Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles

We have identified an unusual potential dual Akt/protein kinase B consensus phosphorylation motif in the protein Synip (RxKxRS97xS99). Surprisingly, serine 97 is not appreciably phosphorylated, whereas serine 99 is only a specific substrate for Akt2 but not Akt1 or Akt3. Although wild-type Synip (WT-Synip) undergoes an insulin-stimulated dissociation from Syntaxin4, the Synip serine 99 to phenylalanine mutant (S99F-Synip) is resistant to Akt2 phosphorylation and fails to display insulin-stimulated Syntaxin4 dissociation. Furthermore, overexpression of WT-Synip in 3T3L1 adipocytes had no effect on insulin-stimulated recruitment of glucose transporter 4 (GLUT4) to the plasma membrane, whereas overexpression of S99F-Synip functioned in a dominant-interfering manner by preventing insulin-stimulated GLUT4 recruitment and plasma membrane fusion. These data demonstrate that insulin activation of Akt2 specifically regulates the docking/fusion step of GLUT4-containing vesicles at the plasma membrane through the regulation of Synip phosphorylation and Synip–Syntaxin4 interaction

Curcumin analog, GO-Y078, overcomes resistance to tumor angiogenesis inhibitors

Tumor angiogenesis inhibition is one of the most potent strategies in cancer chemotherapy. From past clinical studies, inhibition of the vascular endothelial growth factor pathway successfully treats malignant tumors. However, vascular endothelial growth factor inhibitors alone cannot cure tumors. Moreover, resistance to small molecule inhibitors has also been reported. Herein, we show the antiangiogenic potential of a newly synthesized curcumin analog, GO-Y078, that possibly functions through inhibition of actin stress fiber formation, resulting in mobility inhibition; this mechanism is different from that of vascular endothelial growth factor inhibition. In addition, we examined the detailed mechanism of action of the antiangiogenesis potential of GO-Y078 using human umbilical venous epithelial cells resistant to angiogenesis inhibitors (HUVEC-R). GO-Y078 inhibited the growth and mobility of HUVEC-R at 0.75mol/L concentration. Expression analyses by microarray and RT-PCR showed that expressions of genes including that of fibronectin 1 were significantly suppressed. Among these genes, fibronectin 1 is abundantly expressed and, therefore, seems to be a good target for GO-Y078. In a knockdown experiment using Si-oligo of fibronectin 1 (FN1), FN1 expression was decreased to half of that in mock experiments as well as GO-Y078. Knockdown of FN1 resulted in the suppression of HUVEC-R growth at 24hours after treatment. Fibronectin is a key molecule contributing to angiogenesis that could be inhibited by GO-Y078. Thus, resistance to vascular endothelial growth factor inhibition can be overcome using GO-Y078

Chemical Phase Separation of Superconductive and Ferromagnetic Domains in ZnNNi

Various ZnNyNi3−xCox compounds with differing Co content, x, were synthesized, and their magnetic properties were investigated. Uniform solid solutions could not be obtained at low Co content (x2) the uniform ferromagnetic solid solution ZnNyNi3−xCox (with most likely y=0.5) formed. The phase separation behavior is intrinsic to the system, reflecting the existence of a miscibility gap in ZnNyNi3−xCox for the samples with x<2, and was shown not to be attributable to incomplete synthesis. In the two-phased samples, high-quality granular contact between the superconductor and ferromagnet has been realized, suggesting that the production of useful devices requiring high-quality contacts between superconductors and ferromagnets may be possible by making use of this two-phase situation

The First Observation of Metallic Behaviour in Nd3.5Sm0.5Ni3O8

In Nd3.5Sm0.5Ni3O8 which has basically the same crystal structure and the similar electrical configuration (Ni+ 3d9/Ni2+ 3d8 mix valence state) with high-Tc cuprate, it has been found that this material shows metallic behaviour down to about 20 K by intercalation and subsequent deintercalation with sulfur. This is the first observation of the metallic state in this system. It is unclear why sulfur-intercalation and deintercalation induce the metallic state. We speculate that sulfur works as an effective getter for removing the interstitial apical oxygen which impedes the metallic conduction. However, the weak localization of carriers in the NiO2 planes still remains below 20 K and the localization may be one of the obstacles to occurrence of possible superconductivity

Magnetic and transport properties of single crystalline RCoxSn2 (R = Ce and La)

In this study, single crystals of CeCo0.39Sn2 and LaCo0.43Sn2 were grown by the Czochralski pulling method for the first time. These compounds crystallize to the orthorhombic CeNiSi2 type structure with the space group Cmcm. The inverse magnetic susceptibility χ−1 of CeCo0.39Sn2 obeys a Curie-Weiss law above 100 K. The effective magnetic moment is close to the value expected for the Ce3+ ion, indicating that the Ce 4f electrons in CeCo0.39Sn2 are well localized. No magnetic transition is observed down to 2 K. However, the specific heat exhibits an upturn upon cooling below 8 K, suggesting that a magnetic order would occur below 2 K