| 1. |
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| 2. |
- Saunois, M., et al.
(författare)
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The global methane budget 2000–2012
- 2016
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 8:2, s. 697-751
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Tidskriftsartikel (refereegranskat)abstract
- The global methane (CH4) budget is becoming an increasingly important component for managing realistic pathways to mitigate climate change. This relevance, due to a shorter atmospheric lifetime and a stronger warming potential than carbon dioxide, is challenged by the still unexplained changes of atmospheric CH4 over the past decade. Emissions and concentrations of CH4 are continuing to increase, making CH4 the second most important human-induced greenhouse gas after carbon dioxide. Two major difficulties in reducing uncertainties come from the large variety of diffusive CH4 sources that overlap geographically, and from the destruction of CH4 by the very short-lived hydroxyl radical (OH). To address these difficulties, we have established a consortium of multi-disciplinary scientists under the umbrella of the Global Carbon Project to synthesize and stimulate research on the methane cycle, and producing regular (∼ biennial) updates of the global methane budget. This consortium includes atmospheric physicists and chemists, biogeochemists of surface and marine emissions, and socio-economists who study anthropogenic emissions. Following Kirschke et al. (2013), we propose here the first version of a living review paper that integrates results of top-down studies (exploiting atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up models, inventories and data-driven approaches (including process-based models for estimating land surface emissions and atmospheric chemistry, and inventories for anthropogenic emissions, data-driven extrapolations). For the 2003–2012 decade, global methane emissions are estimated by top-down inversions at 558 Tg CH4 yr−1, range 540–568. About 60 % of global emissions are anthropogenic (range 50–65 %). Since 2010, the bottom-up global emission inventories have been closer to methane emissions in the most carbon-intensive Representative Concentrations Pathway (RCP8.5) and higher than all other RCP scenarios. Bottom-up approaches suggest larger global emissions (736 Tg CH4 yr−1, range 596–884) mostly because of larger natural emissions from individual sources such as inland waters, natural wetlands and geological sources. Considering the atmospheric constraints on the top-down budget, it is likely that some of the individual emissions reported by the bottom-up approaches are overestimated, leading to too large global emissions. Latitudinal data from top-down emissions indicate a predominance of tropical emissions (∼ 64 % of the global budget, < 30° N) as compared to mid (∼ 32 %, 30–60° N) and high northern latitudes (∼ 4 %, 60–90° N). Top-down inversions consistently infer lower emissions in China (∼ 58 Tg CH4 yr−1, range 51–72, −14 %) and higher emissions in Africa (86 Tg CH4 yr−1, range 73–108, +19 %) than bottom-up values used as prior estimates. Overall, uncertainties for anthropogenic emissions appear smaller than those from natural sources, and the uncertainties on source categories appear larger for top-down inversions than for bottom-up inventories and models. The most important source of uncertainty on the methane budget is attributable to emissions from wetland and other inland waters. We show that the wetland extent could contribute 30–40 % on the estimated range for wetland emissions. Other priorities for improving the methane budget include the following: (i) the development of process-based models for inland-water emissions, (ii) the intensification of methane observations at local scale (flux measurements) to constrain bottom-up land surface models, and at regional scale (surface networks and satellites) to constrain top-down inversions, (iii) improvements in the estimation of atmospheric loss by OH, and (iv) improvements of the transport models integrated in top-down inversions. The data presented here can be downloaded from the Carbon Dioxide Information Analysis Center (http://doi.org/10.3334/CDIAC/GLOBAL_METHANE_BUDGET_2016_V1.1) and the Global Carbon Project.
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| 3. |
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| 4. |
- Saunois, M., et al.
