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| 3. |
- Ahluwalia, T. S., et al.
(författare)
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Genome-wide association study of circulating interleukin 6 levels identifies novel loci
- 2021
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 30:5, s. 393-409
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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| 5. |
- Kukkonen, J., et al.
(författare)
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Towards a Comprehensive Evaluation of the Environmental and Health Impacts of Shipping Emissions
- 2022
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Ingår i: Springer Proceedings in Complexity. - Cham : Springer International Publishing. - 2213-8684 .- 2213-8692. ; , s. 329-336
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Konferensbidrag (refereegranskat)abstract
- We present a new concept for marine research, applied in the EU-funded project EMERGE, “Evaluation, control and Mitigation of the EnviRonmental impacts of shippinG Emissions” (2020–2024; https://emerge-h2020.eu/ ). For the first time, both the various marine and atmospheric impacts of the shipping sector have been and will be comprehensively analyzed, using a concerted modelling and measurements framework. The experimental part of the project focuses on five European geographical case studies in different ecologically vulnerable regions, and a mobile onboard case study. The EMERGE consortium has also developed a harmonised and integrated modelling framework to assess the combined impacts of shipping emissions, both (i) on the marine ecosystems and (ii) the atmospheric environment. The first results include substantial refinements of a range of models to be applied, especially those for the STEAM and OpenDrift models. In particular, the STEAM (Ship Traffic Emission Assessment Model) model has been extended to allow for the effects of atmospheric and oceanographic factors on the fuel consumption and emissions of the ships. The OpenDrift model has been improved to take into account the partitioning, degradation, and volatilization of pollutants in water. The predicted emission and discharge values have been used as input for both regional scale atmospheric dispersion models, such as WRF-CMAQ (Weather Research and Forecasting—Community Multiscale Air Quality Model) and SILAM (System for Integrated modeLling of Atmospheric composition), and water quality and circulation models, such as OpenDrift (Open source model for the drifting of substances in the ocean) and Delft3D (oceanographic model). The case study regions are Eastern Mediterranean, Northern Adriatic Sea, the Lagoon of Aveiro, the Solent Strait and the Öresund Strait. We have also conducted a substantial part of the experimental campaigns scheduled in the project. The final assessment will include the benefits and costs of control and mitigation options affecting water quality, air pollution exposure, health impacts, climate forcing, and ecotoxicological effects and bioaccumulation of pollutants in marine biota.
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| 8. |
- Hagert, C., et al.
(författare)
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Chronic Active Arthritis Driven by Macrophages Without Involvement of T Cells : A Novel Experimental Model of Rheumatoid Arthritis
- 2018
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Ingår i: Arthritis & Rheumatology. - Hoboken : Wiley. - 2326-5191 .- 2326-5205 .- 1529-0131. ; 70:8, s. 1343-1353
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To develop a new chronic rheumatoid arthritis model that is driven by the innate immune system. METHODS: Injection of a cocktail of 4 monoclonal antibodies against type II collagen, followed on days 5 and 60 by intraperitoneal injections of mannan (from Saccharomyces cerevisiae), was used to induce development of chronic arthritis in B10.Q mice. The role of the innate immune system as compared to the adaptive immune system in this arthritis model was investigated using genetically modified mouse strains. RESULTS: A new model of chronic relapsing arthritis was characterized in B10.Q mice, in which a persistently active, chronic disease was found. This relapsing disease was driven by macrophages lacking the ability to mount a reactive oxygen species response against pathogens, and was associated with the classical/alternative pathway, but not the lectin pathway, of complement activation. The disease was independent of Fcgamma receptor type III, and also independent of the activity of adaptive immune cells (B and T cells), indicating that the innate immune system, involving complement activation, could be the sole driver of chronicity. CONCLUSION: Chronic active arthritis can be driven innately by macrophages without the involvement of T and B cells in the adaptive immune system.
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| 13. |
- Kuisma, H, et al.
(författare)
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Parity associates with chromosomal damage in uterine leiomyomas
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 5448-
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical forces in a constrained cellular environment were recently established as a facilitator of chromosomal damage. Whether this could contribute to tumorigenesis is not known. Uterine leiomyomas are common neoplasms that display relatively few chromosomal aberrations. We hypothesized that if mechanical forces contribute to chromosomal damage, signs of this could be seen in uterine leiomyomas from parous women. We examined the karyotypes of 1946 tumors, and found a striking overrepresentation of chromosomal damage associated with parity. We then subjected myometrial cells to physiological forces similar to those encountered during pregnancy, and found this to cause DNA breaks and a DNA repair response. While mechanical forces acting in constrained cellular environments may thus contribute to neoplastic degeneration, and genesis of uterine leiomyoma, further studies are needed to prove possible causality of the observed association. No evidence for progression to malignancy was found.
