Bardet-Biedl Syndrome ciliopathy is linked to altered hematopoiesis and dysregulated self-tolerance

Bardet–Biedl Syndrome (BBS) is a pleiotropic genetic disease caused by the dysfunction of primary cilia. The immune system of patients with ciliopathies has not been investigated. However, there are multiple indications that the impairment of the processes typically associated with cilia may have influence on the hematopoietic compartment and immunity. In this study, we analyze clinical data of BBS patients and corresponding mouse models carrying mutations in Bbs4 or Bbs18. We find that BBS patients have a higher prevalence of certain autoimmune diseases. Both BBS patients and animal models have altered red blood cell and platelet compartments, as well as elevated white blood cell levels. Some of the hematopoietic system alterations are associated with BBS‐induced obesity. Moreover, we observe that the development and homeostasis of B cells in mice is regulated by the transport complex BBSome, whose dysfunction is a common cause of BBS. The BBSome limits canonical WNT signaling and increases CXCL12 levels in bone marrow stromal cells. Taken together, our study reveals a connection between a ciliopathy and dysregulated immune and hematopoietic systems

Arctic sea ice simulation in the PlioMIP ensemble

Eight general circulation models have simulated the mid-Pliocene warm period (mid-Pliocene, 3.264 to 3.025 Ma) as part of the Pliocene Modelling Intercomparison Project (PlioMIP). Here, we analyse and compare their simulation of Arctic sea ice for both the pre-industrial period and the mid-Pliocene. Mid-Pliocene sea ice thickness and extent is reduced, and the model spread of extent is more than twice the pre-industrial spread in some summer months. Half of the PlioMIP models simulate ice-free conditions in the mid-Pliocene. This spread amongst the ensemble is in line with the uncertainties amongst proxy reconstructions for mid-Pliocene sea ice extent. Correlations between mid-Pliocene Arctic temperatures and sea ice extents are almost twice as strong as the equivalent correlations for the pre-industrial simulations. The need for more comprehensive sea ice proxy data is highlighted, in order to better compare model performances

Sea Surface Temperature of the mid-Piacenzian Ocean:A Data-Model Comparison

The mid-Piacenzian climate represents the most geologically recent interval of long-term average warmth relative to the last million years, and shares similarities with the climate projected for the end of the 21st century. As such, it represents a natural experiment from which we can gain insight into potential climate change impacts, enabling more informed policy decisions for mitigation and adaptation. Here, we present the first systematic comparison of Pliocene sea surface temperature (SST) between an ensemble of eight climate model simulations produced as part of PlioMIP (Pliocene Model Intercomparison Project) with the PRISM (Pliocene Research, Interpretation and Synoptic Mapping) Project mean annual SST field. Our results highlight key regional and dynamic situations where there is discord between the palaeoenvironmental reconstruction and the climate model simulations. These differences have led to improved strategies for both experimental design and temporal refinement of the palaeoenvironmental reconstruction

Dynamic light scattering study on phase separation of a protein-water mixture: Application on cold cataract development in the ocular lens

We present a detailed dynamic light scattering study on the phase separation in the ocular lens emerging during cold cataract development. Cold cataract is a phase separation effect that proceeds via spinodal decomposition of the lens cytoplasm with cooling. Intensity auto-correlation functions of the lens protein content are analyzed with the aid of two methods providing information on the populations and dynamics of the scattering elements associated with cold cataract. It is found that the temperature dependence of many measurable parameters changes appreciably at the characteristic temperature ~16+1 oC which is associated with the onset of cold cataract. Extending the temperature range of this work to previously inaccessible regimes, i.e. well below the phase separation or coexistence curve at Tcc, we have been able to accurately determine the temperature dependence of the collective and self-diffusion coefficient of proteins near the spinodal. The analysis showed that the dynamics of proteins bears some resemblance to the dynamics of structural glasses where the apparent activation energy for particle diffusion increases below Tcc indicating a highly cooperative motion. Application of ideas developed for studying the critical dynamics of binary protein/solvent mixtures, as well as the use of a modified Arrhenius equation, enabled us to estimate the spinodal temperature Tsp of the lens nucleus. The applicability of dynamic light scattering as a non-invasive, early-diagnostic tool for ocular diseases is also demonstrated in the light of the findings of the present paper

