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In this work we report the synthesis and characterization of a new nanostructured platinum/tin/telluride inorganic/surfactant composite. The material is synthesized from soluble SnTe(4)(4-) clusters and is shown to have well-defined nanometer scale periodicity along with unique optical properties. Small-angle X-ray scattering indicates that the material forms with a 2D hexagonal honeycomb structure, which is size tunable based on surfactant tail length. Multinuclear EXAFS is used as a probe of local order in these materials. The results indicate that the tetrahedral SnTe(4) unit dimerizes during assembly, and these clusters are coordinated to square planar platinum ions. Near-IR/visible reflectance spectroscopy indicates that the material is a narrow band gap semiconductor with a band gap of 0.8 eV. The extension of the ideas of surfactant templating to a narrow band gap semiconductor opens up the exciting potential for future optoelectronic applications.

Nicotinamide 8-Br-hypoxanthine dinucleotide (8-Br-NHD+) was cyclised at the N-1 position by ADP-ribosyl cyclase from Aplysia californica to give cyclic 8-Br-inosine diphosphoribose, a novel membrane-permeant analogue of cyclic-ADP ribose and agonist in human T cells. Adenine-substituted analogues of adenophostin A with potent Ca2+ releasing activity were synthesized; docking studies using the binding core of the Ins(1,4,5)P3 receptor identified specific residues that could be of importance in determining the hyperagonist nature of adenophostin activity.

Purpose: To assess the changes in pachymetry after routine corneal and scleral tunnel phacoemulsification., Setting: Discipline of Ophthalmology, University of Auckland, Auckland, New Zealand., Method: This prospective study comprised 174 eyes of 174 consecutive patients having uneventful, small-incision, sutureless, phacoemulsification cataract surgery; 124 patients had a clear corneal incision and 50, a superior scleral tunnel incision. Difference pachymetry maps were derived from Orbscan II elevation topography data obtained before and 4 weeks after surgery. Corneal thickness changes at 12 midperipheral areas located in 12 meridians were derived from difference (subtraction) maps. The mean corneal thickness within a single area corresponding to the center of the surgical incision was compared to the mean pachymetry readings of all 12 midperipheral measurements., Results: The overall mean midperipheral corneal thickness (12 samples per cornea) increased by a mean of 5.89 microm +/- 16.09 (SD) in the clear corneal incision group and 6.89 +/- 14.50 microm in the scleral tunnel group. The mean central corneal thickness increased by 7.28 +/- 20.98 microm and 7.74 +/- 21.34 microm, respectively. The corneal thickness in the meridian closest to the incision was significantly higher than the mean value of the 12 meridians measured in both groups, with means of 14.95 +/- 26.86 microm in the clear corneal group (P =.001) and 16.22 +/- 21.23 microm in the scleral tunnel group (P =.002). There were no statistically significant postoperative differences in the central, midperipheral, or incision-site corneal thickness measurements between the 2 surgical techniques (P =.77)., Conclusions: Time-dependent (fourth-dimensional) pachymetry subtraction maps are useful for following corneal dynamics over time. This study found that small-incision phacoemulsification techniques--scleral and corneal tunnel--had a minor but similar effect on corneal thickness 4 weeks after surgery.

The distances between the inositol 1,4,5-trisphosphate (IP(3))-binding sites of tetrameric IP(3) receptors were probed using dimers of IP(3) linked by poly(ethylene glycol) (PEG) molecules of differing lengths (1-8 nm). Each of the dimers potently stimulated (45)Ca(2+) release from permeabilized cells expressing predominantly type 1 (SH-SY5Y cells) or type 2 (hepatocytes) IP(3) receptors. The shortest dimers, with PEG linkers of an effective length of 1.5 nm or less, were the most potent, being 3-4-fold more potent than IP(3). In radioligand binding experiments using cerebellar membranes, the shortest dimers bound with highest affinity, although the longest dimer (8 nm) also bound with almost 4-fold greater affinity than IP(3). The affinity of monomeric IP(3) with only the PEG attached was 2-fold weaker than IP(3), confirming that the increased affinity of the dimers requires the presence of both IP(3) motifs. The increased affinity of the long dimer probably results from the linked IP(3) molecules binding to sites on different receptors, because the dimer bound with greater affinity than IP(3) to cerebellar membranes, where receptors are densely packed, but with the same affinity as IP(3) to purified receptors. IP(3) and the IP(3) dimers, irrespective of their length, bound with similar affinity to a monomeric IP(3)-binding domain of the type 1 IP(3) receptor expressed in bacteria. Short dimers therefore bind with increased affinity only when the receptor is tetrameric. We conclude that the four IP(3)-binding sites of an IP(3) receptor may be separated by as little as 1.5 nm and are therefore likely to be placed centrally in this large (25 x 25 nm) structure, consistent with previous work indicating a close association between the central pore and the IP(3)-binding sites of the IP(3) receptor.

