The novel Cer-like protein Caronte mediates the establishment of embryonic left-right asymmetry.

In the chick embryo, left-right asymmetric patterns of gene expression in the lateral plate mesoderm are initiated by signals located in and around Hensen's node. Here we show that Caronte (Car), a secreted protein encoded by a member of the Cerberus/Dan gene family, mediates the Sonic hedgehog (Shh)-dependent induction of left-specific genes in the lateral plate mesoderm. Car is induced by Shh and repressed by fibroblast growth factor-8 (FGF-8). Car activates the expression of Nodal by antagonizing a repressive activity of bone morphogenic proteins (BMPs). Our results define a complex network of antagonistic molecular interactions between Activin, FGF-8, Lefty-1, Nodal, BMPs and Car that cooperate to control left-right asymmetry in the chick embryo.     

Determination of surface topography of biological specimens at high resolution by scanning tunnelling microscopy

Although techniques are available for the determination of the three-dimensional structure of biological specimens, for example scanning electron microscopy, they all have some serious drawback, such as low resolution, the requirement for crystals or for the sample to be analysed in a high vacuum. In an attempt to develop a technique for high-resolution three-dimensional structure analysis of non-crystalline biological material, we have tested the applicability of scanning tunnelling microscopy (STM), a method that has been used successfully in the analysis of metal and semiconductor surface structures. We report here that scanning tunnelling electron microscopy can be used to determine the surface topography of biological specimens at atmospheric pressure and room temperature, giving a vertical resolution of the order of 1 A. Our results show that quantum mechanical tunnelling of electrons through biological material is possible provided that the specimen is deposited on a conducting surface.     

Unesco

Ohne Zusammenfassung     

Cell-permeable dual inhibitors of protein kinases CK2 and PIM-1: structural features and pharmacological potential

It has been proposed that dual inhibitors of protein kinases CK2 and PIM-1 are tools particularly valuable to induce apoptosis of cancer cells, a property, however, implying cell permeability, which is lacking in the case of selective CK2/PIM-1 inhibitors developed so far. To fill this gap, we have derivatized the scaffold of the promiscuous CK2 inhibitor TBI with a deoxyribose moiety, generating TDB, a selective, cell-permeable inhibitor of CK2 and PIM-1. Here, we shed light on the structural features underlying the potency and narrow selectivity of TDB by exploiting a number of TDB analogs and by solving the 3D structure of the TDB/CK2 complex at 1.25?Å resolution, one of the highest reported so far for this kinase. We also show that the cytotoxic efficacy of TDB is almost entirely due to apoptosis, is accompanied by parallel inhibition of cellular CK2 and PIM-1, and is superior to both those observed combining individual inhibitors of CK2 and PIM-1 and by treating cells with the CK2 inhibitor CX4945. These data, in conjunction with the observations that cancer cells are more susceptible than non-cancer cells to TDB and that such a sensitivity is maintained in a multi-drug resistance background, highlight the pharmacological potential of this compound.