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Mutant synthetases allow selective labeling. Ngo et al. (p 715) describe the combination of azidonorleucine, a non-natural amino acid that can be used in 'click' reactions, with a mutant methionyl-tRNA synthetase selective for this new residue, which allows for the specific modification of proteins in mutant cell strains within mixed cell cultures. The cover shows a three-dimensional topographic rendering of an infection of mouse macrophages by Escherichia coli labeled with azidonorleucine and further modified with a fluorescent dye. Cover art by Erin Dewalt, based on an original image from Julie A. Champion.
Phenotypic diversity exists even within isogenic populations of cells. Such nongenetic individuality may have wide implications for our understanding of many biological processes. The field of study concerned with the investigation of nongenetic individuality, also known as the 'biology of noise', is ripe with exciting scientific opportunities and challenges.
Parathyroid hormone (PTH) and PTH-related protein activate the same receptor but can produce divergent effects. Reports now describe two active conformations for the PTH receptor, one of which moves intracellularly—complexed with hormone and G protein—to produce a continued cAMP signal.
Chemo-metabolic processes such as redox remodeling and amino acid availability act as immunity rheostats, revealing a new mechanism regulating intercellular cross-talk between dendritic cells, regulatory T lymphocytes and effector T lymphocytes.
Hydrolysis of the phosphodiester linkages in DNA is a notoriously difficult reaction. Deoxyribozymes that use Zn2+ and Mn2+ ions to accelerate this reaction by a factor of one hundred million (or more) have been identified and characterized.