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

Uniting the classification of cultured and uncultured bacteria and archaea using 16S rRNA gene sequences

Publicly available sequence databases of the small subunit ribosomal RNA gene, also known as 16S rRNA in bacteria and archaea, are growing rapidly, and the number of entries currently exceeds 4 million. However, a unified classification and nomenclature framework for all bacteria and archaea does not yet exist. In this Analysis article, we propose rational taxonomic boundaries for high taxa of bacteria and archaea on the basis of 16S rRNA gene sequence identities and suggest a rationale for the circumscription of uncultured taxa that is compatible with the taxonomy of cultured bacteria and archaea. Our analyses show that only nearly complete 16S rRNA sequences give accurate measures of taxonomic diversity. In addition, our analyses suggest that most of the 16S rRNA sequences of the high taxa will be discovered in environmental surveys by the end of the current decade. © 2014 Macmillan Publishers LimitedThis work has been co-funded by the Max Planck Society and the European Union (EU) project SYMBIOMICS (grant number 264774). R.R.M. acknowledges the scientific support given by the Spanish Ministry of Economy with the projects CE-CSD2007-0005 and CGL2012-39627-C03-03, which are both also supported with European Regional Development Fund (FEDER) funds, and the preparatory phase of Microbial Resource Research Infrastructure (MIRRI) funded by the EU (grant number 312251). W.B.W. acknowledges support of the Dimensions in Biodiversity program at the US National Science Foundation (NSF). P.Y. acknowledges support of the EU's Seventh Framework Program funds BioVeL, grant no. 283359Peer Reviewe

The autonomic nervous system

The autonomic nervous system innervates the visceral organs, the glands and the blood vessels. It regulates the internal environment, and it is largely responsible for maintaining normal bodily functions such as respiration, blood pressure and micturition. The peripheral autonomic nervous system consists of two parts, a thoracolumbar or sympathetic and a craniosacral or parasympathetic division, which usually have antagonistic effects (Sect. 12.2). The sympathetic system is organized to mobilize the body for activities, especially in stressful situations (Cannon’s fight or flight), whereas the parasympathetic system in particular stimulates the peristaltic and secretory activities of the gastrointestinal tract (also known as rest and digest response). The peripheral part of the autonomic nervous system includes neurons in the viscera and peripheral ganglia, which are innervated by the lateral horn of the spinal cord and certain brain stem nuclei. Neuronal plexuses in the gastrointestinal tract form the enteric nervous system, which is often viewed as the third component of the autonomic nervous system. Tonically active bulbar centres control vital functions such as blood pressure and respiration. The autonomic centres in the brain stem and spinal cord are reciprocally connected with the central autonomic network (Sect. 12.3), which includes the hypothalamus and several other forebrain (in particular the extended amygdala and the insula) and brain stem structures such as the periaqueductal grey and the parabrachial nucleus. This network is essential for the integration of autonomic, endocrine and somatomotor functions. The peripheral and central autonomic pathways may be affected by many diseases, which cause derangement of autonomic functions as exemplified in several Clinical Cases on disorders of the neural control of blood pressure, breathing and micturition. The English terms of the Terminologia Neuroanatomica are used throughout