TY - JOUR A1 - Allan, Eric A1 - Bossdorf, Oliver A1 - Dormann, Carsten F. A1 - Prati, Daniel A1 - Gossner, Martin M. A1 - Tscharntke, Teja A1 - Blüthgen, Nico A1 - Bellach, Michaela A1 - Birkhofer, Klaus A1 - Boch, Steffen A1 - Böhm, Stefan A1 - Börschig, Carmen A1 - Chatzinotas, Antonis A1 - Christ, Sabina A1 - Daniel, Rolf A1 - Diekötter, Tim A1 - Fischer, Christiane A1 - Friedl, Thomas A1 - Glaser, Karin A1 - Hallmann, Christine A1 - Hodac, Ladislav A1 - Hölzel, Norbert A1 - Jung, Kirsten A1 - Klein, Alexandra-Maria A1 - Klaus, Valentin H. A1 - Kleinebecker, Till A1 - Krauss, Jochen A1 - Lange, Markus A1 - Morris, E. Kathryn A1 - Müller, Jörg A1 - Nacke, Heiko A1 - Pasalic, Esther A1 - Rillig, Matthias C. A1 - Rothenwoehrer, Christoph A1 - Schally, Peter A1 - Scherber, Christoph A1 - Schulze, Waltraud X. A1 - Socher, Stephanie A. A1 - Steckel, Juliane A1 - Steffan-Dewenter, Ingolf A1 - Türke, Manfred A1 - Weiner, Christiane N. A1 - Werner, Michael A1 - Westphal, Catrin A1 - Wolters, Volkmar A1 - Wubet, Tesfaye A1 - Gockel, Sonja A1 - Gorke, Martin A1 - Hemp, Andreas A1 - Renner, Swen C. A1 - Schöning, Ingo A1 - Pfeiffer, Simone A1 - König-Ries, Birgitta A1 - Buscot, Francois A1 - Linsenmair, Karl Eduard A1 - Schulze, Ernst-Detlef A1 - Weisser, Wolfgang W. A1 - Fischer, Markus T1 - Interannual variation in land-use intensity enhances grassland multidiversity JF - Proceedings of the National Academy of Sciences of the United States of America N2 - Although temporal heterogeneity is a well-accepted driver of biodiversity, effects of interannual variation in land-use intensity (LUI) have not been addressed yet. Additionally, responses to land use can differ greatly among different organisms; therefore, overall effects of land-use on total local biodiversity are hardly known. To test for effects of LUI (quantified as the combined intensity of fertilization, grazing, and mowing) and interannual variation in LUI (SD in LUI across time), we introduce a unique measure of whole-ecosystem biodiversity, multidiversity. This synthesizes individual diversity measures across up to 49 taxonomic groups of plants, animals, fungi, and bacteria from 150 grasslands. Multidiversity declined with increasing LUI among grasslands, particularly for rarer species and aboveground organisms, whereas common species and belowground groups were less sensitive. However, a high level of interannual variation in LUI increased overall multidiversity at low LUI and was even more beneficial for rarer species because it slowed the rate at which the multidiversity of rare species declined with increasing LUI. In more intensively managed grasslands, the diversity of rarer species was, on average, 18% of the maximum diversity across all grasslands when LUI was static over time but increased to 31% of the maximum when LUI changed maximally over time. In addition to decreasing overall LUI, we suggest varying LUI across years as a complementary strategy to promote biodiversity conservation. KW - biodiversity loss KW - agricultural grasslands KW - Biodiversity Exploratories Y1 - 2014 U6 - https://doi.org/10.1073/pnas.1312213111 SN - 0027-8424 VL - 111 IS - 1 SP - 308 EP - 313 PB - National Acad. of Sciences CY - Washington ER - TY - GEN A1 - Weisser, Karin A1 - Stübler, Sabine A1 - Matheis, Walter A1 - Huisinga, Wilhelm T1 - Towards toxicokinetic modelling of aluminium exposure from adjuvants in medicinal products T2 - Regulatory toxicology and pharmacology : official journal of the International Society for Regulatory Toxicology and Pharmacology N2 - As a potentially toxic agent on nervous system and bone, the safety of aluminium exposure from adjuvants in vaccines and