Sphingomyelin synthase-related protein (SMSr) synthesizes the sphingomyelin analog ceramide phosphoethanolamine (CPE) in cells. Previous cell studies indicated that SMSr is involved in ceramide homeostasis and is crucial for cell function. To further examine SMSr function in vivo, we generated Smsr KO mice that were fertile and had no obvious phenotypic alterations. Quantitative MS analyses of plasma, liver, and macrophages from the KO mice revealed only marginal changes in CPE and ceramide as well as other sphingolipid levels. Because SMS2 also has CPE synthase activity, we prepared Smsr/Sms2 double KO mice. We found that CPE levels were not significantly changed in macrophages, suggesting that CPE levels are not exclusively dependent on SMSr and SMS2 activities. We then measured CPE levels in Sms1 KO mice and found that Sms1 deficiency also reduced plasma CPE levels. Importantly, we found that expression of Sms1 or Sms2 in SF9 insect cells significantly increased not only SM but also CPE formation, indicating that SMS1 also has CPE synthase activity. Moreover, we measured CPE synthase Km and Vmax for SMS1, SMS2, and SMSr using different NBD ceramides. Our study reveals that all mouse SMS family members (SMSr, SMS1, and SMS2) have CPE synthase activity. However, neither CPE nor SMSr appears to be a critical regulator of ceramide levels in vivo.

Sphingolipid

Ceramide synthase

10.1194/jlr.m054627

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Modeling the Volatility of Rubber Futures by Exchange Rate and Climate Change

Jiajie Guo Weichen Sang Jibin Dong

Natural rubber is a plant of economic importance of Thailand, which has been the world's biggest producer and exporter since 1991. In 2014, Thailand covers the cultivation area of natural rubber of 3.6 million hectares, of which tapping area is 2.78 million hectares. In this paper, we applied the Gaussian copula, T copula, Clayton copula, Frank copula, Gumbel copula, Joe copula, BB1 copula, BB6 copula, BB7 copula, BB8 copula and rotate copulas to determine the relationship between the volatility of Thai rubber futures return, exchange rate of Thai baht and climatic factors. Based on these results, climatic factors and fluctuations in the exchange rate market have significant effects on Thai rubber futures returns. With regards the analysis methods, no single method can provide a complete picture of the dependencies and interrelatedness of the various asset markets. We hope that the results of this study can be used by investor of Thai rubber futures, as well as other key stakeholders in the rubber futures.

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Identification of small molecule sphingomyelin synthase inhibitors

European Journal of Medicinal Chemistry (2013)

Xiaodong Deng Lin Fu Ya Zhang Yan Li Lu Zhou

Sphingolipid

Structure–activity relationship

10.1016/j.ejmech.2013.12.002

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Discovery of N-hydroxy-3-alkoxybenzamides as direct acid sphingomyelinase inhibitors using a ligand-based pharmacophore model