Anthropogenic organic micro-pollutants and pathogens in the urban water cycle: assessment, barriers and risk communication (ASKURIS)

In urban areas, water often flows along a partially closed water cycle in which treated municipal wastewater is discharged into surface waters which are one source of raw waters used for drinking water supply. A number of organic micro-pollutants (OMP) can be found in different water compartments. In the near future, climatic and demographic changes will probably contribute to an increase of OMP and antibiotic-resistant pathogens in aquatic ecosystems. The occurrence of OMP, possible adverse effects on aquatic organisms and human health and the public perception must be carefully assessed to properly manage and communicate potentially associated risks and to implement appropriate advanced treatment options at the optimum location within the water cycle. Therefore, the interdisciplinary research project ASKURIS focuses on identification and quantification, toxicological assessment and removal of organic micro-pollutants and antibiotic-resistant pathogens in the Berlin water cycle, life cycle-based economic and environmental assessment, public perception and management of potential risks

TIF-IA, the factor mediating growth-dependent control of ribosomal RNA synthesis, is the mammalian homolog of yeast Rrn3p

Cells carefully modulate the rate of rRNA transcription in order to prevent an overinvestment in ribosome synthesis under less favorable nutritional conditions. In mammals, growth-dependent regulation of RNA polymerase I (Pol I) transcription is mediated by TIF-IA, an essential initiation factor that is active in extracts from growing but not starved or cycloheximide-treated mammalian cells. Here we report the molecular cloning and functional characterization of recombinant TIF-IA, which turns out to be the mammalian homolog of the yeast factor Rrn3p. We demonstrate that TIF-IA interacts with Pol I in the absence of template DNA, augments Pol I transcription in vivo and rescues transcription in extracts from growth-arrested cells in vitro

Anthropogenic organic micro-pollutants and pathogens in the urban water cycle : assessment, barriers and risk communication (ASKURIS)

Gedruckt erschienen im Universitätsverlag der TU Berlin, ISBN 978-3-7983-2814-3Im Forschungsprojekt ASKURIS wurden das Auftreten und die Entfernung organischer Spurenstoffe und resistenter Krankheitserreger in urbanen Wasserkreisläufen erforscht. Neueste analytische Methoden wurden eingesetzt, um entlang des Wasserkreislaufes bekannte Substanzen in kleinsten Konzentrationen zu quantifizieren und unbekannte Spurenstoffe zu identifizieren. Deren Entfernung durch bestehende und zusätzliche technische Barrieren (Aktivkohle und/oder Ozon) wurde an unterschiedlichen Stellen des Wasserkreislaufes untersucht. Für eine Bewertung der technischen Barrieren wurden Kosten und Auswirkungen auf die Umwelt bilanziert. Toxische Effekte auf Mensch und Umwelt wurden untersucht, um ein eventuelles Risiko abschätzen zu können. Mit empirischen, sozialwissenschaftlichen Methoden wurde die Wahrnehmung von Risiken in der Bevölkerung analysiert. Die Forschungsergebnisse aus ASKURIS wurden in das Risikomanagementsystem des größten deutschen Wasserver- und -entsorgers integriert.A partially closed water cycle may exist in urban areas, whereby treated municipal wastewater is discharged into surface waters used as a source for the drinking water supply. A number of organic micro-pollutants (OMP) can be found in the different water compartments. In the near future, climatic and demographic changes probably contribute to an increase of OMP in aquatic eco-systems. The occurrence of OMP, possible adverse effects on aquatic organisms and human health and the public perception must be carefully assessed to properly manage and communicate potential risks and to implement advanced treatment options (activated carbon or ozone) at the optimum point within the water cycle. Therefore, the interdisciplinary research project ASKURIS focused on the identification and quantification of OMP, on the toxicological assessment and removal of organic micro-pollutants and antibiotic-resistant pathogens in the Berlin water cycle, on life-cycle based economic and environmental assessments, the public perception and management of potential risks.BMBF, 02WRS1278, RiSKWa - Verbundprojekt ASKURIS: Anthropogene Spurenstoffe und Krankheitserreger im urbanen Wasserkreislauf: Bewertung, Barrieren und Risikokommunikatio

Tox-Box: securing drops of life - an enhanced health-related approach for risk assessment of drinking water in Germany Tox-Box: Die Tropfen des Lebens bewahren - Gesundheitsbasierte Risikobewertung für Trinkwasser in Deutschland

