Variability of extracellular vesicle release during storage of red blood cell concentrates is associated with differential membrane alterations, including loss of cholesterol-enriched domains

Transfusion of red blood cell concentrates is the most common medical procedure to treat anaemia. However, their storage is associated with development of storage lesions, including the release of extracellular vesicles. These vesicles affect in vivo viability and functionality of transfused red blood cells and appear responsible for adverse post-transfusional complications. However, the biogenesis and release mechanisms are not fully understood. We here addressed this issue by comparing the kinetics and extents of extracellular vesicle release as well as red blood cell metabolic, oxidative and membrane alterations upon storage in 38 concentrates. We showed that extracellular vesicle abundance increased exponentially during storage. The 38 concentrates contained on average 7 × 1012 extracellular vesicles at 6 weeks (w) but displayed a ∼40-fold variability. These concentrates were subsequently classified into 3 cohorts based on their vesiculation rate. The variability in extracellular vesicle release was not associated with a differential red blood cell ATP content or with increased oxidative stress (in the form of reactive oxygen species, methaemoglobin and band3 integrity) but rather with red blood cell membrane modifications, i.e., cytoskeleton membrane occupancy, lateral heterogeneity in lipid domains and transversal asymmetry. Indeed, no changes were noticed in the low vesiculation group until 6w while the medium and the high vesiculation groups exhibited a decrease in spectrin membrane occupancy between 3 and 6w and an increase of sphingomyelin-enriched domain abundance from 5w and of phosphatidylserine surface exposure from 8w. Moreover, each vesiculation group showed a decrease of cholesterol-enriched domains associated with a cholesterol content increase in extracellular vesicles but at different storage time points. This observation suggested that cholesterol-enriched domains could represent a starting point for vesiculation. Altogether, our data reveal for the first time that the differential extent of extracellular vesicle release in red blood cell concentrates did not simply result from preparation method, storage conditions or technical issues but was linked to membrane alterations

Inter-model comparison of sub-seasonal tropical variability in aquaplanet experimets: effect of a warm pool

This study compares the simulation of sub-seasonal tropical variability by a set of six state-of-the-art AGCMs in two experiments in aqua-planet configuration: a zonally-symmetric experiment, and an experiment with a warm pool centered on the equator. In all six models, the presence of the warm pool generates zonal asymmetries in the simulated mean states in the form of a “Gill-type” response, made more complex by feedbacks between moisture, convective heating and circulation. Noticeable differences appear from one model to another. Only half the models simulate mean low-level equatorial westerlies over the warm pool area. The presence of the warm pool can also favor the development of large-scale variability consistent with observed Madden-Julian Oscillation (MJO) characteristics, but this happens only in half the models. Our results do not support the idea that the presence of the warm pool and/or of mean low-level equatorial westerlies are sufficient conditions for MJO-like variability to arise in the models. Comparing spectral characteristics of the simulated Convectively Coupled Equatorial Waves (CCEWs) in the aquaplanet experiments and the corresponding coupled atmosphere-ocean (i.e. CMIP) and atmosphere-only (i.e. AMIP) simulations, we also show that there is more consistency for a given model across its configurations, than for a given configuration across the six models. Overall, our results confirm that the simulation of sub-seasonal variability by given model is significantly influenced by the parameterization of sub-grid physical processes (most-likely cloud processes), both directly and through modulation of the mean state

