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

Housing: An Under-Explored Influence on Children’s Well-Being and Becoming

Research on housing has tended to focus on adult outcomes, establishing relationships between housing and a number of aspects of health and well-being. Research exploring the influence of housing on children has been more limited, and has tended to focus on adult concerns around risk behaviours, behavioural problems and educational attainment. While these outcomes are important, they neglect the impact of housing on children’s lives beyond these concerns. There are a number of reasons to believe that housing would play an important role in children’s well-being more broadly. Family stress and strain models highlight how housing difficulties experienced by adults may have knock on effects for children, while Bronfenbrenner’s ecological approach to human development emphasises the importance of children’s experiences of their environments, of which the home is among the most important. This paper summaries the existing evidence around housing and child outcomes, predominantly educational and behavioural outcomes, and argues for the extension of this work to consider the impact of housing on children’s lives more broadly, especially their subjective well-being

Paradigm of Monoterpene (β-phellandrene) Hydrocarbons Production via Photosynthesis in Cyanobacteria

A direct "photosynthesis-to-fuels" approach envisions application of a single organism, absorbing sunlight, photosynthesizing, and converting the primary products of photosynthesis into ready-made fuel. The work reported here applied this concept for the photosynthetic generation of monoterpene (β-phellandrene) hydrocarbons in the unicellular cyanobacteria Synechocystis sp. PCC 6803. Heterologous expression of a codon-optimized Lavandula angustifolia β-phellandrene synthase (β-PHLS) gene in Synechocystis enabled photosynthetic generation of β-phellandrene in these microorganisms. β-phellandrene accumulation occurred constitutively and in tandem with biomass accumulation, generated from sunlight, CO2, and H2O. Results showed that β-phellandrene diffused through the plasma membrane and cell wall of the cyanobacteria and accumulated on the surface of the liquid culture. Spontaneous β-phellandrene separation from the biomass and its removal from the liquid phase alleviated product inhibition of cellular metabolism and enabled a continuous production process. The work showed that oxygenic photosynthesis can be directed to generate monoterpene hydrocarbons, while consuming CO2, without a prior requirement for the harvesting, dewatering, and processing of the respective biomass. © 2013 Springer Science+Business Media New York

S100 protein-annexin interactions:a model of the (Anx2-p11)(2) heterotetramer complex

AbstractThe (Anx2)2(p11)2 heterotetramer has been implicated in endo- and exocytosis in vivo and in liposome aggregation in vitro. Here we report on the modelling of the heterotetramer complex using docking algorithms. Two types of models are generated–heterotetramer and heterooctamer. On the basis of the agreement between the calculated (X-ray) electron density and the observed projected density from cryo-electron micrographs on the one hand, and calculated energy criteria on the other hand, the heterotetramer models are proposed as the most probable, and one of them is selected as the best model. Analysis of this model at an atomic level suggests that the interaction between the Anx2 core and p11 has an electrostatic character, being stabilised primarily through charged residues

Isoprene production in Synechocystis under alkaline and saline growth conditions

Photosynthesis for the generation of isoprene in cyanobacteria was demonstrated with Synechocystis, entailing a process where a single host microorganism acts as both photocatalyst and processor, photosynthesizing and emitting isoprene hydrocarbons. A practical aspect of the commercial exploitation of this process in mass culture is the need to prevent invading microorganisms that might cause a culture to crash, and to provide an alternative to freshwater in scale-up applications. Growth media poised at alkaline pH are desirable in this respect, as high pH might favor the growth of the cyanobacteria, while at the same time discouraging the growth of invading predatory microbes and grazers. In addition, demonstration of salinity tolerance would enable the use of seawater for cyanobacteria cultivations. However, it is not known if Synechocystis growth and the isoprene-producing metabolism can be retained under such theoretically non-physiological conditions. We applied the gaseous/aqueous two-phase photobioreactor system with Synechocystis transformed with the isoprene synthase gene (SkIspS) of Pueraria montana (kudzu). Rates of growth and isoprene production are reported under control, and a combination of alkalinity and salinity conditions. The results showed that alkalinity and salinity do not exert a negative effect on either cell growth or isoprene production rate and yield in Synechocystis. The work points to a practical approach in the design of cyanobacterial growth media for applications in commercial scale-up and isoprene production