Staurosporine induces necroptotic cell death under caspase-compromised conditions in U937 cells

For a long time necrosis was thought to be an uncontrolled process but evidences recently have revealed that necrosis can also occur in a regulated manner. Necroptosis, a type of programmed necrosis is defined as a death receptor-initiated process under caspase-compromised conditions. The process requires the kinase activity of receptor-interacting protein kinase 1 and 3 (RIPK1 and RIPK3) and mixed lineage kinase domain-like protein (MLKL), as a substrate of RIPK3. The further downstream events remain elusive. We applied known inhibitors to characterize the contributing enzymes in necroptosis and their effect on cell viability and different cellular functions were detected mainly by flow cytometry. Here we report that staurosporine, the classical inducer of intrinsic apoptotic pathway can induce necroptosis under caspase-compromised conditions in U937 cell line. This process could be hampered at least partially by the RIPK1 inhibitor necrotstin-1 and by the heat shock protein 90 kDa inhibitor geldanamycin. Moreover both the staurosporine-triggered and the classical death ligand-induced necroptotic pathway can be effectively arrested by a lysosomal enzyme inhibitor CA-074-OMe and the recently discovered MLKL inhibitor necrosulfonamide. We also confirmed that the enzymatic role of poly(ADP-ribose)polymerase (PARP) is dispensable in necroptosis but it contributes to membrane disruption in secondary necrosis. In conclusion, we identified a novel way of necroptosis induction that can facilitate our understanding of the molecular mechanisms of necroptosis. Our results shed light on alternative application of staurosporine, as a possible anticancer therapeutic agent. Furthermore, we showed that the CA-074-OMe has a target in the signaling pathway leading to necroptosis. Finally, we could differentiate necroptotic and secondary necrotic processes based on participation of PARP enzyme

Ichneumoniden aus Franken (Hymenoptera: Ichneumonidae).

Insgesamt habe ich 915 Arten in der näheren Umgebung von Nürnberg-Erlangen gefangen; einige Arten wurden nur in der Umgebung von Ebensfeld und Prächting in Oberfanken 1954, wo ich einige Monate fing, erbeutet.The author reports 915 species of Ichneumonidae from the environment of Nürnberg-Erlangen with a German summary containing additional notes on distribution and biology of these species

An Innovative Integration Methodology of Independent Data Sources to Improve the Quality of Freight Transport Surveys

AbstractPast experiences show that data of the official Austrian freight transport statistics are often underestimated. Therefore, a methodology was developed, merging existing independent road freight transport data to a consistent and valid road freight matrix. The methodology comprises four steps, using data of the Austrian and European freight transport statistics, data of roadside interviews of truck drivers, and data of counting stations and toll gantries. The methodology was applied to data from the year 2009. Results show the reliability and plausibility of the methodology, indicated by a high correlation with high quality roadside traffic counts

E-Notopterol

The title compound (systematic name: 4-{[(2E)-5-hydr­oxy-3,7-dimethylocta-2,6-dien-1-yl]­oxy}-7H-furo[3,2-g][1]benzopyran-7-one), C21H22O5, is a known furan­ocoumarin, which was isolated from the Chinese herbal product Radix seu Rhizoma Notopterygii. The crystal structure shows a weak O—H⋯O hydrogen bond