Distinct Allostery Induced in the Cyclic GMP-binding, Cyclic GMP-specific Phosphodiesterase (PDE5) by Cyclic GMP, Sildenafil, and Metal Ions

The activity of many proteins orchestrating different biological processes is regulated by allostery, where ligand binding at one site alters the function of another site. Allosteric changes can be brought about by either a change in the dynamics of a protein, or alteration in its mean structure. We have investigated the mechanisms of allostery induced by chemically distinct ligands in the cGMP-binding, cGMP-specific phosphodiesterase, PDE5. PDE5 is the target for catalytic site inhibitors, such as sildenafil, that are used for the treatment of erectile dysfunction and pulmonary hypertension. PDE5 is a multidomain protein and contains two N-terminal cGMP-specific phosphodiesterase, bacterial adenylyl cyclase, FhLA transcriptional regulator (GAF) domains, and a C-terminal catalytic domain. Cyclic GMP binding to the GAFa domain and sildenafil binding to the catalytic domain result in conformational changes, which to date have been studied either with individual domains or with purified enzyme. Employing intramolecular bioluminescence resonance energy transfer, which can monitor conformational changes both in vitro and in intact cells, we show that binding of cGMP and sildenafil to PDE5 results in distinct conformations of the protein. Metal ions bound to the catalytic site also allosterically modulated cGMP- and sildenafil-induced conformational changes. The sildenafil-induced conformational change was temperature-sensitive, whereas cGMP-induced conformational change was independent of temperature. This indicates that different allosteric ligands can regulate the conformation of a multidomain protein by distinct mechanisms. Importantly, this novel PDE5 sensor has general physiological and clinical relevance because it allows the identification of regulators that can modulate PDE5 conformation in vivo.

Growth and characterization of laser-deposited Ag-doped YBa2Cu3O7−x thin films on bare sapphire

Microstructural and superconducting properties of YBa2Cu3O7-x thin films grown in situ on bare sapphire by pulsed laser deposition using YBa2Cu3O7-x targets doped with 7 and 10 wt% Ag have been studied. Ag-doped films grown at 730 degrees C on sapphire have shown very significant improvement over the undoped YBa2Cu3O7-x films grown under identical condition. A zero resistance temperature of 90 K and a critical current density of 1.2 x 10(6) A/cm(2) at 77 K have been achieved on bare sapphire for the first time. Improved connectivity among grains and reduced reaction rate between the substrate and the film caused due to Ag in the film are suggested to be responsible for this greatly improved transport properties.

Influence of Bi 3+ ions in enhancing the magnitude of positive temperature coefficients of resistance in n-BaTiO3 ceramics

Bi3+ ions substituting at Ba-sites in a limited concentration range with another donor dopant occupying the Ti-sites in polycrystalline BaTiO3 enhanced the positive temperature coefficient of resistance (PTCR) by over seven orders of magnitude. These ceramics did not require normal post sinter annealing or a change to an oxygen atmosphere during annealing. These ceramics had low porosities coupled with better stabilities to large applied electric fields and chemically reducing atmospheres. Bi3+ ions limited the grain growth to less than 8 mum in size, they enhanced the concentration of acceptor-type trap centres at the grain-boundary-layer regions and maintained complete tetragonality at low grain sizes in BaTiO3 ceramics.

Differential influence of ions on the copy number of plasmids in Thiobacillus ferrooxidans

Thiobacillus ferrooxidans MAL4-1, an isolate from Malanjkhand copper mines, India, was adapted to grow in the presence of high concentration (30 gL(-1)) of Cu2+, resulting in a 15-fold increase in its tolerance to Cu2+. While wild-type T. ferrooxidans MAL4-1 contained multiple plasmids, cultures adapted to Cu2+ concentrations of 20 gL(-1) or more showed a drastic reduction in the copy number of the plasmids. The reduction for three of the plasmids was estimated to be over 50-fold. Examination of the plasmid profiles of the strains adapted to high concentration of SO42- anion (as Na2SO4 or ZnSO4) indicated that the reduction in plasmid copy number is not owing to SO42- anion, but is specific for Cu2+. The effect of mercury on the plasmids was similar to that of copper. Deadaptation of the Cu2+- Or Hg2+-adapted T. ferrooxidans resulted in restoration of the plasmids to the original level within the first passage. The fact that the plasmid copy number, in general, is drastically reduced in Cu2+-adapted T. ferrooxidans suggests that resistance to copper is chromosome mediated. This is the first report of a selective negative influence of copper ions on the copy number of plasmids in T. ferrooxidans.