(författare)
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Variability and quasi-decadal changes in the methane budget over the period 2000–2012
- 2017
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 17:18, s. 11135-11161
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Tidskriftsartikel (refereegranskat)abstract
- Following the recent Global Carbon Project (GCP) synthesis of the decadal methane (CH4) budget over 2000–2012 (Saunois et al., 2016), we analyse here the same dataset with a focus on quasi-decadal and inter-annual variability in CH4 emissions. The GCP dataset integrates results from top-down studies (exploiting atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up models (including process-based models for estimating land surface emissions and atmospheric chemistry), inventories of anthropogenic emissions, and data-driven approaches. The annual global methane emissions from top-down studies, which by construction match the observed methane growth rate within their uncertainties, all show an increase in total methane emissions over the period 2000–2012, but this increase is not linear over the 13 years. Despite differences between individual studies, the mean emission anomaly of the top-down ensemble shows no significant trend in total methane emissions over the period 2000–2006, during the plateau of atmospheric methane mole fractions, and also over the period 2008–2012, during the renewed atmospheric methane increase. However, the top-down ensemble mean produces an emission shift between 2006 and 2008, leading to 22 [16–32] Tg CH4 yr−1 higher methane emissions over the period 2008–2012 compared to 2002–2006. This emission increase mostly originated from the tropics, with a smaller contribution from mid-latitudes and no significant change from boreal regions. The regional contributions remain uncertain in top-down studies. Tropical South America and South and East Asia seem to contribute the most to the emission increase in the tropics. However, these two regions have only limited atmospheric measurements and remain therefore poorly constrained. The sectorial partitioning of this emission increase between the periods 2002–2006 and 2008–2012 differs from one atmospheric inversion study to another. However, all top-down studies suggest smaller changes in fossil fuel emissions (from oil, gas, and coal industries) compared to the mean of the bottom-up inventories included in this study. This difference is partly driven by a smaller emission change in China from the top-down studies compared to the estimate in the Emission Database for Global Atmospheric Research (EDGARv4.2) inventory, which should be revised to smaller values in a near future. We apply isotopic signatures to the emission changes estimated for individual studies based on five emission sectors and find that for six individual top-down studies (out of eight) the average isotopic signature of the emission changes is not consistent with the observed change in atmospheric 13CH4. However, the partitioning in emission change derived from the ensemble mean is consistent with this isotopic constraint. At the global scale, the top-down ensemble mean suggests that the dominant contribution to the resumed atmospheric CH4 growth after 2006 comes from microbial sources (more from agriculture and waste sectors than from natural wetlands), with an uncertain but smaller contribution from fossil CH4 emissions. In addition, a decrease in biomass burning emissions (in agreement with the biomass burning emission databases) makes the balance of sources consistent with atmospheric 13CH4 observations. In most of the top-down studies included here, OH concentrations are considered constant over the years (seasonal variations but without any inter-annual variability). As a result, the methane loss (in particular through OH oxidation) varies mainly through the change in methane concentrations and not its oxidants. For these reasons, changes in the methane loss could not be properly investigated in this study, although it may play a significant role in the recent atmospheric methane changes as briefly discussed at the end of the paper.
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| 5. |
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| 6. |
- Ito, A., et al.
(författare)
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Cold-Season Methane Fluxes Simulated by GCP-CH4 Models
- 2023
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Ingår i: Geophysical Research Letters. - 0094-8276. ; 50:14
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Tidskriftsartikel (refereegranskat)abstract
- Cold-season methane (CH4) emissions may be poorly constrained in wetland models. We examined cold-season CH4 emissions simulated by 16 models participating in the Global Carbon Project model intercomparison and analyzed temporal and spatial patterns in simulation results using prescribed inundation data for 2000–2020. Estimated annual CH4 emissions from northern (>60°N) wetlands averaged 10.0 ± 5.5 Tg CH4 yr−1. While summer CH4 emissions were well simulated compared to in-situ flux measurement observations, the models underestimated CH4 during September to May relative to annual total (27 ± 9%, compared to 45% in observations) and substantially in the months with subzero air temperatures (5 ± 5%, compared to 27% in observations). Because of winter warming, nevertheless, the contribution of cold-season emissions was simulated to increase at 0.4 ± 0.8% decade−1. Different parameterizations of processes, for example, freezing–thawing and snow insulation, caused conspicuous variability among models, implying the necessity of model refinement.
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| 7. |
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| 8. |
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| 9. |
- Fisher, J. B., et al.
