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| 2. |
- Bryois, J., et al.
(författare)
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 3. |
- van Gils, Jos, et al.
(författare)
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Computational material flow analysis for thousands of chemicals of emerging concern in European waters
- 2020
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Ingår i: Journal of Hazardous Materials. - : Elsevier BV. - 0304-3894 .- 1873-3336. ; 397
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of exposure to a wide range of chemicals, and the spatio-temporal variability thereof, is urgently needed in the context of protecting and restoring aquatic ecosystems. This paper discusses a computational material flow analysis to predict the occurrence of thousands of man-made organic chemicals on a European scale, based on a novel temporally and spatially resolved modelling framework. The goal was to increase understanding of pressures by emerging chemicals and to complement surface water monitoring data. The ambition was to provide a first step towards a real-life mixture exposure situation accounting for as many chemicals as possible. Comparison of simulated concentrations and chemical monitoring data for 226 substance/basin combinations showed that the simulated concentrations were accurate on average. For 65% and 90% of substance/basin combinations the error was within one and two orders of magnitude respectively. An analysis of the relative importance of uncertainties revealed that inaccuracies in use volume or use type information contributed most to the error for individual substances. To resolve this, we suggest better registration of use types of industrial chemicals, investigation of presence/absence of industrial chemicals in wastewater and runoff samples and more scientific information exchange.
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| 4. |
- de Zwart, Dick, et al.
(författare)
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Toward Harmonizing Ecotoxicity Characterization in Life Cycle Impact Assessment
- 2018
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 37:12, s. 2955-2971
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Tidskriftsartikel (refereegranskat)abstract
- Ecosystem quality is an important area of protection in life cycle impact assessment (LCIA). Chemical pollution has adverse impacts on ecosystems on a global scale. To improve methods for assessing ecosystem impacts, the Life Cycle Initiative hosted by the United Nations Environment Programme established a task force to evaluate the state-of-the-science in modeling chemical exposure of organisms and the resulting ecotoxicological effects for use in LCIA. The outcome of the task force work will be global guidance and harmonization by recommending changes to the existing practice of exposure and effect modeling in ecotoxicity characterization. These changes will reflect the current science and ensure the stability of recommended practice. Recommendations must work within the needs of LCIA in terms of 1) operating on information from any inventory reporting chemical emissions with limited spatiotemporal information, 2) applying best estimates rather than conservative assumptions to ensure unbiased comparison with results for other impact categories, and 3) yielding results that are additive across substances and life cycle stages and that will allow a quantitative expression of damage to the exposed ecosystem. We describe the current framework and discuss research questions identified in a roadmap. Primary research questions relate to the approach toward ecotoxicological effect assessment, the need to clarify the method's scope and interpretation of its results, the need to consider additional environmental compartments and impact pathways, and the relevance of effect metrics other than the currently applied geometric mean of toxicity effect data across species. Because they often dominate ecotoxicity results in LCIA, we give metals a special focus, including consideration of their possible essentiality and changes in environmental bioavailability. We conclude with a summary of key questions along with preliminary recommendations to address them as well as open questions that require additional research efforts.
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| 5. |
- Gustavsson, Mikael, et al.
(författare)
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Using species sensitivity distributions to determine boundaries for chemical pollution
- 2015
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Ingår i: Oral presentation at the SETAC conference, Barcelona, Spain.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Species sensitivity distributions (SSDs) and distributions of toxicity values are used for determining toxicological and ecotoxicological thresholds, the HC5 (hazardous concentration for 5% of the species) and the TTC (threshold of toxicological concern), respectively. An SSD describes the sensitivity distribution of a range of species towards a single toxicant, while the TTC is based on the toxicity distribution of a range of different compounds towards the same species or group of species. Both concepts can be combined by using the distribution of HC5 values for a group of substances in order to estimate the TTC. HC5- as well as TTC-values are usually based on toxicity data from standard single species assays. However, the ecological impact of a compound is the result of the reaction of a range of interacting species. In order to explore the impact of using data from ecological communities instead of single species, we performed a comparison of the TTC based on HC5-values with the TTC based on community ecotoxicological data (threshold of concern for community toxicity, TCCT). This study was performed by using toxicity data for Photosystem II- inhibiting herbicides to single algal species and algal communities. Single-species based SSDs and the corresponding HC5 values were established for seven different herbicides. Community ecotoxicity data were collected for 17 herbicides. The resulting thresholds were 6.8 nmol/L for the TTC based on HC5 values and 3.5 nmol/L for the TTC based on community data. This indicates that indirect ecological effects and species interactions do not seem to play a major role, as long as photosynthesis is in focus.
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| 6. |
- van Gils, Jos, et al.
(författare)
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The European Collaborative Project SOLUTIONS developed models to provide diagnostic and prognostic capacity and fill data gaps for chemicals of emerging concern
- 2019
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Ingår i: Environmental Sciences Europe. - : Springer Science and Business Media LLC. - 2190-4707 .- 2190-4715. ; 31:1
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Tidskriftsartikel (refereegranskat)abstract
- The European Union Water Framework Directives aims at achieving good ecological status in member states' water bodies. Insufficient ecological status could be the result of different interacting stressors, among them the presence of many thousands of chemicals. The diagnosis of the likelihood that these chemicals negatively affect the ecological status of surface waters or human health, and the subsequent development of abatement measures usually relies on water quality monitoring. This gives an incomplete picture of chemicals' contamination, due to the limited number of monitoring stations, samples and substances. Information gaps thus limit the possibilities to protect against and effectively manage chemicals in aquatic ecosystems. The EU FP7 SOLUTIONS project has developed and validated a collection of integrated models (Model Train) to increase our understanding of issues related to emerging chemicals in Europe's river basins and to complement information and knowledge derived from field data. Unlike pre-existing models, the Model Train is suitable to model mixtures of thousands of chemicals, to better approach a real-life mixture exposure situation. It can also be used to model new chemicals at a stage where not much is known about them. The application of these models on a European scale provides temporally and spatially variable concentration data to fill gaps in the space, time and substance domains left open by water quality monitoring, and it provides homogeneous data across Europe where water quality data from monitoring are missing. Thus, it helps to avoid overlooking candidate chemicals and possible hot spots for management intervention. The application of the SOLUTIONS Model Train on a European scale presents a relevant line of evidence for water system level prognostic and diagnostic impact assessment related to chemical pollution. The application supports the design of cost-effective programmes of measures by helping to identify the most affected sites and the responsible substances, by evaluating alternative abatement options and by exploring the consequences of future trends.
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