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3.
  • Bousquet, J., et al. (author)
  • Building Bridges for Innovation in Ageing : Synergies between Action Groups of the EIP on AHA
  • 2017
  • In: The Journal of Nutrition, Health & Aging. - : Springer Nature. - 1279-7707 .- 1760-4788. ; 21:1, s. 92-104
  • Journal article (peer-reviewed)abstract
    • The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).
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  • Bousquet, J, et al. (author)
  • Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper
  • 2012
  • In: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 158:3, s. 216-231
  • Journal article (peer-reviewed)abstract
    • Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.
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  • Chatzikonstantinou, T, et al. (author)
  • COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study
  • 2021
  • In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:12, s. 3444-3454
  • Journal article (peer-reviewed)abstract
    • Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.
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  • Poyatos, R., et al. (author)
  • Global transpiration data from sap flow measurements: the SAPFLUXNET database
  • 2021
  • In: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 13:6, s. 2607-2649
  • Journal article (peer-reviewed)abstract
    • Plant transpiration links physiological responses of vegetation to water supply and demand with hydrological, energy, and carbon budgets at the land-atmosphere interface. However, despite being the main land evaporative flux at the global scale, transpiration and its response to environmental drivers are currently not well constrained by observations. Here we introduce the first global compilation of whole-plant transpiration data from sap flow measurements (SAPFLUXNET, https://sapfluxnet.creaf.cat/, last access: 8 June 2021). We harmonized and quality-controlled individual datasets supplied by contributors worldwide in a semi-automatic data workflow implemented in the R programming language. Datasets include sub-daily time series of sap flow and hydrometeorological drivers for one or more growing seasons, as well as metadata on the stand characteristics, plant attributes, and technical details of the measurements. SAPFLUXNET contains 202 globally distributed datasets with sap flow time series for 2714 plants, mostly trees, of 174 species. SAPFLUXNET has a broad bioclimatic coverage, with woodland/shrubland and temperate forest biomes especially well represented (80 % of the datasets). The measurements cover a wide variety of stand structural characteristics and plant sizes. The datasets encompass the period between 1995 and 2018, with 50 % of the datasets being at least 3 years long. Accompanying radiation and vapour pressure deficit data are available for most of the datasets, while on-site soil water content is available for 56 % of the datasets. Many datasets contain data for species that make up 90 % or more of the total stand basal area, allowing the estimation of stand transpiration in diverse ecological settings. SAPFLUXNET adds to existing plant trait datasets, ecosystem flux networks, and remote sensing products to help increase our understanding of plant water use, plant responses to drought, and ecohydrological processes. SAPFLUXNET version 0.1.5 is freely available from the Zenodo repository (https://doi.org/10.5281/zenodo.3971689; Poyatos et al., 2020a). The "sapfluxnetr" R package - designed to access, visualize, and process SAPFLUXNET data - is available from CRAN.
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  • Wingate, L., et al. (author)
  • Interpreting canopy development and physiology using a European phenology camera network at flux sites
  • 2015
  • In: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 12:20, s. 5995-6015
  • Journal article (peer-reviewed)abstract
    • Plant phenological development is orchestrated through subtle changes in photoperiod, temperature, soil moisture and nutrient availability. Presently, the exact timing of plant development stages and their response to climate and management practices are crudely represented in land surface models. As visual observations of phenology are laborious, there is a need to supplement long-term observations with automated techniques such as those provided by digital repeat photography at high temporal and spatial resolution. We present the first synthesis from a growing observational network of digital cameras installed on towers across Europe above deciduous and evergreen forests, grasslands and croplands, where vegetation and atmosphere CO2 fluxes are measured continuously. Using colour indices from digital images and using piecewise regression analysis of time series, we explored whether key changes in canopy phenology could be detected automatically across different land use types in the network. The piecewise regression approach could capture the start and end of the growing season, in addition to identifying striking changes in colour signals caused by flowering and management practices such as mowing. Exploring the dates of green-up and senescence of deciduous forests extracted by the piecewise regression approach against dates estimated from visual observations, we found that these phenological events could be detected adequately (RMSE < 8 and 11 days for leaf out and leaf fall, respectively). We also investigated whether the seasonal patterns of red, green and blue colour fractions derived from digital images could be modelled mechanistically using the PROSAIL model parameterised with information of seasonal changes in canopy leaf area and leaf chlorophyll and carotenoid concentrations. From a model sensitivity analysis we found that variations in colour fractions, and in particular the late spring 'green hump' observed repeatedly in deciduous broadleaf canopies across the network, are essentially dominated by changes in the respective pigment concentrations. Using the model we were able to explain why this spring maximum in green signal is often observed out of phase with the maximum period of canopy photosynthesis in ecosystems across Europe. Coupling such quasi-continuous digital records of canopy colours with co-located CO2 flux measurements will improve our understanding of how changes in growing season length are likely to shape the capacity of European ecosystems to sequester CO2 in the future.
