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

Polarity, Planes of Cell Division, and the Evolution of Plant Multicellularity

Organisms as diverse as bacteria, fungi, plants, and animals manifest a property called polarity. The literature shows that polarity emerges as a consequence of different mechanisms in different lineages. However, across all unicellular and multicellular organisms, polarity is evident when cells, organs, or organisms manifest one or more of the following: orientation, axiation, and asymmetry. Here, we review the relationships among these three features in the context of cell division and the evolution of multicellular polarity primarily in plants (defined here to include the algae). Data from unicellular and unbranched filamentous organisms (e.g., Chlamydomonas and Ulothrix) show that cell orientation and axiation are marked by cytoplasmic asymmetries. Branched filamentous organisms (e.g., Cladophora and moss protonema) require an orthogonal reorientation of axiation, or a localized cell asymmetry (e.g., tip growth in pollen tubes and fungal hyphae). The evolution of complex multicellular meristematic polarity required a third reorientation of axiation. These transitions show that polarity and the orientation of the future plane(s) of cell division are dyadic dynamical patterning modules that were critical for multicellular eukaryotic organisms