In This Issue
Proceedings of the National Academy of Sciences of the United States of America
12780 E. coli-produced antidote to organophosphates 12938 Symmetry and beauty in the body 12985 Watching fat on the rebound 13003 Tumors tolerize T cells 13027 A microRNA family involved in cardiac fibrosis APPLIED BIOLOGICAL SCIENCES E. coli-produced antidote to organophosphates The mammalian enzyme paraoxonase 1 (PON1) is a catalytic scavenger that hydrolyzes a wide range of substrates, including organophosphate pesticides and nerve agents. Richard Stevens et al. present an Escherichia
... Escherichia coli-based system for expressing variants of PON1 that may aid researchers seeking enzymes with improved catalytic properties and show that knockout mice injected with human PON1 are protected against two organophosphates: diazoxon and chlorpyrifos-oxon. The authors expressed two variants of PON1 in E. coli: PON1 R192 , the more efficient of the two human alloforms, and PON1 K192 , identical in sequence except for the replacement of arginine with lysine-a substitution identical to rabbit PON1 at this position. In kinetic assays, the authors found that PON1 K192 was significantly more efficient than PON1 R192 against several organophosphates. Injected into PON1-knockout mice, PON1 K192 protected them against several times the lethal dose of diazoxon. Plasma levels of PON1 K192 peaked 8 hours after injection and were effective for at least 48 hours. The authors say their system provides the basis for larger-scale screening assays and the production of PON1 variants, some of which could prove useful as antidotes to nerve agents. -K.M. "Engineered recombinant human paraoxonase 1 (rHuPON1) purified from Escherichia coli protects against organophosphate poisoning" Previous studies have demonstrated a positive association between facial symmetry and attractiveness. Evolutionary theory predicts that body asymmetry (termed "fluctuating asymmetry") reflects insults suffered from poor environment and disease, and hence indicates poor health and low mate value. But does bodily symmetry affect attractiveness to the other sex? William Brown et al. find that it does. The authors used a 3D optical scanner to characterize the bodily topography of 77 volunteers. Other volunteers then assessed how attractive the bodies of the opposite sex were, in a color-neutral, computer-rendered form minus the heads. Both men and women reported that symmetric bodies were more attractive than asymmetric ones. Using principal component analysis, the authors identified a component they dubbed "body masculinity," which included properties such as greater height, wider shoulders, and smaller breasts. Brown et al. observed that the volunteers identified similar traits in attractive men and women associated with body symmetry: they rated symmetric men with high body masculinity most attractive and preferred evenly proportioned women with low body masculinity. -K.M. "Fluctuating asymmetry and preferences for sex-typical bodily characteristics" Fat lost during dieting or fasting-or during treatment with the hunger-controlling hormone leptin-can quickly return after resumption of normal feeding or withdrawal of the leptin. This rebound effect causes fat (lipid) to rapidly reaccumulate in the previously "skinny" fat cells, but the molecular mechanisms responsible are unclear. To study how fat cells (adipocytes) respond to changes in weight, Kivanc Birsoy et al. developed transgenic mice in which leptin in adipose tissue "lights up" with the help of a firef ly enzyme, allowing for noninvasive imaging of adipose mass in vivo. Leptin levels are known to correlate strongly with fat mass and are considered A symmetric body is attractive to the opposite sex.