The impact of species and cell type on the nanosafety profile of iron oxide nanoparticles in neural cells

Background: While nanotechnology is advancing rapidly, nanosafety tends to lag behind since general mechanistic insights into cell-nanoparticle (NP) interactions remain rare. To tackle this issue, standardization of nanosafety assessment is imperative. In this regard, we believe that the cell type selection should not be overlooked since the applicability of cell lines could be questioned given their altered phenotype. Hence, we evaluated the impact of the cell type on in vitro nanosafety evaluations in a human and murine neuroblastoma cell line, neural progenitor cell line and in neural stem cells. Acute toxicity was evaluated for gold, silver and iron oxide (IO) NPs, and the latter were additionally subjected to a multiparametric analysis to assess sublethal effects. Results: The stem cells and murine neuroblastoma cell line respectively showed most and least acute cytotoxicity. Using high content imaging, we observed cell type-and species-specific responses to the IONPs on the level of reactive oxygen species production, calcium homeostasis, mitochondrial integrity and cell morphology, indicating that cellular homeostasis is impaired in distinct ways. Conclusions: Our data reveal cell type-specific toxicity profiles and demonstrate that a single cell line or toxicity end point will not provide sufficient information on in vitro nanosafety. We propose to identify a set of standard cell lines for screening purposes and to select cell types for detailed nanosafety studies based on the intended application and/or expected exposure

Drie nieuwe Ponto-Kaspische inwijkelingen dringen door tot in kanalen in de provincie Antwerpen: De zoetwaterpolychaet <i>Hypania invalida</i> (Grube, 1860) en, voor het eerst in België, de platworm <i>Dendrocoelum romanodanubiale</i> (Codreanu, 1949) en de Donaupissebed <i>Jaera istri</i> Veuille, 1979

Since 2000 three Ponto-Caspian invaders have been found in canals in the province of Antwerp (N.E.-Belgium): the freshwater polychaete Hypania invalida (Grube, 1860), the triclad Dendrocoelum romanodanubiale (Codreanu, 1949) and the freshwater isopod Jaera istri Veuille, 1979. Staff members of the 'Vlaamse Milieumaatschappij (Flemish Environmental Agency) collected these species on artificial substrates (nets filled with broken bricks). H. invalida had been discovered before in Belgium in the river Meuse in 2000 (Vanden Bossche et.al., 2001). D. romanodanubiale and J. istri were never recorded before in Belgium. Before its discovery in the Belgian Meuse in August-September 2000, H.invalida had already been found in May 2000 in the Albert Canal at Genk in the province of Limbourg. Between 2001 and 2003, the polychaete was sampled at several stations of the Albert Canal and its adjacent canals in the provinces of Antwerp and Limbourg. Here, it often is accompanied by D. romanodanubiale and J. istri. In 2003 the polychaet had also been encountered in the Sea canal Brussels - Scheldt in the province of Antwerp. The discontinuous distribution indicates that navigation plays an important role in the dispersal of the species. Other Ponto-Caspian species such as Dikerogammarus villosus (Sovinskij, 1894) are either already present in the canals or soon to be expected there. Some of these species will probably also invade the Scheldt basin

Safety and tolerability of etravirine (ETR; TMC125) in hepatitis B and/or C co-infected patients in DUET-1 and DUET-2: pooled 48-week results

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Improved convergence and stability properties in a three-dimensional higher-order ice sheet model

We present a finite difference implementation of a three-dimensional higher-order ice sheet model. In comparison to a conventional centred difference discretisation it enhances both numerical stability and convergence. In order to achieve these benefits the discretisation of the governing force balance equation makes extensive use of information on staggered grid points. Using the same iterative solver, a centred difference discretisation that operates exclusively on the regular grid serves as a reference. The reprise of the ISMIP-HOM experiments indicates that both discretisations are capable of reproducing the higher-order model inter-comparison results. This setup allows a direct comparison of the two numerical implementations also with respect to their convergence behaviour. First and foremost, the new finite difference scheme facilitates convergence by a factor of up to 7 and 2.6 in average. In addition to this decrease in computational costs, the accuracy for the resultant velocity field can be chosen higher in the novel finite difference implementation. Changing the discretisation also prevents build-up of local field irregularites that occasionally cause divergence of the solution for the reference discretisation. &lt;br&gt;&lt;br&gt; The improved behaviour makes the new discretisation more reliable for extensive application to real ice geometries. Higher accuracy and robust numerics are crucial in time dependent applications since numerical oscillations in the velocity field of subsequent time steps are attenuated and divergence of the solution is prevented