WRF/ARPEGE-CLIMAT simulated climate trends over West Africa

International audienceThe Weather Regional Forecast (WRF) model is used in this study to downscale low-resolution data over West Africa. First, the performance of the regional model is estimated through contemporary period experiments (1981- 1990) forced by ARPEGE-CLIMAT GCM output (ARPEGE) and ERA-40 re-analyses. Key features of the West African monsoon circulation are reasonably well represented. WRF atmospheric dynamics and summer rainfall compare better to observations than ARPEGE forcing data. WRF simulated moisture transport over West Africa is also consistent in both structure and variability with re-analyses, emphasizing the substantial role played by the West African Monsoon (WAM) and African Easterly Jet (AEJ) flows. The statistical significance of potential climate changes for the A2 scenario between 2032-2041 is enhanced in the downscaling from ARPEGE by the regional experiments, with substantial rainfall increases over the Guinea Gulf and eastern Sahel. Future scenario WRF simulations are characterized by higher temperatures over the eastern Tropical Atlantic suggesting more evaporation available locally. This leads to increased moisture advection towards eastern regions of the Guinea Gulf where rainfall is enhanced through a strengthened WAM flow, supporting surface moisture convergence over West Africa. Warmer conditions over both the Mediterranean region and northeastern Sahel could also participate in enhancing moisture transport within the AEJ. The strengthening of the thermal gradient between the Sahara and Guinean regions, particularly pronounced north of 10◦N, would support an intensification of the AEJ northwards, given the dependance of the jet to the position/intensity of the meridional gradient. In turn, mid-tropospheric moisture divergence tends to be favored within the AEJ region supporting southwards ascents of moister air and deep convection over the Sahel where late summer rainfall regimes are sustained in the context of the A2 scenario regional projections. In conclusion, WRF proved to be a valuable and efficient tool to help downscaling GCM projections over West Africa, and thus assessing issues such as water ressources vulnerability locally

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface.

BACKGROUND/AIMS: Red blood cells (RBC) have been shown to exhibit stable submicrometric lipid domains enriched in cholesterol (chol), sphingomyelin (SM), phosphatidylcholine (PC) or ganglioside GM1, which represent the four main lipid classes of their outer plasma membrane leaflet. However, whether those lipid domains co-exist at the RBC surface or are spatially related and whether and how they are subjected to reorganization upon RBC deformation are not known. METHODS: Using fluorescence and/or confocal microscopy and well-validated probes, we compared these four lipid-enriched domains for their abundance, curvature association, lipid order, temperature dependence, spatial dissociation and sensitivity to RBC mechanical stimulation. RESULTS: Our data suggest that three populations of lipid domains with decreasing abundance coexist at the RBC surface: (i) chol-enriched ones, associated with RBC high curvature areas; (ii) GM1/PC/chol-enriched ones, present in low curvature areas; and (iii) SM/PC/chol-enriched ones, also found in low curvature areas. Whereas chol-enriched domains gather in increased curvature areas upon RBC deformation, low curvature-associated lipid domains increase in abundance either upon calcium influx during RBC deformation (GM1/PC/chol-enriched domains) or upon secondary calcium efflux during RBC shape restoration (SM/PC/chol-enriched domains). Hence, abrogation of these two domain populations is accompanied by a strong impairment of the intracellular calcium balance. CONCLUSION: Lipid domains could contribute to calcium influx and efflux by controlling the membrane distribution and/or the activity of the mechano-activated ion channel Piezo1 and the calcium pump PMCA. Whether this results from lipid domain biophysical properties, the strength of their anchorage to the underlying cytoskeleton and/or their correspondence with inner plasma membrane leaflet lipids remains to be demonstrated

An energetics study of wintertime Northern Hemisphere storm tracks under 4 × CO2_2 conditions in two ocean–atmosphere coupled models