Evaluation of Arctic warming in mid-Pliocene climate simulations

Palaeoclimate simulations improve our understanding of the climate, inform us about the performance of climate models in a different climate scenario, and help to identify robust features of the climate system. Here, we analyse Arctic warming in an ensemble of 16 simulations of the mid-Pliocene Warm Period (mPWP), derived from the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2). The PlioMIP2 ensemble simulates Arctic (60–90∘ N) annual mean surface air temperature (SAT) increases of 3.7 to 11.6 ∘C compared to the pre-industrial period, with a multi-model mean (MMM) increase of 7.2 ∘C. The Arctic warming amplification ratio relative to global SAT anomalies in the ensemble ranges from 1.8 to 3.1 (MMM is 2.3). Sea ice extent anomalies range from −3.0 to −10.4×10^{6} km^{2}, with a MMM anomaly of −5.6×10^{6} km^{2}, which constitutes a decrease of 53 % compared to the pre-industrial period. The majority (11 out of 16) of models simulate summer sea-ice-free conditions (≤1×10^{6} km^{2}) in their mPWP simulation. The ensemble tends to underestimate SAT in the Arctic when compared to available reconstructions, although the degree of underestimation varies strongly between the simulations. The simulations with the highest Arctic SAT anomalies tend to match the proxy dataset in its current form better. The ensemble shows some agreement with reconstructions of sea ice, particularly with regard to seasonal sea ice. Large uncertainties limit the confidence that can be placed in the findings and the compatibility of the different proxy datasets. We show that while reducing uncertainties in the reconstructions could decrease the SAT data–model discord substantially, further improvements are likely to be found in enhanced boundary conditions or model physics. Lastly, we compare the Arctic warming in the mPWP to projections of future Arctic warming and find that the PlioMIP2 ensemble simulates greater Arctic amplification than CMIP5 future climate simulations and an increase instead of a decrease in Atlantic Meridional Overturning Circulation (AMOC) strength compared to pre-industrial period. The results highlight the importance of slow feedbacks in equilibrium climate simulations, and that caution must be taken when using simulations of the mPWP as an analogue for future climate change

On the climatic influence of CO2 forcing in the Pliocene

Understanding the dominant climate forcings in the Pliocene is crucial to assessing the usefulness of the Pliocene as an analogue for our warmer future. Here, we implement a novel yet simple linear factorisation method to assess the relative influence of CO2 forcing in seven models of the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2) ensemble. Outputs are termed “FCO2” and show the fraction of Pliocene climate change driven by CO2. The accuracy of the FCO2 method is first assessed through comparison to an energy balance analysis previously used to assess drivers of surface air temperature in the PlioMIP1 ensemble. After this assessment, the FCO2 method is applied to achieve an understanding of the drivers of Pliocene sea surface temperature and precipitation for the first time. CO2 is found to be the most important forcing in the ensemble for Pliocene surface air temperature (global mean FCO2=0.56), sea surface temperature (global mean FCO2=0.56), and precipitation (global mean FCO2=0.51). The range between individual models is found to be consistent between these three climate variables, and the models generally show good agreement on the sign of the most important forcing. Our results provide the most spatially complete view of the drivers of Pliocene climate to date and have implications for both data–model comparison and the use of the Pliocene as an analogue for the future. That CO2 is found to be the most important forcing reinforces the Pliocene as a good palaeoclimate analogue, but the significant effect of non-CO2 forcing at a regional scale (e.g. orography and ice sheet forcing at high latitudes) reminds us that it is not perfect, and these additional influencing factors must not be overlooked. This comparison is further complicated when considering the Pliocene as a state in quasi-equilibrium with CO2 forcing compared to the transient warming being experienced at present

A return to large-scale features of Pliocene climate: the Pliocene Model Intercomparison Project Phase 2

The Pliocene epoch has great potential to improve our understanding of the long-term climatic and environmental consequences of an atmospheric CO2 concentration near ~ 400 parts per million by volume. Here we present the large-scale features of Pliocene climate as simulated by a new ensemble of climate models of varying complexity and spatial resolution and based on new reconstructions of boundary conditions (the Pliocene Model Intercomparison Project Phase 2; PlioMIP2). As a global annual average, modelled surface air temperatures increase by between 1.4 and 4.7 °C relative to pre-industrial with a multi-model mean value of 2.8 °C. Annual mean total precipitation rates increase by 6 % (range: 2 %–13 %). On average, surface air temperature (SAT) increases are 1.3 °C greater over the land than over the oceans, and there is a clear pattern of polar amplification with warming polewards of 60° N and 60° S exceeding the global mean warming by a factor of 2.4. In the Atlantic and Pacific Oceans, meridional temperature gradients are reduced, while tropical zonal gradients remain largely unchanged. Although there are some modelling constraints, there is a statistically significant relationship between a model's climate response associated with a doubling in CO2 (Equilibrium Climate Sensitivity; ECS) and its simulated Pliocene surface temperature response. The mean ensemble earth system response to doubling of CO2 (including ice sheet feedbacks) is approximately 50 % greater than ECS, consistent with results from the PlioMIP1 ensemble. Proxy-derived estimates of Pliocene sea-surface temperatures are used to assess model estimates of ECS and indicate a range in ECS from 2.5 to 4.3 °C. This result is in general accord with the range in ECS presented by previous IPCC Assessment Reports

