Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in beta-islet cell hyperplasia.

To ascertain the role of cyclin-dependent kinase 4 (Cdk4) in vivo, we have targeted the mouse Cdk4 locus by homologous recombination to generate two strains of mice, one that lacks Cdk4 expression and one that expresses a Cdk4 molecule with an activating mutation. Embryonic fibroblasts proliferate normally in the absence of Cdk4 but have a delayed S phase on re-entry into the cell cycle. Moreover, mice devoid of Cdk4 are viable, but small in size and infertile. These mice also develop insulin-deficient diabetes due to a reduction in beta-islet pancreatic cells. In contrast, mice expressing a mutant Cdk4 that cannot bind the cell-cycle inhibitor P16INK4a display pancreatic hyperplasia due to abnormal proliferation of beta-islet cells. These results establish Cdk4 as an essential regulator of specific cell types.     

Direct detection of pulsations of the Cepheid star zeta Gem and an independent calibration of the period-luminosity relation

Cepheids are a class of variable (pulsating) stars whose absolute luminosities are related in a simple manner to their pulsational periods. By measuring the period and using the 'period-luminosity' relationship, astronomers can use the observed visual brightness to determine the distance to the star. Because these stars are very luminous, they can be observed in other galaxies, and therefore can be used to help determine the expansion rate of the Universe (the Hubble constant). Calibration of the period-luminosity relation is a necessary first step, but the small number of sufficiently nearby Cepheids has forced the use of a number of indirect means, with associated systematic uncertainties. Here we present a distance to the Cepheid zeta Geminorum, determined using a direct measurement (by an optical interferometer) of its changes in diameter as it pulsates. Within our uncertainty of 15 per cent, our distance is in agreement with previous indirect determinations. Planned improvements to the instrument will allow us to calibrate directly the period-luminosity relation to better than a few per cent.