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  • Cochius-den Otter, S, et al. (author)
  • The CoDiNOS trial protocol: an international randomised controlled trial of intravenous sildenafil versus inhaled nitric oxide for the treatment of pulmonary hypertension in neonates with congenital diaphragmatic hernia
  • 2019
  • In: BMJ open. - : BMJ. - 2044-6055. ; 9:11, s. e032122-
  • Journal article (peer-reviewed)abstract
    • Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that impairs normal lung development, causing pulmonary hypertension (PH). PH in CDH newborns is the main determinant for morbidity and mortality. Different therapies are still mainly based on ‘trial and error’. Inhaled nitric oxide (iNO) is often the drug of first choice. However, iNO does not seem to improve mortality. Intravenous sildenafil has reduced mortality in newborns with PH without CDH, but prospective data in CDH patients are lacking.Methods and analysisIn an open label, multicentre, international randomised controlled trial in Europe, Canada and Australia, 330 newborns with CDH and PH are recruited over a 4-year period (2018–2022). Patients are randomised for intravenous sildenafil or iNO. Sildenafil is given in a loading dose of 0.4 mg/kg in 3 hours; followed by continuous infusion of 1.6 mg/kg/day, iNO is dosed at 20 ppm. Primary outcome is absence of PH on day 14 without pulmonary vasodilator therapy and/or absence of death within the first 28 days of life. Secondary outcome measures include clinical and echocardiographic markers of PH in the first year of life. We hypothesise that sildenafil gives a 25% reduction in the primary outcome from 68% to 48% on day 14, for which a sample size of 330 patients is needed. An intention-to-treat analysis will be performed. A p-value (two-sided) <0.05 is considered significant in all analyses.Ethics and disseminationEthics approval has been granted by the ethics committee in Rotterdam (MEC-2017-324) and the central Committee on Research Involving Human Subjects (NL60229.078.17) in the Netherlands. The principles of the Declaration of Helsinki, the Medical Research Involving Human Subjects Act and the national rules and regulations on personal data protection will be used. Parental informed consent will be obtained.Trial registration numberNTR6982; Pre-results.
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  • Jiang, Mingkai, et al. (author)
  • The fate of carbon in a mature forest under carbon dioxide enrichment
  • 2020
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 580:7802, s. 227-231
  • Journal article (peer-reviewed)abstract
    • Atmospheric carbon dioxide enrichment (eCO2) can enhance plant carbon uptake and growth1–5, thereby providing an important negative feedback to climate change by slowing the rate of increase of the atmospheric CO2 concentration6. Although evidence gathered from young aggrading forests has generally indicated a strong CO2 fertilization effect on biomass growth3–5, it is unclear whether mature forests respond to eCO2 in a similar way. In mature trees and forest stands7–10, photosynthetic uptake has been found to increase under eCO2 without any apparent accompanying growth response, leaving the fate of additional carbon fixed under eCO2 unclear4,5,7–11. Here using data from the first ecosystem-scale Free-Air CO2 Enrichment (FACE) experiment in a mature forest, we constructed a comprehensive ecosystem carbon budget to track the fate of carbon as the forest responded to four years of eCO2 exposure. We show that, although the eCO2 treatment of +150 parts per million (+38 per cent) above ambient levels induced a 12 per cent (+247 grams of carbon per square metre per year) increase in carbon uptake through gross primary production, this additional carbon uptake did not lead to increased carbon sequestration at the ecosystem level. Instead, the majority of the extra carbon was emitted back into the atmosphere via several respiratory fluxes, with increased soil respiration alone accounting for half of the total uptake surplus. Our results call into question the predominant thinking that the capacity of forests to act as carbon sinks will be generally enhanced under eCO2, and challenge the efficacy of climate mitigation strategies that rely on ubiquitous CO2 fertilization as a driver of increased carbon sinks in global forests.
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  • Pluta, J, et al. (author)
  • Identification of 22 susceptibility loci associated with testicular germ cell tumors
  • 2021
  • In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 4487-
  • Journal article (peer-reviewed)abstract
    • Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95th percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation.
