Cyanotoxins associated with macrophytes in Berlin (Germany) water bodies – Occurrence and risk assessment

Publisher Copyright: © 2022Fatal dog poisoning after uptake of neurotoxic cyanobacteria associated with aquatic macrophytes in Tegeler See (Berlin, Germany) raised concerns about critical exposure of humans, especially children, to cyanotoxins produced by macrophyte associated cyanobacteria during recreational activity. From 2017 to 2021 a total of 398 samples of macrophytes washed ashore at bathing sites located at 19 Berlin lakes were analysed for anatoxins, microcystins, and cylindrospermopsins, as were 463 water samples taken in direct proximity to macrophyte accumulations. Cyanotoxins were detected in 66 % of macrophyte samples and 50 % of water samples, with anatoxins being the most frequently detected toxin group in macrophyte samples (58 %) and cylindrospermopsins in water samples (41 %). Microcoleus sp. associated with the water moss Fontinalis antipyretica was identified as anatoxin producing cy-anobacterium in isolated strains as well as in field samples from Tegeler See. Anatoxin contents in macrophyte samples rarely exceeded 1 mu g/g macrophyte fresh weight and peaked at 9.2 mu g/g f.w. Based on established toxicological points of departure, a critical anatoxin content of macrophyte samples of 3 mu g/g f.w. is proposed. Five samples, all taken in Tegeler See and all associated with the water moss Fontinalis antipyretica, exceeded this value. Contents and concentra-tions of microcystins and cylindrospermopsins did not reach critical levels. The potential exposure risks to anatoxins for children and dogs are assessed and recommendations are given.Peer reviewe

Three-dimensional architecture and biogenesis of membrane structures associated with hepatitis C virus replication

All positive strand RNA viruses are known to replicate their genomes in close association with intracellular membranes. In case of the hepatitis C virus (HCV), a member of the family Flaviviridae, infected cells contain accumulations of vesicles forming a membranous web (MW) that is thought to be the site of viral RNA replication. However, little is known about the biogenesis and three-dimensional structure of the MW. In this study we used a combination of immunofluorescence- and electron microscopy (EM)-based methods to analyze the membranous structures induced by HCV in infected cells. We found that the MW is derived primarily from the endoplasmic reticulum (ER) and contains markers of rough ER as well as markers of early and late endosomes, COP vesicles, mitochondria and lipid droplets (LDs). The main constituents of the MW are single and double membrane vesicles (DMVs). The latter predominate and the kinetic of their appearance correlates with kinetics of viral RNA replication. DMVs are induced primarily by NS5A whereas NS4B induces single membrane vesicles arguing that MW formation requires the concerted action of several HCV replicase proteins. Three-dimensional reconstructions identify DMVs as protrusions from the ER membrane into the cytosol, frequently connected to the ER membrane via a neck-like structure. In addition, late in infection multi-membrane vesicles become evident, presumably as a result of a stress-induced reaction. Thus, the morphology of the membranous rearrangements induced in HCV-infected cells resemble those of the unrelated picorna-, corona- and arteriviruses, but are clearly distinct from those of the closely related flaviviruses. These results reveal unexpected similarities between HCV and distantly related positive-strand RNA viruses presumably reflecting similarities in cellular pathways exploited by these viruses to establish their membranous replication factories

Identification of Model Uncertainty via Optimal Design of Experiments Applied to a Mechanical Press

In engineering applications almost all processes are described with the help of models. Especially forming machines heavily rely on mathematical models for control and condition monitoring. Inaccuracies during the modeling, manufacturing and assembly of these machines induce model uncertainty which impairs the controller's performance. In this paper we propose an approach to identify model uncertainty using parameter identification, optimal design of experiments and hypothesis testing. The experimental setup is characterized by optimal sensor positions such that specific model parameters can be determined with minimal variance. This allows for the computation of confidence regions in which the real parameters or the parameter estimates from different test sets have to lie. We claim that inconsistencies in the estimated parameter values, considering their approximated confidence ellipsoids as well, cannot be explained by data uncertainty but are indicators of model uncertainty. The proposed method is demonstrated using a component of the 3D Servo Press, a multi-technology forming machine that combines spindles with eccentric servo drives

