The Melanocortin-4 Receptor Integrates Circadian Light Cues and Metabolism

The melanocortin system directs diverse physiological functions from coat color to body weight homoeostasis. A commonality among melanocortin-mediated processes is that many animals modulate similar processes on a circannual basis in response to longer, summer days, suggesting an underlying link between circadian biology and the melanocortin system. Despite key neuroanatomical substrates shared by both circadian and melanocortin-signaling pathways, little is known about the relationship between the two. Here we identify a link between circadian disruption and the control of glucose homeostasis mediated through the melanocortin-4 receptor (Mc4r). Mc4r-deficient mice exhibit exaggerated circadian fluctuations in baseline blood glucose and glucose tolerance. Interestingly, exposure to lighting conditions that disrupt circadian rhythms improve their glucose tolerance. This improvement occurs through an increase in glucose clearance by skeletal muscle and is food intake and body weight independent. Restoring Mc4r expression to the paraventricular nucleus prevents the improvement in glucose tolerance, supporting a role for the paraventricular nucleus in the integration of circadian light cues and metabolism. Altogether these data suggest that Mc4r signaling plays a protective role in minimizing glucose fluctuations due to circadian rhythms and environmental light cues and demonstrate a previously undiscovered connection between circadian biology and glucose metabolism mediated through the melanocortin system

Interview with Justice Randy J. Holland

For transcript, click the Download button above. For video index, click the link below. Randy J. Holland (L \u2772) served as a Justice of the Delaware Supreme Court from 1986 until his retirement in 2017. At the time of his appointment he was the youngest person ever to serve on that court

The Hubble Space Telescope Extragalactic Distance Scale Key Project XXIII. The Discovery of Cepheids In NGC 3319

The distance to NGC 3319 has been determined from Cepheid variable stars as part of the Hubble Space Telescope Key Project on the Extragalactic Distance Scale. Thirteen and four epochs of observations, using filters F555W (V) and F814W (I) respectively, were made with the Wide Field Planetary Camera 2. Thirty-three Cepheid variables between periods of 8 and 47 days were discovered. Adopting a Large Magellanic Cloud distance modulus of 18.50 +- 0.10 mag and extinction of E(V-I)=0.13 mag, a true reddening-corrected distance modulus (based on an analysis employing the ALLFRAME software package) of 30.78 +- 0.14 (random) +- 0.10 (systematic) mag and the extinction of E(V-I) = 0.06 mag were determined for NGC 3319. This galaxy is the last galaxy observed for the HST H0 Key Project.Comment: 22 pages. A gzipped tar file containing 16 figures can be obtained from http://www.ipac.caltech.edu/H0kp/n3319/n3319.htm

The Hubble Space Telescope Extragalactic Distance Scale Key Project. X. The Cepheid Distance to NGC 7331

The distance to NGC 7331 has been derived from Cepheid variables observed with HST/WFPC2, as part of the Extragalactic Distance Scale Key Project. Multi-epoch exposures in F555W (V) and F814W (I), with photometry derived independently from DoPHOT and DAOPHOT/ALLFRAME programs, were used to detect a total of 13 reliable Cepheids, with periods between 11 and 42 days. The relative distance moduli between NGC 7331 and the LMC, imply an extinction to NGC 7331 of A_V = 0.47+-0.15 mag, and an extinction-corrected distance modulus to NGC 7331 of 30.89+-0.14(random) mag, equivalent to a distance of 15.1 Mpc. There are additional systematic uncertainties in the distance modulus of +-0.12 mag due to the calibration of the Cepheid Period-Luminosity relation, and a systematic offset of +0.05+-0.04 mag if we applied the metallicity correction inferred from the M101 results of Kennicutt et al 1998.Comment: To be published in The Astrophysical Journal, 1998 July 1, v501 note: Figs 1 and 2 (JPEG files) and Fig 7 (multipage .eps file) need to be viewed/printed separatel

The Extragalactic Distance Scale Key Project. XVI. Cepheid Variables in an Inner Field of M101

We report on the identification of 255 candidate variable stars in a field located some 1.7 from the center of the late-type spiral galaxy M101 = NGC 5457, based on observations made with the Wide Field and Planetary Camera 2 on board the Hubble Space Telescope