This article introduces ‘Tox-Box’, a joint research project designed to develop a holistic approach towards a harmonized testing strategy for exposure- and hazard-based risk management of anthropogenic trace substances in drinking water to secure a long-term drinking water supply. The main task of the Tox-Box consortium is to enhance the existing health-related indicator value concept (German: GOW-Konzept - Gesundheitlicher Orientierungswert) through development and prioritization of additional end point-related testing strategies for genotoxicity, neurotoxicity, germ cell damage, and endocrine effects. In this context, substance-specific modes of action will be identified and characterized. Toxicological data collected by the 12 Tox-Box subprojects will be evaluated and weighted to structure a hierarchical testing strategy for an improved risk assessment. A technical guidance document for exposure and hazard-based risk management of anthropogenic trace substances in drinking water will eventually be prepared

Microplastic in the water cycle : sampling, sample preparation, analyses, occurrence and assessment

Gedruckt erschienen im Universitätsverlag der TU Berlin, ISBN 978-3-7983-3162-4Das interdisziplinäre Forschungsprojekt MiWa widmete sich grundlegenden Fragestellungen zur Analytik und Wirkung von Mikroplastik-Partikeln im Wasserkreislauf. Es wurden Methoden der Umweltprobennahme, der Probenaufbereitung und verschiedene Detektionsverfahren zur Charakterisierung und Quantifizierung von Mikroplastik intensiv untersucht, miteinander verglichen und weiterentwickelt. Öko- und humantoxikologische Untersuchungen dienten dem Zweck, die potenziell von Mikroplastik ausgehende Gefährdung für die aquatische Umwelt und den Menschen zu analysieren und zu bewerten. Eine Harmonisierung und Standardisierung von Methoden der Probennahme, Probenaufbereitung und Mikroplastik-Detektion sind trotz der erheblichen Fortschritte derzeit nur teilweise möglich. Die ökotoxikologischen Studien zeigen zwar die Aufnahme von Mikroplastik-Partikeln durch einige Organismen, jedoch konnte bisher keine schädigende Wirkung nachgewiesen werden. Dabei wurden für eine Auswahl aquatischer Modellspezies sowohl Szenarien direkter als auch indirekter Exposition innerhalb einer Nahrungskette betrachtet. Interaktionen mit menschlichen Modellzellen wurden bislang nur bei Mikroplastik-Partikeln mit Größen weit unterhalb von 1 µm (also Nanoplastik) beobachtet. Eine umfassende Bewertung ist bislang nicht möglich.The interdisciplinary research project MiWa focused on principle knowledge gaps of analytical detection and effects of microplastic in fresh water cycles. Methods for environmental sampling, sample preparation and different analytical identification and quantification were intensively investigated, compared and further developed. Toxicological studies were conducted to assess potential risks of microplastic particles towards the environment and human health. Harmonization and standardization are still only partially possible despite various improvements. The eco-toxicological experiments confirmed the intake of microplastic particles by different organisms but no hazardous effects could be found. Both direct ingestions and indirect exposition within food webs were tested. Interactions with exemplary human cells were only observed for particle sizes far below 1 µm (thus nanoplastic). An assessment is currently only possible to a limited extent.BMBF, 02WRS1378, Mikroplastik im Wasserkreislauf (MiWa

Identification of a Hormone-regulated Dynamic Nuclear Actin Network Associated with Estrogen Receptor α in Human Breast Cancer Cell Nuclei*

Estrogen receptor α (ERα) is a modular protein of the steroid/nuclear receptor family of transcriptional regulators that upon binding to the hormone undergoes structural changes, resulting in its nuclear translocation and docking to specific chromatin sites. In the nucleus, ERα assembles in multiprotein complexes that act as final effectors of estrogen signaling to the genome through chromatin remodeling and epigenetic modifications, leading to dynamic and coordinated regulation of hormone-responsive genes. Identification of the molecular partners of ERα and understanding their combinatory interactions within functional complexes is a prerequisite to define the molecular basis of estrogen control of cell functions. To this end, affinity purification was applied to map and characterize the ERα interactome in hormone-responsive human breast cancer cell nuclei. MCF-7 cell clones expressing human ERα fused to a tandem affinity purification tag were generated and used to purify native nuclear ER-containing complexes by IgG-Sepharose affinity chromatography and glycerol gradient centrifugation. Purified complexes were analyzed by two-dimensional DIGE and mass spectrometry, leading to the identification of a ligand-dependent multiprotein complex comprising β-actin, myosins, and several proteins involved in actin filament organization and dynamics and/or known to participate in actin-mediated regulation of gene transcription, chromatin dynamics, and ribosome biogenesis. Time course analyses indicated that complexes containing ERα and actin are assembled in the nucleus early after receptor activation by ligands, and gene knockdown experiments showed that gelsolin and the nuclear isoform of myosin 1c are key determinants for assembly and/or stability of these complexes. Based on these results, we propose that the actin network plays a role in nuclear ERα actions in breast cancer cells, including coordinated regulation of target gene activity, spatial and functional reorganization of chromatin, and ribosome biogenesis