| 1. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 5. |
- Dulio, Valeria, et al.
(författare)
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Beyond target chemicals : updating the NORMAN prioritisation scheme to support the EU chemicals strategy with semi-quantitative suspect/non-target screening data
- 2024
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Ingår i: Environmental Sciences Europe. - : Springer Nature. - 2190-4707 .- 2190-4715. ; 36:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prioritisation of chemical pollutants is a major challenge for environmental managers and decision-makers alike, which is essential to help focus the limited resources available for monitoring and mitigation actions on the most relevant chemicals. This study extends the original NORMAN prioritisation scheme beyond target chemicals, presenting the integration of semi-quantitative data from retrospective suspect screening and expansion of existing exposure and risk indicators. The scheme utilises data retrieved automatically from the NORMAN Database System (NDS), including candidate substances for prioritisation, target and suspect screening data, ecotoxicological effect data, physico-chemical data and other properties. Two complementary workflows using target and suspect screening monitoring data are applied to first group the substances into six action categories and then rank the substances using exposure, hazard and risk indicators. The results from the ‘target’ and ‘suspect screening’ workflows can then be combined as multiple lines of evidence to support decision-making on regulatory and research actions.Results: As a proof-of-concept, the new scheme was applied to a combined dataset of target and suspect screening data. To this end, > 65,000 substances on the NDS, of which 2579 substances supported by target wastewater monitoring data, were retrospectively screened in 84 effluent wastewater samples, totalling > 11 million data points. The final prioritisation results identified 677 substances as high priority for further actions, 7455 as medium priority and 326 with potentially lower priority for actions. Among the remaining substances, ca. 37,000 substances should be considered of medium priority with uncertainty, while it was not possible to conclude for 19,000 substances due to insufficient information from target monitoring and uncertainty in the identification from suspect screening. A high degree of agreement was observed between the categories assigned via target analysis and suspect screening-based prioritisation. Suspect screening was a valuable complementary approach to target analysis, helping to prioritise thousands of substances that are insufficiently investigated in current monitoring programmes.Conclusions: This updated prioritisation workflow responds to the increasing use of suspect screening techniques. It can be adapted to different environmental compartments and can support regulatory obligations, including the identification of specific pollutants in river basins and the marine environments, as well as the confirmation of environmental occurrence levels predicted by modelling tools. Graphical Abstract: (Figure presented.)
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| 6. |
- Gomez-Gener, L., et al.
(författare)
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Global carbon dioxide efflux from rivers enhanced by high nocturnal emissions
- 2021
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Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 14, s. 289-294
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Tidskriftsartikel (refereegranskat)abstract
- Carbon dioxide (CO2) emissions to the atmosphere from running waters are estimated to be four times greater than the total carbon (C) flux to the oceans. However, these fluxes remain poorly constrained because of substantial spatial and temporal variability in dissolved CO2 concentrations. Using a global compilation of high-frequency CO2 measurements, we demonstrate that nocturnal CO2 emissions are on average 27% (0.9 gC m(-2) d(-1)) greater than those estimated from diurnal concentrations alone. Constraints on light availability due to canopy shading or water colour are the principal controls on observed diel (24 hour) variation, suggesting this nocturnal increase arises from daytime fixation of CO2 by photosynthesis. Because current global estimates of CO2 emissions to the atmosphere from running waters (0.65-1.8 PgC yr(-1)) rely primarily on discrete measurements of dissolved CO2 obtained during the day, they substantially underestimate the magnitude of this flux. Accounting for night-time CO2 emissions may elevate global estimates from running waters to the atmosphere by 0.20-0.55 PgC yr(-1). Failing to account for emission differences between day and night will lead to an underestimate of global CO2 emissions from rivers by up to 0.55 PgC yr(-1), according to analyses of high-frequency CO2 measurements.
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| 7. |
- Mann, P. J., et al.
(författare)
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The biogeochemistry of carbon across a gradient of streams and rivers within the Congo Basin
- 2014
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Ingår i: Journal of Geophysical Research: Biogeosciences. - 2169-8953. ; 119:4, s. 687-702
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Tidskriftsartikel (refereegranskat)abstract
- Dissolved organic carbon (DOC) and inorganic carbon (DIC, pCO(2)), lignin biomarkers, and theoptical properties of dissolved organic matter (DOM) were measured in a gradient of streams and rivers within the Congo Basin, with the aim of examining how vegetation cover and hydrology influences the composition and concentration of fluvial carbon (C). Three sampling campaigns (February 2010, November 2010, and August 2011) spanning 56 sites are compared by subbasin watershed land cover type (savannah, tropical forest, and swamp) and hydrologic regime (high, intermediate, and low). Land cover properties predominately controlled the amount and quality of DOC, chromophoric DOM (CDOM) and lignin phenol concentrations (Sigma(8)) exported in streams and rivers throughout the Congo Basin. Higher DIC concentrations and changing DOM composition (lower molecular weight, less aromatic C) during periods of low hydrologic flow indicated shifting rapid overland supply pathways in wet conditions to deeper groundwater inputs during drier periods. Lower DOC concentrations in forest and swamp subbasins were apparent with increasing catchment area, indicating enhanced DOC loss with extended water residence time. Surface water pCO(2) in savannah and tropical forest catchments ranged between 2,600 and 11,922 mu atm, with swamp regions exhibiting extremely high pCO(2) (10,598-15,802 mu atm), highlighting their potential as significant pathways for water-air efflux. Our data suggest that the quantity and quality of DOM exported to streams and rivers are largely driven by terrestrial ecosystem structure and that anthropogenic land use or climate change may impact fluvial C composition and reactivity, with ramifications for regional C budgets and future climate scenarios.
