One single mRNA encodes the centrosomal protein CCD41 and the endothelial cell protein C receptor (EPCR)

AbstractThe cDNA encoding the centrosomal protein CCD41 is identical with the cDNA for the endothelial cell protein C receptor. This finding is not due to an artefact, e.g. caused by selection of false positive clones. The segment of the CCD41 cDNA encoding the protein originally termed CCD41 and deletion mutants of it were fused with the nucleotide sequence encoding the enhanced green fluorescent protein (EGFP). Transfection and expression of the full length construct produces a fusion protein mainly located in cell membranes reflecting the receptor-type protein. Deletion mutants, e.g. those where the signal sequence is deleted, result in fusion proteins which are exclusively incorporated into a small perinuclear structure which is the site of the centrosome. This result suggests that post-translational modification, namely deletion of the signal sequence, is decisive for the centrosomal location of the resulting centrosomal protein while the unprocessed protein is incorporated into cell membranes

PDB3: USE OF BOOTSTRAP IN A COST-OF-ILLNESS STUDY TO DERIVE ACCURACY OF ESTIMATES

Farrando, Jordi;Febles, Maria Dolors ;Henrich, Jordi;Tarrasó, Olga ;Fuertes, J.C.;Pérez, S

Initializing decadal climate predictions with the GECCO oceanic synthesis

This study aims at improving the forecast skill of climate predictions through the use of ocean synthesis data for initial conditions of a coupled climate model. For this purpose, the coupled model of the Max Planck Institute (MPI) for Meteorology, which consists of the atmosphere model ECHAM5 and the MPI Ocean Model (MPI-OM), is initialized with oceanic synthesis fields available from the German contribution to Estimating the Circulation and Climate of the Ocean (GECCO) project. The use of an anomaly coupling scheme during the initialization avoids the main problems with drift in the climate predictions. Thus, the coupled model is continuously forced to follow the density anomalies of the GECCO synthesis over the period 1952-2001. Hindcast experiments are initialized from this experiment at constant intervals. The results show predictive skill through the initialization up to the decadal time scale, particularly over the North Atlantic. Viewed over the time scales analyzed here (annual, 5-yr, and 10-yr mean), greater skill for the North Atlantic sea surface temperature (SST) is obtained in the hindcast experiments than in either a damped persistence or trend forecast. The Atlantic meridional overturning circulation hindcast closely follows that of the GECCO oceanic synthesis. Hindcasts of global-mean temperature do not obtain greater skill than either damped persistence or a trend forecast, owing to the SST errors in the GECCO synthesis, outside the North Atlantic. An ensemble of forecast experiments is subsequently performed over the period 2002-11. North Atlantic SST from the forecast experiment agrees well with observations until the year 2007, and it is higher than if simulated without the oceanic initialization (averaged over the forecast period). The results confirm that both the initial and the boundary conditions must be accounted for in decadal climate predictions

Sea level changes mechanisms in the MPI-ESM under FAFMIP forcing conditions

Mechanistic causes for sea level (SL) change patterns are analyzed as they emerge from the Coupled Model Intercomparison Project Phase 6 (CMIP6) endorsed Flux-Anomaly-Forced Model Intercomparison Project (FAFMIP) coupled climate experiments imposing individual forcing anomalies in wind stress, heatflux and freshwater flux to the Max-Planck-Institute Earth System Model (MPI-ESM). It appears that the heat flux perturbations have the largest effect on the sea level. In contrast, the direct impact of momentum and freshwater flux anomalies on SL anomalies appear to be limited to some region e.g. the Southern Ocean, Arctic Ocean and to some extent the North Pacific and North Atlantic Ocean. We find that thermosteric changes dominate the total SL change over large parts of the global ocean, except north of 60 °N where halosteric changes prevail. An analysis of added and redistributed components of heat and freshwater further suggests that the added component dominates the thermosteric SL and the redistributed component dominates the halosteric SL. Due to feedback processes a superposition of all forcing components together leads to the simulated sea level changes in each individual experiment. As a result, large surface heat flux anomalies over the Atlantic lead to wind stress change outside of the Atlantic through teleconnections, which in turn appear to be the primary driving agent for changes of sea level outside of the Atlantic in all three experiments. The associated wind driven Sverdrup stream function implicates that outside of the Atlantic most of the feedback can be explained by changes in the Sverdrup circulation

On the Mid-Depth Circulation in the Labrador and Irminger Seas

A numerical circulation model with 1/6° resolution and an accurate topography formulation explains details of the observed circulation in the Irminger and Labrador Seas that were recently revealed by Lavender et al. [2000]. We show that the recirculation pattern is established through a locally wind induced flow controlled by the bottom topography and enhanced through remote baroclinic forcing by the dense plume of Denmark Strait overflow water. The basic circulation is a robust feature in a hierarchy of model setups. It exists in the purely barotropic case driven by steady winds and is even maintained when realistic daily forcing is added. The narrow recirculation zone is manifested by a sea level depression spanning from the Denmark Strait across the Irminger into the Labrador Sea