Short-term health effects in the general population following a major train accident with acrylonitrile in Belgium

Background: Following a train derailment, several tons of acrylonitrile (ACN) exploded, inflamed and part of the ACN ended up in the sewage system of the village of Wetteren. More than 2000 residents living in the close vicinity of the accident and along the sewage system were evacuated. A human biomonitoring study of the adduct N-2-cyanoethylvaline (CEV) was carried out days 14-21 after the accident. Objectives: (1) To describe the short-term health effects that were reported by the evacuated residents following the train accident, and (2) to explore the association between the CEV concentrations, extrapolated at the time of the accident, and the self-reported short-term health effects. Methods: Short-term health effects were reported in a questionnaire (n=191). An omnibus test of independence was used to investigate the association between the CEV concentrations and the symptoms. Dose-response relationships were quantified by Generalized Additive Models (GAMs). Results: The most frequently reported symptoms were local symptoms of irritation. In non-smokers, dose-dependency was observed between the CEV levels and the self-reporting of irritation (p=0.007) and nausea (p=0.007). Almost all non-smokers with CEV concentrations above 100 pmol/g globin reported irritation symptoms. Both absence and presence of symptoms was reported by non-smokers with CEV concentrations below the reference value and up to 10 times the reference value. Residents who visited the emergency services reported more symptoms. This trend was seen for the whole range of CEV concentrations, and thus independently of the dose. Discussion and conclusion: The present study is one of the first to relate exposure levels to a chemical released during a chemical incident to short-term (self-reported) health effects. A dose-response relation was observed between the CEV concentrations and the reporting of short-term health effects in the non-smokers. Overall, the value of self-reported symptoms to assess exposure showed to be limited. The results of this study confirm that a critical view should be taken when considering self-reported health complaints and that ideally biomarkers are monitored to allow an objective assessment of exposure

Calcium puffs are generic InsP₃-activated elementary calcium signals and are downregulated by prolonged hormonal stimulation to inhibit cellular calcium responses

Elementary Ca2+ signals, such as "Ca2+ puffs", which arise from the activation of inositol 1,4,5-trisphosphate receptors, are building blocks for local and global Ca2+ signalling. We characterized Ca2+ puffs in six cell types that expressed differing ratios of the three inositol 1,4,5-trisphosphate receptor isoforms. The amplitudes, spatial spreads and kinetics of the events were similar in each of the cell types. The resemblance of Ca2+ puffs in these cell types suggests that they are a generic elementary Ca2+ signal and, furthermore, that the different inositol 1,4,5-trisphosphate isoforms are functionally redundant at the level of subcellular Ca2+ signalling. Hormonal stimulation of SH-SY5Y neuroblastoma cells and HeLa cells for several hours downregulated inositol 1,4,5-trisphosphate expression and concomitantly altered the properties of the Ca2+ puffs. The amplitude and duration of Ca2+ puffs were substantially reduced. In addition, the number of Ca2+ puff sites active during the onset of a Ca2+ wave declined. The consequence of the changes in Ca2+ puff properties was that cells displayed a lower propensity to trigger regenerative Ca2+ waves. Therefore, Ca2+ puffs underlie inositol 1,4,5-trisphosphate signalling in diverse cell types and are focal points for regulation of cellular responses

Regulation of inositol 1,4,5-trisphosphate-induced Ca2+ release by reversible phosphorylation and dephosphorylation

AbstractThe inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) is a universal intracellular Ca2+-release channel. It is activated after cell stimulation and plays a crucial role in the initiation and propagation of the complex spatio-temporal Ca2+ signals that control cellular processes as different as fertilization, cell division, cell migration, differentiation, metabolism, muscle contraction, secretion, neuronal processing, and ultimately cell death. To achieve these various functions, often in a single cell, exquisite control of the Ca2+ release is needed. This review aims to highlight how protein kinases and protein phosphatases can interact with the IP3R or with associated proteins and so provide a large potential for fine tuning the Ca2+-release activity and for creating efficient Ca2+ signals in subcellular microdomains