A Spatial Survey of Environmental Indicators for Kazakhstan: An Examination of Current Conditions and Future Needs

The Republic of Kazakhstan, located in Central Asia, has experienced many years of environmental degradation, largely as a result of the poor management of its significant natural resources. In this survey, data relating to different environmental factors are critically analysed in order to understand the state of the environment. It was found that: warming trends are seen in sensitive areas (e.g. the steppe and near glaciers); drying trends are seen where there is already water stress (e.g. the Aral Sea); air quality has been declining recently (following improvements on the decadal timescale) in major urban centres, particularly Almaty; water quality appears to be improving in some areas (e.g. important lakes in the Aktobe and Zhambyl regions); and levels of exposure to radioactivity are below internationally recommended levels (where data have been found). More generally, there is an issue with data availability and quality, which requires attention if Kazakhstan is going to make the best use of its increasing investment in environmental actions. Current policies are reviewed and recommendations are made for future interventions

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

Spatial prediction of N2O emissions in pasture: a Bayesian model averaging analysis

Nitrous oxide (NO) is one of the greenhouse gases that can contribute to global warming. Spatial variability of NO can lead to large uncertainties in prediction. However, previous studies have often ignored the spatial dependency to quantify the NO - environmental factors relationships. Few researches have examined the impacts of various spatial correlation structures (e.g. independence, distance-based and neighbourhood based) on spatial prediction of NO emissions. This study aimed to assess the impact of three spatial correlation structures on spatial predictions and calibrate the spatial prediction using Bayesian model averaging (BMA) based on replicated, irregular point-referenced data. The data were measured in 17 chambers randomly placed across a 271 m field between October 2007 and September 2008 in the southeast of Australia. We used a Bayesian geostatistical model and a Bayesian spatial conditional autoregressive (CAR) model to investigate and accommodate spatial dependency, and to estimate the effects of environmental variables on NO emissions across the study site. We compared these with a Bayesian regression model with independent errors. The three approaches resulted in different derived maps of spatial prediction of NO emissions. We found that incorporating spatial dependency in the model not only substantially improved predictions of NO emission from soil, but also better quantified uncertainties of soil parameters in the study. The hybrid model structure obtained by BMA improved the accuracy of spatial prediction of NO emissions across this study region

Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia.

Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca(2+)]i) measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs and [Ca(2+)]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca(2+). Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca(2+)]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na(+)-Ca(2+) exchange. These results suggest that LQTS mutations act partly on cytosolic Ca(2+) cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site

Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia.

Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca(2+)]i) measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs and [Ca(2+)]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca(2+). Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca(2+)]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na(+)-Ca(2+) exchange. These results suggest that LQTS mutations act partly on cytosolic Ca(2+) cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site