Industrielle Mikroplastikemissionen - Handlungsempfehlungen

EmiStop ist ein Projekt, welches in der Initiative „Plastik in der Umwelt“ des Bundesministeriums für Bildung und Forschung über drei Jahre die Eintragspfade von Mikroplastik (ausgenommen Fasern und Rezyklate) in der kunststoffproduzierenden und -verarbeitenden Industrie sowie der zwischengeschalteten Logistik mit Fokus auf das Wassermanagement und die (Ab)Wasserinfrastruktur untersucht hat. In enger Zusammenarbeit mit einzelnen Betriebsstandorten und Industrieverbänden sowie durch Betriebsbegehungen, Probenahmen und Laboranalysen wurden angepasste Probenahmestrategien und -methoden, analytische Verfahren für Mikroplastik sowie Maßnahmen zur Vermeidung des Eintrags von Mikroplastik in die Umwelt entwickelt. Ein Projektergebnis stellen diese Handlungsempfehlungen für Akteur:innen aus der Industrie dar. Sie sollen als Leitfaden dienen, um Mikroplastikemissionen in die Umwelt an Betriebsstandorten zu vermeiden oder zu vermindern

Does phonological recoding occur during silent reading, and is it necessary for orthographic learning?

Two studies were conducted to test the central claim of the self-teaching hypothesis (i.e., phonological recoding is necessary for orthographic learning) in silent reading. The first study aimed to demonstrate the use of phonological recoding during silent reading. Texts containing pseudowords were read silently or aloud. Two days later, target spellings were recognized more often than their homophone spellings. In both reading conditions, homophone alternatives were named faster than nonexposed pseudowords, suggesting that phonological recoding had occurred. The second study aimed to suppress phonological recoding to demonstrate its necessity for orthographic learning. Lexical decisions were performed in a standard condition, with concurrent articulation, or with tapping. One day later, target spellings were recognized less often after lexical decisions with concurrent articulation. Target and homophone naming speed was not affected by lexical decision condition. The results support the use of phonological recoding during silent reading and specify its role in orthographic learning.16 page(s

Heterologous Expression of ethA and katG in Mycobacterium marinum Enables the Rapid Identification of New Prodrugs Active against Mycobacterium tuberculosis

Screening strategies for antituberculosis compounds using Mycobacterium tuberculosis are time consuming and require biosafety level 3 (BSL3) facilities, which makes the development of high-throughput assays difficult and expensive. Mycobacterium marinum, a close genetic relative of M. tuberculosis, possesses several advantages as a suitable model for tuberculosis drug screening. However, despite the high genetic similarity, there are some obvious differences in susceptibility to some tuberculosis drugs between these two species, especially for the prodrugs ethionamide and isoniazid. In this study, we aimed to improve M. marinum as a model for antituberculosis drug identification by heterologous expression of two common drug activators, EthA and KatG. These two activators were overexpressed in M. marinum, and the strains were tested against ethionamide, isoniazid, and a library of established antimycobacterial compounds from TB Alliance to compare drug susceptibility. Both in vitro and in vivo using zebrafish larvae, these genetically modified M. marinum strains showed significantly higher susceptibility against ethionamide and isoniazid, which require activation by EthA and KatG. More importantly, a strain overexpressing both ethA and katG was potentially more susceptible to approximately 20% of the antituberculosis hit compounds from the TB Alliance library. Most of these compounds were activated by EthA in M. marinum. Four of these compounds were selected for further analysis, and three of them showed obvious EthA-dependent activity against M. tuberculosis. Overall, our developed M. marinum strains are valuable tools for high-throughput discovery of potential novel antituberculosis prodrugs

Dysregulation of Mycobacterium marinum ESX-5 Secretion by Novel 1,2,4-oxadiazoles

The ESX-5 secretion system is essential for the viability and virulence of slow-growing pathogenic mycobacterial species. In this study, we identified a 1,2,4-oxadiazole derivative as a putative effector of the ESX-5 secretion system. We confirmed that this 1,2,4-oxadiazole and several newly synthesized derivatives inhibited the ESX-5-dependent secretion of active lipase LipY by Mycobacterium marinum (M. marinum). Despite reduced lipase activity, we did not observe a defect in LipY secretion itself. Moreover, we found that several other ESX-5 substrates, especially the high molecular-weight PE_PGRS MMAR_5294, were even more abundantly secreted by M. marinum treated with several 1,2,4-oxadiazoles. Analysis of M. marinum grown in the presence of different oxadiazole derivatives revealed that the secretion of LipY and the induction of PE_PGRS secretion were, in fact, two independent phenotypes, as we were able to identify structural features in the compounds that specifically induced only one of these phenotypes. Whereas the three most potent 1,2,4-oxadiazoles displayed only a mild effect on the growth of M. marinum or M. tuberculosis in culture, these compounds significantly reduced bacterial burden in M. marinum-infected zebrafish models. In conclusion, we report a 1,2,4-oxadiazole scaffold that dysregulates ESX-5 protein secretion

An anti-tuberculosis compound screen using a zebrafish infection model identifies an aspartyl-tRNA synthetase inhibitor

