Immune to weight loss

Mixed-up DNA I nterphase human chromosomes show signifi cant intermingling, say Miguel Branco and Ana Pombo (MRC Clinical Sciences Centre, London, UK). The idea is a counter to the most extreme view of chromosome territories. Territories were so named based on microscopists’ early observations: that individual chromosomes did not spread out over an entire nucleus. DNA labeling also indicated that nuclei had gaps between DNA, although it was not clear if these were between DNA of the same or different chromosomes. Still, this was enough to spark talk of an interchromatin domain separating territories. “In this model, it will always be right because two pieces of chromosome will never be in exactly the same place,” says Pombo. “The fi eld couldn’t move forward.” She and Branco responded by labeling two different chromosomes in ultrathin slices and following up with EM for even higher resolution. Based on extrapolation, an average of 46% of each chromosome territory intermingles with other chromosomes. Furthermore, extents of intermingling for different chromosomes correlated with translocation frequencies. The nucleus is not a complete tangled mess, however. “Chromosomes as polymers will tend to expand,” says Pombo. “But what stops them is interaction with each other and with the nuclear membrane.” She is now seeing if transcription factories help keep particular chromosomes fi xed to themselves or each other. Reference: Branco, M.R., and A. Pombo. 2006. PLoS. 4:e138. Immune to weight loss L eptin always seemed a bit too good to be true. Why would our chronically undernourished ancestors have evolved a hormone for weight loss? Now, Ke Chen, Allan Zhao (University of Pittsburgh, PA), and colleagues explain why leptin doesn’t work as the weight loss wonder drug that initially seemed a possibility. Leptin was discovered as a hormone produced by fat cells. When reinstated in leptin-defi cient mice and humans it drastically reduced their obesity. But individuals who were obese for other reasons had paradoxically high leptin levels, and adding more leptin did not induce signifi cant weight loss.