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In This Issue
Ubiquitin-like protein fights free radicals
To survive in an ever-changing environment, cells must respond to oxidative free radicals, stressful byproducts of both normal intracellular metabolism and UV-induced damage. Annemarthe Van der Veen et al. (pp. 1763–1770) reveal that oxidative stress in both human and yeast cells engages a protein called ubiquitin-related modifier 1 (Urm1), which was previously shown to modify the function, localization, and turnover of newly translated proteins in yeast. Researchers have known for some time that Urm1 is essential for the chemical modification of certain transfer RNAs, which help attach amino acids to growing polypeptide chains, but the role of Urm1 in eukaryotic protein modification remains unclear. The authors performed proteomic analyses of yeast and human cells, and found that Urm1 tags components of its own pathway, as well as a protein called “cellular apoptosis susceptibility factor,” which helps shuttle molecules to and from the nucleus and cytoplasm. Urmylation—attachment of Urm1 to another protein—occurred on lysine residues of the target proteins and involved a thioester intermediate, resulting in the formation of a covalent peptide bond; a process that the authors say resembles the biochemistry of ubiquitylation, which targets proteins for destruction in eukaryotic cells. According to the authors, the study expands on previous findings in yeast and demonstrates a dual role for this conserved molecule across biological domains. —F.A.
Taste receptors might control a hunger hormone
The hunger hormone ghrelin stimulates appetite and helps quell the burning of body fat, thus contributing to weight gain. Previous studies have linked nutrient sensing in the stomach to bitter taste receptors in the stomach and their signaling partner proteins. To determine whether bitter taste receptors control the secretion of ghrelin in the stomach, Sara Janssen et al. (pp. 2094–2099) administered bitter-tasting compounds to normal mice and to mice lacking a signaling protein called α-gustducin. Compounds that trigger bitter taste receptors increased plasma ghrelin levels in normal mice but to a lesser extent in mice without α-gustducin. The compounds caused normal mice to increase their food intake for 30 minutes; no such effect was observed in mice lacking either α-gustducin or the ghrelin receptor, suggesting that α-gustducin triggers ghrelin release, which stimulates feeding. The short-lived rise in food intake was accompanied by rising levels of the RNA message for a neuropeptide in the hypothalamus that has been thought to stimulate feeding. In addition, the authors found, the release of ghrelin likely stimulates gastric emptying—the process by which food is emptied from the stomach into the small intestine. The findings suggest that bitter taste receptors stimulate the secretion of ghrelin, and could lead to a therapeutic approach for weight and gastrointestinal motility disorders, according to the authors. — P.N.
Eyeball camera zooms in with elastic photodetector arrays
The focused image formed by a simple convex lens lies on a curved, approximately hemispheric surface. Hemispherical imaging systems, or “eyeball” cameras, use curved arrays of photodetectors to capture this surface without the need for complex multilens focusing systems. Inhwa Jung et al. (pp. 1788–1793) describe a digital imaging device with photo-detectors embedded in deformable elastomer membranes that can be dynamically reshaped using hydraulics. Previous studies have demonstrated promising eyeball camera designs, but those systems are not compatible with variable zoom; optical magnification changes the curvature of the clearly focused surface, and those cameras employ rigid detector arrays that have a fixed curvature. By contrast, the authors’ system uses interconnected silicon photodetectors on a thin, elastomeric membrane. Beneath the arrays, a fluid-filled chamber can be triggered with hydraulics to change the array's radius of curvature. An integrated, fluid-filled lens that is similarly activated, the authors report, yields a complete and hemispherical camera system that can accommodate continuously adjustable zoom by matching the detector geometry to the varying curvature of the image surface. Future versions of the system can potentially come equipped with alternate reshaping mechanisms, such as microactuators embedded directly on the array, according to the authors. — T.J.
Potential broad-spectrum therapy for asthma
Asthma afflicts about 30 million people in the United States alone, claiming nearly 5,000 lives every year. Current treatments help manage symptoms in many people with asthma, but the molecular mechanisms that underlie the onset of the disease are poorly understood. Shutang Zhou et al. (pp. 2100–2105) used two mouse models of lung airway hyperreactivity and inflammation to test the role of a neuropeptide called gastrin-releasing peptide (GRP) secreted by epithelial cells in lung airways, in the onset of asthma. The authors exposed mice to an air pollutant, ozone, or an allergen, ovalbumin, known to trigger bouts of asthma. They then blocked GRP by using a chemical compound or an antibody. Blocking GRP abrogated airway hyperreactivity and reduced the levels of inflammatory immune chemicals implicated in asthma. In addition, blocking GRP diminished the level of phosphorylation—a chemical modification that marks active receptors—of the GRP receptor in the mouse lung. The authors found that blocking GRP was more effective than treatment with dexamethasone, a standard-of-care drug for asthma, in alleviating the signs of asthma in both models of the disease. Because GRP is a potent bronchoconstrictor in some animals, the authors suggest, it might also mediate asthma in people. Hence, blocking GRP could be a preventive or therapeutic approach worthy of clinical trials, according to the authors. — P.N.