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An interdisciplinary team of biological imaging experts from the University of California San Diego (National Center for Microscopy and Imaging Research, Pharmacology Dept. , Chemistry and Biochemistry Dept. , and the Howard Hughes Medical Institute) recently contrasted the characteristic benefits and limitations of many new classes of fluorescent probes for studying proteins. Sharing the perspective that major advances in the life sciences are strongly tied to the ability to directly observe dynamic processes in living systems, and to localize the responsible molecular machinery in situ by electron microscopy, they published a review of relevant fluorescent imaging technologies in the 14-April-2006 issue of Science.