Expression of the bacterial type III effector DspA/E in Saccharomyces cerevisiae downregulates the sphingolipid biosynthetic pathway leading to growth-arrest

Erwinia amylovora, the bacterium responsible for fire blight, relies on a type III secretion system and a single injected effector, DspA/E, to induce disease in host plants. DspA/E belongs to the widespread AvrE family of type III effectors which suppress plant defense responses and promote bacterial growth followinginfection. Ectopic expression of DspA/E in plant or in Saccharomyces cerevisiae is toxic indicating that DspA/E likely targets a cellular process conserved between yeast and plant. To unravel the mode of action of DspA/E, we screened the Euroscarf, S. cerevisiae library for mutants resistant toDspA/E-induced growth arrest. The most resistant mutants (Δsur4, Δfen1, Δipt1,Δskn1, Δcsg1, Δcsg2, Δorm1, Δorm2) were impaired in the sphingolipid biosynthetic pathway. Exogenously supplied sphingolipid precursors such as the long chain bases(LCBs) phytosphingosine and dihydrosphingosine also suppressed DspA/E-induced yeast growth defect. Expression of DspA/E in yeast downregulated LCBs biosynthesis and induced a rapid decrease in LCB levels,indicating that SPT, the first and rate limiting enzyme of the sphingolipid biosynthetic pathway was repressed. SPT downregulation was mediated by dephosphorylation and activation of Orm proteins that negatively regulate SPT. A Δcdc55 mutation, affecting Cdc55-PP2A protein phosphatase activity, prevented Orm dephosphorylation and suppressed DspA/E-induced growth arrest

The VOLNA-OP2 tsunami code (version 1.5)

In this paper, we present the VOLNA-OP2 tsunami model and implementation; a finite-volume non-linear shallow-water equation (NSWE) solver built on the OP2 domain-specific language (DSL) for unstructured mesh computations. VOLNA-OP2 is unique among tsunami solvers in its support for several high-performance computing platforms: central processing units (CPUs), the Intel Xeon Phi, and graphics processing units (GPUs). This is achieved in a way that the scientific code is kept separate from various parallel implementations, enabling easy maintainability. It has already been used in production for several years; here we discuss how it can be integrated into various workflows, such as a statistical emulator. The scalability of the code is demonstrated on three supercomputers, built with classical Xeon CPUs, the Intel Xeon Phi, and NVIDIA P100 GPUs. VOLNA-OP2 shows an ability to deliver productivity as well as performance and portability to its users across a number of platforms.</p

C16 ceramide is crucial for triacylglycerol-induced apoptosis in macrophages

Triacylglycerol (TG) accumulation caused by adipose triglyceride lipase (ATGL) deficiency or very low-density lipoprotein (VLDL) loading of wild-type (Wt) macrophages results in mitochondrial-mediated apoptosis. This phenotype is correlated to depletion of Ca2+ from the endoplasmic reticulum (ER), an event known to induce the unfolded protein response (UPR). Here, we show that ER stress in TG-rich macrophages activates the UPR, resulting in increased abundance of the chaperone GRP78/BiP, the induction of pancreatic ER kinase-like ER kinase, phosphorylation and activation of eukaryotic translation initiation factor 2A, the translocation of activating transcription factor (ATF)4 and ATF6 to the nucleus and the induction of the cell death executor CCAAT/enhancer-binding protein homologous protein. C16:0 ceramide concentrations were increased in Atgl–/– and VLDL-loaded Wt macrophages. Overexpression of ceramide synthases was sufficient to induce mitochondrial apoptosis in Wt macrophages. In accordance, inhibition of ceramide synthases in Atgl–/– macrophages by fumonisin B1 (FB1) resulted in specific inhibition of C16:0 ceramide, whereas intracellular TG concentrations remained high. Although the UPR was still activated in Atgl–/– macrophages, FB1 treatment rescued Atgl–/– macrophages from mitochondrial dysfunction and programmed cell death. We conclude that C16:0 ceramide elicits apoptosis in Atgl–/– macrophages by activation of the mitochondrial apoptosis pathway

CWH43 is required for the introduction of ceramides into GPI anchors in Saccharomyces cerevisiae

After glycosylphosphatidylinositols (GPIs) are added to GPI proteins of Saccharomyces cerevisiae, the fatty acid in sn-2 of the diacylglycerol moiety can be replaced by a C26:0 fatty acid by a deacylation–reacylation cycle catalysed by Per1p and Gup1p. Furthermore the diacylglycerol moiety of the yeast GPI anchor can also be replaced by ceramides. CWH43 of yeast is homologous to PGAP2, a gene that recently was implicated in a similar deacylation reacylation cycle of GPI proteins in mammalian cells, where PGAP2 is required for the reacylation of monoradylglycerol-type GPI anchors. Here we show that mutants lacking CWH43 are unable to synthesize ceramide-containing GPI anchors, while the replacement of C18 by C26 fatty acids on the primary diacylglycerol anchor by Per1p and Gup1p is still intact. CWH43 contains the COG3568 metal hydrolase motif, which is found in many eukaryotic and prokaryotic enzymes. The conserved His 802 residue of this motif was identified as being essential for ceramide remodelling. Ceramide remodelling is not required for the normal integration of GPI proteins into the cell wall. All remodelling reactions are dependent on prior removal of the inositol-linked fatty acid by Bst1p