Fly ash as a pre-filter material for the retention of lead ions

Clay liners have been widely used to contain toxic and hazardous waste materials. Clays absorb contaminant cations due to their exchange capacity. To improve the performance of the clay liner, fly ash, a waste material arising from the combustion of coal has been studied as a pre-filter material. In particular, the retention of lead by two different fly ashes was studied. The influence of pH on retention as well as leaching characteristics are also examined. The results obtained from the retention experiments by the permeameter method indicate that fly ash retains the lead ions through precipitation in the pores as well as onto the surface when the ambient pH value is more than 5.5, and through adsorption when the pH value is less than 5.5. It has been observed that fly ash did not release the retained lead ions when the pH value is between 3.5 and 10.0. Hence, the retention of lead ions by fly ash is likely to be permanent since the pH of most of the municipal landfill leachates are within 3.7 to 8.8. However, for highly acidic or alkaline leachates, the retained ions can get released.

Influence of pH on the retention of heavy metal ions by fly ash

Clay liners have been widely used to contain toxic and hazardous wastes. Clays adsorb the contaminant cations due to their exchange capacity. To improve the performance of the clay liner, fly ash, a waste material arising out of combustion of coal has been studied as a pre-filter material. The results indicate that fly ash has the potential to retain heavy metal ions. This study concerns the retention of zinc by fly ash. The influence of pH on retention as well as leaching characteristics are examined. The results obtained from the retention experiments by permeameter method indicate that fly ash retains the zinc ions through precipitation in the pores as well as onto the surface when the ambient pH value is more than 6.9, and only through adsorption when the pH value is less than 6.9. It has been observed that fly ash did not release the retained zinc ions when the pH value is between 3.5 and 10.0. Hence, the retention of zinc ions by fly ash is likely to be permanent since the pH of most of the landfill leachates are between 3.7 to 8.8.

Modulation of vesicular properties by variation of shapes of bolaform counter ions in hybrid-ion paired surfactants

Four new vesicle-forming bolaphile/amphiphile ion pairs are synthesized; the bolaphile shapes in such hybrid systems strongly control their vesicular properties.

New uniform solid catalyst for the low-temperature oxidation of carbon monoxide: A triple-layered rare earth perovskite containing Co and Cu ions

Oxygen reactivity and catalytic activity of the cobalt-containing layered defect perovskites, YBa2Cu2CoO7+delta and LaBa2Cu2CoO7+delta, in comparison with LaBa2Cu3O7-delta have been investigated employing temperature-programmed desorption (TPD) and temperature-programmed surface reactions (TPSR) in the stoichiometric and catalytic mode using carbon monoxide as a probe molecule. TPD studies showed evidence for the presence of two distinct labile oxygen species, one at (0 0 1/2) sites and the other at (0 1/2 0) sites in LaBa2Cu2CoO7+delta against a single labile species at (0 1/2 0) in the case of two other oxides. The activation energies for the catalytic oxidation of carbon monoxide by oxygen over LaBa2Cu3O7-delta, YBa2Cu2CoO7+delta, and LaBa2Cu2CoO7+delta have been estimated to be 24.2, 15.9, and 13.6 kcal/mol, respectively. The reactivity and catalytic activity of the oxide systems have been interpreted in terms of the structural changes brought about by substituents, guided by a directing effect of the larger rare earth cation. TPSR profiles, structural analysis, and infrared spectroscopic investigations suggest that the oxygen present at (0 0 1/2) sites in the case of LaBa2Cu2CoO7+delta is accessible to catalytic oxidation of CO through a Mars-Van Krevelen pathway. Catalytic conversion of CO to CO2 over LaBa2Cu2CoO7+delta occurs at 200 degrees C. The enhanced reactivity is explained in terms of changes brought about in the coordination polyhedra around transition metals, enhanced basal plane oxygen diffusivity, and redox potentials of the different transition metal cations.

Coordination aggregation of mesoaryl substituted porphyrins

Synthesis of the free-base tetrakis (3'-nitro/aminophenyl), (H2TNP/H(2)TAP) has been accomplished and its coordination behaviour towards Mg(II), Co(II), Zn(II) and Ag(II) ions is investigated. Optical and magnetic resonance properties of the metal derivatives MTNP and MTAP reveal that the aminoporphyrins exist as aggregates in solution. The aggregation is promoted by the coordination of the peripheral amino groups to neighbouring metalloporphyrins. Possible structures of aggregated species are proposed from the model studies.

