Development of Phosphodiesterase–Protein-Kinase Complexes as Novel Targets for Discovery of Inhibitors with Enhanced Specificity

Phosphodiesterases (PDEs) hydrolyze cyclic nucleotides to modulate multiple signaling events in cells. PDEs are recognized to actively associate with cyclic nucleotide receptors (protein kinases, PKs) in larger macromolecular assemblies referred to as signalosomes. Complexation of PDEs with PKs generates an expanded active site that enhances PDE activity. This facilitates signalosome-associated PDEs to preferentially catalyze active hydrolysis of cyclic nucleotides bound to PKs and aid in signal termination. PDEs are important drug targets, and current strategies for inhibitor discovery are based entirely on targeting conserved PDE catalytic domains. This often results in inhibitors with cross-reactivity amongst closely related PDEs and attendant unwanted side effects. Here, our approach targeted PDE–PK complexes as they would occur in signalosomes, thereby offering greater specificity. Our developed fluorescence polarization assay was adapted to identify inhibitors that block cyclic nucleotide pockets in PDE–PK complexes in one mode and disrupt protein-protein interactions between PDEs and PKs in a second mode. We tested this approach with three different systems—cAMP-specific PDE8–PKAR, cGMP-specific PDE5–PKG, and dual-specificity RegA–R_D complexes—and ranked inhibitors according to their inhibition potency. Targeting PDE–PK complexes offers biochemical tools for describing the exquisite specificity of cyclic nucleotide signaling networks in cells.     

Photoluminescence of Gallate Glass-Ceramics: Al2O3 Influence

Glass and Ceramics - The influence of Al2O3 as an additive and the heat-treatment regime on the luminescence spectra of gallate glass-ceramics was investigated. It is shown that its luminescence...     

Evaluation of the Range of Stable and Efficient Operation of Column Mass Transfer Devices with Jet-Film Contact Devices

Chemical and Petroleum Engineering - A contact device for heat and mass transfer devices with the ability to maintain the uniformity of flow distribution over the cross section of the device is...     

Investigation of Natural Radioactivity in Wadi El Reddah Stream Sediments and Its Radiological Implications

Radiochemistry - Wadi El Reddah has radiation exposure due to the presence of different types of complexed rocks along with a huge sector of Hammamat sedimentary rocks, monzongranites of Gabal El...     

Strain mediated enhancement in magnetoelectric properties of sonochemically synthesized piezoelectric and piezomagnetic composites

Materials with magneto-electric (ME) properties are of great importance because of their demand in electronic industries. Three dimensional nano-particles of the ME-composites having the general formula (1-x)CoCr_0.3Fe_1.7O₄(CCFO)+(x)BaTiO₃(BTO) (x = 0.0, 0.2, 0.4, 0.6, 0.8 and 1.0) were obtained by comprising the piezoelectric-BTO and piezomagnetic-CCFO phases. The individual phases of CCFO and BTO were synthesized separately by ultrasonic irradiation assisted sonochemical and sol-gel routs. X-ray diffraction patterns (XRD) confirmed the well-crystalline nature of both the phases. BTO and CCFO phases were under tensile strain as confirmed by the variation in lattice constants with varying proportion of BTO and CCFO. An energy-dispersive X-ray spectroscopy spectrum confirmed the phase purity of the samples and stoichiometric concentration of elements. Magnetic properties were investigated by M ? H loop measurements and dielectric properties by using RF impedance analyzer. Dielectric constant increased with the increasing percentage of BTO. The maximum value of ME coefficient (24.7 mV/cm?Oe) is observed for the 60%CCFO+40%BTO sample. The obtained results were discussed in the light of grain size, strain and the basic properties of the individual phases. The prepared materials can be applicable in electronic devices where high magneto-electric coefficient is desirable.     

Effect of CdO addition on photon,electron, and neutron attenuation properties of boro-tellurite glasses

This research article aims to study the effect of CdO addition on the radiation shielding characteristics of boro-tellurite glasses in the composition of 50B₂O₃ - (50-x) TeO2- xCdO, where x = 0, 10, 20, 30, 40 and 50 mol%. These glasses were exposed to gamma radiation and the transmitted gamma photons were evaluated for energies varying from 15 keV to 15 MeV using Geant4 simulation toolkit. The number of transmitted photons was then used to characterize the gamma shielding for the studied glasses in terms of linear/mass attenuation coefficients, MFP, Z_eff, and HVL. The simulation outcomes were theoretically confirmed by using Phy-X software. The beta (electron) shielding characterization of the involved glasses was also investigated by determining the projectile range and stopping power using ESTAR software. Additionally, the fast neutron shielding characterization of the glasses was achieved by evaluating removal cross-section (Σ_R). The results reveal that the CdO has a small influence on the shielding performance of the boro-tellurite glasses against gamma, beta, and neutron radiations. The shielding performance of the boro-tellurite glasses was compared with that of common shielding materials in terms of MFP. It can be concluded that the boro-tellurite glasses regardless of the concentration of CdO content have promising shielding performance to be used for radiation applications.     

A Generator of High-Power Volume Discharges of Nanosecond Duration

Instruments and Experimental Techniques - A generator of high-power nanosecond pulses is described that contains a high-voltage unit, which is based on a magnetic-compression circuit and a diode...     

Agro-Waste Generated Pd/CAP-Ash Catalyzed Ligand-Free Approach for Suzuki–Miyaura Coupling Reaction

Catalysis Letters - We converted agro-waste Custard Apple Peels (CAP) to ash via thermal treatment, on which Pd(OAc)2 was immobilized easily that produced a low-cost, highly efficient Pd/CAP-ash...     

Applicability Boron-Containing Materials Obtained by Self-Propagating High-Temperature Synthesis in Radiation Protection Technology

Atomic Energy - An implementation assessment of PSKD-600 type power reactors was made. It was established that the readiness level of all PSKD-600 nuclear fuel cycle technologies is no lower than...     

Mechanical properties and thermal shock in thin ZrO2–Y2O3–Al2O3 films obtained by the sol-gel method

Thin multilayer coatings of ZrO₂–Y₂O₃–Al₂O₃ were prepared using the sol-gel method and dip-coating technique in order to advance in the study of what influence the incorporation of Al₂O₃ has on films of Y₂O₃-doped ZrO₂, investigating its role in the synthesis of the solutions and in the characteristics and properties of the coatings. After the characterization of the solutions used in the process, the microstructure of the films was studied and their mechanical behaviour and resistance to thermal shock were determined so as to optimize the characteristics and functionality of these coatings. With increased alumina content, 3YSZ-Al₂O₃ (20 mol%), the cubic phase of the zirconia disappeared completely at the sintering temperature used (700 °C), resulting in the tetragonal phase with Al in solution. There was also a decrease in the coatings' hardness and Young's modulus, and an increase in toughness and resistance to thermal shock. These results allow guidelines to be established for the design of multilayer structures that are, tougher, more resistant, and have improved surface properties.