Environmental Impact on Vascular Development Predicted by High-Throughput Screening

Background: Understanding health risks to embryonic development from exposure to environmental chemicals is a significant challenge given the diverse chemical landscape and paucity of data for most of these compounds. High-throughput screening (HTS) in the U.S. Environmental Protection Agency (EPA) ToxCast™ project provides vast data on an expanding chemical library currently consisting of > 1,000 unique compounds across > 500 in vitro assays in phase I (complete) and Phase II (under way). This public data set can be used to evaluate concentration-dependent effects on many diverse biological targets and build predictive models of prototypical toxicity pathways that can aid decision making for assessments of human developmental health and disease

Trafficking of Siderophore Transporters in Saccharomyces cerevisiae and Intracellular Fate of Ferrioxamine B Conjugates

We have studied the intracellular trafficking of Sit1 [ferrioxamine B (FOB) transporter] and Enb1 (enterobactin transporter) in Saccharomyces cerevisiae using green fluorescent protein (GFP) fusion proteins. Enb1 was constitutively targeted to the plasma membrane. Sit1 was essentially targeted to the vacuolar degradation pathway when synthesized in the absence of substrate. Massive plasma membrane sorting of Sit1 was induced by various siderophore substrates of Sit1, and by coprogen, which is not a substrate of Sit1. Thus, different siderophore transporters use different regulated trafficking processes. We also studied the fate of Sit1-mediated internalized siderophores. Ferrioxamine B was recovered in isolated vacuolar fractions, where it could be detected spectrophotometrically. Ferrioxamine B coupled to an inhibitor of mitochondrial protoporphyrinogen oxidase (acifluorfen) could not reach its target unless the cells were disrupted, confirming the tight compartmentalization of siderophores within cells. Ferrioxamine B coupled to a fluorescent moiety, FOB-nitrobenz-2-oxa-1,3-diazole, used as a Sit1-dependent iron source, accumulated in the vacuolar lumen even in mutants displaying a steady-state accumulation of Sit1 at the plasma membrane or in endosomal compartments. Thus, the fates of siderophore transporters and siderophores diverge early in the trafficking process

Evaluation of 309 Environmental Chemicals Using a Mouse Embryonic Stem Cell Adherent Cell Differentiation and Cytotoxicity Assay

The vast landscape of environmental chemicals has motivated the need for alternative methods to traditional whole-animal bioassays in toxicity testing. Embryonic stem (ES) cells provide an in vitro model of embryonic development and an alternative method for assessing developmental toxicity. Here, we evaluated 309 environmental chemicals, mostly food-use pesticides, from the ToxCast™ chemical library using a mouse ES cell platform. ES cells were cultured in the absence of pluripotency factors to promote spontaneous differentiation and in the presence of DMSO-solubilized chemicals at different concentrations to test the effects of exposure on differentiation and cytotoxicity. Cardiomyocyte differentiation (α,β myosin heavy chain; MYH6/MYH7) and cytotoxicity (DRAQ5™/Sapphire700™) were measured by In-Cell Western™ analysis. Half-maximal activity concentration (AC50) values for differentiation and cytotoxicity endpoints were determined, with 18% of the chemical library showing significant activity on either endpoint. Mining these effects against the ToxCast Phase I assays (∼500) revealed significant associations for a subset of chemicals (26) that perturbed transcription-based activities and impaired ES cell differentiation. Increased transcriptional activity of several critical developmental genes including BMPR2, PAX6 and OCT1 were strongly associated with decreased ES cell differentiation. Multiple genes involved in reactive oxygen species signaling pathways (NRF2, ABCG2, GSTA2, HIF1A) were strongly associated with decreased ES cell differentiation as well. A multivariate model built from these data revealed alterations in ABCG2 transporter was a strong predictor of impaired ES cell differentiation. Taken together, these results provide an initial characterization of metabolic and regulatory pathways by which some environmental chemicals may act to disrupt ES cell growth and differentiation

Synthesis of functional ‘polyolefins’: state of the art and remaining challenges

Functional polyolefins (i.e., polyethene or polypropene bearing functional groups) are highly desired materials, due to their beneficial surface properties. Many different pathways exist for the synthesis of these materials, each with its own advantages and drawbacks. This review focuses on those synthetic pathways that build up a polymer chain from ethene/propene and functionalised polar vinyl monomers. Despite many recent advances in the various fields of olefin polymerisation, it still remains a challenge to synthesise high molecular- weight copolymers with tuneable amounts of functional groups, preferably with consecutive insertions of polar monomers occurring in a stereoselective way. To overcome some of these challenges, polymerisation of alternative functionalised monomers is explored as well