subcutaneous immune therapy (SCIT) products has to be continuously reevaluated, especially regarding concomitant administrations. For this purpose, knowledge on absorption and disposition of aluminium in plasma and tissues is essential. Pharmacokinetic data after vaccination in humans, however, are not available, and for methodological and ethical reasons difficult to obtain. To overcome these limitations, we discuss the possibility of an in vitro-in silico approach combining a toxicokinetic model for aluminium disposition with biorelevant kinetic absorption parameters from adjuvants. We critically review available kinetic aluminium-26 data for model building and, on the basis of a reparameterized toxicokinetic model (Nolte et al., 2001), we identify main modelling gaps. The potential of in vitro dissolution experiments for the prediction of intramuscular absorption kinetics of aluminium after vaccination is explored. It becomes apparent that there is need for detailed in vitro dissolution and in vivo absorption data to establish an in vitro-in vivo correlation (IVIVC) for aluminium adjuvants. We conclude that a combination of new experimental data and further refinement of the Nolte model has the potential to fill a gap in aluminium risk assessment. (C) 2017 Elsevier Inc. All rights reserved. KW - Aluminium KW - Aluminium adjuvants KW - Absorption kinetics KW - Toxicokinetic modelling KW - In vitro dissolution Y1 - 2017 U6 - https://doi.org/10.1016/j.yrtph.2017.02.018 SN - 0273-2300 SN - 1096-0295 VL - 88 SP - 310 EP - 321 PB - Elsevier CY - San Diego ER - TY - JOUR A1 - Hethey, Christoph Philipp A1 - Hartung, Niklas A1 - Wangorsch, Gaby A1 - Weisser, Karin A1 - Huisinga, Wilhelm T1 - Physiology-based toxicokinetic modelling of aluminium in rat and man JF - Archives of toxicology : official journal of EUROTOX N2 - A sufficient quantitative understanding of aluminium (Al) toxicokinetics (TK) in man is still lacking, although highly desirable for risk assessment of Al exposure. Baseline exposure and the risk of contamination severely limit the feasibility of TK studies administering the naturally occurring isotope Al-27, both in animals and man. These limitations are absent in studies with Al-26 as a tracer, but tissue data are limited to animal studies. A TK model capable of inter-species translation to make valid predictions of Al levels in humans-especially in toxicological relevant tissues like bone and brain-is urgently needed. Here, we present: (i) a curated dataset which comprises all eligible studies with single doses of Al-26 tracer administered as citrate or chloride salts orally and/or intravenously to rats and humans, including ultra-long-term kinetic profiles for plasma, blood, liver, spleen, muscle, bone, brain, kidney, and urine up to 150 weeks; and (ii) the development of a physiology-based (PB) model for Al TK after intravenous and oral administration of aqueous Al citrate and Al chloride solutions in rats and humans. Based on the comprehensive curated Al-26 dataset, we estimated substance-dependent parameters within a non-linear mixed-effect modelling context. The model fitted the heterogeneous Al-26 data very well and was successfully validated against datasets in rats and humans. The presented PBTK model for Al, based on the most extensive and diverse dataset of Al exposure to date, constitutes a major advancement in the field, thereby paving the way towards a more quantitative risk assessment in humans. KW - PBTK KW - Toxicokinetics KW - Al-26 KW - Aluminium Y1 - 2021 U6 - https://doi.org/10.1007/s00204-021-03107-y SN - 0340-5761 SN - 1432-0738 VL - 95 IS - 9 SP - 2977 EP - 3000 PB - Springer CY - Berlin ; Heidelberg ER -