International audienceDifferent possible behaviors of winter Northern Hemisphere storm tracks under 4 × CO$_2$ forcing are considered by analyzing the response of two of the ocean–atmosphere coupled models that were run for the fourth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC-AR4), namely the Institut Pierre Simon Laplace’s global coupled model (IPSL-CM4) and the Centre National de Recherches Meteorologiques’s coupled ocean–atmosphere model (CNRM-CM3). It is interesting to compare these models due to their very different responses, especially concerning the North Atlantic storm track.A local energetics study of the synoptic variability in both models is performed, derived from the eddy energy equations, including diabatic terms. The ability of both models to simulate the present-day eddy energetics is considered, indicating no major discrepancies.Both models indicate that the primary cause for synoptic activity changes at the western end of the storm tracks is related to the baroclinic conversion process, due to mean temperature gradient changes in some localized regions of the western oceanic basins, but also resulting from changes in the eddy efficiency to convert energy from the mean flow. Farther downstream, latent heat release during the developing and mature stages of eddies becomes an important eddy energy source especially in terms of changes between 4 × CO$_2$ and preindustrial conditions. This diabatic process amplifies the upstream synoptic (hence usually baroclinic) changes, with more and/or stronger storms implying more latent heat being released (and the converse being true for weaker synoptic activity). This amplification is asymmetrical for the models considered under the simulated 4 × CO$_2$ conditions, due to a greater amount of water vapor contained in warmer air and hence the potential for more condensation for a given synoptic activity. The magnitude of the reduced latent heating is attenuated, whereas increased latent heating is strengthened. Ageostrophic geopotential fluxes are also important in relocating eddy kinetic energy, especially in the vertical

Tropical influence on boreal summer mid-latitude stationary waves

International audienceWhile organized tropical convection is a well-known source of extratropical planetary waves, state-of-the-art climate models still show serious deficiencies in simulating accurately the atmospheric response to tropical sea surface temperature (SST) anomalies and the associated teleconnections. In the present study, the remote influence of the tropical atmospheric circulation is evaluated in ensembles of global boreal summer simulations in which the Arpege-Climat atmospheric General Circulation Model (GCM) is nudged towards 6-h reanalyses. The nudging is applied either in the whole tropical band or in a regional summer monsoon domain. Sensitivity tests to the experimental design are first conducted using prescribed climatological SST. They show that the tropical relaxation does not improve the zonal mean extratropical climatology but does lead to a significantly improved representation of the mid-latitude stationary waves in both hemispheres. Low-pass filtering of the relaxation fields has no major effect on the model response, suggesting that high-frequency tropical variability is not responsible for extratropical biases. Dividing the nudging strength by a factor 10 only decreases the magnitude of the response. Model errors in each monsoon domain contribute to deficiencies in the model's mid-latitude climatology, although an exaggerated large-scale subsidence in the central equatorial Pacific appears as the main source of errors for the representation of stationary waves in the Arpege-Climat model. Case studies are then conducted using either climatological or observed SST. The focus is first on summer 2003 characterized by a strong and persistent anticyclonic anomaly over western Europe. This pattern is more realistic in nudging experiments than in simulations only driven by observed SST, especially when the nudging domain is centred over Central America. Other case studies also show a significant tropical forcing of the summer mid-latitude stationary waves and suggest a weak influence of prescribed observed SST in the northern extratropics. Results therefore indicate that improving the tropical divergent circulation and its response to tropical SST anomalies remains a key issue for increasing the skill of extratropical seasonal predictions, not only in the winter hemisphere but also in the boreal summer hemisphere where the prediction of heatwave and drought likelihood is expected to become an important challenge with increasing concentrations of greenhouse gases

Probing PIEZO1 Localization upon Activation Using High-Resolution Atomic Force and Confocal Microscopy

PIEZO1 ion channels are activated by mechanical stimuli, triggering intracellular chemical signals. Recent structural studies suggest that plasma membrane tension or local curvature changes modulate PIEZO1 channel gating and activation. However, whether PIEZO1 localization is governed by tension gradients or long-range mechanical perturbations across the cells is still unclear. Here, we probe the nanoscale localization of PIEZO1 on red blood cells (RBCs) at high resolution (∼30 nm), and we report for the first time the existence of submicrometric PIEZO1 clusters in native conditions. Upon interaction with Yoda1, an allosteric modulator, PIEZO1 clusters increase in abundance in regions of higher membrane tension and lower curvature. We further show that PIEZO1 ion channels interact with the spectrin cytoskeleton in both resting and activated states. Our results point toward a strong interplay between plasma membrane tension gradients, curvature, and cytoskeleton association of PIEZO1