New insights into the association of air pollution and kidney diseases by tracing gold nanoparticles with inductively coupled plasma mass spectrometry

Exposure to particles in air pollution has been associated with kidney disease, however, the underlying biological mechanisms are incompletely understood. Inhaled particles can gain access to the circulation and, depending on their size, pass into urine, raising the possibility that particles may also sequester in the kidney and directly alter renal function. This study optimised an inductively coupled plasma mass spectrometry (ICP-MS) method to investigate the size dependency of particle accumulation in the kidney in mice following pulmonary instillation (0.8 mg in total over 4 weeks) to gold nanoparticles (2, 3-4, 7-8, 14 or 40 nm, or saline control). Due to the smallest particle sizes being below the limit of detection in single particle mode, ICP-MS was operated in the total quantification mode. Gold was detected in all matrices of interest (blood, urine and kidney) from animals treated with all sizes of gold nanoparticles, at orders of magnitude higher than the methodological limit of detection in biological matrices (0.013 ng/mL). A size-dependent effect was observed, with smaller particles leading to greater levels of accumulation in tissues. This study highlights the value of a robust and reliable method by ICP-MS to detect extremely low levels of gold in biological samples for indirect particle tracing. The finding that nano-sized particles translocate from the lung to the kidney may provide a biological explanation for the associations between air pollution and kidney disease

Uranium diffusion and time-dependent adsorption–desorption in soil: a model and experimental testing of the model

Most past research on uranium (U) transport and reaction in the environment has been concerned with groundwater contamination and not with uptake by plants or soil biota, both of which operate over much smaller time and distance scales. We developed and tested a model of U diffusion and reaction in soil at scales appropriate for uptake by plant roots, based on a model we developed in an earlier paper. The model allows for the speciation of U with hydroxyl, carbonate and organic ligands in the soil solution, and the nature and kinetics of sorption reactions with the soil solid. The model predictions were compared with experimentally‐measured concentration‐distance profiles of U in soil adjusted to different pHs and CO2 pressures. Excellent agreement between observed and predicted profiles was obtained using model input parameters measured or otherwise estimated independently of the concentration‐distance profiles, showing that the model was a correct description of the system and all important processes were allowed for. The importance of the kinetics of U adsorption and desorption on the time‐scale of diffusion through the soil is highlighted. The results are discussed in terms of the uptake of U by plant root systems, as modelled in the earlier paper

Assessing the role of bed sediments in the persistence of red mud pollution in a shallow lake (Kinghorn Loch, UK)

Red mud is a by-product of alumina production. Little is known about the long-term fate of red mud constituents in fresh waters or of the processes regulating recovery of fresh waters following pollution control. In 1983, red mud leachate was diverted away from Kinghorn Loch, UK, after many years of polluting this shallow and monomictic lake. We hypothesised that the redox-sensitive constituents of red mud leachate, phosphorus (P), arsenic (As) and vanadium (V), would persist in the Kinghorn Loch for many years following pollution control as a result of cycling between the lake bed sediment and the overlying water column. To test this hypothesis, we conducted a 12-month field campaign in Kinghorn Loch between May 2012 and April 2013 to quantify the seasonal cycling of P, As, and V in relation to environmental conditions (e.g., dissolved oxygen (DO) concentration, pH, redox chemistry and temperature) in the lake surface and bottom waters. To confirm the mechanisms for P, As and V release, a sediment core incubation experiment was conducted using lake sediment sampled in July 2012, in which DO concentrations were manipulated to create either oxic or anoxic conditions similar to the bed conditions found in the lake. The effects on P, As, and V concentrations and species in the water column were measured daily over an eight-day incubation period. Phosphate (PO4-P) and dissolved As concentrations were significantly higher in the bottom waters (75.9 ± 30.2 μg L−1 and 23.5 ± 1.83 μg L−1, respectively) than in the surface waters (12.9 ± 1.50 μg L−1 and 14.1 ± 2.20 μg L−1, respectively) in Kinghorn Loch. Sediment release of As and P under anoxic conditions was confirmed by the incubation experiment and by the significant negative correlations between DO and P and As concentrations in the bottom waters of the lake. In contrast, the highest dissolved V concentrations occurred in the bottom waters of Kinghorn Loch under oxic conditions (15.0 ± 3.35 μg L−1), with the release from the bed sediment apparently being controlled by a combination of competitive ion concentrations, pH and redox conditions

Daily magnesium fluxes regulate cellular timekeeping and energy balance

Circadian clocks are fundamental to the biology of most eukaryotes, coordinating behaviour and physiology to resonate with the environmental cycle of day and night through complex networks of clock-controlled genes1, 2, 3. A fundamental knowledge gap exists, however, between circadian gene expression cycles and the biochemical mechanisms that ultimately facilitate circadian regulation of cell biology4, 5. Here we report circadian rhythms in the intracellular concentration of magnesium ions, [Mg2+]i, which act as a cell-autonomous timekeeping component to determine key clock properties both in a human cell line and in a unicellular alga that diverged from each other more than 1 billion years ago6. Given the essential role of Mg2+ as a cofactor for ATP, a functional consequence of [Mg2+]i oscillations is dynamic regulation of cellular energy expenditure over the daily cycle. Mechanistically, we find that these rhythms provide bilateral feedback linking rhythmic metabolism to clock-controlled gene expression. The global regulation of nucleotide triphosphate turnover by intracellular Mg2+ availability has potential to impact upon many of the cell’s more than 600 MgATP-dependent enzymes7 and every cellular system where MgNTP hydrolysis becomes rate limiting. Indeed, we find that circadian control of translation by mTOR8 is regulated through [Mg2+]i oscillations. It will now be important to identify which additional biological processes are subject to this form of regulation in tissues of multicellular organisms such as plants and humans, in the context of health and disease

Phosphoglycerate mutase from Trypanosoma brucei is hyperactivated by cobalt in vitro, but not in vivo

Production of ATP by the glycolytic pathway in the mammalian pathogenic stage of protists from the genus Trypanosoma is required for the survival of the parasites. Cofactor-independent phosphoglycerate mutase (iPGAM) is particularly attractive as a drug target because it shows no similarity to the corresponding enzyme in humans, and has also been genetically validated as a target by RNAi experiments. It has previously been shown that trypanosomatid iPGAMs require Co 2+ to reach maximal activity, but the biologically relevant metal has remained unclear. In this paper the metal content in the cytosol of procyclic and bloodstream-form T. brucei (analysed by inductively coupled plasma-optical emission spectroscopy) shows that Mg 2+, Zn 2+ and Fe 2+ were the most abundant, whereas Co 2+ was below the limit of detection (<0.035 μM). The low concentration indicates that Co 2+ is unlikely to be the biologically relevant metal, but that instead, Mg 2+ and/or Zn 2+ may assume this role. Results from metal analysis of purified Leishmania mexicana iPGAM by inductively coupled plasma-mass spectrometry also show high concentrations of Mg 2+ and Zn 2+, and are consistent with this proposal. Our data suggest that in vivo cellular conditions lacking Co 2+ are unable to support the maximal activity of iPGAM, but instead maintain its activity at a relatively low level by using Mg 2+ and/or Zn 2+. The physiological significance of these observations is being pursued by structural, biochemical and biophysical studies. © 2011 The Royal Society of Chemistry