Accuracy and precision of tidal wetland soil carbon mapping in the conterminous United States

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 8 (2018): 9478, doi:10.1038/s41598-018-26948-7.Tidal wetlands produce long-term soil organic carbon (C) stocks. Thus for carbon accounting purposes, we need accurate and precise information on the magnitude and spatial distribution of those stocks. We assembled and analyzed an unprecedented soil core dataset, and tested three strategies for mapping carbon stocks: applying the average value from the synthesis to mapped tidal wetlands, applying models fit using empirical data and applied using soil, vegetation and salinity maps, and relying on independently generated soil carbon maps. Soil carbon stocks were far lower on average and varied less spatially and with depth than stocks calculated from available soils maps. Further, variation in carbon density was not well-predicted based on climate, salinity, vegetation, or soil classes. Instead, the assembled dataset showed that carbon density across the conterminous united states (CONUS) was normally distributed, with a predictable range of observations. We identified the simplest strategy, applying mean carbon density (27.0 kg C m−3), as the best performing strategy, and conservatively estimated that the top meter of CONUS tidal wetland soil contains 0.72 petagrams C. This strategy could provide standardization in CONUS tidal carbon accounting until such a time as modeling and mapping advancements can quantitatively improve accuracy and precision.Synthesis efforts were funded by NASA Carbon Monitoring System (CMS; NNH14AY67I), USGS LandCarbon and the Smithsonian Institution. J.R.H. was additionally supported by the NSF-funded Coastal Carbon Research Coordination Network while completing this manuscript (DEB-1655622). J.M.S. coring efforts were funded by NSF (EAR-1204079). B.P.H. coring efforts were funded by Earth Observatory (Publication Number 197)

Feilke revisited : 60 Stellenbesuche

Weitere Hrsg.: Thorsten Pohl, Sara Rezat, Torsten Steinhoff, Martin SteinseiferAnlässlich des 60. Geburtstags des Linguisten und Sprachdidaktikers Helmuth Feilke wurden Wegbegleiterinnen und Wegbegleiter gebeten, einzelne Stellen in seinen wissenschaftlichen Schriften erneut zu besuchen. Entstanden sind pointierte Kommentare, kurze wissenschaftliche Abhandlungen und Analysen, Varianten auch des kritischen und kontroversen Nach- und Weiterdenkens und Ansätze zur Neu- oder Re-Kontextualisierung. Je nach wissenschaftlicher Vita der Autorinnen und Autoren kann es sich um Stellen handeln, deren Rezeption zeitlich weit zurückliegt, oder um Passagen, die ganz aktuelle Fragen der eigenen Forschungsarbeit tangieren. Abgesehen davon, dass ein kurzes Format für die Beiträge gewählt und die Autorinnen und Autoren gebeten wurden, die ausgewählte Stelle knapp zu verorten und zu erläutern, war die Bearbeitungsform gänzlich freigestellt. So sind Texte in einer Bandbreite von pointierten Kommentaren, kurzen wissenschaftlichen Abhandlungen und Analysen, Varianten des Nach- und Weiterdenkens, Ansätze zur Neu- oder Re-Kontextualisierung bis hin zu Formen des kritischen Hinterfragens und der kontroversen Auseinandersetzung entstanden

Impacts of Hurricanes on Nutrient Export and Ecosystem Metabolism in a Blackwater River Estuary Complex

Hurricanes have the ability to export uncharacteristically large amounts of nutrients from terrestrial systems into riverine and estuarine networks, altering rates of ecosystem metabolism throughout the aquatic continuum. In order to explore these impacts and compare these values to common precipitation events, water quality and chemistry data from the National Estuarine Research Reserve’s System Wide Monitoring Program (NERR-SWMP) were combined with discharge data from the United States Geological Survey (USGS) to calculate biogeochemical export from a Florida coastal blackwater river. This analysis was focused on the years 2016–2020, when Hurricanes Matthew, Irma, and Dorian impacted the landscape of Florida’s Atlantic coast. Hurricane Irma, the only hurricane to occur after especially wet summer conditions, dwarfed the other two hurricanes in the export of dissolved organic carbon (DOC), with an increase from −1 to approximately 250 kg DOC day−1. Soluble reactive phosphorus (SRP) and most nitrogen species export exhibited similar trends. Additionally, other spikes in export occurred during non-hurricane months, and no significant differences between monthly export values were found between hurricane and non-hurricane months. However, net ecosystem metabolism (NEM) was calculated at similar intervals and revealed significantly lower NEM during months of hurricane passage. On monthly timescales, this work suggests that lower-category hurricanes might not significantly impact organic matter export, but the shortened export interval associated with hurricane impacts produces significant implications for NEM