Finding new anti-tuberculosis compounds with convincing in vivo activity is an ongoing global challenge to fight the emergence of multidrug-resistant Mycobacterium tuberculosis isolates. In this study, we exploited the medium-throughput capabilities of the zebrafish embryo infection model with Mycobacterium marinum as a surrogate for M. tuberculosis. Using a representative set of clinically established drugs, we demonstrate that this model could be predictive and selective for antibiotics that can be administered orally. We further used the zebrafish infection model to screen 240 compounds from an anti-tuberculosis hit library for their in vivo activity and identified 14 highly active compounds. One of the most active compounds was the tetracyclic compound TBA161, which was studied in more detail. Analysis of resistant mutants revealed point mutations in aspS (rv2572c), encoding an aspartyl-tRNA synthetase. The target was genetically confirmed, and molecular docking studies propose the possible binding of TBA161 in a pocket adjacent to the catalytic site. This study shows that the zebrafish infection model is suitable for rapidly identifying promising scaffolds with in vivo activity

Dysregulation of Mycobacterium marinum ESX-5 Secretion by Novel 1,2,4-oxadiazoles

The ESX-5 secretion system is essential for the viability and virulence of slow-growing pathogenic mycobacterial species. In this study, we identified a 1,2,4-oxadiazole derivative as a putative effector of the ESX-5 secretion system. We confirmed that this 1,2,4-oxadiazole and several newly synthesized derivatives inhibited the ESX-5-dependent secretion of active lipase LipY by Mycobacterium marinum (M. marinum). Despite reduced lipase activity, we did not observe a defect in LipY secretion itself. Moreover, we found that several other ESX-5 substrates, especially the high molecular-weight PE_PGRS MMAR_5294, were even more abundantly secreted by M. marinum treated with several 1,2,4-oxadiazoles. Analysis of M. marinum grown in the presence of different oxadiazole derivatives revealed that the secretion of LipY and the induction of PE_PGRS secretion were, in fact, two independent phenotypes, as we were able to identify structural features in the compounds that specifically induced only one of these phenotypes. Whereas the three most potent 1,2,4-oxadiazoles displayed only a mild effect on the growth of M. marinum or M. tuberculosis in culture, these compounds significantly reduced bacterial burden in M. marinum-infected zebrafish models. In conclusion, we report a 1,2,4-oxadiazole scaffold that dysregulates ESX-5 protein secretion

Dysregulation of <i>Mycobacterium marinum</i> ESX-5 Secretion by Novel 1,2,4-oxadiazoles

The ESX-5 secretion system is essential for the viability and virulence of slow-growing pathogenic mycobacterial species. In this study, we identified a 1,2,4-oxadiazole derivative as a putative effector of the ESX-5 secretion system. We confirmed that this 1,2,4-oxadiazole and several newly synthesized derivatives inhibited the ESX-5-dependent secretion of active lipase LipY by Mycobacterium marinum (M. marinum). Despite reduced lipase activity, we did not observe a defect in LipY secretion itself. Moreover, we found that several other ESX-5 substrates, especially the high molecular-weight PE_PGRS MMAR_5294, were even more abundantly secreted by M. marinum treated with several 1,2,4-oxadiazoles. Analysis of M. marinum grown in the presence of different oxadiazole derivatives revealed that the secretion of LipY and the induction of PE_PGRS secretion were, in fact, two independent phenotypes, as we were able to identify structural features in the compounds that specifically induced only one of these phenotypes. Whereas the three most potent 1,2,4-oxadiazoles displayed only a mild effect on the growth of M. marinum or M. tuberculosis in culture, these compounds significantly reduced bacterial burden in M. marinum-infected zebrafish models. In conclusion, we report a 1,2,4-oxadiazole scaffold that dysregulates ESX-5 protein secretion

Measuring Users’ Receptivity Toward an Integral Intervention Model Based on mHealth Solutions for Patients With Treatment-Resistant Schizophrenia (m-RESIST): A Qualitative Study

BACKGROUND: Despite the theoretical potential of mHealth solutions in the treatment of patients with schizophrenia, there remains a lack of technological tools in clinical practice. OBJECTIVE: The aim of this study was to measure the receptivity of patients, informal carers, and clinicians to a European integral intervention model focused on patients with persistent positive symptoms: Mobile Therapeutic Attention for Patients with Treatment-Resistant Schizophrenia (m-RESIST). METHODS: Before defining the system requirements, a qualitative study of the needs of outpatients with treatment-resistant schizophrenia was carried out in Spain, Israel, and Hungary. We analyzed the opinions of patients, informal carers, and clinicians concerning the services originally intended to be part of the solution. A total of 9 focus groups (72 people) and 35 individual interviews were carried out in the 3 countries, using discourse analysis as the framework. RESULTS: A webpage and an online forum were perceived as suitable to get both reliable information on the disease and support. Data transmission by a smart watch (monitoring), Web-based visits, and instant messages (clinical treatment) were valued as ways to improve contact with clinicians. Alerts were appreciated as reminders of daily tasks and appointments. Avoiding stressful situations for outpatients, promoting an active role in the management of the disease, and maintaining human contact with clinicians were the main suggestions provided for improving the effectiveness of the solution. CONCLUSIONS: Positive receptivity toward m-RESIST services is related to its usefulness in meeting user needs, its capacity to empower them, and the possibility of maintaining human contact