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| 15. |
- McCarroll, D., et al.
(författare)
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A 1200-year multiproxy record of tree growth and summer temperature at the northern pine forest limit of Europe
- 2013
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Ingår i: Holocene. - : SAGE Publications. - 0959-6836 .- 1477-0911. ; 23:4, s. 471-484
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Tidskriftsartikel (refereegranskat)abstract
- Combining nine tree growth proxies from four sites, from the west coast of Norway to the Kola Peninsula of NW Russia, provides a well replicated (> 100 annual measurements per year) mean index of tree growth over the last 1200 years that represents the growth of much of the northern pine timberline forests of northern Fennoscandia. The simple mean of the nine series, z-scored over their common period, correlates strongly with mean June to August temperature averaged over this region (r = 0.81), allowing reconstructions of summer temperature based on regression and variance scaling. The reconstructions correlate significantly with gridded summer temperatures across the whole of Fennoscandia, extending north across Svalbard and south into Denmark. Uncertainty in the reconstructions is estimated by combining the uncertainty in mean tree growth with the uncertainty in the regression models. Over the last seven centuries the uncertainty is < 4.5% higher than in the 20th century, and reaches a maximum of 12% above recent levels during the 10th century. The results suggest that the 20th century was the warmest of the last 1200 years, but that it was not significantly different from the 11th century. The coldest century was the 17th. The impact of volcanic eruptions is clear, and a delayed recovery from pairs or multiple eruptions suggests the presence of some positive feedback mechanism. There is no clear and consistent link between northern Fennoscandian summer temperatures and solar forcing.
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| 20. |
- Treydte, Kerstin, et al.
(författare)
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Recent human-induced atmospheric drying across Europe unprecedented in the last 400 years
- 2024
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Ingår i: NATURE GEOSCIENCE. - 1752-0894 .- 1752-0908. ; 17, s. 58-65
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Tidskriftsartikel (refereegranskat)abstract
- The vapor pressure deficit reflects the difference between how much moisture the atmosphere could and actually does hold, a factor that fundamentally affects evapotranspiration, ecosystem functioning, and vegetation carbon uptake. Its spatial variability and long-term trends under natural versus human-influenced climate are poorly known despite being essential for predicting future effects on natural ecosystems and human societies such as crop yield, wildfires, and health. Here we combine regionally distinct reconstructions of pre-industrial summer vapor pressure deficit variability from Europe's largest oxygen-isotope network of tree-ring cellulose with observational records and Earth system model simulations with and without human forcing included. We demonstrate that an intensification of atmospheric drying during the recent decades across different European target regions is unprecedented in a pre-industrial context and that it is attributed to human influence with more than 98% probability. The magnitude of this trend is largest in Western and Central Europe, the Alps and Pyrenees region, and the smallest in southern Fennoscandia. In view of the extreme drought and compound events of the recent years, further atmospheric drying poses an enhanced risk to vegetation, specifically in the densely populated areas of the European temperate lowlands. The atmosphere has dried across most regions of Europe in recent decades, a trend that can be attributed primarily to human impacts, according to tree ring records spanning 400 years and Earth system model simulations.
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| 23. |
- Bodin, Per, et al.
(författare)
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Comparing the performance of different stomatal conductance models using modelled and measured plant carbon isotope ratios (δ(13) C): implications for assessing physiological forcing
- 2013
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013. ; 19:6, s. 1709-1719
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Tidskriftsartikel (refereegranskat)abstract
- Accurate modelling of long-term changes in plant stomatal functioning is vital to global climate change studies because changes in evapotranspiration influence temperature via physiological forcing of the climate. Various stomatal models are included in land surface schemes, but their robustness over longer timescales is difficult to validate. We compare the performance of three stomatal models, varying in their degree of complexity, and coupled to a land surface model. This is done by simulating the carbon isotope ratio of tree leaves (δ(13) Cleaf ) over a period of 53 years, and comparing the results with carbon isotope ratios obtained from tree rings (δ(13) Cstem ) measured at six sites in northern Europe. All three stomatal models fail to capture the observed inter-annual variability in the measured δ(13) Cstem time series. However, the Soil-Plant-Atmosphere (SPA) model performs significantly better than the Ball-Berry (BB) or COX models when tested for goodness of fit against measured δ(13) Cstem . The δ(13) Cleaf time series simulated using the SPA model are significantly positively correlated (p < 0.05) with measured results over the full time period tested, at all six sites. The SPA model underestimates inter-annual variability measured in δ(13) Cstem , but is no worse than the BB model and significantly better than the COX model. The inability of current models to adequately replicate changes in stomatal response to rising levels of CO2 concentrations, and thus to quantify the associated physiological forcing, warrants further investigation. © 2013 Blackwell Publishing Ltd.
