Summary A new non-invasive method for monitoring apoptosis has been developed using high frequency (40 MHz) ultrasound imaging. Conventional ultrasound backscatter imaging techniques were used to observe apoptosis occurring in response to anticancer agents in cells in vitro, in tissues ex vivo and in live animals. The mechanism behind this ultrasonic detection was identified experimentally to be the subcellular nuclear changes, condensation followed by fragmentation, that cells undergo during apoptosis. These changes dramatically increase the high frequency ultrasound scattering efficiency of apoptotic cells over normal cells (25-to 50-fold change in intensity). The result is that areas of tissue undergoing apoptosis become much brighter in comparison to surrounding viable tissues. The results provide a framework for the possibility of using high frequency ultrasound imaging in the future to non-invasively monitor the effects of chemotherapeutic agents and other anticancer treatments in experimental animal systems and in patients.

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The three-dimensional (3D) structure of the intrinsically dimeric insulin receptor bound to its ligand, insulin, was determined by electron cryomicroscopy. Gold-labeled insulin served to locate the insulin-binding domain. The 3D structure was then fitted with available known high-resolution domain substructures to obtain a detailed contiguous model for this heterotetrameric transmembrane receptor. The 3D reconstruction indicates that the two alpha subunits jointly participate in insulin binding and that the kinase domains in the two beta subunits are in a juxtaposition that permits autophosphorylation of tyrosine residues in the first step of insulin receptor activation.