Inositol 1,4,5-trisphosphate (IP(3)) receptors from cerebellum and recombinant type 1 IP(3) receptors expressed in Sf9 cells had indistinguishable affinities for IP(3) ( K (d)=6.40+/-0.48 nM) and adenophostin A ( K (d)=0.89+/-0.05 nM). In cytosol-like medium, each of the three mammalian IP(3) receptor subtypes when expressed in Sf9 cells bound adenophostin A with greater affinity than IP(3). It has been suggested that adenophostin A binds with high affinity only in the presence of ATP, but we found that adenophostin A similarly displaced [(3)H]IP(3) from type 1 IP(3) receptors whatever the ATP concentration. N-terminal fragments of the type 1 receptor were expressed with and without the S1 splice site; its removal had no effect on [(3)H]IP(3) binding to the 1-604 protein, but abolished binding to the 224-604 protein. The 1-604 fragment and full-length receptor bound adenophostin A with the same affinity, but the fragment had 3-fold greater affinity for IP(3), suggesting that C-terminal residues selectively inhibit IP(3) binding. The 224-604S1(+) fragment bound IP(3) and adenophostin A with increased affinity, but as with the 1-604 fragment it bound adenophostin A with only 2-fold greater affinity than IP(3). High-affinity binding of adenophostin A may be partially determined by its 2'-phosphate interacting more effectively than the 1-phosphate of IP(3) with residues within the IP(3)-binding core. This may account for the 2-fold greater affinity of adenophostin A relative to IP(3) for the minimal IP(3)-binding domain. In addition we suggest that C-terminal residues, which impede access of IP(3), may selectively interact with adenophostin A to allow it unhindered access to the IP(3)-binding domain.

Adenophostins A and B are naturally occurring glyconucleotides that interact potently with receptors for D-myo-inositol 1,4,5-trisphosphate, an important second messenger molecule in most cell types. Here we describe the design and synthesis of glucopyranoside-based analogues of adenophostin A lacking the adenine component. The key synthetic strategy involves glycosylation of selectively protected alcohols, derived from methyl beta-D-ribofuranoside or 1,4-anhydroerythritol, using glycosyl donors synthesised from 2,6-di-O-benzyl-D-glucopyranose derivatives. Further elaboration and deprotection of the coupled products gave two trisphosphate analogues; methyl 3-O-alpha-D-glucopyranosyl-beta-D-ribofuranoside 2,3',4'-trisphosphate ("ribophostin") and (3'S,4'R)-3'-hydroxytetrahydrofuran-4'-yl alpha-D-glucopyranoside 3,4,3'-trisphosphosphate ("furanophostin"). The route to furanophostin was further modified to give (3'S,4'R)-3'-hydroxytetrahydrofuran-4'-yl alpha-D-glucopyranoside 3'-phosphate 3,4-bisphosphorothioate, the first phosphorothioate-containing adenophostin analogue.

The purpose of the study was to perform quantitative analysis of the sub-basal epithelial nerve plexus of healthy, living human cornea,using real time in vivo confocal microscopy and the analySIS software system. The study was based on in vivo confocalmicrostructural analysis of 50 eyes of 50 subjects, divided into two age groups: group 1 (n = 25)25 +/- 5 years of age, and group 2 (n = 25) 70 +/- 5 years of age. All subjects exhibited clinically healthy corneas. The overall nerve density was 632.35 +/- 287.57 microm/mm2 for group 1 and 582.39 +/- 327.13 microm/mm2 for group 2. The mean fibre dia-meter was measured at 0.52 +/- 0.23 microm for group 1 and at 0.56 +/- 0.27 microm for group 2. Beadings of the nerve fibres were recorded at a density of 213 +/- 123/mm for group 1 and 201 +/- 192/mm for group 2. Establishing standards for normal nerve density and morphology of the living human cornea at different ages may be beneficial, both in early detection and follow up of various corneal diseases and in post-surgical management following corneal surgery.

Regulation of Cl(-) channel conductance by Ins(3,4,5,6)P(4) provides receptor-dependent control over salt and fluid secretion, cell volume homeostasis, and electrical excitability of neurones and smooth muscle. Ignorance of how Ins(3,4,5,6)P(4) is synthesized has long hindered our understanding of this signaling pathway. We now show Ins(3,4,5,6)P(4) synthesis by Ins(1,3,4,5,6)P(5) 1-phosphatase activity by an enzyme previously characterized as an Ins(3,4,5,6)P(4) 1-kinase. Rationalization of these phenomena with a ligand binding model unveils Ins(1,3,4)P(3) as not simply an alternative kinase substrate, but also an activator of Ins(1,3,4,5,6)P(5) 1-phosphatase. Stable overexpression of the enzyme in epithelial monolayers verifies its physiological role in elevating Ins(3,4,5,6)P(4) levels and inhibiting secretion. It is exceptional for a single enzyme to catalyze two opposing signaling reactions (1-kinase/1-phosphatase) under physiological conditions. Reciprocal coordination of these opposing reactions offers an alternative to general doctrine that intracellular signals are regulated by integrating multiple, distinct phosphatases and kinases.