(författare)
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Carbon cycle uncertainty in the Alaskan Arctic
- 2014
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 11:15, s. 4271-4288
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Tidskriftsartikel (refereegranskat)abstract
- Climate change is leading to a disproportionately large warming in the high northern latitudes, but the magnitude and sign of the future carbon balance of the Arctic are highly uncertain. Using 40 terrestrial biosphere models for the Alaskan Arctic from four recent model intercomparison projects - NACP (North American Carbon Program) site and regional syntheses, TRENDY (Trends in net land atmosphere carbon exchanges), and WETCHIMP (Wetland and Wetland CH4 Inter-comparison of Models Project) - we provide a baseline of terrestrial carbon cycle uncertainty, defined as the multi-model standard deviation (sigma) for each quantity that follows. Mean annual absolute uncertainty was largest for soil carbon (14.0+/-9.2 kgCm(-2)), then gross primary production (GPP) (0.22+/-0.50 kgCm(-2) yr(-1)), ecosystem respiration (Re) (0.23+/-0.38 kgCm(-2) yr(-1)), net primary production (NPP) (0.14+/-0.33 kgCm(-2) yr(-1)), autotrophic respiration (Ra) (0.09+/-0.20 kgCm(-2) yr(-1)), heterotrophic respiration (Rh) (0.14+/-0.20 kgCm(-2) yr(-1)), net ecosystem exchange (NEE) (-0.01+/-0.19 kgCm(-2) yr(-1)), and CH4 flux (2.52+/-4.02 g CH4 m(-2) yr(-1)). There were no consistent spatial patterns in the larger Alaskan Arctic and boreal regional carbon stocks and fluxes, with some models showing NEE for Alaska as a strong carbon sink, others as a strong carbon source, while still others as carbon neutral. Finally, AmeriFlux data are used at two sites in the Alaskan Arctic to evaluate the regional patterns; observed seasonal NEE was captured within multi-model uncertainty. This assessment of carbon cycle uncertainties may be used as a baseline for the improvement of experimental and modeling activities, as well as a reference for future trajectories in carbon cycling with climate change in the Alaskan Arctic and larger boreal region.
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| 10. |
- Kanis, J A, et al.
(författare)
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A meta-analysis of previous fracture and subsequent fracture risk.
- 2004
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 35:2, s. 375-82
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Tidskriftsartikel (refereegranskat)abstract
- Previous fracture is a well-documented risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 15259 men and 44902 women from 11 cohorts comprising EVOS/EPOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and two cohorts from Gothenburg. Cohorts were followed for a total of 250000 person-years. The effect of a prior history of fracture on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex, and BMD. The results of the different studies were merged by using the weighted beta-coefficients. A previous fracture history was associated with a significantly increased risk of any fracture compared with individuals without a prior fracture (RR = 1.86; 95% CI = 1.75-1.98). The risk ratio was similar for the outcome of osteoporotic fracture or for hip fracture. There was no significant difference in risk ratio between men and women. Risk ratio (RR) was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any fracture (8%) and for hip fracture (22%). The risk ratio was stable with age except in the case of hip fracture outcome where the risk ratio decreased significantly with age. We conclude that previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.
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| 11. |
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| 12. |
- Kupers, LK, et al.
(författare)
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Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1893-
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Tidskriftsartikel (refereegranskat)abstract
- Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
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| 13. |
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| 14. |
- Parmar, Priyanka, et al.
(författare)
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Association of maternal prenatal smoking GFI1-locus and cardiometabolic phenotypes in 18,212 adults
- 2018
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 38, s. 206-216
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Tidskriftsartikel (refereegranskat)abstract
- Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n= 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP). Findings: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0.012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 x 10(-7) < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 x 10(-8) < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels. Interpretation: Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. Fund: European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH.
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| 15. |
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| 16. |
- Hantson, Stijn, et al.
(författare)
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Quantitative assessment of fire and vegetation properties in simulations with fire-enabled vegetation models from the Fire Model Intercomparison Project
- 2020
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 13:7, s. 3299-3318
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Tidskriftsartikel (refereegranskat)abstract
- Global fire-vegetation models are widely used to assess impacts of environmental change on fire regimes and the carbon cycle and to infer relationships between climate, land use and fire. However, differences in model structure and parameterizations, in both the vegetation and fire components of these models, could influence overall model performance, and to date there has been limited evaluation of how well different models represent various aspects of fire regimes. The Fire Model Intercomparison Project (FireMIP) is coordinating the evaluation of state-of-the-art global fire models, in order to improve projections of fire characteristics and fire impacts on ecosystems and human societies in the context of global environmental change. Here we perform a systematic evaluation of historical simulations made by nine FireMIP models to quantify their ability to reproduce a range of fire and vegetation benchmarks. The FireMIP models simulate a wide range in global annual total burnt area (39-536 Mha) and global annual fire carbon emission (0.91-4.75 Pg C yr-1) for modern conditions (2002-2012), but most of the range in burnt area is within observational uncertainty (345-468 Mha). Benchmarking scores indicate that seven out of nine FireMIP models are able to represent the spatial pattern in burnt area. The models also reproduce the seasonality in burnt area reasonably well but struggle to simulate fire season length and are largely unable to represent interannual variations in burnt area. However, models that represent cropland fires see improved simulation of fire seasonality in the Northern Hemisphere. The three FireMIP models which explicitly simulate individual fires are able to reproduce the spatial pattern in number of fires, but fire sizes are too small in key regions, and this results in an underestimation of burnt area. The correct representation of spatial and seasonal patterns in vegetation appears to correlate with a better representation of burnt area. The two older fire models included in the FireMIP ensemble (LPJ-GUESS-GlobFIRM, MC2) clearly perform less well globally than other models, but it is difficult to distinguish between the remaining ensemble members; some of these models are better at representing certain aspects of the fire regime; none clearly outperforms all other models across the full range of variables assessed.
