The carbon budget of terrestrial ecosystems at country-scale – a European case study

We summed estimates of the carbon balance of forests, grasslands, arable lands and peatlands to obtain country-specific estimates of the terrestrial carbon balance during the 1990s. Forests and grasslands were a net sink for carbon, whereas croplands were carbon sources in all European countries. Hence, countries dominated by arable lands tended to be losing carbon from their terrestrial ecosystems, whereas forest-dominated countries tended to be sequestering carbon. In some countries, draining and extraction of peatlands caused substantial reductions in the net carbon balance. Net terrestrial carbon balances were typically an order of magnitude smaller than the fossil fuel-related carbon emissions. Exceptions to this overall picture were countries where population density and industrialization are small. It is, however, of utmost importance to acknowledge that the typically small net carbon balance represents the small difference between two large but opposing fluxes: uptake by forests and grasslands and losses from arable lands and peatlands. This suggests that relatively small changes in either or both of these large component fluxes could induce large effects on the net total, indicating that mitigation schemes should not be discarded a priori. In the absence of carbon-oriented land management, the current net carbon uptake is bound to decline soon. Protecting it will require actions at three levels; a) maintaining the current sink activity of forests, b) altered agricultural management practices to reduce the emissions from arable soils or turn into carbon sinks and c) protecting current large reservoirs (wetlands and old forests), since carbon is lost more rapidly than sequestered

A bispecific inhibitor of the EGFR/ADAM17 axis decreases cell proliferation and migration of EGFR-dependent cancer cells

Dysregulated epidermal growth factor receptor (EGFR) is an oncogenic driver of many human cancers, promoting aberrant cell proliferation, migration, and survival. Pharmacological targeting of EGFR is often challenged by acquired mechanisms of resistance. Ligand-dependent mechanisms in EGFR wild-type cells rely on ligand or receptor overexpression, allowing cells to outcompete inhibitors and perpetuate signaling in an autocrine manner. Importantly, EGFR ligands are synthesized as membrane-bound precursors that must be solubilized to enable receptor-ligand interactions. The A disintegrin and metalloproteinase 17 (ADAM17) is considered the main sheddase of several EGFR ligands, and a potential pharmacological target. However, its broad substrate range and ubiquitous expression complicate its therapeutic targeting. Here, we present a novel bispecific fusion protein construct consisting of the inhibitory prodomain of ADAM17 (TPD), fused to an EGFR-targeting designed ankyrin repeat protein (DARPin). TPD is a natural inhibitor of ADAM17, maintaining the protease in a zymogen-like form. Meanwhile, the high affinity anti-EGFR DARPin E01 binds to EGFR and inhibits ligand binding. The resulting fusion protein E01-GS-TPD retained binding ability to both molecular targets EGFR and ADAM17. The large difference in affinity for each target resulted in enrichment of the fusion protein in EGFR-positive cells compared to EGFR-negative cells, suggesting a possible application in autocrine signaling inhibition. Accordingly, E01-GS-TPD decreased migration and proliferation of EGFR-dependent cell lines with no significant increase in apoptotic cell death. Finally, inhibition of proliferation was observed through EGFR ligand-dependent mechanisms as growth inhibition was not observed in EGFR mutant or KRAS mutant cell lines. The use of bispecific proteins targeting the EGFR/ADAM17 axis could be an innovative strategy for the treatment of EGFR-dependent cancers

Trees as carbon sinks and sources in the European Union

http://www.elsevier.com/locate/issn/14629011The carbon (C) sinks and sources of trees that may be accounted for under Article 3.3 of the Kyoto Protocol during the first commitment period from 2008 to 2012 were estimated for the countries of the European Union (EU) based on existing forest inventory data. Two sets of definitions for the accounted activities, afforestation, reforestation and deforestation, were applied. Applying the definitions by the Food and Agricultural Organization of the United Nations (FAO), the trees were estimated to be a C source in eight and a C sink in seven countries, and in the whole EU a C source of 5.4 Tg year-1. Applying the definitions by the Intergovernmental Panel of Climate Change (IPCC), the trees were estimated to be a C source in three and a C sink in 12 countries, and in the whole EU a C sink of 0.1 Tg year-1. These estimates are small compared with the C sink of trees in all EU forests, 63 Tg year-1, the anthropogenic CO2 emissions of the EU, 880 Tg C year-1, and the reduction target of the CO2 emissions, 8%. In individual countries, the estimated C sink of the trees accounted for under Article 3.3 was at largest 8% and the C source 12% compared with the CO2 emissions. 7 2000 Elsevier Science Ltd. All rights reserved