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| 31. |
- Kerr, A. G., et al.
(författare)
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The long noncoding RNA ADIPINT regulates human adipocyte metabolism via pyruvate carboxylase
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The pleiotropic function of long noncoding RNAs is well recognized, but their direct role in governing metabolic homeostasis is less understood. Here, we describe a human adipocyte-specific lncRNA, ADIPINT, that regulates pyruvate carboxylase, a pivotal enzyme in energy metabolism. We developed an approach, Targeted RNA-protein identification using Orthogonal Organic Phase Separation, which identifies that ADIPINT binds to pyruvate carboxylase and validated the interaction with electron microscopy. ADIPINT knockdown alters the interactome and decreases the abundance and enzymatic activity of pyruvate carboxylase in the mitochondria. Reduced ADIPINT or pyruvate carboxylase expression lowers adipocyte lipid synthesis, breakdown, and lipid content. In human white adipose tissue, ADIPINT expression is increased in obesity and linked to fat cell size, adipose insulin resistance, and pyruvate carboxylase activity. Thus, we identify ADIPINT as a regulator of lipid metabolism in human white adipocytes, which at least in part is mediated through its interaction with pyruvate carboxylase.
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| 32. |
- Lim, Elaine T, et al.
(författare)
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Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5-5%) variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p<5×10-8) including splice variants in LPA that lowered plasma lipoprotein(a) levels (P = 1.5×10-117). Through accessing the national medical records of these participants, we evaluate the LPA finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10-4), demonstrating for the first time the correlation between very low levels of LPA in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health Registers.
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| 33. |
- Loader, N. J., et al.
(författare)
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Inter-annual carbon isotope analysis of tree-rings by laser ablation
- 2017
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Ingår i: Chemical Geology. - : Elsevier BV. - 0009-2541 .- 1872-6836. ; 466, s. 323-326
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Tidskriftsartikel (refereegranskat)abstract
- The stable carbon isotopic analysis of tree-rings for environmental, plant physiological and archaeological applications using conventional methods is occasionally limited by physical constraints (narrow rings) or administrative concerns (requirement for non-destructive sampling) that prevent researcher access to scientifically valuable wood samples. Analysis of such archives by laser-ablation can potentially address these issues and facilitate access to restricted archives. Smaller quantities of wood are required for analysis by laser ablation, hence the approach may be considered less-invasive and is virtually non-destructive compared to standard preparation methods. High levels of intra-annual isotopic variability reported elsewhere mean that a single measurement may not faithfully represent the inter-annual isotopic signal, so before such an approach can be used with confidence it is necessary to compare the stable carbon isotopic data produced using these two methods. This paper presents stable carbon isotope (delta C-13) data from the resin-extracted wood of dated Scots Pine (Pinus sylvestris L.) tree-rings analysed using a modified Schulze-type laser-ablation system with results obtained using conventional manual sampling and analysis of alpha-cellulose prepared from the same tree-ring groups. The laser sampling system is found to perform very well against established more invasive methods. High correlations are observed between the methods for both raw and Suess corrected data (r > 0.90 n = 50). These results highlight the potential for using laser-sampling to support the development of long isotope chronologies, for sampling narrow rings or for pre-screening cores prior to analysis using more detailed or labour intensive methods.
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| 35. |
- Mwase, Nandi S, et al.
(författare)
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Health Impact of Air Pollution from Shipping in the Baltic Sea: Effects of Different Spatial Resolutions in Sweden.