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| 17. |
- Hantson, Stijn, et al.
(författare)
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The status and challenge of global fire modelling
- 2016
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 13:11, s. 3359-3375
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Tidskriftsartikel (refereegranskat)abstract
- Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, using either well-founded empirical relationships or process-based models with good predictive skill. While a large variety of models exist today, it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central question underpinning the creation of the Fire Model Intercomparison Project (FireMIP), an international initiative to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we review how fires have been represented in fire-enabled dynamic global vegetation models (DGVMs) and give an overview of the current state of the art in fire-regime modelling. We indicate which challenges still remain in global fire modelling and stress the need for a comprehensive model evaluation and outline what lessons may be learned from FireMIP.
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| 18. |
- Kanis, J A, et al.
(författare)
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A family history of fracture and fracture risk: a meta-analysis.
- 2004
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 35:5, s. 1029-37
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Tidskriftsartikel (refereegranskat)abstract
- The aims of the present study were to determine whether a parental history of any fracture or hip fracture specifically are significant risk factors for future fracture in an international setting, and to explore the effects of age, sex and bone mineral density (BMD) on this risk. We studied 34,928 men and women from seven prospectively studied cohorts followed for 134,374 person-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, DOES and cohorts at Sheffield, Rochester and Gothenburg. The effect of family history of osteoporotic fracture or of hip fracture in first-degree relatives, BMD and age on all clinical fracture, osteoporotic fracture and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. A parental history of fracture was associated with a modest but significantly increased risk of any fracture, osteoporotic fracture and hip fracture in men and women combined. The risk ratio (RR) for any fracture was 1.17 (95% CI=1.07-1.28), for any osteoporotic fracture was 1.18 (95% CI=1.06-1.31), and for hip fracture was 1.49 (95% CI=1.17-1.89). The risk ratio was higher at younger ages but not significantly so. No significant difference in risk was seen between men and women with a parental history for any fracture (RR=1.17 and 1.17, respectively) or for an osteoporotic fracture (RR=1.17 and 1.18, respectively). For hip fracture, the risk ratios were somewhat higher, but not significantly higher, in men than in women (RR=2.02 and 1.38, respectively). A family history of hip fracture in parents was associated with a significant risk both of all osteoporotic fracture (RR 1.54; 95CI=1.25-1.88) and of hip fracture (RR=2.27; 95% CI=1.47-3.49). The risk was not significantly changed when BMD was added to the model. We conclude that a parental history of fracture (particularly a family history of hip fracture) confers an increased risk of fracture that is independent of BMD. Its identification on an international basis supports the use of this risk factor in case-finding strategies.
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| 19. |
- Kanis, John A, et al.
(författare)
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A meta-analysis of prior corticosteroid use and fracture risk.
- 2004
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Ingår i: Journal of bone and mineral research. - 0884-0431 .- 1523-4681. ; 19:6, s. 893-9
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between use of corticosteroids and fracture risk was estimated in a meta-analysis of data from seven cohort studies of approximately 42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD. INTRODUCTION: The aims of this study were to validate that corticosteroid use is a significant risk factor for fracture in an international setting and to explore the effects of age and sex on this risk. MATERIALS AND METHODS: We studied 42,500 men and women from seven prospectively studied cohorts followed for 176,000 patient-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, Dubbo Osteoporosis Epidemiology Study (DOES), and prospective cohorts at Sheffield, Rochester, and Gothenburg. The effect of ever use of corticosteroids, BMD, age, and sex on all fracture, osteoporotic fracture, and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. RESULTS: Previous corticosteroid use was associated with a significantly increased risk of any fracture, osteoporotic fracture, and hip fracture when adjusted for BMD. Relative risk of any fracture ranged from 1.98 at the age of 50 years to 1.66 at the age of 85 years. For osteoporotic fracture, the range of relative risk was 2.63-1.71, and for hip fracture 4.42-2.48. The estimate of relative risk was higher at younger ages, but not significantly so. No significant difference in risk was seen between men and women. The risk was marginally and not significantly upwardly adjusted when BMD was excluded from the model. The risk was independent of prior fracture. In the three cohorts that documented current corticosteroid use, BMD was significantly reduced at the femoral neck, but fracture risk was still only partly explained by BMD. CONCLUSION: We conclude that prior and current exposure to corticosteroids confers an increased risk of fracture that is of substantial importance beyond that explained by the measurement of BMD. Its identification on an international basis validates the use of this risk factor in case-finding strategies.
