Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

A brown dwarf orbiting an M-dwarf: MOA 2009–BLG–411L

peer reviewedContext. Caustic crossing is the clearest signature of binary lenses in microlensing. In the present context, this signature is diluted by the large source star but a detailed analysis has allowed the companion signal to be extracted. Aims: MOA 2009-BLG-411 was detected on August 5, 2009 by the MOA-Collaboration. Alerted as a high-magnification event, it was sensitive to planets. Suspected anomalies in the light curve were not confirmed by a real-time model, but further analysis revealed small deviations from a single lens extended source fit. Methods: Thanks to observations by all the collaborations, this event was well monitored. We first decided to characterize the source star properties by using a more refined method than the classical one: we measure the interstellar absorption along the line of sight in five different passbands (VIJHK). Secondly, we model the lightcurve by using the standard technique: make (s,q,α) grids to look for local minima and refine the results by using a downhill method (Markov chain Monte Carlo). Finally, we use a Galactic model to estimate the physical properties of the lens components. Results: We find that the source star is a giant G star with radius 9 R[SUB]&sun;[/SUB]. The grid search gives two local minima, which correspond to the theoretical degeneracy s ≡ s[SUP]-1[/SUP]. We find that the lens is composed of a brown dwarf secondary of mass M[SUB]S[/SUB] = 0.05 M[SUB]&sun;[/SUB] orbiting a primary M-star of mass M[SUB]P[/SUB] = 0.18 M[SUB]&sun;[/SUB]. We also reveal a new mass-ratio degeneracy for the central caustics of close binaries. Conclusions: As far as we are aware, this is the first detection using the microlensing technique of a binary system in our Galaxy composed of an M-star and a brown dwarf. Appendix is available in electronic form at http://www.aanda.org</A

The Jupiter System Through the Eyes of Voyager 1

The cameras aboard Voyager 1 have provided a closeup view of the Jupiter system, revealing heretofore unknown characteristics and phenomena associated with the planet's atmosphere and the surfaces of its five major satellites. On Jupiter itself, atmospheric motions-the interaction of cloud systems-display complex vorticity. On its dark side, lightning and auroras are observed. A ring was discovered surrounding Jupiter. The satellite surfaces display dramatic differences including extensive active volcanism on Io, complex tectonism on Ganymede and possibly Europa, and flattened remnants of enormous impact features on Callisto

The Galilean Satellites and Jupiter: Voyager 2 Imaging Science Results

Voyager 2, during its encounter with the Jupiter system, provided images that both complement and supplement in important ways the Voyager 1 images. While many changes have been observed in Jupiter's visual appearance, few, yet significant, changes have been detected in the principal atmospheric currents. Jupiter's ring system is strongly forward scattering at visual wavelengths and consists of a narrow annulus of highest particle density, within which is a broader region in which the density is lower. On Io, changes are observed in eruptive activity, plume structure, and surface albedo patterns. Europa's surface retains little or no record of intense meteorite bombardment, but does reveal a complex and, as yet, little-understood system of overlapping bright and dark linear features. Ganymede is found to have at least one unit of heavily cratered terrain on a surface that otherwise suggests widespread tectonism. Except for two large ringed basins, Callisto's entire surface is heavily cratered

Regional specialization within the intestinal immune system.

The intestine represents the largest compartment of the immune system. It is continually exposed to antigens and immunomodulatory agents from the diet and the commensal microbiota, and it is the port of entry for many clinically important pathogens. Intestinal immune processes are also increasingly implicated in controlling disease development elsewhere in the body. In this Review, we detail the anatomical and physiological distinctions that are observed in the small and large intestines, and we suggest how these may account for the diversity in the immune apparatus that is seen throughout the intestine. We describe how the distribution of innate, adaptive and innate-like immune cells varies in different segments of the intestine and discuss the environmental factors that may influence this. Finally, we consider the implications of regional immune specialization for inflammatory disease in the intestine

The role of GABAA receptors in the acute and chronic effects of ethanol: a decade of progress

The past decade has brought many advances in our understanding of GABA(A) receptor-mediated ethanol action in the central nervous system. We now know that specific GABA(A) receptor subtypes are sensitive to ethanol at doses attained during social drinking while other subtypes respond to ethanol at doses attained by severe intoxication. Furthermore, ethanol increases GABAergic neurotransmission through indirect effects, including the elevation of endogenous GABAergic neuroactive steroids, presynaptic release of GABA, and dephosphorylation of GABA(A) receptors promoting increases in GABA sensitivity. Ethanol’s effects on intracellular signaling also influence GABAergic transmission in multiple ways that vary across brain regions and cell types. The effects of chronic ethanol administration are influenced by adaptations in GABA(A) receptor function, expression, trafficking, and subcellular localization that contribute to ethanol tolerance, dependence, and withdrawal hyperexcitability. Adolescents exhibit altered sensitivity to ethanol actions, the tendency for higher drinking and longer lasting GABAergic adaptations to chronic ethanol administration. The elucidation of the mechanisms that underlie adaptations to ethanol exposure are leading to a better understanding of the regulation of inhibitory transmission and new targets for therapies to support recovery from ethanol withdrawal and alcoholism