Impact of long-range correlations on trend detection in total ozone

Total ozone trends are typically studied using linear regression models that assume a first-order autoregression of the residuals [so-called AR(1) models]. We consider total ozone time series over 60°S–60°N from 1979 to 2005 and show that most latitude bands exhibit long-range correlated (LRC) behavior, meaning that ozone autocorrelation functions decay by a power law rather than exponentially as in AR(1). At such latitudes the uncertainties of total ozone trends are greater than those obtained from AR(1) models and the expected time required to detect ozone recovery correspondingly longer. We find no evidence of LRC behavior in southern middle-and high-subpolar latitudes (45°–60°S), where the long-term ozone decline attributable to anthropogenic chlorine is the greatest. We thus confirm an earlier prediction based on an AR(1) analysis that this region (especially the highest latitudes, and especially the South Atlantic) is the optimal location for the detection of ozone recovery, with a statistically significant ozone increase attributable to chlorine likely to be detectable by the end of the next decade. In northern middle and high latitudes, on the other hand, there is clear evidence of LRC behavior. This increases the uncertainties on the long-term trend attributable to anthropogenic chlorine by about a factor of 1.5 and lengthens the expected time to detect ozone recovery by a similar amount (from ∼2030 to ∼2045). If the long-term changes in ozone are instead fit by a piecewise-linear trend rather than by stratospheric chlorine loading, then the strong decrease of northern middle- and high-latitude ozone during the first half of the 1990s and its subsequent increase in the second half of the 1990s projects more strongly on the trend and makes a smaller contribution to the noise. This both increases the trend and weakens the LRC behavior at these latitudes, to the extent that ozone recovery (according to this model, and in the sense of a statistically significant ozone increase) is already on the verge of being detected. The implications of this rather controversial interpretation are discussed

Corrigendum to "Trends in stratospheric ozone profiles using functional mixed models" published in Atmos. Chem. Phys., 13, 11473&ndash;11501, 2013

No abstract available

Trends in stratospheric ozone profiles using functional mixed models

This paper is devoted to the modeling of altitude-dependent patterns of ozone variations over time. Umkehr ozone profiles (quarter of Umkehr layer) from 1978 to 2011 are investigated at two locations: Boulder (USA) and Arosa (Switzerland). The study consists of two statistical stages. First we approximate ozone profiles employing an appropriate basis. To capture primary modes of ozone variations without losing essential information, a functional principal component analysis is performed. It penalizes roughness of the function and smooths excessive variations in the shape of the ozone profiles. As a result, data-driven basis functions (empirical basis functions) are obtained. The coefficients (principal component scores) corresponding to the empirical basis functions represent dominant temporal evolution in the shape of ozone profiles. We use those time series coefficients in the second statistical step to reveal the important sources of the patterns and variations in the profiles. We estimate the effects of covariates – month, year (trend), quasi-biennial oscillation, the solar cycle, the Arctic oscillation, the El Niño/Southern Oscillation cycle and the Eliassen–Palm flux – on the principal component scores of ozone profiles using additive mixed effects models. The effects are represented as smooth functions and the smooth functions are estimated by penalized regression splines. We also impose a heteroscedastic error structure that reflects the observed seasonality in the errors. The more complex error structure enables us to provide more accurate estimates of influences and trends, together with enhanced uncertainty quantification. Also, we are able to capture fine variations in the time evolution of the profiles, such as the semi-annual oscillation. We conclude by showing the trends by altitude over Boulder and Arosa, as well as for total column ozone. There are great variations in the trends across altitudes, which highlights the benefits of modeling ozone profiles

Corrigendum to "Trends in stratospheric ozone profiles using functional mixed models" published in Atmos. Chem. Phys., 13, 11473&ndash;11501, 2013

No abstract available

Expression of the bacterial type III effector DspA/E in Saccharomyces cerevisiae downregulates the sphingolipid biosynthetic pathway leading to growth-arrest

Erwinia amylovora, the bacterium responsible for fire blight, relies on a type III secretion system and a single injected effector, DspA/E, to induce disease in host plants. DspA/E belongs to the widespread AvrE family of type III effectors which suppress plant defense responses and promote bacterial growth followinginfection. Ectopic expression of DspA/E in plant or in Saccharomyces cerevisiae is toxic indicating that DspA/E likely targets a cellular process conserved between yeast and plant. To unravel the mode of action of DspA/E, we screened the Euroscarf, S. cerevisiae library for mutants resistant toDspA/E-induced growth arrest. The most resistant mutants (Δsur4, Δfen1, Δipt1,Δskn1, Δcsg1, Δcsg2, Δorm1, Δorm2) were impaired in the sphingolipid biosynthetic pathway. Exogenously supplied sphingolipid precursors such as the long chain bases(LCBs) phytosphingosine and dihydrosphingosine also suppressed DspA/E-induced yeast growth defect. Expression of DspA/E in yeast downregulated LCBs biosynthesis and induced a rapid decrease in LCB levels,indicating that SPT, the first and rate limiting enzyme of the sphingolipid biosynthetic pathway was repressed. SPT downregulation was mediated by dephosphorylation and activation of Orm proteins that negatively regulate SPT. A Δcdc55 mutation, affecting Cdc55-PP2A protein phosphatase activity, prevented Orm dephosphorylation and suppressed DspA/E-induced growth arrest

The VOLNA-OP2 tsunami code (version 1.5)

In this paper, we present the VOLNA-OP2 tsunami model and implementation; a finite volume non-linear shallow water equations (NSWE) solver built on the OP2 domain specific language (DSL) for unstructured mesh computations. VOLNA-OP2 is unique among tsunami solvers in its support for several high performance computing platforms: CPUs, the Intel Xeon Phi, and GPUs. This is achieved in a way that the scientific code is kept separate from various parallel implementations, enabling easy maintainability. It has already been used in production for several years, here we discuss how it can be integrated into various workflows, such as a statistical emulator. The scalability of the code is demonstrated on three supercomputers, built with classical Xeon CPUs, the Intel Xeon Phi, and NVIDIA P100 GPUs. VOLNA-OP2 shows an ability to deliver productivity to its users, as well as performance and portability across a number of platforms