Design,synthesis and characterization of tin‐based cancer chemotherapy drug entity: In vitro DNA binding,cleavage, induction of cancer cell apoptosis by triggering DNA damage‐mediated p53 phosphorylation and molecular docking

A new organotin complex derived from propyl gallate and 1,10‐phenanthroline was designed, synthesized and characterized using spectroscopic and elemental analytical methods. The underlying mechanisms of the anticancer action of the tin complex were further elucidated by evaluating its in vitro DNA interaction and the regulating signaling pathways. Our results showed that the tin complex could effectively activate DNA strand breaks in MCF‐7 cells in a dose‐dependent manner after cellular internalization. Phosphorylation of a DNA damage marker, histone H2A.X (Ser139), was thus upregulated in treated cells. Additionally, our results indicate that p53 is phosphorylated in response to DNA damage, and that this phosphorylation may be involved in the subsequent induction and activation of p53. In vitro DNA binding of the complex in Tris–HCl buffer was studied using various biophysical methods, revealing that the tin complex binds to DNA non‐covalently via electrostatic interaction. The higher K_b value of the complex suggested greater DNA binding propensity. Further, to evaluate the mode of action at the molecular level, interaction studies of the tin complex with nucleotide (5′‐GMP) were carried out. The complex exhibits DNA cleavage activity with supercoiled pBR322 in the presence of different activators. The complex cleaves DNA efficiently via oxidative cleavage pathway. Molecular docking studies were performed to understand the binding mode of the tin complex with DNA (PDB ID: 1BNA).     

The role of Rho GTPases in the regulation of the rearrangement of actin cytoskeleton and cell movement

The rearrangement of the actin cytoskeleton has been shown to play a critical role in the development of transformation and malignant phenotype of cancer cells. Rho family GTPases regulate the arrangement of the actin cytoskeleton. By wound-healing assay, we have found that NIH 3T3 fibroblast cells move towards the wound- gaps by extending filopodial and lamellipdial structures at the leading edge of the moving cells. We have inactivated the function of Rho GTPases of v-Ras transformed NIH 3T3 cells by overexpressing Rho GTPase-activating (RhoGAP) domain of RhoGAP of p190. We have observed that inactivation of Rho, Rac and Cdc42 GTPases by overexpressing RHG causes inhibition of: (i) polymerization of actin to form filaments, (ii) formation of lamellipodia, filopodia and stress fibres, (iii) cell motility, (iv) cell spreading and (v) cell-to-cell adhesions. These results further strengthen the current knowledge on the role of Rho, Rac and Cdc42 GTPases in the regulation of the rearrangement of actin cytoskeleton. Our results, for the first time, demonstrate that RhoGAP domain of RhoGAP could be used to study the molecular mechanism of Ras-mediated signalling in growth, differentiation and carcinogenesis.     

Uptake of pyrene by NaCl, NaNO3, and MgCl2 aerosol particles

Photoelectric charging experiments measure heterogeneous uptake coefficients for pyrene on model marine aerosol particles, including NaCl, NaNO(3), and MgCl(2). The analysis employs a multilayer kinetic model that contains adsorption and desorption rate constants for the bare aerosol surface and for pyrene-coated surfaces. First coating the aerosol particles with a pyrene layer and following the desorption using both t-DMA and photoelectric charging yields the desorption rate constants. Separate experiments monitor the increase in surface coverage of initially bare aerosol particles after exposure to pyrene vapor in a sliding-injector flow tube. Analyzing these data using the multilayer model constrained by the measured desorption rate constants yields the adsorption rate constants. The calculated initial heterogeneous uptake coefficient, γ(0)(295 K), is 1.1 × 10(-3) for NaCl, 6.6 × 10(-4) for NaNO(3), and 6.0 × 10(-4) for MgCl(2). The results suggest that a free energy barrier controls the uptake rate rather than kinematics.     

The morphology and thermal properties of liquid natural rubber (LNR)-compatibilized 60/40 NR/LLDPE blends

The effects of LNR as a compatibilizer in binary blends of 60/40 NR/LLDPE have been investigated by means of differential scanning calorimetry, dynamic mechanical analysis and scanning electron microscopy. Special emphasis was given to the role of LNR in inducing interactions between NR and LLDPE. It has been observed that increasing LNR content decreases T_m and ΔH_f which are indicators of the crystalline part of the blends. The decrease reflects a reduction in the degree of crystallinity which is due to the interference in the form of NR dissolution into the LLDPE phase. The phenomenon leads to a shift in T_g of the amorphous part of LLDPE to higher temperatures as observed by DMA thermograms. The dissolution effect creates better interactions between the phases leading to improvements in the compatibility of the blends. Further confirmation was obtained through SEM examination.     