- 2020
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 17:21
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Tidskriftsartikel (refereegranskat)abstract
- In 2015, stricter regulations to reduce sulfur dioxide emissions and particulate air pollution from shipping were implemented in the Baltic Sea. We investigated the effects on population exposure to particles <2.5 µm (PM2.5) from shipping and estimated related morbidity and mortality in Sweden's 21 counties at different spatial resolutions. We used a regional model to estimate exposure in Sweden and a city-scale model for Gothenburg. Effects of PM2.5 exposure on total mortality, ischemic heart disease, and stroke were estimated using exposure-response functions from the literature and combining them into disability-adjusted life years (DALYS). PM2.5 exposure from shipping in Gothenburg decreased by 7% (1.6 to 1.5 µg/m3) using the city-scale model, and 35% (0.5 to 0.3 µg/m3) using the regional model. Different population resolutions had no effects on population exposures. In the city-scale model, annual premature deaths due to shipping PM2.5 dropped from 97 with the high-sulfur scenario to 90 in the low-sulfur scenario, and in the regional model from 32 to 21. In Sweden, DALYs lost due to PM2.5 from Baltic Sea shipping decreased from approximately 5700 to 4200. In conclusion, sulfur emission restrictions for shipping had positive effects on health, but the model resolution affects estimations.
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| 36. |
- Reckermann, M., et al.
(författare)
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Human impacts and their interactions in the Baltic Sea region
- 2022
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Ingår i: Earth Syst. Dynam.. - : Copernicus GmbH. - 2190-4987 .- 2190-4979. ; 13:1, s. 1-80
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Forskningsöversikt (refereegranskat)abstract
- Coastal environments, in particular heavily populated semi-enclosed marginal seas and coasts like the Baltic Sea region, are strongly affected by human activities. A multitude of human impacts, including climate change, affect the different compartments of the environment, and these effects interact with each other. As part of the Baltic Earth Assessment Reports (BEAR), we present an inventory and discussion of different human-induced factors and processes affecting the environment of the Baltic Sea region, and their interrelations. Some are naturally occurring and modified by human activities (i.e. climate change, coastal processes, hypoxia, acidification, submarine groundwater discharges, marine ecosystems, non-indigenous species, land use and land cover), some are completely human-induced (i.e. agriculture, aquaculture, fisheries, river regulations, offshore wind farms, shipping, chemical contamination, dumped warfare agents, marine litter and microplastics, tourism, and coastal management), and they are all interrelated to different degrees. We present a general description and analysis of the state of knowledge on these interrelations. Our main insight is that climate change has an overarching, integrating impact on all of the other factors and can be interpreted as a background effect, which has different implications for the other factors. Impacts on the environment and the human sphere can be roughly allocated to anthropogenic drivers such as food production, energy production, transport, industry and economy. The findings from this inventory of available information and analysis of the different factors and their interactions in the Baltic Sea region can largely be transferred to other comparable marginal and coastal seas in the world.
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| 38. |
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| 39. |
- Saurer, Matthias, et al.
(författare)
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Spatial variability and temporal trends in water-use efficiency of European forests
- 2014
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 20:12, s. 3700-3712
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Tidskriftsartikel (refereegranskat)abstract
- The increasing carbon dioxide (CO2) concentration in the atmosphere in combination with climatic changes throughout the last century are likely to have had a profound effect on the physiology of trees: altering the carbon and water fluxes passing through the stomatal pores. However, the magnitude and spatial patterns of such changes in natural forests remain highly uncertain. Here, stable carbon isotope ratios from a network of 35 tree-ring sites located across Europe are investigated to determine the intrinsic water-use efficiency (iWUE), the ratio of photosynthesis to stomatal conductance from 1901 to 2000. The results were compared with simulations of a dynamic vegetation model (LPX-Bern 1.0) that integrates numerous ecosystem and land-atmosphere exchange processes in a theoretical framework. The spatial pattern of tree-ring derived iWUE of the investigated coniferous and deciduous species and the model results agreed significantly with a clear south-to-north gradient, as well as a general increase in iWUE over the 20th century. The magnitude of the iWUE increase was not spatially uniform, with the strongest increase observed and modelled for temperate forests in Central Europe, a region where summer soil-water availability decreased over the last century. We were able to demonstrate that the combined effects of increasing CO2 and climate change leading to soil drying have resulted in an accelerated increase in iWUE. These findings will help to reduce uncertainties in the land surface schemes of global climate models, where vegetation-climate feedbacks are currently still poorly constrained by observational data.
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