Common variants near MC4R are associated with fat mass, weight and risk of obesity

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.     

Alopecia induced in young mice by exposure to excess dietary zinc

Summary Second generation mice were exposed to normal (50 ppm, Group I) or excess (2000 ppm, Group II) zinc in the maternal diet during gestation and lactation, then weaned and continued on the mother's diet until sacrifice at 8 weeks. Tibia zinc reflected dietary intake. Group II had reduced plasma copper, body weight, and hematocrit; the second coat of hair appeared late and was lighter in color than Group I, possibly as an effect of copper and pigmentation development and hair growth.     

Luffolide,a novel anti-inflammatory terpene from the spongeLuffariella sp.

Summary Luffolide (4) is a minor metabolite of the spongeLuffariella sp. from Palau. The structure of luffolide was determined by single crystal X-ray analysis. Luffolide is relatively unstable and undergoes a complex cyclization reaction to give the hexacyclic products5 and6. Luffolide (4) has some of the anti-inflammatory properties of manoalide (1): this may help to define the chemical reaction between manoalide (1) and phospholipase A₂.All crystallographic calculations were done on a PRIME 9950 computer operated by the Cornell Chemistry Computing Facility. Principal programs employed were: FOBS, a data reduction program by G.D. Van Duyne, Cornell University, 1987; MULTAN 80, and RANTAN 80, systems of computer programs for the automatic solution of crystal structures from X-ray diffraction data (locally modified to perform all Fourier calculations including Patterson syntheses) written by P. Main, S. E. Hull, L. Lessinger, G. Germain, J. P. Declercq and M. M. Woolfson, University of York, England, 1980 BDLS, an, anisotropic block diagonal least squares refinement written by K. Hirotsu, E. Arnold, and G. D. Van Duyne, Cornell University, 1987; PLUTO 78, a locally modified crystallographic illustration program by W. D. S. Motherwell, Cambridge Crystallographic Data Centre, 1978; and BOND, a program to calculate molecular parameters and prepare tables written by K. Hirotsu and G. Van Duyne, Cornell University, 1985.Acknowledgment. We thank the Government of the Republic of Palau for a scientific research permit. We thank Dr Klaus Rützler, Smithsonian Institution, Washington, D.C. for identifying the sponge and Mary Kay Harper for performing additional bioassays. This research was supported by grants from the Sea Grant College Programs of California [Projects R/MP-30 to DJF) and R/MP-31 (to RSJ)] and New York (to JC) and the National Institutes of Health (CA 24487 to JC).     

Retinal ganglion cells act largely as independent encoders

Correlated firing among neurons is widespread in the visual system. Neighbouring neurons, in areas from retina to cortex, tend to fire together more often than would be expected by chance. The importance of this correlated firing for encoding visual information is unclear and controversial. Here we examine its importance in the retina. We present the retina with natural stimuli and record the responses of its output cells, the ganglion cells. We then use information theoretic techniques to measure the amount of information about the stimuli that can be obtained from the cells under two conditions: when their correlated firing is taken into account, and when their correlated firing is ignored. We find that more than 90% of the information about the stimuli can be obtained from the cells when their correlated firing is ignored. This indicates that ganglion cells act largely independently to encode information, which greatly simplifies the problem of decoding their activity.