Prediction of outcome in individuals with diabetic foot ulcers: focus on the differences between individuals with and without peripheral arterial disease. The EURODIALE Study

Aims/hypothesis Outcome data on individuals with diabetic foot ulcers are scarce, especially in those with peripheral arterial disease (PAD). We therefore examined the clinical characteristics that best predict poor outcome in a large population of diabetic foot ulcer patients and examined whether such predictors differ between patients with and without PAD. Methods Analyses were conducted within the EURODIALE Study, a prospective cohort study of 1,088 diabetic foot ulcer patients across 14 centres in Europe. Multiple logistic regression modelling was used to identify independent predictors of outcome (i.e. non-healing of the foot ulcer). Results After 1 year of follow-up, 23% of the patients had not healed. Independent baseline predictors of non-healing in the whole study population were older age, male sex, heart failure, the inability to stand or walk without help, end-stage renal disease, larger ulcer size, peripheral neuropathy and PAD. When analyses were performed according to PAD status, infection emerged as a specific predictor of non-healing in PAD patients only. Conclusions/Interpretation Predictors of healing differ between patients with and without PAD, suggesting that diabetic foot ulcers with or without concomitant PAD should be defined as two separate disease states. The observed negative impact of infection on healing that was confined to patients with PAD needs further investigation

The consolidated European synthesis of CO2 emissions and removals for the European Union and United Kingdom: 1990-2018

Reliable quantification of the sources and sinks of atmospheric carbon dioxide (CO2), including that of their trends and uncertainties, is essential to monitoring the progress in mitigating anthropogenic emissions under the Kyoto Protocol and the Paris Agreement. This study provides a consolidated synthesis of estimates for all anthropogenic and natural sources and sinks of CO2 for the European Union and UK (EU27 + UK), derived from a combination of state-of-the-art bottom-up (BU) and top-down (TD) data sources and models. Given the wide scope of the work and the variety of datasets involved, this study focuses on identifying essential questions which need to be answered to properly understand the differences between various datasets, in particular with regards to the less-well-characterized fluxes from managed ecosystems. The work integrates recent emission inventory data, process-based ecosystem model results, data-driven sector model results and inverse modeling estimates over the period 1990-2018. BU and TD products are compared with European national greenhouse gas inventories (NGHGIs) reported under the UNFCCC in 2019, aiming to assess and understand the differences between approaches. For the uncertainties in NGHGIs, we used the standard deviation obtained by varying parameters of inventory calculations, reported by the member states following the IPCC Guidelines. Variation in estimates produced with other methods, like atmospheric inversion models (TD) or spatially disaggregated inventory datasets (BU), arises from diverse sources including within-model uncertainty related to parameterization as well as structural differences between models. In comparing NGHGIs with other approaches, a key source of uncertainty is that related to different system boundaries and emission categories (CO2 fossil) and the use of different land use definitions for reporting emissions from land use, land use change and forestry (LULUCF) activities (CO2 land). At the EU27 + UK level, the NGHGI (2019) fossil CO2 emissions (including cement production) account for 2624 Tg CO2 in 2014 while all the other seven bottom-up sources are consistent with the NGHGIs and report a mean of 2588 (± 463 Tg CO2). The inversion reports 2700 Tg CO2 (± 480 Tg CO2), which is well in line with the national inventories. Over 2011-2015, the CO2 land sources and sinks from NGHGI estimates report-90 Tg C yr-1 ± 30 Tg C yr-1 while all other BU approaches report a mean sink of-98 Tg C yr-1 (± 362 Tg of C from dynamic global vegetation models only). For the TD model ensemble results, we observe a much larger spread for regional inversions (i.e., mean of 253 Tg C yr-1 ± 400 Tg C yr-1). This concludes that (a) current independent approaches are consistent with NGHGIs and (b) their uncertainty is too large to allow a verification because of model differences and probably also because of the definition of "CO2 flux"obtained from different approaches. The referenced datasets related to figures are visualized. © 2021 Ana Maria Roxana Petrescu et al

Simulation tools for decision support to adaptive forest management in Europe

Peer reviewe