| 1. |
- Drakvik, E., et al.
(författare)
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Statement on advancing the assessment of chemical mixtures and their risks for human health and the environment
- 2020
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, “Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment” was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages: • We are at a turning point: multiple exposures and their combined effects require better management to protect public health and the environment from hazardous chemical mixtures. • Regulatory initiatives should be launched to investigate the opportunities for all relevant regulatory frameworks to include prospective mixture risk assessment and consider combined exposures to (real-life) chemical mixtures to humans and wildlife, across sectors. • Precautionary approaches and intermediate measures (e.g. Mixture Assessment Factor) can already be applied, although, definitive mixture risk assessments cannot be routinely conducted due to significant knowledge and data gaps. • A European strategy needs to be set, through stakeholder engagement, for the governance of combined exposure to multiple chemicals and mixtures. The strategy would include research aimed at scientific advancement in mechanistic understanding and modelling techniques, as well as research to address regulatory and policy needs. Without such a clear strategy, specific objectives and common priorities, research, and policies to address mixtures will likely remain scattered and insufficient. © 2019 The Authors
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| 2. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Klimkowska, Agata, et al.
(författare)
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Are we restoring functional fens? : The outcomes of restoration projects in fens re-analysed with plant functional traits
- 2019
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- In peatland restoration we often lack an information whether re-established ecosystems are functionally similar to non-degraded ones. We re-analysed the long-term outcomes of restoration on vegetation and plant functional traits in 38 European fens restored by rewetting (18 sites) and topsoil removal (20 sites). We used traits related to nutrient acquisition strategies, competitiveness, seed traits, and used single- and multi-trait metrics. A separate set of vegetation records from near-natural fens with diverse plant communities was used to generate reference values to aid the comparisons. We found that both restoration methods enhanced the similarity of species composition to non-degraded systems but trait analysis revealed differences between the two approaches. Traits linked to nutrient acquisition strategies indicated that topsoil removal was more effective than rewetting. After topsoil removal competitive species in plant communities had decreased, while stress-tolerant species had increased. A substantial reduction in nutrient availability ruled out the effect of initial disturbance. An ability to survive and grow in anoxic conditions was enhanced after restoration, but the reference values were not achieved. Rewetting was more effective than topsoil removal in restricting variation in traits values permitted in re-developing vegetation. We found no indication of a shift towards reference in seed traits, which suggested that dispersal constraint and colonization deficit can be a widespread phenomena. Two functional diversity indices: functional richness and functional dispersion showed response to restoration and shifted values towards reference mires and away from the degraded systems. We concluded that targeting only one type of environmental stressor does not lead to a recovery of fens, as it provides insufficient level of stress to restore a functional ecosystem. In general, restoration efforts do not ensure the re-establishment and long-term persistence of fens. Restoration efforts result in recovery of fen ecosystems, confirmed with our functional trait analysis, although more rigid actions are needed for restoring fully functional mires, by achieving high and constant levels of anoxia and nutrient stresses.
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| 4. |
- Krebs, Alice, et al.
(författare)
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The EU-ToxRisk method documentation, data processing and chemical testing pipeline for the regulatory use of new approach methods
- 2020
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 94:7, s. 2435-2461
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Tidskriftsartikel (refereegranskat)abstract
- Hazard assessment, based on new approach methods (NAM), requires the use of batteries of assays, where individual tests may be contributed by different laboratories. A unified strategy for such collaborative testing is presented. It details all procedures required to allow test information to be usable for integrated hazard assessment, strategic project decisions and/or for regulatory purposes. The EU-ToxRisk project developed a strategy to provide regulatorily valid data, and exemplified this using a panel of > 20 assays (with > 50 individual endpoints), each exposed to 19 well-known test compounds (e.g. rotenone, colchicine, mercury, paracetamol, rifampicine, paraquat, taxol). Examples of strategy implementation are provided for all aspects required to ensure data validity: (i) documentation of test methods in a publicly accessible database; (ii) deposition of standard operating procedures (SOP) at the European Union DB-ALM repository; (iii) test readiness scoring accoding to defined criteria; (iv) disclosure of the pipeline for data processing; (v) link of uncertainty measures and metadata to the data; (vi) definition of test chemicals, their handling and their behavior in test media; (vii) specification of the test purpose and overall evaluation plans. Moreover, data generation was exemplified by providing results from 25 reporter assays. A complete evaluation of the entire test battery will be described elsewhere. A major learning from the retrospective analysis of this large testing project was the need for thorough definitions of the above strategy aspects, ideally in form of a study pre-registration, to allow adequate interpretation of the data and to ensure overall scientific/toxicological validity.
