The proapoptotic Bcl-2 protein Bax is predominantly found in the cytosol of nonapoptotic cells and is commonly thought to translocate to mitochondria following an apoptotic stimulus. The current ...model for Bax activation is that BH3 proteins bind to cytosolic Bax, initiating mitochondrial targeting and outer-membrane permeabilization. Here, we challenge this and show that Bax is constitutively targeted to mitochondria but in nonapoptotic cells is constantly translocated back to the cytosol. Using live-cell spinning-disk confocal imaging with a combination of FLIP, FRAP, and photoactivatable GFP-Bax, we demonstrate that disrupting adhesion-dependent survival signals slows the rate of Bax’s dissociation from mitochondria, leading to its accumulation on the outer mitochondrial membrane. The overall accumulation of mitochondrial Bax following loss of survival signaling sensitizes cells to proapoptotic BH3 proteins. Our findings show that Bax is normally in a dynamic equilibrium between cytosol and mitochondria, enabling fluctuations in survival signals to finely adjust apoptotic sensitivity.
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► Bax exists in equilibrium between the cytosol and mitochondria ► The retrotranslocation of Bax is independent of direct-activator BH3 proteins ► Changes in survival signaling modulate the dissociation rate of mitochondrial Bax ► Accumulation of Bax on mitochondria sensitizes cells to apoptosis
UKESM1: Description and Evaluation of the U.K. Earth System Model Sellar, Alistair A.; Jones, Colin G.; Mulcahy, Jane P. ...
Journal of advances in modeling earth systems,
December 2019, 2019-12-00, 20191201, 2019-12-01, Letnik:
11, Številka:
12
Journal Article
Recenzirano
Odprti dostop
We document the development of the first version of the U.K. Earth System Model UKESM1. The model represents a major advance on its predecessor HadGEM2‐ES, with enhancements to all component models ...and new feedback mechanisms. These include a new core physical model with a well‐resolved stratosphere; terrestrial biogeochemistry with coupled carbon and nitrogen cycles and enhanced land management; tropospheric‐stratospheric chemistry allowing the holistic simulation of radiative forcing from ozone, methane, and nitrous oxide; two‐moment, five‐species, modal aerosol; and ocean biogeochemistry with two‐way coupling to the carbon cycle and atmospheric aerosols. The complexity of coupling between the ocean, land, and atmosphere physical climate and biogeochemical cycles in UKESM1 is unprecedented for an Earth system model. We describe in detail the process by which the coupled model was developed and tuned to achieve acceptable performance in key physical and Earth system quantities and discuss the challenges involved in mitigating biases in a model with complex connections between its components. Overall, the model performs well, with a stable pre‐industrial state and good agreement with observations in the latter period of its historical simulations. However, global mean surface temperature exhibits stronger‐than‐observed cooling from 1950 to 1970, followed by rapid warming from 1980 to 2014. Metrics from idealized simulations show a high climate sensitivity relative to previous generations of models: Equilibrium climate sensitivity is 5.4 K, transient climate response ranges from 2.68 to 2.85 K, and transient climate response to cumulative emissions is 2.49 to 2.66 K TtC−1.
Plain Language Summary
We describe the development and behavior of UKESM1, a novel climate model that includes improved representations of processes in the atmosphere, ocean, and on land. These processes are inter‐related: For example, dust is produced on the land and blown up into the atmosphere where it affects the amount of sunlight falling on Earth. Dust can also be dissolved in the ocean, where it affects marine life. This in turn changes both the amount of carbon dioxide absorbed by the ocean and the material emitted from the surface into the atmosphere, which has an affect on the formation of clouds. UKESM1 includes many processes and interactions such as these, giving it a high level of complexity. Ensuring realistic process behavior is a major challenge in the development of our model, and we have carefully tested this. UKESM1 performs well, correctly exhibiting stable results from a continuous pre‐industrial simulation (used to provide a reference for future experiments) and showing good agreement with observations toward the end of its historical simulations. Results for some properties—including the degree to which average surface temperature changes with increased amounts of carbon dioxide in the atmosphere—are examined in detail.
Key Points
UKESM1 represents a major advance over its predecessor HadGEM2‐ES, both in the complexity of its components and its internal coupling
The complex coupling presents challenges to the model development; we document the tuning process employed to obtain acceptable performance
UKESM1 performs well, having a stable pre‐industrial state and showing good agreement with observations in a wide variety of contexts
Tropospheric ozone in CMIP6 simulations Griffiths, Paul T; Murray, Lee T; Zeng, Guang ...