Thermally Controlled Cyclic Insertion/Ejection of Dopant Ions and Reversible Zinc Blende/Wurtzite Phase Changes in ZnS Nanostructures

We report a reversible phase transformation of platelet-shaped ZnS nanostructures between wurtzite (WZ) and zinc blende (ZB) phases by reversible insertion/ ejection of dopant Mn(II) ions induced by a thermocyclic process. In a reaction flask loaded with WZ ZnS platelets and Mn molecular precursors, during heating Mn ions are incorporated and change the phase of the host nanostructures to ZB; during cooling Mn ions are spontaneously ejected, returning the host nanoplatelets to the original WZ phase. These reversible changes are monitored for several cycles with PL, EPR, XRD, and HRTEM. Interestingly, the (0001) WZ platelets transform to (110) ZB following a nucleation and growth process triggered by a local increase/depletion of the Mn2+ concentration in the nanocrystals.

Thermally Controlled Cyclic Insertion/Ejection of Dopant Ions and Reversible Zinc Blende/Wurtzite Phase Changes in ZnS Nanostructures

We report a reversible phase transformation of platelet-shaped ZnS nanostructures between wurtzite (WZ) and zinc blende (ZB) phases by reversible insertion/ ejection of dopant Mn(II) ions induced by a thermocyclic process. In a reaction flask loaded with WZ ZnS platelets and Mn molecular precursors, during heating Mn ions are incorporated and change the phase of the host nanostructures to ZB; during cooling Mn ions are spontaneously ejected, returning the host nanoplatelets to the original WZ phase. These reversible changes are monitored for several cycles with PL, EPR, XRD, and HRTEM. Interestingly, the (0001) WZ platelets transform to (110) ZB following a nucleation and growth process triggered by a local increase/depletion of the Mn2+ concentration in the nanocrystals.

Oxidation of substituted benzylic hydrocarbons and naphthalenes by peroxydisulphate in the presence of metal ions

Oxidations of various substituted benzylic hydrocarbons with peroxydisulphate in the presence of metal ion catalysts like iron, nickel, copper, cobalt, silver and cerium were examined. Among the metal ions copper (II) catalysed reaction gives products in excellent yield, whereas oxidation of naphthalene and substituted naphthalenes gives low to moderate yield of the products with peroxydisulphate- copper (II).

Role of Li+ ions in corrosion behaviour of 8090 Al-Li alloy and aluminium in pH 12 aqueous solutions

The influence of Li+ ions on the corrosion behaviour of the Al-Li alloy 8090-T851 and of commercially pure aluminium in aqueous solutions at pH 12 was studied by weight loss and electrochemical polarisation methods. The inhibiting role of Li+ was concentration dependent, corrosion rate decreasing lineally with log[Li+] in the concentration range 10(-4)-10(-1) mol L(-1). A change from general to pitting corrosion was evident from scanning election microscopy studies. Polarisation studies revealed that Li+ primarily acts as an anodic inhibitor (passivator). Passive film formation and stability also become more feasible with increasing Li+ concentration. Fitting potential was dependent on the Cl- ion concentration in the solution. Both materials were affected similarly by the presence of Li+ ions, the corrosion rate of the alloy being slightly lower. This is attributed to the lithium in the alloy acting as a source of lithium for passive film formation. (C) 1995 The Institute of Materials.

Surface resistance and residual losses of Ag?doped YBa2Cu3O7?? thin films on sapphire

High?quality Ag?doped YBa2Cu3O7?? thin films have been grown by laser ablation on R?plane ?1102? sapphire without any buffer layer. Thin films have been found to be highly c?axis oriented with Tc=90 K, transition width ?T?1 K, and transport Jc=1.2×106 A?cm?2 at 77 K in self?field conditions. The microwave surface resistance of these films measured on patterned microstrip resonators has been found to be 530 ?? at 10 GHz at 77 K which is the lowest reported on unbuffered sapphire. Improved in?plane epitaxy and reduced reaction rate between the substrate and the film caused due to Ag in the film are believed to be responsible for this greatly improved microwave surface resistance. © 1995 American Institute of Physics.