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Chemical regulation of angiogenesis in adult zebrafish. Bayliss (p 265) developed a regenerative angiogenesis assay in the tail fin of adult zebrafish (Danio rerio). In the assay, a kinase inhibitor (PTK787) blocked angiogenesis in adult caudal fins. Vascular endothelial growth factor receptor (VEGFR) signaling was required for blood vessel regeneration, but bone and tissue growth were unaffected by this chemical inhibitor. The study offers a way to discover genes and biochemical mechanisms involved in angiogenesis and a method for the identification and evaluation of anti-angiogenic compounds (see also News and Views by De Smet, Carmeliet and Autiero, p 228). Cover art by Erin Boyle, based on an image of a zebrafish tail fin that has undergone regeneration, provided by Heather Robbins.
Eukaryotic cells are specialized, interdependent functional units of complex tissues that are composed of metabolically integrated systems defined by chemically distinct organelles that operate as reaction vessels. It is now clear that the small-molecule and polymer-based composition of these organelles plays a crucial role in generating and maintaining protein folds and functions through the systems chemistry of the local environments.
There is a growing medical need for additional anti-angiogenic drugs. A new model of regenerative angiogenesis in the fin of adult zebrafish promises to accelerate discovery of genes and drugs related to angiogenesis.
Small-molecule probes that chemically tag targets by virtue of their enzymatic activities offer a means to focus system-wide experiments and provide functional information for entire families of proteins. Recent advances in the design and application of light-activated probes that target metalloproteases have created the opportunity to study this medically important family of enzymes in unprecedented detail.
Translation starts with the assembly of the ribosome from its subunits, which requires the formation of intersubunit bridges. A combinatorial mutagenesis approach has now identified a number of the 16S rRNA residues involved in intersubunit bridging that are functionally important for the ribosome.
The crystal structures of two chain-building megasynthases, the fatty acid synthases of mammals and fungi, have recently been reported. Although both are composed of modules derived from the discrete enzymes that catalyze bacterial fatty acid synthesis, the two synthases have dramatically different architectures.
Oxidation of cysteine residues is a well-described means of sensing oxidative stress. Analysis of a bacterial transcriptional repressor protein indicates that metal-catalyzed oxidation of histidine residues can provide oxidative stress control in a cysteine-independent fashion.