21 research outputs found

    Publicações de teatro em 2013

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    O texto procede ao levantamento bibliográfico, selecção da tipologia e listagem das edições de / sobre teatro no ano indicado, inclui adenda aos anos anterioresinfo:eu-repo/semantics/publishedVersio

    First cross-border outbreak of foodborne botulism in the European Union associated with the consumption of commercial dried roach (Rutilus rutilus)

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    Botulism outbreaks due to commercial products are extremely rare in the European Union. Here we report on the first international outbreak of foodborne botulism caused by commercial salt-cured, dried roach (Rutilus rutilus). Between November and December 2016, an outbreak of six foodborne botulism type E cases from five unrelated households was documented in Germany and Spain. The outbreak involved persons of Russian and Kazakh backgrounds, all consumed unheated salt-cured, dried roach-a snack particularly favored in Easter-European countries. The implicated food batches had been distributed by an international wholesaler and were recalled from Europe-wide outlets of a supermarket chain and other independent retailers. Of interest, and very unlike to other foodborne disease outbreaks which usually involves a single strain or virus variant, different Clostridium botulinum strains and toxin variants could be identified even from a single patient's sample. Foodborne botulism is a rare but potentially life-threatening disease and almost exclusively involves home-made or artisan products and thus, outbreaks are limited to individual or few cases. As a consequence, international outbreaks are the absolute exception and this is the first one within the European Union. Additional cases were likely prevented by a broad product recall, underscoring the importance of timely public health action. Challenges and difficulties on the diagnostic and epidemiological level encountered in the outbreak are highlighted.The Consultant Laboratory for Neurotoxin-producing Clostridia (Botulism, Tetanus) was funded by the German Federal Ministry of Health and the Robert Koch Institute.S

    Begleitevaluation der arbeitsmarktpolitischen IntegrationsmaĂźnahmen fĂĽr GeflĂĽchtete: zweiter Zwischenbericht

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    Mit der Begleitevaluation der arbeitsmarktpolitischen Integrationsmaßnahmen für Geflüchtete sollen wissenschaftlich fundierte Erkenntnisse über die Inanspruchnahme, Umsetzung und Wirkungen der wesentlichen Instrumente der aktiven Arbeitsmarktpolitik im SGB II und SGB III zur Förderung der Integration von Geflüchteten in Ausbildung und Arbeit gewonnen werden. Dabei werden auch Kontextfaktoren wie z. B. die regionalen Rahmenbedingungen sowie die Bedeutung der Sprachförderung in den Blick genommen. Zielgrößen sind neben Fortschritten auf dem Weg in Ausbildung und Arbeit auch Fortschritte bei Dimensionen sozialer Teilhabe, die gute Frühindikatoren für eine erst später erfolgende Arbeitsmarktintegration von Geflüchteten darstellen. Dieser Zwischenbericht dokumentiert den bis zum 31. Oktober 2019 erreichten Projektfortschritt und präsentiert empirische Befunde auf Grundlage der bis zu diesem Zeitpunkt verfügbaren umfangreichen projektspezifischen Datenbasis

    Optimization of SNAP-25 and VAMP-2 Cleavage by Botulinum Neurotoxin Serotypes A–F Employing Taguchi Design-of-Experiments

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    The detection of catalytically active botulinum neurotoxins (BoNTs) can be achieved by monitoring the enzymatic cleavage of soluble NSF (N-ethylmaleimide-sensitive-factor) attachment protein receptor (SNARE) proteins by the toxins’ light chains (LC) in cleavage-based assays. Thus, for sensitive BoNT detection, optimal cleavage conditions for the clinically relevant A–F serotypes are required. Until now, a systematic evaluation of cleavage conditions for the different BoNT serotypes is still lacking. To address this issue, we optimized cleavage conditions for BoNT/A–F using the Taguchi design-of-experiments (DoE) method. To this aim, we analyzed the influence of buffer composition (pH, Zn2+, DTT (dithiothreitol), NaCl) as well as frequently used additives (BSA (bovine serum albumin), Tween 20, trimethylamine N-oxide (TMAO)) on BoNT substrate cleavage. We identified major critical factors (DTT, Zn2+, TMAO) and were able to increase the catalytic efficiency of BoNT/B, C, E, and F when compared to previously described buffers. Moreover, we designed a single consensus buffer for the optimal cleavage of all tested serotypes. Our optimized buffers are instrumental to increase the sensitivity of cleavage-based assays for BoNT detection. Furthermore, the application of the Taguchi DoE approach shows how the method helps to rationally improve enzymatic assays.Peer Reviewe

    A large travel-associated outbreak of iatrogenic botulism in four European countries following intragastric botulinum neurotoxin injections for weight reduction, TĂĽrkiye, February to March 2023