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| 20. |
- Kanis, J A, et al.
(författare)
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The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women.
- 2007
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Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 18:8, s. 1033-46
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Tidskriftsartikel (refereegranskat)abstract
- SUMMARY: BMD and clinical risk factors predict hip and other osteoporotic fractures. The combination of clinical risk factors and BMD provide higher specificity and sensitivity than either alone. INTRODUCTION AND HYPOTHESES: To develop a risk assessment tool based on clinical risk factors (CRFs) with and without BMD. METHODS: Nine population-based studies were studied in which BMD and CRFs were documented at baseline. Poisson regression models were developed for hip fracture and other osteoporotic fractures, with and without hip BMD. Fracture risk was expressed as gradient of risk (GR, risk ratio/SD change in risk score). RESULTS: CRFs alone predicted hip fracture with a GR of 2.1/SD at the age of 50 years and decreased with age. The use of BMD alone provided a higher GR (3.7/SD), and was improved further with the combined use of CRFs and BMD (4.2/SD). For other osteoporotic fractures, the GRs were lower than for hip fracture. The GR with CRFs alone was 1.4/SD at the age of 50 years, similar to that provided by BMD (GR = 1.4/SD) and was not markedly increased by the combination (GR = 1.4/SD). The performance characteristics of clinical risk factors with and without BMD were validated in eleven independent population-based cohorts. CONCLUSIONS: The models developed provide the basis for the integrated use of validated clinical risk factors in men and women to aid in fracture risk prediction.
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| 21. |
- Peterson, Q. P., et al.
(författare)
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A method for the generation of human stem cell-derived alpha cells
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The generation of pancreatic cell types from renewable cell sources holds promise for cell replacement therapies for diabetes. Although most effort has focused on generating pancreatic beta cells, considerable evidence indicates that glucagon secreting alpha cells are critically involved in disease progression and proper glucose control. Here we report on the generation of stem cell-derived human pancreatic alpha (SC-alpha) cells from pluripotent stem cells via a transient pre-alpha cell intermediate. These pre-alpha cells exhibit a transcriptional profile similar to mature alpha cells and although they produce proinsulin protein, they do not secrete significant amounts of processed insulin. Compound screening identified a protein kinase c activator that promotes maturation of pre-alpha cells into SC-alpha cells. The resulting SC-alpha cells do not express insulin, share an ultrastructure similar to cadaveric alpha cells, express and secrete glucagon in response to glucose and some glucagon secretagogues, and elevate blood glucose upon transplantation in mice. Deriving functional pancreatic cell types from human stem cells may have important clinical applications. Building on previous work, here the authors generate stem cell-derived alpha cells via a polyhormonal intermediate, which have a gene expression pattern similar to human islet alpha cells and behave as such when transplanted into mice.
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| 22. |
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| 23. |
- Saunois, Marielle, et al.