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  • Walsh, Roddy, et al. (author)
  • Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
  • 2021
  • In: Genetics in Medicine. - : Nature Publishing Group. - 1098-3600 .- 1530-0366. ; 23:1, s. 47-58
  • Journal article (peer-reviewed)abstract
    • Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
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  • Alvarez Melcon, A., et al. (author)
  • Scalable haloscopes for axion dark matter detection in the 30 mu eV range with RADES
  • 2020
  • In: Journal of High Energy Physics (JHEP). - : Springer Nature. - 1126-6708 .- 1029-8479. ; :7
  • Journal article (peer-reviewed)abstract
    • RADES (Relic Axion Detector Exploratory Setup) is a project with the goal of directly searching for axion dark matter above the 30 mu eV scale employing custom-made microwave filters in magnetic dipole fields. Currently RADES is taking data at the LHC dipole of the CAST experiment. In the long term, the RADES cavities are envisioned to take data in the BabyIAXO magnet. In this article we report on the modelling, building and characterisation of an optimised microwave-filter design with alternating irises that exploits maximal coupling to axions while being scalable in length without suffering from mode-mixing. We develop the mathematical formalism and theoretical study which justifies the performance of the chosen design. We also point towards the applicability of this formalism to optimise the MADMAX dielectric haloscopes.
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  • Ammirati, Enrico, et al. (author)
  • Acute Myocarditis Associated With Desmosomal Gene Variants
  • 2022
  • In: JACC. Heart failure. - : ELSEVIER SCI LTD. - 2213-1779 .- 2213-1787. ; 10:10, s. 714-727
  • Journal article (peer-reviewed)abstract
    • BACKGROUND The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown.OBJECTIVES The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV.METHODS In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[-]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up.RESULTS In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(-) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM. CONCLUSIONS Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk. (J Am Coll Cardiol HF 2022;10:714-727) (c) 2022 by the American College of Cardiology Foundation.
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  • Cardwell, C R, et al. (author)
  • Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data
  • 2010
  • In: DIABETOLOGIA. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 53:4, s. 641-651
  • Journal article (peer-reviewed)abstract
    • We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes. Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies. Data were available for 29 predominantly European studies (five cohort, 24 case-control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01-1.11]; p = 0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04-1.19]; p = 0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00-1.06]; p = 0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings. Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.
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  • Gardner, A., et al. (author)
  • Optimal stomatal theory predicts CO2 responses of stomatal conductance in both gymnosperm and angiosperm trees
  • 2022
  • In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 237:4, s. 1229-41
  • Journal article (peer-reviewed)abstract
    • Optimal stomatal theory predicts that stomata operate to maximise photosynthesis (A(net)) and minimise transpirational water loss to achieve optimal intrinsic water-use efficiency (iWUE). We tested whether this theory can predict stomatal responses to elevated atmospheric CO2 (eCO(2)), and whether it can capture differences in responsiveness among woody plant functional types (PFTs). We conducted a meta-analysis of tree studies of the effect of eCO(2) on iWUE and its components A(net) and stomatal conductance (g(s)). We compared three PFTs, using the unified stomatal optimisation (USO) model to account for confounding effects of leaf-air vapour pressure difference (D). We expected smaller g(s), but greater A(net), responses to eCO(2) in gymnosperms compared with angiosperm PFTs. We found that iWUE increased in proportion to increasing eCO(2) in all PFTs, and that increases in A(net) had stronger effects than reductions in g(s). The USO model correctly captured stomatal behaviour with eCO(2) across most datasets. The chief difference among PFTs was a lower stomatal slope parameter (g(1)) for the gymnosperm, compared with angiosperm, species. Land surface models can use the USO model to describe stomatal behaviour under changing atmospheric CO2 conditions.
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  • Karlsson, Per Erik, 1957, et al. (author)
  • New critical levels for ozone effects on young trees based on AOT40 and simulated cumulative leaf uptake of ozone
  • 2004
  • In: Atmospheric Environment. - : Elsevier BV. - 1352-2310. ; 38:15, s. 2283-2294
  • Journal article (peer-reviewed)abstract
    • Leaf or needle ozone uptake was estimated for young trees at seven experimental sites across Europe using a stomatal conductance simulation model. Dose-response relationships based on cumulative leaf uptake of ozone (CUO) were calculated using different hourly ozone flux thresholds and these were compared to dose-response relationships based on daylight AOT40, which is currently used within the UNECE Convention on Long-Range Transboundary Air Pollution (CLRTAP). Regression analysis showed that the CUO-biomass response relationships were highly significant for both coniferous and broadleaf trees, and independent of which ozone flux threshold was applied. On the basis of this regressions analysis, an hourly flux threshold of 1.6 nmol m(-2) s(-1) (COO > 1.6) is proposed as the most appropriate for all species categories in deriving dose-response relationships. The analysis indicated that the current critical level for ozone impacts on European forests of AOT40 10 ppm h may not protect the most sensitive receptors and that critical levels for AOT40 and CUO > 1.6 of 5 ppm h and 4 mmol m(-2), respectively, are more appropriate. The research identified weaker dose-response relationships for the CUO exposure index compared with AOT40. Distinguishing between sensitive and less sensitive species substantially improved the CUO-biomass response relationships although, still, to a lesser extent than when exposure was expressed as AOT40. (C) 2004 Elsevier Ltd. All rights reserved.
