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Small-molecule suppression of zebrafish mutants. Using a chemical genetic screen, Stern et al. (p 366) identified persynthamide, a compound that suppresses the crash&burn (crb) mutation in zebrafish by inhibiting S phase of the cell cycle (see also News & Views by Sidi & Look, p 351). The image shows zebrafish embryos immunostained with an antibody specific for phosphorylation of Ser10 of histone H3, a marker of mitotic cells. Cover art by Erin Boyle, based on images provided by Christian Straub.
The zebrafish has become a popular model organism to investigate many biological processes, in part owing to the combination of facile genetic manipulation and rapid, external embryonic development. The application of large-scale screening to identify chemical suppressors of a cancer-prone mutant highlights new technology for whole organism–based small-molecule discovery.
Development of small-molecule agonists against members of the tumor necrosis factor (TNF) receptor superfamily remains a considerable challenge. Presentation of ligand-derived peptides on a trimeric scaffold may point the way toward development of potent small-molecule agonists against this biologically important protein superfamily.
Sir2 is a key regulator in promoting longevity in response to a low-calorie diet. A new role for nitric oxide in promoting mitochondrial synthesis may be the reason why.
Identification of the monocarboxylate transporter 1 as a target of a new class of immunosuppressants shows that aerobic glycolysis and lactate release are essential for the proliferation of activated lymphocytes.