Classification of Static Spherically Symmetric Spacetimes by Noether Symmetries

Noether symmetries of some of the well known spherically symmetric static solutions of the Einstein’s field equations are classified. The resulting Noether symmetries in each case are compared with conservation laws given by Killing vectors and collineations of the Ricci and Riemann tensors for corresponding solutions.     

Visible‐Light‐Induced Directed Gold Microwires by Self‐Organization of Nanoparticles on Aspergillus Niger

A directional point‐to‐point growth of microwires of gold nanoparticles (AuNPs) self‐organized on Aspergillus niger (A. niger) templates by utilizing positive phototropic fungal response to different spectral ranges of visible light is reported. A. niger serves as a living template for the self‐organization of monosodium glutamate (MSG) capped gold colloids under controlled nutrient trigger and appropriate light, temperature, and humidity conditions. The experimental results show that control of these parameters eliminates the need for any microchannels for the directional growth of microwires. The growth rate of fungal hyphae increases exponentially under light illumination compared to its growth in the dark under similar conditions. White light is found to be most suitable to trigger the directional growth. Gold microwires of about 1 to 2 μm diameter and length exceeding 1 mm are grown within a week with a maximum divergence of 40–50° from the light path regardless of the wavelength of the light irradiation. Phototropic response of fungi has been investigated intensively over the last three decades, but this is the first report on the collective use of microbial tropism and directed biomimetic self‐organization of metallic nanoparticles on living organisms.     

Highly relaxing gadolinium based MRI contrast agents responsive to Mg2+ sensing

A Gd complex based on a polyphosphonated pyridyl ligand shows a very high stability in aqueous solution (log?K(EuL) = 25.7), a high relaxivity (8.5 mM(-1) s(-1) at 25 °C and 20 MHz) and a marked and selective relaxivity enhancement (37%) in the presence of Mg(2+), opening interesting perspectives for the design of cation responsive contrast agents.     

Dynamics and control of a system of two non‐interacting preys with common predator

In this paper, we consider a Holling type model, which describes the interaction between two preys with a common predator. First, we give some sufficient conditions for the globally asymptotic stability and prove that local stability implies global stability. Then, we present a set of sufficient conditions for the existence of a positive periodic solution with strictly positive components. Finally, the optimal control strategy is developed to minimize the number of predator and maximize the number of preys. We also show the existence of an optimal control for the optimal control problem and derive the optimality system. The technical tool used to determine the optimal strategy is the Pontryagin Maximum Principle. Finally, the numerical simulations of global stability and the optimal problem are given as the conclusion of this paper. Copyright © 2011 John Wiley & Sons, Ltd.     

Series solution for heat transfer from a continuous surface in a parallel free stream of viscoelastic fluid

This work is concerned with the influence of uniform suction or injection on flow and heat transfer analysis of a second order fluid. The resulting nonlinear problem for velocity is solved by means of homotopy analysis method (HAM). The comparison between the numerical solution of Hady and Gorla (Acta Mec 128 (1998), 201–208 and HAM solution is discussed with the help of numerical tables and graphs. Nonsimilar solutions to the stream function and temperature are developed. The influence of important parameters is seen on the velocity, temperature, skin friction coefficient, and temperature gradient. © 2010 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 27: 1511–1524, 2011     

2,2,9,9‐Tetramethylcyclonona‐3,5,7‐trienylidene vs. its heterocyclic analogues: A quest for stable carbenes at DFT

Replacement of α‐methylenes with BH, AlH, CMe₂, SiH₂, NH, NMe, N^tButyl, NPh, PH, O, and S in non‐planar cyclonona‐3,5,7‐trienylidene (CH₂) alters its status from an unstable transition state to rather stable minima, at B3LYP/6‐311++G**//B3LYP/6‐31 + G* levels of theory. All species appear with singlet closed shell (S_cs) global minima, except for SiH₂ and CH₂ which exhibit triplet electronic ground states. The order of stability based on singlet–triplet energy gap (ΔE_s–t / kcalmol^?1) is: CMe₂ (45.8) > NH (35.8) > NMe (32.3) > O (31.5) > N^tButyl (27.7) ≥ NPh (27.5) ≥ BH (27.4) > S (21.9) > PH (17.0) > CH₂ (?4.4) > SiH₂ (?12.5). In contrast to many reports on N‐heterocyclic carbenes, here alkyl groups appear to exert a higher stabilizing effect than heteroatoms, making CMe₂ the most stable. In addition bulky NMe, N^tButyl, and NPh appear more nucleophilic than their synthesized imidazol‐2‐ylidene congeners. Excluding SiH₂, isodesmic reactions reveal that all substituents stabilize singlet state considerably more than the corresponding triplet. Finally, this work is hoped to pave the path for future matrix isolations and IR studies of these rather stable cyclic non‐planar carbenes. Copyright © 2013 John Wiley & Sons, Ltd.