River delta morphology: wave climate and the role of the subaqueous proffile

Application of a comprehensive wave climate program to seven major deltas indicates that deltaic configurations and coastal landform combinations depend to a considerable degree on the wave power adjacent to the shore and on the river discharge relative to wave forces. Nearshore wave power is not correlative with deepwater wave power but, owing to frictional attenuation, is a function of the subaqueous slope. The subaqueous slope, in turn, depends partially on the slope and width of the continental shelf but primarily on the rate at which the river can supply sediments to the nearshore zone. River-dominated configurations result only when the river is able to build flat offshore profiles, which reduce nearshore wave power; where the subaqueous slope is steep, waves reach the shore comparatively undiminished and wave-built forms prevail.     

Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix

BCL-2 family proteins constitute a critical control point for the regulation of apoptosis. Protein interaction between BCL-2 members is a prominent mechanism of control and is mediated through the amphipathic alpha-helical BH3 segment, an essential death domain. We used a chemical strategy, termed hydrocarbon stapling, to generate BH3 peptides with improved pharmacologic properties. The stapled peptides, called "stabilized alpha-helix of BCL-2 domains" (SAHBs), proved to be helical, protease-resistant, and cell-permeable molecules that bound with increased affinity to multidomain BCL-2 member pockets. A SAHB of the BH3 domain from the BID protein specifically activated the apoptotic pathway to kill leukemia cells. In addition, SAHB effectively inhibited the growth of human leukemia xenografts in vivo. Hydrocarbon stapling of native peptides may provide a useful strategy for experimental and therapeutic modulation of protein-protein interactions in many signaling pathways.     

Structural characterization of a partly folded apomyoglobin intermediate

To understand why proteins adopt particular three-dimensional structures, it is important to elucidate the hierarchy of interactions that stabilize the native state. Proteins in partly folded states can be used to dissect protein organizational hierarchies. A partly folded apomyoglobin intermediate has now been characterized structurally by trapping slowly exchanging peptide NH protons and analyzing them by two-dimensional 1H-NMR (nuclear magnetic resonance). Protons in the A, G, and H helix regions are protected from exchange, while protons in the B and E helix regions exchange freely. On the basis of these results and the three-dimensional structure of native myoglobin, a structural model is presented for the partly folded intermediate in which a compact subdomain retains structure while the remainder of the protein is essentially unfolded.