Polyamide-Scorpion Cyclam Lexitropsins Selectively Bind AT-Rich DNA Independently of the Nature of the Coordinated Metal

Cyclam was attached to 1-, 2- and 3-pyrrole lexitropsins for the first time through a synthetically facile copper-catalyzed “click” reaction. The corresponding copper and zinc complexes were synthesized and characterized. The ligand and its complexes bound AT-rich DNA selectively over GC-rich DNA, and the thermodynamic profile of the binding was evaluated by isothermal titration calorimetry. The metal, encapsulated in a scorpion azamacrocyclic complex, did not affect the binding, which was dominated by the organic tail

Lipid (per) oxidation in mitochondria:an emerging target in the ageing process?

Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation. In addition, senescent cells, which are known to contribute significantly to age-related pathologies, are also associated with impaired mitochondrial function and changes in lipid metabolism. Therapeutic targeting of dysfunctional mitochondrial and pathological lipid metabolism is an emerging strategy for alleviating their negative impact during ageing and the progression to age-related diseases. Such therapies could include the use of drugs that prevent mitochondrial uncoupling, inhibit inflammatory lipid synthesis, modulate lipid transport or storage, reduce mitochondrial oxidative stress and eliminate senescent cells from tissues. In this review, we provide an overview of lipid structure and function, with emphasis on mitochondrial lipids and their potential for therapeutic targeting during ageing and age-related disease

Simulation of the onset of convection in a porous medium layer saturated by a couple-stress nanofluid

Linear and nonlinear stability analyses for the onset of time-dependent convection in a horizontal layer of a porous medium saturated by a couple-stress non-Newtonian nanofluid, intercalated between two thermally insulated plates, are presented. Brinkman and MaxwellGarnett formulations are adopted for nanoscale effects. A modified Darcy formulation that includes the time derivative term is used for the momentum equation. The nanofluid is assumed to be dilute and this enables the porous medium to be treated as a weakly heterogeneous medium with variation of thermal conductivity and viscosity, in the vertical direction. The general transport equations are solved with a Galerkin-type weighted residuals method. A perturbation method is deployed for the linear stability analysis and a Runge– Kutta–Gill (RKG) quadrature scheme for the nonlinear analysis. The critical Rayleigh number, wave numbers for the stationary and oscillatory modes and frequency of oscillations are obtained analytically using linear theory and the non-linear analysis is executed with minimal representation of the truncated Fourier series involving only two terms. The effect of various parameters on the stationary and oscillatory convection behavior is visualized. The effect of couple stress parameter on the stationary and oscillatory convections is also shown graphically. It is found that the couple stress parameter has a stabilizing effect on both the stationary and oscillatory convections. Transient Nusselt number and Sherwood number exhibit an oscillatory nature when time is small. However, at very large values of time both Nusselt number and Sherwood number values approach their steady state values. The study is relevant to the dynamics of biopolymers in solution in microfluidic devices and rheological nanoparticle methods in petroleum recovery

Direct coupling of the cell cycle and cell death machinery by E2F

Unrestrained E2F activity forces S phase entry and promotes apoptosis through p53-dependent and -independent mechanisms. Here, we show that deregulation of E2F by adenovirus E1A, loss of Rb or enforced E2F-1 expression results in the accumulation of caspase proenzymes through a direct transcriptional mechanism. Increased caspase levels seem to potentiate cell death in the presence of p53-generated signals that trigger caspase activation. Our results demonstrate that mitogenic oncogenes engage a tumour suppressor network that functions at multiple levels to efficiently induce cell death. The data also underscore how cell cycle progression can be coupled to the apoptotic machinery