Atmospheric chemistry and physics,
03/2021, Letnik:
21, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The evolution of tropospheric ozone from 1850 to 2100 has been studied using data from Phase 6 of the Coupled Model Intercomparison Project (CMIP6). We evaluate long-term changes using coupled ...atmosphere–ocean chemistry–climate models, focusing on the CMIP Historical and ScenarioMIP ssp370 experiments, for which detailed tropospheric-ozone diagnostics were archived. The model ensemble has been evaluated against a suite of surface, sonde and satellite observations of the past several decades and found to reproduce well the salient spatial, seasonal and decadal variability and trends. The multi-model mean tropospheric-ozone burden increases from 247 ± 36 Tg in 1850 to a mean value of 356 ± 31 Tg for the period 2005–2014, an increase of 44 %. Modelled present-day values agree well with previous determinations (ACCENT: 336 ± 27 Tg; Atmospheric Chemistry and Climate Model Intercomparison Project, ACCMIP: 337 ± 23 Tg; Tropospheric Ozone Assessment Report, TOAR: 340 ± 34 Tg). In the ssp370 experiments, the ozone burden increases to 416 ± 35 Tg by 2100. The ozone budget has been examined over the same period using lumped ozone production (PO3) and loss (LO3) diagnostics. Both ozone production and chemical loss terms increase steadily over the period 1850 to 2100, with net chemical production (PO3-LO3) reaching a maximum around the year 2000. The residual term, which contains contributions from stratosphere–troposphere transport reaches a minimum around the same time before recovering in the 21st century, while dry deposition increases steadily over the period 1850–2100. Differences between the model residual terms are explained in terms of variation in tropopause height and stratospheric ozone burden.
Here we present a description of the UKCA StratTrop chemical mechanism, which is used in the UKESM1 Earth system model for CMIP6. The StratTrop chemical mechanism is a merger of previously ...well-evaluated tropospheric and stratospheric mechanisms, and we provide results from a series of bespoke integrations to assess the overall performance of the model.
Total column ozone (TCO) over the Tibetan Plateau (TP) is lower than that over other regions at the same latitude, particularly in summer. This feature is known as the “TP ozone valley”. This study ...evaluates long-term changes in TCO and the ozone valley over the TP from 1984 to 2100 using Coupled Model Intercomparison Project Phase 6 (CMIP6). The TP ozone valley consists of two low centers, one is located in the upper troposphere and lower stratosphere (UTLS), and the other is in the middle and upper stratosphere. Overall, the CMIP6 models simulate the low ozone center in the UTLS well and capture the spatial characteristics and seasonal cycle of the TP ozone valley, with spatial correlation coefficients between the modeled TCO and the Multi Sensor Reanalysis version 2 (MSR2) TCO observations greater than 0.8 for all CMIP6 models. Further analysis reveals that models which use fully coupled and online stratospheric chemistry schemes simulate the anticorrelation between the 150 hPa geopotential height and zonal anomaly of TCO over the TP better than models without interactive chemistry schemes. This suggests that coupled chemical-radiative-dynamical processes play a key role in the simulation of the TP ozone valley. Most CMIP6 models underestimate the low center in the middle and upper stratosphere when compared with the Microwave Limb Sounder (MLS) observations. However, the bias in the middle and upper stratospheric ozone simulations has a marginal effect on the simulation of the TP ozone valley. Most CMIP6 models predict the TP ozone valley in summer will deepen in the future.
This work presents an analysis of the effect of climate change on surface ozone discussing the related penalties and benefits around the globe from the global modelling perspective based on ...simulations with five CMIP6 (Coupled Model Intercomparison Project Phase 6) Earth System Models. As part of AerChemMIP (Aerosol Chemistry Model Intercomparison Project) all models conducted simulation experiments considering future climate (ssp370SST) and present-day climate (ssp370pdSST) under the same future emissions trajectory (SSP3-7.0). A multi-model global average climate change benefit on surface ozone of −0.96 ± 0.07 ppbv °C−1 is calculated which is mainly linked to the dominating role of enhanced ozone destruction with higher water vapour abundances under a warmer climate. Over regions remote from pollution sources, there is a robust decline in mean surface ozone concentration on an annual basis as well as for boreal winter and summer varying spatially from −0.2 to −2 ppbv °C−1, with strongest decline over tropical oceanic regions. The implication is that over regions remote from pollution sources (except over the Arctic) there is a consistent climate change benefit for baseline ozone due to global warming. However, ozone increases over regions close to anthropogenic pollution sources or close to enhanced natural biogenic volatile organic compounds emission sources with a rate ranging regionally from 0.2 to 2 ppbv C−1, implying a regional surface ozone penalty due to global warming. Overall, the future climate change enhances the efficiency of precursor emissions to generate surface ozone in polluted regions and thus the magnitude of this effect depends on the regional emission changes considered in this study within the SSP3_7.0 scenario. The comparison of the climate change impact effect on surface ozone versus the combined effect of climate and emission changes indicates the dominant role of precursor emission changes in projecting surface ozone concentrations under future climate change scenarios.
