HHMI researcher Vivian Cheung led a study that looked at gene expression differences among people in response to exposure to radiation. In performing genetic linkage and association studies to map regulators of different gene expression phenotypes, the researchers found that for more than 1,200 of these, there was linkage to a specific chromosome region and that nearly all of the regulators are trans-acting. Their work was published in early online.
Nature focuses on cancer this week, with several notable studies. In one, Millennium Pharmaceuticals scientists used cell-based assays to find that MLN4924 inhibits the "never-before-targeted" NEDD8-activating enzyme (NAE), and in vivo, it suppresses the growth of human lung tumor tissue transplanted into mice. "This impressive performance has fanned interest in the potential of drugs that target substrate-specific factors of the UPS, such as the E3 enzymes. But ... instead of targeting E3 enzymes directly, it might be possible to inhibit other enzymes that activate them," says a related Perspective. Over at the Whitehead Institute, colleagues Nada Kalaany and David Sabatini show that dietary-restriction-resistant tumors have mutations that cause continuous activation of the phosphatidylinositol-3-kinase (PI3K) pathway and in vitro proliferate in the absence of insulin or insulin-like growth factor 1. "So it seems that, to exert its anticancer benefits, limited dietary intake must reduce insulin-mediated signalling," says a related story. Finally, a review examines how sequencing will help shape the future of etiological studies of cancer.
Two papers present new techniques to reprogram human and mouse skin cells into iPS cells without using viral vectors to express the reprogramming genes. One used the piggyBac transposon to generate stable iPS cells, after which the individual piggyBac insertions can then be removed. Another used a single-vector system in which a transgene of c-Myc, Klf4, Oct4 and Sox2 linked with 2A peptides was inserted into cells and then removed once they had been reprogrammed.
In Nature Methods, scientists at Georgia Tech have developed fluorescent probes that can detect single RNA molecules at low probe concentration. They created their multiply labeled tetravalent RNA imaging probes (MTRIPs) by attaching fluorophores to a modified nucleic acid and combining the sequences with a protein, enabling them to bind to a target RNA molecule with very high sensitivity.