Development of Cu(ii)-specific peptide shuttles capable of preventing Cu–amyloid beta toxicity and importing bioavailable Cu into cells

Copper (Cu) in its ionic forms is an essential element for mammals and its homeostasis is tightly controlled. Accordingly, Cu-dyshomeostasis can be lethal as is the case in the well-established genetic Wilson''s and Menkes diseases. In Alzheimer''s disease (AD), Cu-accumulation occurs in amyloid plaques, where it is bound to the amyloid-beta peptide (Aβ). In vitro, Cu–Aβ is competent to catalyze the production of reactive oxygen species (ROS) in the presence of ascorbate under aerobic conditions, and hence Cu–Aβ is believed to contribute to the oxidative stress in AD. Several molecules that can recover extracellular Cu from Aβ and transport it back into cells with beneficial effects in cell culture and transgenic AD models were identified. However, all the Cu-shuttles currently available are not satisfactory due to various potential limitations including ion selectivity and toxicity. Hence, we designed a novel peptide-based Cu shuttle with the following properties: (i) it contains a Cu(ii)-binding motif that is very selective to Cu(ii) over all other essential metal ions; (ii) it is tagged with a fluorophore sensitive to Cu(ii)-binding and release; (iii) it is made of a peptide platform, which is very versatile to add new functions. The work presented here reports on the characterization of AKH-αR5W4^NBD, which is able to transport Cu ions selectively into PC12 cells and the imported Cu appeared bioavailable, likely via reductive release induced by glutathione. Moreover, AKH-αR5W4^NBD was able to withdraw Cu from the Aβ_1–16 peptide and consequently inhibited the Cu-Aβ based reactive oxygen species production and related cell toxicity. Hence, AKH-αR5W4^NBD could be a valuable new tool for Cu-transport into cells and suitable for mechanistic studies in cell culture, with potential applications in restoring Cu-homeostasis in Cu-related diseases such as AD.

The synthetic peptide AKH-αR5W4^NBD was designed as a shuttle to counteract copper imbalance in Alzheimer’s disease. In vitro, this shuttle is able to abstract Cu(ii) selectively from amyloid-β and transport it into cells in a bioavailable form.     

The sheath criterion for a collisional plasma sheath at the presence of external magnetic field

The Bohm sheath criterion is modified for collisional plasma containing Boltzmann electrons and cold fluid ions at the presence of external magnetic field. Based on fluid model, the effects of the strength and the orientation of an external magnetic field on the upper and lower limits of Bohm sheath criterion have been studied by considering the collision frequency between ions and neutrals. The results show that the sheath criterion depends on the orientation and magnitude of magnetic field and the ion flow velocity at the sheath boundary.     

Detection of nano scale thin films with polarized neutron reflectometry at the presence of smooth and rough interfaces

By knowing the phase and modules of the reflection coefficient in neutron reflectometry problems, a unique result for the scattering length density (SLD) of a thin film can be determined which will lead to the exact determination of type and thickness of the film. In the past decade, several methods have been worked out to resolve the phase problem such as dwell time method, reference layer method and variation of surroundings, among which the reference method and variation of surroundings by using a magnetic substrate and polarized neutrons is of the most applicability. All of these methods are based on the solution of Schrödinger equation for a discontinuous and step-like potential at each interface. As in a real sample there is some smearing and roughness at the boundaries, and consideration of smoothness and roughness of interfaces would affect the final output result. In this paper, we have investigated the effects of the smoothness of interfaces on the determination of the phase of reflection as well as the retrieval process of the SLD, by using a smooth varying function (Eckart potential). The effects of the roughness of interfaces on the same parameters have also been investigated by random variation of the interface around its mean position.     

IR laser‐induced breakdown in tetramethyltin adjacent to Ag or Au: deposition of β‐Sn nanograin‐containing amorphous Au–Sn/C and Ag–Sn/C films

Pulsed IR laser irradiation of metal (Au or Ag) target in gaseous tetramethyltin (TMT) results in metal ablation and adjacent dielectric breakdown (DB) in TMT and allows gas phase deposition of films containing metal (Au or Ag), Sn and C elements. Volatile products of DB of TMT were examined by FT‐IR spectroscopy and revealed as intermediates of gas phase carbonization reactions. The solid films were analyzed by FT‐IR and Raman spectroscopy, X‐ray diffraction and electron microscopy and shown as amorphous nanostructured Au–Sn/C and Ag–Sn/C phases containing β‐Sn nanograins. These Sn nanograins exhibit irreversible amorphization upon heating and melt below the melting point of bulk β‐Sn phase. Copyright © 2012 John Wiley & Sons, Ltd.     

A facile and effective procedure for synthesis of polyfunctionalized pyrrolines from simultaneously stirring of carbon disulfide,aniline, arylglyoxals and <Emphasis Type="Italic">β</Emphasis>-enaminocarbonyls

An efficient one-pot synthesis of 2H-pyrroline derivatives by a four-component reaction between carbon disulfide, aniline, arylglyoxals and β-enaminocarbonyls in acetonitrile at room temperature under mild reaction conditions is reported. The addition reaction has been done to access broad range of 5-hydroxy-4-phenylcarbamodithioate 2-H pyrroline derivatives after about 6 h stirring. All reactions were performed in acetonitrile at room temperature. Reactions are clean, and products were isolated by simple filtration.     

Synthesis,Antimicrobial and Anti‐HIV Activity of Some Novel Benzenesulfonamides Bearing 2,5‐Disubstituted‐1,3,4‐Oxadiazole Moiety

Twelve novel primary ( 4a‐c , 5a‐c ) and secondary ( 4d‐f, 5d‐f ) benzenesulfonamides bearing 2,5‐disubstituted‐1,3,4‐oxadiazole moiety have successfully been prepared by direct chlorosulfonation of phenyl substitutent present on the 2‐position of 5‐mercapto‐1,3,4‐oxadiazoles 2a‐c and their methylhio derivatives 3a‐c using chlorosulfonic acid under anhydrous conditions. Structures of the synthesized compounds were established by their physical and spectral data. Some of the synthesized compounds have been screened in vitro for their antimicrobial and anti‐HIV activity; the results were in accordance with SAR.