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Cover  Video micrographs of vesicles moving on microtubules. The images (Allen et al., 1985)* were some of the first published video micrographs of vesicles moving on microtubules in the giant axon of the squid. Video microscopy has had a significant impact on cell biology by making it possible to observe dynamic changes of the cytoskeleton in living cells or cell extracts and the movement of vesicles on cytoskeletal filaments. Video-enhanced contrast microscopy is a technique that allows one to detect objects that are below the resolving power of the light microscope by improving the contrast of the image. The detection of fine detail in the specimen depends on the high sensitivity of video cameras and the contrast enhancement features of digital image processors. The video camera, an analog device, improves image contrast by subtracting background light and amplifying the remaining weak signal. The image processor converts the analog signal into a digital one and allows additional contrast enhancement through mathematical manipulation of the image pixel by pixel. One of the major advantages of digital processing is the ability to amplify small differences in gray levels so that differences in shades of gray in the specimen become visible to the eye. Subtraction of dust spots on lenses or other fixed pattern mottle can be removed, and frames can be averaged to reduce background and electronic noise. The final processed image reveals objects in the 20- to 100-nm range, a form of super-resolution (Inoué, 1989). The first major breakthrough achieved with this technique was the direct observation of vesicles moving on microtubules and, suprisingly, of micotubules gliding on the coverslip by molecular motors adsorbed to the glass surface. One of the principal architects of this technique was Robert D. Allen, who developed the Allen video-enhanced contrast-differential interference contrast (AVEC-DIC) technique (Allen et al., 1981a,b). The theoretical basis for this technique was developed simultaneously in the laboratories of Allen (Allen et al., 1981a,b) and Inoué (1981) and has been codified in the two editions of the authoritative text on video microscopy by Inoué (1986, 1997). The AVEC-DIC protocol provides a sophisticated but practical and easy-to-use method for assaying vesicle transport on microtubules and actin filaments. Allen was the first to record the movement of vesicles on microtubules in axoplasm of the squid giant axon with this technique. Motion analysis of transport on microtubules in axoplasm revealed that the velocity at which vesicles moved was equivalent to the rate of fast axonal transport. The images on the cover (Allen et al., 1985) show the bending of microtubules during gliding as a result of forces generated by motors, primarily kinesin, adsorbed to the coverslip. Numbers 1-4 indicate four gliding microtubules undergoing shape changes. A microtubule remains straight while gliding, except when the front end becomes stuck to the glass surface. Pushing forces from the rear of the microtubule causes the microtubules to bend and assume circular shapes. The ability of microtubules to glide on glass led to the development of motility assays for purified microtubule motors (Vale et al., 1985; Paschal et al., 1987). The timer on these micrographs indicates hours, minutes, seconds, and hundredths of seconds. Bar, 2 µm. *Reproduced from The Journal of Cell Biology, 1985, 100, 1736-1752 by copyright permission of the Rockefeller University Press.George M. Langford