express these proteins. The physical and functional interactions between syntaxin 1A and CFTR are blocked by a syntaxin-binding protein of the Munc18 protein family (also called n-Secl). Our results indicate that CFTR function in epithelial cells is regulated by an interplay between syntaxin and Munc18 isoforms.

Aerogels are considered ideal candidates for various applications, because of their low bulk density, highly porous nature, and functional performance. However, the time intensive nature of the complex fabrication process limits their potential application in various fields. Recently, incorporation of a fibrous network has resulted in production of aerogels with improved properties and functionalities. A facile approach is presented to fabricate hybrid sol-gel electrospun silica-cellulose diacetate (CDA)-based nanofibers to generate thermally and mechanically stable nanofiber aerogels. Thermal treatment results in gluing the silica-CDA network strongly together thereby enhancing aerogel mechanical stability and hydrophobicity without compromising their highly porous nature (>98%) and low bulk density (≈10 mg cm −3 ). X-ray photoelectron spectroscopy and in situ Fouriertransform infrared studies demonstrate the development of strong bonds between silica and the CDA network, which result in the fabrication of crosslinked structure responsible for their mechanical and thermal robustness and enhanced affinity for oils. Superhydrophobic nature and high oleophilicity of the hybrid aerogels enable them to be ideal candidates for oil spill cleaning, while their flame retardancy and low thermal conductivity can be explored in various applications requiring stability at high temperatures. and consists of a highly porous (at least 90%) solid network. [2] Their extremely low bulk density, highly porous nature, and large surface area make them ideal candidates for diverse applications ranging from thermal insulation, separation and biomedical to acoustics; [3][4][5][6] however, the time intensive nature of the fabrication process involving complicated steps and general lack of mechanical stability in the traditional aerogels present major challenges for their large scale applications in a cost-effective manner. Lack of flexibility and mechanical stability in an aerogel is primarily caused by the development of "necks" or "pearl-necklace like structure" during the drying process. [7] Introduction of polymeric phase in inorganic gels has helped to overcome this defect but the cost and duration of the process still hinder the large-scale application of these materials. Recent studies indicate that the presence of fibrous network in the aerogels strengthens it mechanically since it minimizes the existence of "necks" in the skeleton. [8][9][10][11][12] While exploring various options for functional fibrous networks, electrospun nanofibers can be considered as one of the leading options because of their fiber diameter in nanoscale, high aspect ratio and strength. [13,14] Electrospun nanofiber based materials demonstrate advanced properties; however, their layered deposition generates a 2D flat mat. [13,15] A 3D self-supportive structure would clearly further enhance the inherent properties of the nanofibers. Whereas techniques such as gas expansion, [16] cool drum, [17] and self-assembly [18,19] are explored to generate 3D nanofibr...

Elemental boron arouses great interest from both scientific and technological areas of research because it has unique chemical and physical properties and its theoretical tubular structures may have higher electrical conductivity than carbon nanotubes. [1][2][3][4][5][6][7] High conductivity and chemical stability of boron or boride nanostructures have made it an attractive candidate for future applications in ideal cold-cathode materials, high-temperature semiconductor devices, or fieldeffect transistors. [8][9][10][11][12][13][14] In particular, for the application of field emission (FE), it is especially useful to synthesize large, vertical arrays of boron nanowires (BNWs) with the desired surface work function and FE behavior. So far, to our knowledge, while both amorphous [15][16][17][18][19][20] and crystalline boron nanowires [21,22] have been fabricated by magnetron sputtering, laser ablation, or chemical vapor methods, vertical arrays of single-crystal boron nanowires over a large area have not been synthesized in a one-step process. In addition, little attention [23][24][25] has been paid to the measurements of the physical properties of an individual boron nanowire. In this Communication, we report the successful synthesis of high-density, vertically aligned single-crystal boron nanowire arrays with a nanowire diameter of approximately 20-40 nm by a thermal carbon-reduction method. Moreover, we have measured the FE behavior and surface work function of a single boron nanowire, which is critical to evaluate the possibility of using boron nanowires as field-emission materials. For the purpose of better understanding the field-emission mechanism of a boron nanowire, the field-emission properties of a BNW film are also measured to compare with those of an individual nanowire. Figure 1 shows large-scale boron nanowire arrays on a Si(001) substrate after approximately 2-4 h of growth. As shown in Figure 1A, the high-density arrays are aligned vertically on the silicon substrate. Figure 1B is the highresolution scanning electron microscopy (SEM) image of the aligned BNWs, in which one can see that the length of the BNW is about 5 mm and the morphology of the nanowires is uniform. The aspect ratio of each boron nanowire is about 200, which is high enough for a field-emission application. The side and top views of the boron nanowire are shown in Figure 1C and D, respectively, which reveals the detailed morphology of the BNWs. The boron nanowires have a diameter of about 20-40 nm and no catalyst is found at their tip. The catalysts, however, were found to lie on the substrate arbitrarily when we peeled off some nanowire film from the substrate, as shown in Figure 1C. Thus, we believe that the growth is through a vapor-liquid-solid (VLS) mechanism and the binding force between the Fe 3 O 4 catalyst and the silicon substrate is strong. This strong binding leads to good conductivity between the boron nanowires and the substrate, which may contribute to their good field-emission properties. The alignment of BNWs can...

We have studied the regulation of whole‐cell chloride current in T84 colonic epithelial cells by inositol 3,4,5,6‐tetrakisphosphate (Ins(3,4,5,6)P4). New information was obtained using (a) microcystin and okadaic acid to inhibit serine/threonine protein phosphatases, and (b) a novel functional tetrakisphosphate analogue, 1,2‐bisdeoxy‐1,2‐bisfluoro‐Ins(3,4,5,6)P4 (i.e. F2‐Ins(3,4,5,6)P4). Calmodulin‐dependent protein kinase II (CaMKII) increased chloride current 20‐fold. This current (ICl,CaMK) continued for 7 ± 1.2 min before its deactivation, or running down, by approximately 60 %. This run‐down was prevented by okadaic acid, whereupon ICl,CaMK remained near its maximum value for ≥ 14.3 ± 0.6 min. F2‐Ins(3,4,5,6)P4 inhibited ICl,CaMK (IC50= 100 μM) stereo‐specifically, since its enantiomer, F2‐Ins(1,4,5,6)P4 had no effect at <= 500 μM. Dose‐response data (Hill coefficient = 1.3) showed that F2‐Ins(3,4,5,6)P4 imitated only the non‐co‐operative phase of inhibition by Ins(3,4,5,6)P4, and not the co‐operative phase. Ins(3,4,5,6)P4 was prevented from blocking ICl,CaMK by okadaic acid (IC50= 1.5 nM) and microcystin (IC50= 0.15 nM); these data lead to the novel conclusion that, in situ, protein phosphatase activity is essential for Ins(3,4,5,6)P4 to function. The IC50 values indicate that more than one species of phosphatase was required. One of these may be PP1, since F2‐Ins(3,4,5,6)P4‐dependent current blocking was inhibited by okadaic acid and microcystin with IC50 values of 70 nM and 0.15 nM, respectively.