A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.     

Some parasites of paddlefish ( Polyodon spathula ) from the Yellowstone River, Montana

One species of copepod ( Ergasilus elongatus ), one trematode ( Diclybothrium hamulatum ), two nematodes ( Camallanus oxycephalus and Contracaecum sp.), and two cestodes ( Marsipometra hastata and M. parva ) were recovered from 17 paddlefish ( Polyodon spathula ) collected from the Yellowstone River, Montana, on 11 and 18 May 1973. The male paddlefish averaged 69.4 nematodes and 157.6 cestodes per infected fish while the females averaged 12.0 nematodes and 415.7 cestodes. The higher intensity of cestode infection in female paddlefish was attributed to their larger size and consequent greater intake of food resulting in more exposure to the cestode intermediate hosts ( Cyclops bicuspidatus ).     

Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP (cases) and 3,247 controls (stage 1) followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the stage 1 SNPs that yielded P ≤ 10(-3). We found significant previously unidentified signals (P < 5 × 10(-8)) associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component.     

Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion

Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.9× coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with β-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 β-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events.     

Henry Dresser and Victorian Ornithology: Birds,Books and Business

The metaphysical commitment to the circle as the essential element in the analysis of celestial motion has long been recognized as the hallmark of classical astronomy. Part I of this paper contains a discussion of how, for Kepler, the circle also functions in geometry to select the basic polygons, in music to select the basic harmonies, and in astrology to select the basic aspects. In Part II, the discussion centres on the question of how the replacement of circular planetary orbits by elliptical orbits in the Astronomia Nova of 1609 affected Kepler's metaphysical commitment to celestial circularity that was made manifest in the derivation of planetary radii in the Mysterium Cosmographicum of 1596. The answer is found in the new and much more accurate derivation of both the planetary radii and their eccentricities in the Harmonice Mundi of 1619. It is the relationship of the diurnal movements of single planets at aphelion and perihelion to specific musical consonances that provides the first step. Then, in the second step, these ratios are ‘tempered’ so that all six planets can provide a heavenly choir. The third and final step employs the ‘mean period’, which is obtained directly from the tempered ratios given by musical theory and diurnal (not annual) motion, in the 3/2 power law to calculate the planetary radii and eccentricities with amazing accuracy. Thus the ellipse is necessary to supply the variation in angular velocities that contain the Creator's archetypal celestial circularity.     

SS3B电力机车新制构架焊接变形的控制

分析了SS3B新制构架及侧梁在焊接过程中易产生的各种变形。针对焊接中的变形问题，通过对焊接材料参数的到定，制定了SS3B新制构架及侧梁的焊接工艺，使焊接变形得到有效控制，保证了新制构架的产品质量。     

Encoding social signals in the mouse main olfactory bulb

Mammalian urine releases complex mixtures of volatile compounds that are used in reproduction, territoriality and conspecific recognition. To understand how such complex mixtures are represented in the main olfactory bulb, we analysed the electrophysiological responses of individual mitral cells to volatile compounds in mouse urine. In both males and females, urine volatile compounds evoke robust responses in a small subset of mitral cells. Fractionation of the volatile compounds using gas chromatography showed that out of the hundreds of compounds present, mitral cells are activated by single compounds. One cohort of mitral cells responded exclusively to male urine; these neurons were activated by (methylthio)methanethiol, a potent, previously unknown semiochemical present only in male urine. When added to urine, synthetic (methylthio)methanethiol significantly enhances urine attractiveness to female mice. We conclude that mitral cells represent natural odorant stimuli by acting as selective feature detectors, and that their activation is largely independent of the presence of other components in the olfactory stimulus.