Epigenetic silencers and Notch collaborate to promote malignant tumours by Rb silencing

Cancer is both a genetic and an epigenetic disease. Inactivation of tumour-suppressor genes by epigenetic changes is frequently observed in human cancers, particularly as a result of the modifications of histones and DNA methylation. It is therefore important to understand how these damaging changes might come about. By studying tumorigenesis in the Drosophila eye, here we identify two Polycomb group epigenetic silencers, Pipsqueak and Lola, that participate in this process. When coupled with overexpression of Delta, deregulation of the expression of Pipsqueak and Lola induces the formation of metastatic tumours. This phenotype depends on the histone-modifying enzymes Rpd3 (a histone deacetylase), Su(var)3-9 and E(z), as well as on the chromodomain protein Polycomb. Expression of the gene Retinoblastoma-family protein (Rbf) is downregulated in these tumours and, indeed, this downregulation is associated with DNA hypermethylation. Together, these results establish a mechanism that links the Notch-Delta pathway, epigenetic silencing pathways and cell-cycle control in the process of tumorigenesis.     

Occurrence and extracellular actions of inositol pentakis- and hexakisphosphate in mammalian brain

Although inositol 1,3,4,5,6-pentakisphosphate (InsP5) and hexakisphosphate (InsP6) have been recognized for some time as naturally-occurring metabolites of inositol, their occurrence in mammalian cell types, including one of neural origin, has only recently been documented. This is of interest because of the recognized second messenger role of inositol 1,4,5-trisphosphate (InsP3) in intracellular signalling; coupling surface stimuli to cytoplasmic calcium discharge. The metabolism, existence in normal mature tissues, and possible functional roles of these inositol polyphosphates are unknown. Here we report evidence that InsP5 and InsP6 are synthesized in intact brain after labelling with [3H]inositol in vivo. We also show that local infusion of InsP5 and InsP6 into a discrete brain stem nucleus implicated in cardiovascular regulation, results in dose-dependent changes in heart rate and blood pressure.     

Modified Dye for Water-Fast Ink-Jet Printing

A quaternary ammonium compound containing amino acid residue was synthesized by Converting 3-chloro-2-hydroxy-propyalkyldimethylammonium chlorides into its epoxide derivatives, then attaching an amino acid to the epoxide derivatives synthesized a quaternary ammonium compound containing amino acid residue. Modified dyes were prepared by the ionotropy of anionic dyes with the quaternary ammonium compound containing amino acid residue. It was discovered that the modified dyes exhibited an excellent pH controllable solubility. These modified dyes have good water solubility at pH> 8.0, but they were water insoluble at pH < 6.5. On the printing paper, modified dyes in water-based ink-jet print ink could convert to water insoluble form and give prints excellent water fastness.