Evaluation of RapidScat Ocean Vector Winds for Data Assimilation and Reanalysis.

The RapidScat scatterometer was built as a low cost follow-on to the QuikSCAT mission. It flew on the International Space Station (ISS) and provided data from 3 October 2014 to 20 August 2016 and provided surface wind vectors retrieved from surface roughness estimates taken at multiple azimuth angles. These measurements were unique to the historical scatterometer record in that the ISS flies in a low inclination, non-sun-synchronous orbit. Scatterometry-derived wind vectors have been routinely assimilated in both forward processing and reanalysis systems run at the Global Modeling and Assimilation Office (GMAO). As the RapidScat retrievals were made available in near-real-time, they were assimilated in the forward processing system, and the methods to assimilate and evaluate these retrievals are described. Time series of data statistics are presented first for the near-real-time data assimilated in GMAO forward processing. Second, the full data products provided by the RapidScat team are compared passively to the MERRA-2 reanalysis. Both sets of results show that the root mean squared (RMS) difference of the observations and the GMAO model background fields increased over the course of the data record. Furthermore, the observations and the backgrounds are shown to be biased for both the zonal and meridional wind components. The retrievals are shown to have had a net forecast error reduction via the forecast sensitivity observation impact (FSOI) metric, which is a quantification of 24 hour forecast error reduction, though the impact became neutral as the signal to noise ratio of the instrument decreased over its lifespan.

Galphaq binds to p110alpha/p85alpha phosphoinositide 3-kinase and displaces Ras.

Several studies have reported that activation of G(q)-coupled receptors inhibits PI3K (phosphoinositide 3-kinase) signalling. In the present study, we used purified proteins to demonstrate that Galpha(q) directly inhibits p110alpha/p85alpha PI3K in a GTP-dependent manner. Activated Galpha(q) binds to the p110alpha/p85alpha PI3K with an apparent affinity that is seven times stronger than that for Galpha(q).GDP as measured by fluorescence spectroscopy. In contrast, Galpha(q) did not bind to the p110gamma PI3K. Fluorescence spectroscopy experiments also showed that Galpha(q) competes with Ras, a PI3K activator, for binding to p110alpha/p85alpha. Interestingly, co-precipitation studies using deletion mutants showed that Galpha(q) binds to the p85-binding domain of p110alpha and not to the Ras-binding domain. Expression of constitutively active Galpha(q)Q209L in cells inhibited Ras activation of the PI3K/Akt pathway but had no effect on Ras/Raf/MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] signalling. These results suggest that activation of G(q)-coupled receptors leads to increased binding of Galpha(q).GTP to some isoforms of PI3K, which might explain why these receptors inhibit this signalling pathway in certain cell types.

Ablation of PI3K p110-α prevents high-fat diet-induced liver steatosis.

OBJECTIVE: To determine whether the phosphoinositide 3-kinase (PI3K) catalytic subunits p110-α and p110-ß play a role in liver steatosis induced by a high-fat diet (HFD). RESEARCH DESIGN AND METHODS: Liver-specific p110-α and p110-ß knockout mice and control animals for each group were fed an HFD or normal chow for 8 weeks. Biochemical assays and quantitative real-time PCR were used to measure triglyceride, expression of lipogenic and gluconeogenic genes, and activity of protein kinases downstream of PI3K in liver lysates. Fatty acid uptake and incorporation into triglycerides were assessed in isolated hepatocytes. RESULTS: Hepatic triglyceride levels in HFD-fed p110-α(-/-) mice were 84 ± 3% lower than in p110-α(+/+) mice, whereas the loss of p110-ß did not significantly alter liver lipid accumulation. p110-α(-/-) livers also showed a reduction in atypical protein kinase C activity and decreased mRNA and protein expression of several lipogenic genes. Hepatocytes isolated from p110-α(-/-) mice exhibited decreased palmitate uptake and reduced fatty acid incorporation into triglycerides as compared with p110-α(+/+) cells, and hepatic expression of liver fatty acid binding protein was lower in p110-α(-/-) mice fed the HFD as compared with controls. Ablation of neither p110-α nor p110-ß ameliorated glucose intolerance induced by the HFD, and genes involved in gluconeogenesis were upregulated in the liver of both knockout animals. CONCLUSIONS: PI3K p110-α, and not p110-ß, promotes liver steatosis in mice fed an HFD. p110-α might exert this effect in part through activation of atypical protein kinase C, upregulation of lipogenesis, and increased uptake of fatty acids.

The class IA phosphatidylinositol 3-kinase p110-beta subunit is a positive regulator of autophagy.

Autophagy is an evolutionarily conserved cell renewal process that depends on phosphatidylinositol 3-phosphate (PtdIns(3)P). In metazoans, autophagy is inhibited by PtdIns(3,4,5)P(3), the product of class IA PI3Ks, which mediates the activation of the Akt-TOR kinase cascade. However, the precise function of class IA PI3Ks in autophagy remains undetermined. Class IA PI3Ks are heterodimeric proteins consisting of an 85-kD regulatory subunit and a 110-kD catalytic subunit. Here we show that the class IA p110-ß catalytic subunit is a positive regulator of autophagy. Genetic deletion of p110-ß results in impaired autophagy in mouse embryonic fibroblasts, liver, and heart. p110-ß does not promote autophagy by affecting the Akt-TOR pathway. Rather, it associates with the autophagy-promoting Vps34-Vps15-Beclin 1-Atg14L complex and facilitates the generation of cellular PtdIns(3)P. Our results unveil a previously unknown function for p110-ß as a positive regulator of autophagy in multicellular organisms.