Global ocean modeling and state estimation in support of climate research

During the last decade it has become obvious that the ocean circulation shows vigorous variability on a wide range of time and space scales and that the concept of a "sluggish" and slowly varying circulation is rather elusive. Increasing emphasis has to be put, therefore, on observing the rapidly changing ocean state on time scales ranging from weeks to decades and beyond, and on understanding the ocean's response to changing atmospheric forcing conditions. As outlined in various strategy and implementation documents (e.g., the implementation plans of WOCE, AMS, CLIVAR, and GODAE) a combination of the global ocean data sets with a state-of-the-art numerical circulation model is required to interpret the various diverse data sets and to produce the best possible estimates of the time-varying ocean circulation. The mechanism of ocean state estimates is a powerful tool for such a "synthesis" of observations, obtained on very complex space-time pattern, into one dynamically consistent picture of the global time-evolving ocean circulation. This process has much in common with ongoing analysis and reanalysis activities in the atmospheric community. But because the ocean is, and will remain for the foreseeable future, substantially under-sampled, the burden put on the modeling and estimations components is substantially larger than in the atmosphere. Moreover, the smaller dynamical eddy scales which need to be properly parameterized or resolved in ocean model simulations, put stringent requirements on computational resources for ongoing and participated climate research

Induction of apoptosis by overexpression of the DNA-binding and DNA-PK-activating protein C1D

Apoptosis is induced in various tumor cell lines by vector-dependent overexpression of the conserved gene C1D that encodes a DNA-binding and DNA-PK-activating protein. C1D is physiologically expressed in 50 human tissues tested, which points to its basic cellular function. The expression of this gene must be tightly regulated because elevated levels of C1D protein, e.g. those induced by transient vector-dependent expression, result in apoptotic cell death. Cells transfected with C1D-expressing constructs show terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling of DNA ends. Transfections with constructs in which C1D is expressed in fusion with the (enhanced) green fluorescent protein from A. victoria (EGFP) allow the transfected cells to be identified and the morphological changes induced to be traced. Starting from intense nuclear spots, green fluorescence reflecting C1D expression increases dramatically at 12-24 hours post-transfection. Expression of C1D-EGFP protein is accompanied by morphological changes typical of apoptotic cell death, e.g. cytoplasmic vacuolation, membrane blebbing and nuclear disintegration. Cell shrinkage and detachment from extracellular matrix are observed in monolayer cultures while suspension cells become progressively flattened. The facility to differentiate between transfected and non-transfected cells reveals that non-transfected cells co-cultured with transfected cells also show the morphological changes of apoptosis, which points to a bystander effect. C1D-dependent apoptosis is not induced in cells with non-functional p53. Accordingly, C1D-induced apoptosis is discussed in relation to its potential to activate DNA-PK, which has been considered to act as an upstream activator of p53

The Flux-Anomaly-Forced Model Intercomparison Project (FAFMIP) contribution to CMIP6: investigation of sea-level and ocean climate change in response to CO₂ forcing

The Flux-Anomaly-Forced Model Intercomparison Project (FAFMIP) aims to investigate the spread in simulations of sea-level and ocean climate change in response to CO2 forcing by atmosphere–ocean general circulation models (AOGCMs). It is particularly motivated by the uncertainties in projections of ocean heat uptake, global-mean sea-level rise due to thermal expansion and the geographical patterns of sea-level change due to ocean density and circulation change. FAFMIP has three tier-1 experiments, in which prescribed surface flux perturbations of momentum, heat and freshwater respectively are applied to the ocean in separate AOGCM simulations. All other conditions are as in the pre-industrial control. The prescribed fields are typical of pattern and magnitude of changes in these fluxes projected by AOGCMs for doubled CO2 concentration. Five groups have tested the experimental design with existing AOGCMs. Their results show diversity in the pattern and magnitude of changes, with some common qualitative features. Heat and water flux perturbation cause the dipole in sea-level change in the North Atlantic, while momentum and heat flux perturbation cause the gradient across the Antarctic Circumpolar Current. The Atlantic meridional overturning circulation (AMOC) declines in response to the heat flux perturbation, and there is a strong positive feedback on this effect due to the consequent cooling of sea-surface temperature in the North Atlantic, which enhances the local heat input to the ocean. The momentum and water flux perturbations do not substantially affect the AMOC. Heat is taken up largely as a passive tracer in the Southern Ocean, which is the region of greatest heat input, while the weakening of the AMOC causes redistribution of heat towards lower latitudes. Future analysis of these and other phenomena with the wider range of CMIP6 FAFMIP AOGCMs will benefit from new diagnostics of temperature and salinity tendencies, which will enable investigation of the model spread in behaviour in terms of physical processes as formulated in the models