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    International audienceIn March 2023, 34 associated cases of iatrogenic botulism were detected in Germany (30 cases), Switzerland (two cases), Austria (one case), and France (one case). An alert was rapidly disseminated via European Union networks and communication platforms (Food- and Waterborne Diseases and Zoonoses Network, EpiPulse, Early Warning and Response System) and the International Health Regulation mechanism; the outbreak was investigated in a European collaboration. We traced sources of the botulism outbreak to treatment of weight loss in TĂĽrkiye, involving intragastric injections of botulinum neurotoxin. Cases were traced using a list of patients who had received this treatment. Laboratory investigations of the first 12 German cases confirmed nine cases. The application of innovative and highly sensitive endopeptidase assays was necessary to detect minute traces of botulinum neurotoxin in patient sera. The botulism notification requirement for physicians was essential to detect this outbreak in Germany. The surveillance case definition of botulism should be revisited and inclusion of cases of iatrogenic botulism should be considered as these cases might lack standard laboratory confirmation yet warrant public health action. Any potential risks associated with the use of botulinum neurotoxins in medical procedures need to be carefully balanced with the expected benefits of the procedure

    A hydrophobic loop is located between the synaptotagmin- and ganglioside-binding site of BoNT/B, DC, and G which confers high-affinity receptor binding and high toxicity of BoNT/B, DC, and G.

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    <p><b>A</b> Superposition of dual-receptor binding of BoNT/B (blue ribbon; PDB IDs 1EPW [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1007048#ppat.1007048.ref055" target="_blank">55</a>] and 4KBB [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1007048#ppat.1007048.ref011" target="_blank">11</a>]) to ganglioside GD1a (space fill model) and synaptotagmin-II (green ribbon), BoNT/G (pink ribbon PDB ID 2VXR [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1007048#ppat.1007048.ref040" target="_blank">40</a>]), and the interaction between BoNT/DC (magenta ribbon) and synaptotagmin-II (dark green ribbon side view; PDB ID 4ISR [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1007048#ppat.1007048.ref022" target="_blank">22</a>]) in proximity to a model membrane. Key amino acids of the hydrophobic loop (B: G1247-F1250, DC: Y1251-F1253; black box and insert) located between the ganglioside and synaptotagmin-binding sites are shown as stick models. <b>B</b> Determination of neurotoxicity of BoNT ΔH<sub>C</sub> loop vs wild-type in MPN assay. The neurotoxicity of single chain (sc) scBoNTBSL ΔG1247-F1250 (n = 4), scH6tBoNTDCS ΔY1251-F1253 (n = 4), and BoNTGS ΔY1252-W1256 (n = 2) was determined in comparison to the corresponding BoNT wild-type using dose-response curves (data are represented as mean ± SD). <b>C</b> GST pull down of wild-type and ΔH<sub>C</sub> loop-mutants of H<sub>C</sub>B, H<sub>C</sub>DC, and H<sub>C</sub>G by GST-synaptotagmin-II with or without gangliosides in Triton X-100 micelles. Binding of 100 pmol of the wild-type or ΔH<sub>C</sub> loop H<sub>C</sub> fragments to 150 pmol GST-rSyt-II 1–61, 1–90, or 1–90 in 20 mM Tris pH 8, 80 mM NaCl, 0.5% Triton X-100 in the presence of 125 μg of ganglioside mix (Gmix) embedded in Triton X-100 micelles immobilized to glutathione-sepharose 4B matrix and subsequent SDS-PAGE analysis (see also <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1007048#ppat.1007048.s002" target="_blank">S2 Fig</a>; data are represented as mean ± SD, n = 3).</p

    Kinetic analysis employing nanodisc-embedded receptor molecules reveals that interactions with gangliosides, proteins, and lipids are crucial for high-affinity binding.

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    <p>SPR-sensorgrams for the determination of binding kinetics of recombinant H<sub>C</sub> receptor-binding domains to isolated GST-Syt-II 1–61 (<b>A</b>), GT1b nanodiscs (<b>B</b>), GST-Syt-II 1–90 nanodiscs (<b>C</b>), or dual-receptor nanodiscs containing both GT1b and GST-Syt-II 1–90 (<b>D</b>). Shown is one representative of two measured binding responses (red) overlaid with fits (black lines) from 1:1 Langmuir interaction models or a heterogeneous binding model (marked by asterisk), see <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1007048#ppat.1007048.t001" target="_blank">Table 1</a> for kinetic data.</p

    Generation and characterization of phospholipid-bilayer nanodiscs containing receptor molecules.

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    <p><b>A</b> Size exclusion chromatography (SEC) elution profiles (absorption at 227 nm over elution volume V<sub>e</sub>) for nanodiscs containing either no receptor molecules (empty), GT1b only, GST-Syt-II 1–90 only, or GT1b and GST-Syt-II 1–90 (dual-receptor nanodiscs; schematic inserts modified from [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1007048#ppat.1007048.ref073" target="_blank">73</a>]). <b>B</b> ELISA results for the detection of membrane scaffold protein (MSP; via His-tag), GT1b, and Syt-II in the SEC-fractions. Brackets embrace the fractions used for the SPR measurements or further purification using the GST-tag on Syt-II (marked by asterisk). <b>C</b> Electron microscopy of the assembled nanodiscs purified by SEC (empty and GT1b nanodiscs) or SEC and batch-purification via the GST-tag (Syt-II nanodiscs and dual-receptor nanodiscs). Arrows indicate assembled discoidal nanodiscs of the correct diameter (13 nm) from top view. Scale bar = 50 nm.</p
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