Hyperstable U1snRNA complementary to the K-ras transcripts induces cell death in pancreatic cancer cells

One of the critical steps that governs the inhibitory effect of antisense RNA on target gene expression is the association of the antisense RNA with the target RNA molecules. However, until now, no systematic method has been available to select the suitable parts of a gene as antisense targets. In this study, we utilised U1 small nuclear RNA (snRNA) that binds physiologically to the 5′ splice site (5′ss) of pre-mRNA, to develop a novel vector system that permits imposed binding of antisense RNA to its target. The 5′ free end of U1snRNA was replaced with the antisense sequence against the K-ras gene to generate a hyperstable U1snRNA, whose binding stability to 5′ss of the K-ras transcript is ten-fold higher than that of wild-type U1snRNA. The efficacy of such hyperstable U1snRNA was examined by transducing the expression plasmids into human pancreatic cancer cell lines. This revealed that two of the hyperstable U1snRNAs induced cell death after gene transduction, and significantly reduced the number of G418-resistant colonies to less than 10% of the controls. Furthermore, hyperstable U1snRNA suppressed intraperitoneal dissemination of pancreatic cancer cells in vivo. Hyperstable U1snRNA might be a novel approach to express effective antisense RNA in target cells

Threshold onset of Marangoni convection in narrow channels

There are several experimental studies where the Marangoni convection begins only at a certain difference in the surface tension, i.e. in a threshold way. This effect contradicts a traditional point of view according to which the surface flow in Newtonian fluids should begin at an arbitrary small difference in surface tension. To explore this phenomenon in detail we investigated the initiation of the Marangoni convection at a free liquid surface caused by injection of a droplet of surfactant. It was found that the surface motion occurs in a threshold manner, i.e. when a surfactant concentration in the droplet approaches a certain critical value. The described phenomenon is more important in narrow channels and essentially depends both on the purity of the basic liquid and on the surfactant used. Based on the experimental results, a hypothesis about an important role of residual impurities contained in basic liquids which can thoroughly change a surface rheology was suggested. The theoretical model taking into account special rheological properties in the free surface is considered. The results of the numerical simulation are in a good agreement with the experimental observations