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| 5. |
- Bansal, Sheel, et al.
(författare)
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Practical Guide to Measuring Wetland Carbon Pools and Fluxes
- 2023
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Ingår i: Wetlands (Wilmington, N.C.). - : SPRINGER. - 0277-5212 .- 1943-6246. ; 43:8
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Forskningsöversikt (refereegranskat)abstract
- Wetlands cover a small portion of the world, but have disproportionate influence on global carbon (C) sequestration, carbon dioxide and methane emissions, and aquatic C fluxes. However, the underlying biogeochemical processes that affect wetland C pools and fluxes are complex and dynamic, making measurements of wetland C challenging. Over decades of research, many observational, experimental, and analytical approaches have been developed to understand and quantify pools and fluxes of wetland C. Sampling approaches range in their representation of wetland C from short to long timeframes and local to landscape spatial scales. This review summarizes common and cutting-edge methodological approaches for quantifying wetland C pools and fluxes. We first define each of the major C pools and fluxes and provide rationale for their importance to wetland C dynamics. For each approach, we clarify what component of wetland C is measured and its spatial and temporal representativeness and constraints. We describe practical considerations for each approach, such as where and when an approach is typically used, who can conduct the measurements (expertise, training requirements), and how approaches are conducted, including considerations on equipment complexity and costs. Finally, we review key covariates and ancillary measurements that enhance the interpretation of findings and facilitate model development. The protocols that we describe to measure soil, water, vegetation, and gases are also relevant for related disciplines such as ecology. Improved quality and consistency of data collection and reporting across studies will help reduce global uncertainties and develop management strategies to use wetlands as nature-based climate solutions.
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| 6. |
- Chen, Xingchen, et al.
(författare)
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A Versatile and Robust Serine Protease Inhibitor Scaffold from Actinia tenebrosa
- 2019
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Ingår i: Marine Drugs. - : MDPI. - 1660-3397 .- 1660-3397. ; 17:12
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Tidskriftsartikel (refereegranskat)abstract
- Serine proteases play pivotal roles in normal physiology and a spectrum of patho-physiological processes. Accordingly, there is considerable interest in the discovery and design of potent serine protease inhibitors for therapeutic applications. This led to concerted efforts to discover versatile and robust molecular scaffolds for inhibitor design. This investigation is a bioprospecting study that aims to isolate and identify protease inhibitors from the cnidarian Actinia tenebrosa. The study isolated two Kunitz-type protease inhibitors with very similar sequences but quite divergent inhibitory potencies when assayed against bovine trypsin, chymostrypsin, and a selection of human sequence-related peptidases. Homology modeling and molecular dynamics simulations of these inhibitors in complex with their targets were carried out and, collectively, these methodologies enabled the definition of a versatile scaffold for inhibitor design. Thermal denaturation studies showed that the inhibitors were remarkably robust. To gain a fine-grained map of the residues responsible for this stability, we conducted in silico alanine scanning and quantified individual residue contributions to the inhibitor’s stability. Sequences of these inhibitors were then used to search for Kunitz homologs in an A. tenebrosa transcriptome library, resulting in the discovery of a further 14 related sequences. Consensus analysis of these variants identified a rich molecular diversity of Kunitz domains and expanded the palette of potential residue substitutions for rational inhibitor design using this domain.
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| 7. |
- Vogel, Celia J., et al.
(författare)
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Cooperative induction of apoptosis in NRAS mutant melanoma by inhibition of MEK and ROCK
- 2015
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Ingår i: Pigment Cell & Melanoma Research. - : Wiley. - 1755-1471 .- 1755-148X. ; 28:3
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Tidskriftsartikel (refereegranskat)abstract
- No effective targeted therapy is currently available for NRAS mutant melanoma. Experimental MEK inhibition is rather toxic and has only limited efficacy in clinical trials. At least in part, this is caused by the emergence of drug resistance, which is commonly seen for single agent treatment and shortens clinical responses. Therefore, there is a dire need to identify effective companion drug targets for NRAS mutant melanoma. Here, we show that at concentrations where single drugs had little effect, ROCK inhibitors GSK269962A or Fasudil, in combination with either MEK inhibitor GSK1120212 (Trametinib) or ERK inhibitor SCH772984 cooperatively caused proliferation inhibition and cell death in vitro. Simultaneous inhibition of MEK and ROCK caused induction of Bim(EL), PARP, and Puma, and hence apoptosis. In vivo, MEK and ROCK inhibition suppressed growth of established tumors. Our findings warrant clinical investigation of the effectiveness of combinatorial targeting of MAPK/ERK and ROCK in NRAS mutant melanoma.
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