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| 8. |
- Mauritsen, Thorsten, et al.
(författare)
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Developments in the MPI-M Earth System Model version 1.2 (MPI-ESM1.2) and Its Response to Increasing CO2
- 2019
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Ingår i: Journal of Advances in Modeling Earth Systems. - 1942-2466. ; 11:4, s. 998-1038
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Tidskriftsartikel (refereegranskat)abstract
- A new release of the Max Planck Institute for Meteorology Earth System Model version 1.2 (MPI-ESM1.2) is presented. The development focused on correcting errors in and improving the physical processes representation, as well as improving the computational performance, versatility, and overall user friendliness. In addition to new radiation and aerosol parameterizations of the atmosphere, several relatively large, but partly compensating, coding errors in the model's cloud, convection, and turbulence parameterizations were corrected. The representation of land processes was refined by introducing a multilayer soil hydrology scheme, extending the land biogeochemistry to include the nitrogen cycle, replacing the soil and litter decomposition model and improving the representation of wildfires. The ocean biogeochemistry now represents cyanobacteria prognostically in order to capture the response of nitrogen fixation to changing climate conditions and further includes improved detritus settling and numerous other refinements. As something new, in addition to limiting drift and minimizing certain biases, the instrumental record warming was explicitly taken into account during the tuning process. To this end, a very high climate sensitivity of around 7 K caused by low-level clouds in the tropics as found in an intermediate model version was addressed, as it was not deemed possible to match observed warming otherwise. As a result, the model has a climate sensitivity to a doubling of CO2 over preindustrial conditions of 2.77 K, maintaining the previously identified highly nonlinear global mean response to increasing CO2 forcing, which nonetheless can be represented by a simple two-layer model.
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| 9. |
- Wittwer, Raphaël A., et al.
(författare)
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Organic and conservation agriculture promote ecosystem multifunctionality
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:34
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Tidskriftsartikel (refereegranskat)abstract
- Ecosystems provide multiple services to humans. However, agricultural systems are usually evaluated on their productivity and economic performance, and a systematic and quantitative assessment of the multifunctionality of agroecosystems including environmental services is missing. Using a long-term farming system experiment, we evaluated and compared the agronomic, economic, and ecological performance of the most widespread arable cropping systems in Europe: Organic, conservation, and conventional agriculture. We analyzed 43 agroecosystem properties and determined overall agroecosystem multifunctionality. We show that organic and conservation agriculture promoted ecosystem multifunctionality, especially by enhancing regulating and supporting services, including biodiversity preservation, soil and water quality, and climate mitigation. In contrast, conventional cropping showed reduced multifunctionality but delivered highest yield. Organic production resulted in higher economic performance, thanks to higher product prices and additional support payments. Our results demonstrate that different cropping systems provide opposing services, enforcing the productivity-environmental protection dilemma for agroecosystem functioning.
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| 10. |
- Yu, Longfei, et al.
(författare)
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What can we learn from N2O isotope data? - Analytics, processes and modelling
- 2020
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 34:20
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Tidskriftsartikel (refereegranskat)abstract
- The isotopic composition of nitrous oxide (N2O) provides useful information for evaluating N2O sources and budgets. Due to the co-occurrence of multiple N2O transformation pathways, it is, however, challenging to use isotopic information to quantify the contribution of distinct processes across variable spatiotemporal scales. Here, we present an overview of recent progress in N2O isotopic studies and provide suggestions for future research, mainly focusing on: analytical techniques; production and consumption processes; and interpretation and modelling approaches. Comparing isotope-ratio mass spectrometry (IRMS) with laser absorption spectroscopy (LAS), we conclude that IRMS is a precise technique for laboratory analysis of N2O isotopes, while LAS is more suitable forin situ/inline studies and offers advantages for site-specific analyses. When reviewing the link between the N2O isotopic composition and underlying mechanisms/processes, we find that, at the molecular scale, the specific enzymes and mechanisms involved determine isotopic fractionation effects. In contrast, at plot-to-global scales, mixing of N2O derived from different processes and their isotopic variability must be considered. We also find that dual isotope plots are effective for semi-quantitative attribution of co-occurring N2O production and reduction processes. More recently, process-based N2O isotopic models have been developed for natural abundance and(15)N-tracing studies, and have been shown to be effective, particularly for data with adequate temporal resolution. Despite the significant progress made over the last decade, there is still great need and potential for future work, including development of analytical techniques, reference materials and inter-laboratory comparisons, further exploration of N2O formation and destruction mechanisms, more observations across scales, and design and validation of interpretation and modelling approaches. Synthesizing all these efforts, we are confident that the N2O isotope community will continue to advance our understanding of N2O transformation processes in all spheres of the Earth, and in turn to gain improved constraints on regional and global budgets.
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