Signal transduction by reactive oxygen species

Although historically viewed as purely harmful, recent evidence suggests that reactive oxygen species (ROS) function as important physiological regulators of intracellular signaling pathways. The specific effects of ROS are modulated in large part through the covalent modification of specific cysteine residues found within redox-sensitive target proteins. Oxidation of these specific and reactive cysteine residues in turn can lead to the reversible modification of enzymatic activity. Emerging evidence suggests that ROS regulate diverse physiological parameters ranging from the response to growth factor stimulation to the generation of the inflammatory response, and that dysregulated ROS signaling may contribute to a host of human diseases

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

Study of the photon remnant in resolved photoproduction at HERA

Photoproduction at HERA is studied in ep collisions, with the ZEUS detector, for yp centre-of-mass energies ranging from 130-270 GeV. A sample of events with two high-p(T) jets (p(T) > 6 GeV, eta < 1.6) and a third cluster in the approximate direction of the electron beam is isolated using a clustering algorithm. These events are mostly due to resolved photoproduction. The third duster is identified as the photon remnant, Its properties, such as the transverse and longitudinal energy flows around the axis of the cluster, are consistent with those commonly attributed to jets, and in particular with those found for the two jets in these events. The mean value of the photon remnant p(T) with respect to the beam axis is measured to be 2.1 +/- 0.2 GeV, which demonstrates substantial mean transverse momenta for the photon remnant