Reduced Nitro-oxidative Stress and Neural Cell Death Suggests a Protective Role for Microglial Cells in TNFα−/− Mice in Ischemic Retinopathy

Purpose. Neovascularization occurs in response to tissue ischemia and growth factor stimulation. In ischemic retinopathies, however, new vessels fail to restore the hypoxic tissue; instead, they infiltrate the transparent vitreous. In a model of oxygen-induced retinopathy (OIR), TNFa and iNOS, upregulated in response to tissue ischemia, are cytotoxic and inhibit vascular repair. The aim of this study was to investigate the mechanism for this effect.

Methods. Wild-type C57/BL6 (WT) and TNFa-/- mice were subjected to OIR by exposure to 75% oxygen (postnatal days 7–12). The retinas were removed during the hypoxic phase of the model. Retinal cell death was determined by TUNEL staining, and the microglial cells were quantified after Z-series capture with a confocal microscope. In situ peroxynitrite and superoxide were measured by using the fluorescent dyes DCF and DHE. iNOS, nitrotyrosine, and arginase were analyzed by real-time PCR, Western blot analysis, and activity determined by radiolabeled arginine conversion. Astrocyte coverage was examined after GFAP immunostaining.

Results. The TNFa-/- animals displayed a significant reduction in TUNEL-positive apoptotic cells in the inner nuclear layer of the avascular retina compared with that in the WT control mice. The reduction coincided with enhanced astrocytic survival and an increase in microglial cells actively engaged in phagocytosing apoptotic debris that displayed low ROS, RNS, and NO production and high arginase activity.

Conclusions. Collectively, the results suggest that improved vascular recovery in the absence of TNFa is associated with enhanced astrocyte survival and that both phenomena are dependent on preservation of microglial cells that display an anti-inflammatory phenotype during the early ischemic phase of OIR.

Whole-Life Costing for Capability

In recent years, there has been growing emphasis on the need to provide transparency in the costs of engineering programmes, leading to growing emphasis on Whole Life Cost (WLC) modelling techniques. This has arisen largely due to the increased interested in longer timescale projects and programmes, combined with the emergence of system-of-systems and network enabled capability concepts. This change in the implementation and management of large scale projects has necessitated the development of alternative methods of evaluating performance. This work seeks to address the shortfalls in current costing methodologies when applied to these highly flexible environments, and to propose a conceptual model for dealing with the encountered complexities. The approach has a fundamental role and potential significance in the future of whole life costing for Network Enabled Capability (NEC) but can also offer a potential paradigm shift for costing in traditional engineering environments.

Alkynyl-Bridged Ruthenium(II) 4 '-Diferroceny1-2,2 ':6 ',2 ''-terpyridine Electron Transfer Complexes: Synthesis, Structures, and Electrochemical and Spectroscopic Studiese

The novel ligand 4'-diferrocenylallcyne-2,2':6',2 ''-terpyridine (7; Fc-C C-Fc-tpy; tpy = terpyridyl; Fc = ferrocenyl) and its Ru2+ complexes 8-10 have been synthesized and characterized by single-crystal X-ray diffraction, cyclic voltammetry, and UV-vis and luminescence spectroscopy. Electrochemical data and UV absorption and emission spectra indicate that the insertion of an ethynyl group causes delocalization of electrons in the extended pi* orbitals. Cyclic voltammetric measurements of 7 show two successive reversible one-electron-oxidation processes with half-wave potentials of 0.53 and 0.78 V. The small variations of the E-1/2 values for the Fe2+/Fe3+ redox couples after the coordination of the Ru2+ ion suggest a weak interaction between the Ru2+ and Fe2+ centers. After insertion of an ethynyl group, UV-vis absorption spectra show a red shift of the absorption peak of the (1)[(d(pi)(Fe))(6)]->(1)[(d(pi)(Fe))(5)(pi*(Ru)(tpy))(1)] MMLCT of the Ru2+ complexes. The Ru2+ complex 8 exhibits the strongest luminescence intensity (lambda(em)(max) 712 nm, Phi(em) = 2.63 x 10(-4), tau = 323 ns) relative to analogous ferrocene-based terpyridine Ru(II) complexes in H2O/CH3CN (4/1 v/v) solution.

Microflare Activity Driven By Forced Magnetic Reconnection.

High cadence, multiwavelength, optical observations of a solar active region, obtained with the Swedish Solar Telescope, are presented. Two magnetic bright points are seen to separate in opposite directions at a constant velocity of 2.8 km s(-1). After a separation distance of approximate to 4400 km is reached, multiple Ellerman bombs are observed in both Ha and Ca-K images. As a result of the Ellerman bombs, periodic velocity perturbations in the vicinity of the magnetic neutral line, derived from simultaneous Michelson Doppler Imager data, are generated with amplitude +/-6 km s(-1) and wavelength approximate to 1000 km. The velocity oscillations are followed by an impulsive brightening visible in Ha and Ca-K, with a peak intensity enhancement of 63%. We interpret these velocity perturbations as the magnetic field deformation necessary to trigger forced reconnection. A time delay of approximate to 3 minutes between the Ha-wing and Ca-K observations indicates that the observed magnetic reconnection occurs at a height of similar to 200 km above the solar surface. These observations are consistent with theoretical predictions and provide the first observational evidence of microflare activity driven by forced magnetic reconnection.