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  • Karlsson, Per Erik, 1957, et al. (author)
  • Risk assessments for forest trees: The performance of the ozone flux versus the AOT concepts
  • 2007
  • In: Environmental Pollution. - : Elsevier BV. - 0269-7491. ; 146:3, s. 608-616
  • Journal article (peer-reviewed)abstract
    • Published ozone exposure-response relationships from experimental studies with young trees performed at different sites across Europe were re-analysed in order to test the performance of ozone exposure indices based on AOTX (Accumulated exposure Over a Threshold of X nmol mol(-1)) and AF(st)Y (Accumulated Stomatal Flux above a threshold of Y nmol m(-2) s(-1)). AF(st)1.6 was superior, as compared to AOT40, for explaining biomass reductions, when ozone sensitive species with differing leaf morphology were included in the analysis, while this was not the case for less sensitive species. A re-analysis of data with young black cherry trees, subject to different irrigation regimes, indicated that leaf visible injuries were more strongly related to the estimated stomatal ozone uptake, as compared to the ozone concentration in the air. Experimental data with different clones of silver birch indicated that leaf thickness was also an important factor influencing the development of ozone induced leaf visible injury. (c) 2006 Elsevier Ltd. All rights reserved.
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  • Peaucelle, Marc, et al. (author)
  • Covariations between plant functional traits emerge from constraining parameterization of a terrestrial biosphere model
  • 2019
  • In: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 28:9, s. 1351-1365
  • Journal article (peer-reviewed)abstract
    • Aim: The mechanisms of plant trait adaptation and acclimation are still poorly understood and, consequently, lack a consistent representation in terrestrial biosphere models (TBMs). Despite the increasing availability of geo-referenced trait observations, current databases are still insufficient to cover all vegetation types and environmental conditions. In parallel, the growing number of continuous eddy-covariance observations of energy and CO2 fluxes has enabled modellers to optimize TBMs with these data. Past attempts to optimize TBM parameters mostly focused on model performance, overlooking the ecological properties of ecosystems. The aim of this study was to assess the ecological consistency of optimized trait-related parameters while improving the model performances for gross primary productivity (GPP) at sites. Location: Worldwide. Time period: 1992–2012. Major taxa studied: Trees and C3 grasses. Methods: We optimized parameters of the ORCHIDEE model against 371 site-years of GPP estimates from the FLUXNET network, and we looked at global covariation among parameters and with climate. Results: The optimized parameter values were shown to be consistent with leaf-scale traits, in particular, with well-known trade-offs observed at the leaf level, echoing the leaf economic spectrum theory. Results showed a marked sensitivity of trait-related parameters to local bioclimatic variables and reproduced the observed relationships between traits and climate. Main conclusions: Our approach validates some biological processes implemented in the model and enables us to study ecological properties of vegetation at the canopy level, in addition to some traits that are difficult to observe experimentally. This study stresses the need for: (a) implementing explicit trade-offs and acclimation processes in TBMs; (b) improving the representation of processes to avoid model-specific parameterization; and (c) performing systematic measurements of traits at FLUXNET sites in order to gather information on plant ecophysiology and plant diversity, together with micro-meteorological conditions.
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  • Timmons, James A, et al. (author)
  • Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages.
  • 2007
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:11, s. 4401-4406
  • Journal article (peer-reviewed)abstract
    • Attainment of a brown adipocyte cell phenotype in white adipocytes, with their abundant mitochondria and increased energy expenditure potential, is a legitimate strategy for combating obesity. The unique transcriptional regulators of the primary brown adipocyte phenotype are unknown, limiting our ability to promote brown adipogenesis over white. In the present work, we used microarray analysis strategies to study primary preadipocytes, and we made the striking discovery that brown preadipocytes demonstrate a myogenic transcriptional signature, whereas both brown and white primary preadipocytes demonstrate signatures distinct from those found in immortalized adipogenic models. We found a plausible SIRT1-related transcriptional signature during brown adipocyte differentiation that may contribute to silencing the myogenic signature. In contrast to brown preadipocytes or skeletal muscle cells, white preadipocytes express Tcf21, a transcription factor that has been shown to suppress myogenesis and nuclear receptor activity. In addition, we identified a number of developmental genes that are differentially expressed between brown and white preadipocytes and that have recently been implicated in human obesity. The interlinkage between the myocyte and the brown preadipocyte confirms the distinct origin for brown versus white adipose tissue and also represents a plausible explanation as to why brown adipocytes ultimately specialize in lipid catabolism rather than storage, much like oxidative skeletal muscle tissue.
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