Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer

We conducted a genome-wide SNP association study on prostate cancer on over 23,000 Icelanders, followed by a replication study including over 15,500 individuals from Europe and the United States. Two newly identified variants were shown to be associated with prostate cancer: rs5945572 on Xp11.22 and rs721048 on 2p15 (odds ratios (OR) = 1.23 and 1.15; P = 3.9 x 10(-13) and 7.7 x 10(-9), respectively). The 2p15 variant shows a significantly stronger association with more aggressive, rather than less aggressive, forms of the disease.     

Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer

We carried out a genome-wide association study of breast cancer predisposition with replication and refinement studies involving 6,145 cases and 33,016 controls and identified two SNPs (rs4415084 and rs10941679) on 5p12 that confer risk, preferentially for estrogen receptor (ER)-positive tumors (OR = 1.27, P = 2.5 x 10(-12) for rs10941679). The nearest gene, MRPS30, was previously implicated in apoptosis, ER-positive tumors and favorable prognosis. A recently reported signal in FGFR2 was also found to associate specifically with ER-positive breast cancer.     

ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma

Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations comprising 2,121 individuals with CM, 2,163 individuals with BCC and over 40,000 controls. A haplotype near ASIP, known to affect a similar spectrum of pigmentation traits as MC1R variants, conferred significant risk of CM (odds ratio (OR) = 1.45, P = 1.2 x 10(-9)) and BCC (OR = 1.33, P = 1.2 x 10(-6)). The variant in TYR encoding the R402Q amino acid substitution, previously shown to affect eye color and tanning response, conferred risk of CM (OR = 1.21, P = 2.8 x 10(-7)) and BCC (OR = 1.14, P = 6.1 x 10(-4)). An eye color variant in TYRP1 was associated with risk of CM (OR = 1.15, P = 4.6 x 10(-4)). The association of all three variants is robust with respect to adjustment for the effect of pigmentation.     

A reconnaissance of the Cu isotopic compositions of hydrothermal vein-type cop-per deposit, Jinman, Yunnan,China

The Jinman deposit is a low-temperature hydrothermal vein-type copper deposit, which occurs along faults and fractures within Middle Jurassic sandstone and mudstone units of the Lanping-Simao Mesozoic-Cenozoic basin of Yunnan Province. In this note, we report for the first time the Cu isotopic compositions of Cu-sulfides from the Jinman deposit. The data show large variations and low 65Cu values of 3.70‰ to +0.30‰, which are in sharp contrast to the 65Cu values of high-temperature magmatic-hydrothermal copper deposits (0.62‰ to +0.40‰) and the modern ocean-floor massive sulfide deposits (0.48‰ to +1.15‰). It is suggested that the Cu isotope fractionation at Jinman is affected mainly by the following factors, i.e. a low temperature of ore formation (150-286℃); a sedimentary source for ore materials; various stages of ore deposition; and involvement of organic matter in the ore-forming processes.     

Noise correlations improve response fidelity and stimulus encoding

Computation in the nervous system often relies on the integration of signals from parallel circuits with different functional properties. Correlated noise in these inputs can, in principle, have diverse and dramatic effects on the reliability of the resulting computations. Such theoretical predictions have rarely been tested experimentally because of a scarcity of preparations that permit measurement of both the covariation of a neuron's input signals and the effect on a cell's output of manipulating such covariation. Here we introduce a method to measure covariation of the excitatory and inhibitory inputs a cell receives. This method revealed strong correlated noise in the inputs to two types of retinal ganglion cell. Eliminating correlated noise without changing other input properties substantially decreased the accuracy with which a cell's spike outputs encoded light inputs. Thus, covariation of excitatory and inhibitory inputs can be a critical determinant of the reliability of neural coding and computation.     

A screen of the complete protein kinase gene family identifies diverse patterns of somatic mutations in human breast cancer

We examined the coding sequence of 518 protein kinases, approximately 1.3 Mb of DNA per sample, in 25 breast cancers. In many tumors, we detected no somatic mutations. But a few had numerous somatic mutations with distinctive patterns indicative of either a mutator phenotype or a past exposure.     

Exceptional astronomical seeing conditions above Dome C in Antarctica

One of the most important considerations when planning the next generation of ground-based optical astronomical telescopes is to choose a site that has excellent 'seeing'--the jitter in the apparent position of a star that is caused by light bending as it passes through regions of differing refractive index in the Earth's atmosphere. The best mid-latitude sites have a median seeing ranging from 0.5 to 1.0 arcsec (refs 1-5). Sites on the Antarctic plateau have unique atmospheric properties that make them worth investigating as potential observatory locations. Previous testing at the US Amundsen-Scott South Pole Station has, however, demonstrated poor seeing, averaging 1.8 arcsec (refs 6, 7). Here we report observations of the wintertime seeing from Dome C (ref. 8), a high point on the Antarctic plateau at a latitude of 75 degrees S. The results are remarkable: the median seeing is 0.27 arcsec, and below 0.15 arcsec 25 per cent of the time. A telescope placed at Dome C would compete with one that is 2 to 3 times larger at the best mid-latitude observatories, and an interferometer based at this site could work on projects that would otherwise require a space mission.     

Lung cancer: intragenic ERBB2 kinase mutations in tumours

The protein-kinase family is the most frequently mutated gene family found in human cancer and faulty kinase enzymes are being investigated as promising targets for the design of antitumour therapies. We have sequenced the gene encoding the transmembrane protein tyrosine kinase ERBB2 (also known as HER2 or Neu) from 120 primary lung tumours and identified 4% that have mutations within the kinase domain; in the adenocarcinoma subtype of lung cancer, 10% of cases had mutations. ERBB2 inhibitors, which have so far proved to be ineffective in treating lung cancer, should now be clinically re-evaluated in the specific subset of patients with lung cancer whose tumours carry ERBB2 mutations.