Mid-Pliocene Atlantic Meridional Overturning Circulation Not Unlike Modern

In the Pliocene Model Intercomparison Project (PlioMIP), eight state-of-the-art coupled climate models have simulated the mid-Pliocene warm period (mPWP, 3.264 to 3.025 Ma). Here, we compare the Atlantic Meridional Overturning Circulation (AMOC), northward ocean heat transport and ocean stratification simulated with these models. None of the models participating in PlioMIP simulates a strong mid-Pliocene AMOC as suggested by earlier proxy studies. Rather, there is no consistent increase in AMOC maximum among the PlioMIP models. The only consistent change in AMOC is a shoaling of the overturning cell in the Atlantic, and a reduced influence of North Atlantic Deep Water (NADW) at depth in the basin. Furthermore, the simulated mid-Pliocene Atlantic northward heat transport is similar to the pre-industrial. These simulations demonstrate that the reconstructed high-latitude mid-Pliocene warming can not be explained as a direct response to an intensification of AMOC and concomitant increase in northward ocean heat transport by the Atlantic

The Pliocene Model Intercomparison Project Phase 2: large-scale climate features and climate sensitivity

The Pliocene epoch has great potential to improve our understanding of the long-term climatic and environmental consequences of an atmospheric CO2 concentration near ∼400 parts per million by volume. Here we present the large-scale features of Pliocene climate as simulated by a new ensemble of climate models of varying complexity and spatial resolution based on new reconstructions of boundary conditions (the Pliocene Model Intercomparison Project Phase 2; PlioMIP2). As a global annual average, modelled surface air temperatures increase by between 1.7 and 5.2 ∘C relative to the pre-industrial era with a multi-model mean value of 3.2 ∘C. Annual mean total precipitation rates increase by 7 % (range: 2 %–13 %). On average, surface air temperature (SAT) increases by 4.3 ∘C over land and 2.8 ∘C over the oceans. There is a clear pattern of polar amplification with warming polewards of 60∘ N and 60∘ S exceeding the global mean warming by a factor of 2.3. In the Atlantic and Pacific oceans, meridional temperature gradients are reduced, while tropical zonal gradients remain largely unchanged. There is a statistically significant relationship between a model's climate response associated with a doubling in CO2 (equilibrium climate sensitivity; ECS) and its simulated Pliocene surface temperature response. The mean ensemble Earth system response to a doubling of CO2 (including ice sheet feedbacks) is 67 % greater than ECS; this is larger than the increase of 47 % obtained from the PlioMIP1 ensemble. Proxy-derived estimates of Pliocene sea surface temperatures are used to assess model estimates of ECS and give an ECS range of 2.6–4.8 ∘C. This result is in general accord with the ECS range presented by previous Intergovernmental Panel on Climate Change (IPCC) Assessment Reports

Large-scale features of Last Interglacial climate: Results from evaluating the lig127k simulations for the Coupled Model Intercomparison Project (CMIP6)-Paleoclimate Modeling Intercomparison Project (PMIP4)

Abstract. The modeling of paleoclimate, using physically based tools, is increasingly seen as a strong out-of-sample test of the models that are used for the projection of future climate changes. New to the Coupled Model Intercomparison Project (CMIP6) is the Tier 1 Last Interglacial experiment for 127 000 years ago (lig127k), designed to address the climate responses to stronger orbital forcing than the midHolocene experiment, using the same state-of-the-art models as for the future and following a common experimental protocol. Here we present a first analysis of a multi-model ensemble of 17 climate models, all of which have completed the CMIP6 DECK (Diagnostic, Evaluation and Characterization of Klima) experiments. The equilibrium climate sensitivity (ECS) of these models varies from 1.8 to 5.6 ∘C. The seasonal character of the insolation anomalies results in strong summer warming over the Northern Hemisphere continents in the lig127k ensemble as compared to the CMIP6 piControl and much-reduced minimum sea ice in the Arctic. The multi-model results indicate enhanced summer monsoonal precipitation in the Northern Hemisphere and reductions in the Southern Hemisphere. These responses are greater in the lig127k than the CMIP6 midHolocene simulations as expected from the larger insolation anomalies at 127 than 6 ka. New synthesis for surface temperature and precipitation, targeted for 127 ka, have been developed for comparison to the multi-model ensemble. The lig127k model ensemble and data reconstructions are in good agreement for summer temperature anomalies over Canada, Scandinavia, and the North Atlantic and for precipitation over the Northern Hemisphere continents. The model–data comparisons and mismatches point to further study of the sensitivity of the simulations to uncertainties in the boundary conditions and of the uncertainties and sparse coverage in current proxy reconstructions. The CMIP6–Paleoclimate Modeling Intercomparison Project (PMIP4) lig127k simulations, in combination with the proxy record, improve our confidence in future projections of monsoons, surface temperature, and Arctic sea ice, thus providing a key target for model evaluation and optimization. </jats:p