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

Bat Systematics in the Light of Unconstrained Analyses of a Comprehensive Molecular Supermatrix

Bats (Chiroptera) represent the largest diversification of extant mammals after rodents. Here we report the results of a large-scale phylogeny of bats based on unconstrained searches for a data matrix of 804 non-chimeric, taxonomically updated bat terminals (796 species represented by a single terminal plus three species represented by ≥2 genetically distinct subspecies), able to preliminary test the systematics of most groups simultaneously. We used nine nuclear and mitochondrial DNA sequence markers fragmentary represented for ingroups (c. 90% and 64% of extant diversity at genus and species level, respectively) and 20 diverse placental outgroups. Maximum Likelihood and Parsimony analyses applied to the concatenated dataset yielded a highly resolved, variously supported phylogeny that recovered the majority of currently recognized clades at all levels of the chiropteran tree. Calibration points based on 44 key fossils allowed the Bayesian dating of bat origins at c. 4 my after the K-Pg boundary, and the determination of stem and crown ages of intraordinal clades. As expected, bats appeared nested in Laurasiatheria and split into Yinpterochiroptera and Yangochiroptera. More remarkable, all polytypic, currently recognized families were monophyletic, including Miniopteridae, Cistugidae, and Rhinonycteridae, as well as most polytypic genera with few expected exceptions (e.g., Hipposideros). The controversial Myzopodidae appeared in a novel position as sister of Emballonuroidea―a result with interesting biogeographic implications. Most recently recognized subfamilies, genera, and species groups were supported or only minor adjustments to the current taxonomy would be required, except Molossidae, which should be revised thoroughly. In light of our analysis, current bat systematics is strongly supported at all levels; the emergent perception of a strong biogeographic imprint on many recovered bat clades is emphasized.Fil: Amador, Lucila Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Moyers Arévalo, Reyna Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Cunha Almeida, Francisca. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Catalano, Santiago Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Giannini, Norberto Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentina. American Museum of Natural History ; Estados Unido