(författare)
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The Global Methane Budget 2000–2017
- 2020
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3516 .- 1866-3508. ; 12:3, s. 1561-1623
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Tidskriftsartikel (refereegranskat)abstract
- Understanding and quantifying the global methane (CH4) budget is important for assessing realistic pathways to mitigate climate change. Atmospheric emissions and concentrations of CH4 continue to increase, making CH4 the second most important human-influenced greenhouse gas in terms of climate forcing, after carbon dioxide (CO2). The relative importance of CH4 compared to CO2 depends on its shorter atmospheric lifetime, stronger warming potential, and variations in atmospheric growth rate over the past decade, the causes of which are still debated. Two major challenges in reducing uncertainties in the atmospheric growth rate arise from the variety of geographically overlapping CH4 sources and from the destruction of CH4 by short-lived hydroxyl radicals (OH). To address these challenges, we have established a consortium of multidisciplinary scientists under the umbrella of the Global Carbon Project to synthesize and stimulate new research aimed at improving and regularly updating the global methane budget. Following Saunois et al. (2016), we present here the second version of the living review paper dedicated to the decadal methane budget, integrating results of top-down studies (atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up estimates (including process-based models for estimating land surface emissions and atmospheric chemistry, inventories of anthropogenic emissions, and data-driven extrapolations).For the 2008–2017 decade, global methane emissions are estimated by atmospheric inversions (a top-down approach) to be 576 Tg CH4 yr−1 (range 550–594, corresponding to the minimum and maximum estimates of the model ensemble). Of this total, 359 Tg CH4 yr−1 or ∼ 60 % is attributed to anthropogenic sources, that is emissions caused by direct human activity (i.e. anthropogenic emissions; range 336–376 Tg CH4 yr−1 or 50 %–65 %). The mean annual total emission for the new decade (2008–2017) is 29 Tg CH4 yr−1 larger than our estimate for the previous decade (2000–2009), and 24 Tg CH4 yr−1 larger than the one reported in the previous budget for 2003–2012 (Saunois et al., 2016). Since 2012, global CH4 emissions have been tracking the warmest scenarios assessed by the Intergovernmental Panel on Climate Change. Bottom-up methods suggest almost 30 % larger global emissions (737 Tg CH4 yr−1, range 594–881) than top-down inversion methods. Indeed, bottom-up estimates for natural sources such as natural wetlands, other inland water systems, and geological sources are higher than top-down estimates. The atmospheric constraints on the top-down budget suggest that at least some of these bottom-up emissions are overestimated. The latitudinal distribution of atmospheric observation-based emissions indicates a predominance of tropical emissions (∼ 65 % of the global budget, < 30∘ N) compared to mid-latitudes (∼ 30 %, 30–60∘ N) and high northern latitudes (∼ 4 %, 60–90∘ N). The most important source of uncertainty in the methane budget is attributable to natural emissions, especially those from wetlands and other inland waters.Some of our global source estimates are smaller than those in previously published budgets (Saunois et al., 2016; Kirschke et al., 2013). In particular wetland emissions are about 35 Tg CH4 yr−1 lower due to improved partition wetlands and other inland waters. Emissions from geological sources and wild animals are also found to be smaller by 7 Tg CH4 yr−1 by 8 Tg CH4 yr−1, respectively. However, the overall discrepancy between bottom-up and top-down estimates has been reduced by only 5 % compared to Saunois et al. (2016), due to a higher estimate of emissions from inland waters, highlighting the need for more detailed research on emissions factors. Priorities for improving the methane budget include (i) a global, high-resolution map of water-saturated soils and inundated areas emitting methane based on a robust classification of different types of emitting habitats; (ii) further development of process-based models for inland-water emissions; (iii) intensification of methane observations at local scales (e.g., FLUXNET-CH4 measurements) and urban-scale monitoring to constrain bottom-up land surface models, and at regional scales (surface networks and satellites) to constrain atmospheric inversions; (iv) improvements of transport models and the representation of photochemical sinks in top-down inversions; and (v) development of a 3D variational inversion system using isotopic and/or co-emitted species such as ethane to improve source partitioning.The data presented here can be downloaded from https://doi.org/10.18160/GCP-CH4-2019 (Saunois et al., 2020) and from the Global Carbon Project.
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| 24. |
- Teo, Kevin, et al.
(författare)
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rs641738C>T near MBOAT7 is associated with liver fat, ALT, and fibrosis in NAFLD: a meta-analysis.
- 2021
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Ingår i: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 74:1, s. 20-30
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Tidskriftsartikel (refereegranskat)abstract
- A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and characterize its role in the regulation of related metabolic phenotypes through meta-analysis.We performed meta-analysis of studies with data on the association between rs641738C>T genotype and: liver fat, NAFLD histology, and serum ALT, lipids, or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed random effects meta-analysis using recessive, additive, and dominant genetic models.Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI: 0.02 - 0.05], pz=4.8x10-5) and diagnosis of NAFLD (OR 1.17 [95% CI 1.05 - 1.3], pz=0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI: 1.03 - 1.45], pz=0.021) in Caucasian adults using a recessive model of inheritance (CC+CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz=0.002) and lower serum triglycerides (pz=1.5x10-4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD.Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.
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