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Relationship between sleep duration and dietary intake in 4- to 14-year-old Danish children

A negative association between sleep duration and BMI has been observed in children. However, knowledge about the association between sleep duration and diet is limited. The objective was to examine the association between sleep duration and intake of foods and nutrients in children. In the present cross-sectional study, dietary intake and sleep duration were recorded by the parents for seven consecutive days in a food and sleep record in a representative sample of 802 4- to 14-year-old children. No sex differences were found regarding age and sleep duration. Sleep duration was negatively correlated to age (ρ = –0·68; P < 0·001) and BMI (ρ = –0·41; P < 0·001). In multiple linear regression analyses, sleep duration was not associated with energy intake (b = –0·015; P = 0·20), but there was a trend towards a positive association with intake of dietary fibre (b = 0·006; P = 0·05) and vegetables (b = 0·011; P = 0·05), and a negative association with intake of poultry (b = –0·002; P = 0·02), and a trend towards a negative association with intake of liquid ‘discretionary calories’ (b = –0·01; P = 0·05). Furthermore, in a comparison of dietary intake between age-dependent tertiles of sleep duration, only intake of liquid ‘discretionary calories’ was significantly lower in long sleepers than in short and medium sleepers (P = 0·03). In conclusion, sleep duration was not associated with energy intake and the proposal that children with short sleep duration have less healthy eating habits than children with longer sleep duration was only weakly supported by the present findings

HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology

We present HepatoNet1, a manually curated large-scale metabolic network of the human hepatocyte that encompasses >2500 reactions in six intracellular and two extracellular compartments.Using constraint-based modeling techniques, the network has been validated to replicate numerous metabolic functions of hepatocytes corresponding to a reference set of diverse physiological liver functions.Taking the detoxification of ammonia and the formation of bile acids as examples, we show how these liver-specific metabolic objectives can be achieved by the variable interplay of various metabolic pathways under varying conditions of nutrients and oxygen availability

Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance

<p>Abstract</p> <p>Background</p> <p>Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>OCT1 (<it>SLC22A1</it>) and OCT3 (<it>SLC22A3</it>) mRNA expression was measured in primary human HCC and corresponding non neoplastic tumor surrounding tissue (TST) by real time PCR (n = 53). Protein expression was determined by western blot analysis and immunofluorescence. Data were correlated with the clinicopathological parameters of HCCs.</p> <p>Results</p> <p>Real time PCR showed a downregulation of <it>SLC22A1 </it>and <it>SLC22A3 </it>in HCC compared to TST (p ≤ 0.001). A low <it>SLC22A1 </it>expression was associated with a worse patient survival (p < 0.05). Downregulation was significantly associated with advanced HCC stages, indicated by a higher number of T3 tumors (p = 0.025) with a larger tumor diameter (p = 0.035), a worse differentiation (p = 0.001) and higher AFP-levels (p = 0.019). In accordance, <it>SLC22A1 </it>was less frequently downregulated in tumors with lower stages who underwent transarterial chemoembolization (p < 0.001) and liver transplantation (p = 0.001). Tumors with a low <it>SLC22A1 </it>expression (< median) showed a higher <it>SLC22A3 </it>expression compared to HCC with high <it>SLC22A1 </it>expression (p < 0.001). However, there was no significant difference in tumor characteristics according to the level of the <it>SLC22A3 </it>expression.</p> <p>In the western blot analysis we found a different protein expression pattern in tumor samples with a more diffuse staining in the immunofluorescence suggesting that especially OCT1 is not functional in advanced HCC.</p> <p>Conclusion</p> <p>The downregulation of OCT1 is associated with tumor progression and a worse patient survival.</p