The Arctic stratospheric polar vortex is a key component of the climate system, which has significant impacts on surface temperatures in the mid-latitudes and polar regions. Therefore, understanding ...polar vortex variability is helpful for extended-range weather forecasting. The present study evaluates long-term changes in the position and strength of the polar vortex in the Arctic lower stratosphere during the winters from 1980/81 to 2013/14. Simulations of the Coupled Model Intercomparison Project Phase 6 (CMIP6) models are compared with Modern-Era Retrospective analysis for Research and Applications Version 2 (MERRA2) reanalysis dataset. Overall, the CMIP6 models well capture the spatial characteristics of the polar vortex with spatial correlation coefficients between the potential vorticity (PV) in the lower stratosphere from simulations and MERRA2 products generally greater than 0.85 for all CMIP6 models during winter. There is a good agreement in the position and shape of the polar vortex between the CMIP6 multi-model mean and MERRA2, although there exist differences between simulations of individual CMIP6 models. However, most CMIP6 models underestimate the strength of polar vortex in the lower stratosphere, with the largest negative bias up to about −20%. The present study further reveals that there is an anticorrelation between the polar vortex strength bias and area bias simulated by CMIP6 models. In addition, there is a positive correlation between the trend of EP-flux divergence for wavenumber one accumulated in early winter and the trend in zonal mean zonal wind averaged in late winter. As for the long-term change in polar vortex position, CanESM5, IPSL-CM5A2-INCA, UKESM1-0-LL, and IPSL-CM6A-LR well capture the persistent shift of polar vortex towards the Eurasian continent and away from North America in February, which has been reported in observations. These models reproduce the positive trend of wavenumber-1 planetary waves since the 1980s seen in the MERRA2 dataset. This suggests that realistic wave activity processes in CMIP6 models play a key role not only in the simulation of the strength of the stratospheric polar vortex but also in the simulation of the polar vortex position shift.
Water vapor plays an important role in many aspects of the climate system, by affecting radiation, cloud formation, atmospheric chemistry and dynamics. Even the low stratospheric water vapor content ...provides an important climate feedback, but current climate models show a substantial moist bias in the lowermost stratosphere. Here we report crucial sensitivity of the atmospheric circulation in the stratosphere and troposphere to the abundance of water vapor in the lowermost stratosphere. We show from a mechanistic climate model experiment and inter-model variability that lowermost stratospheric water vapor decreases local temperatures, and thereby causes an upward and poleward shift of subtropical jets, a strengthening of the stratospheric circulation, a poleward shift of the tropospheric eddy-driven jet and regional climate impacts. The mechanistic model experiment in combination with atmospheric observations further shows that the prevailing moist bias in current models is likely caused by the transport scheme, and can be alleviated by employing a less diffusive Lagrangian scheme. The related effects on atmospheric circulation are of similar magnitude as climate change effects. Hence, lowermost stratospheric water vapor exerts a first order effect on atmospheric circulation and improving its representation in models offers promising prospects for future research.
Two strains of mice (BALB/c and CB6F1) were vaccinated with a range of Bacille Calmette-Guérin (BCG) Danish doses from 3 × 10
to 30 CFU/mouse, followed by aerosol infection with Mtb (H37Rv or ...West-Beijing HN878 strain). The results indicated that both strains of mice when infected with HN878 exhibited significant protection in their lungs with BCG doses at 3 × 10
-3000 CFU (BALB/c) and 3 × 10
-300 CFU (CB6F1). Whereas, a significant protection was seen in both strains of mice with BCG doses at 3 × 10
-300 CFU when infected with H37Rv. A significant increase in the frequencies of BCG-specific IFNγ
IL2
TNFα
CD4 T cells in the BCG doses at 3 × 10
-3000 CFU (BALB/c) and 3 × 10
-300 CFU (CB6F1) was seen. The IFNγ
IL2
TNFα
CD4 T cells correlated with the Mtb burden in the lungs of HN878 infected mice (BALB/c and CB6F1) whereas, IFNγ
TNFα
CD4 T cells correlated with the BALB/c mice infected with H37Rv or HN878. The BCG dose at 3000 CFU (an equivalent single human dose in the mice by body weight) is protective in both strains of mice infected with H37Rv or HN878 and may serve an interesting dose to test new TB vaccine in a preclinical animal model.
Different cell types interpret their distinct extracellular matrix (ECM) environments to bring about specific cell fate decisions, and can differentiate or undergo apoptosis depending on their local ...adhesive interactions. Apoptosis in response to an inappropriate ECM environment is termed `anoikis', or homelessness. Several studies, utilising a variety of cell types, have indicated a common, crucial role for focal adhesion kinase (FAK) in suppressing anoikis. A wide range of different integrins can activate FAK, raising the question of how cell type specific effects are regulated. In this study, we have used a constitutively active form of FAK to examine the mechanism of FAK-mediated survival signalling in cell types from distinct embryonic lineages that show differing sensitivities to anoikis. We demonstrate that both fibroblasts and epithelial cells prevent anoikis through FAK activation. We show that FAK activates multiple downstream pathways in order to suppress anoikis. However FAK regulates survival through a more restricted set of pathways in the more anoikis-sensitive epithelial cells. Furthermore, we identify a novel role for paxillin in apoptosis suppression.
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