A defective response to Hedgehog signaling in disorders of cholesterol biosynthesis

Smith-Lemli-Opitz syndrome (SLOS), desmosterolosis and lathosterolosis are human syndromes caused by defects in the final stages of cholesterol biosynthesis. Many of the developmental malformations in these syndromes occur in tissues and structures whose embryonic patterning depends on signaling by the Hedgehog (Hh) family of secreted proteins. Here we report that response to the Hh signal is compromised in mutant cells from mouse models of SLOS and lathosterolosis and in normal cells pharmacologically depleted of sterols. We show that decreasing levels of cellular sterols correlate with diminishing responsiveness to the Hh signal. This diminished response occurs at sterol levels sufficient for normal autoprocessing of Hh protein, which requires cholesterol as cofactor and covalent adduct. We further find that sterol depletion affects the activity of Smoothened (Smo), an essential component of the Hh signal transduction apparatus.     

The extent and patterns of usage of Agent Orange and other herbicides in Vietnam

Herbicides including Agent Orange were sprayed by United States forces for military purposes during the Vietnam War (1961-1971) at a rate more than an order of magnitude greater than for similar domestic weed control. In 1974, the US National Academy of Sciences published estimates of the extent and distribution of herbicides sprayed. Here we present revised estimates, developed using more-complete data. The spray inventory is expanded by more than seven million litres, in particular with heavily dioxin-contaminated herbicides. Estimates for the amount of dioxin sprayed are almost doubled. Hamlet census data reveal that millions of Vietnamese were likely to have been sprayed upon directly. Our identification of specific military herbicide targets has led to a more coherent understanding of spraying. Common errors in earlier interpretations of the spray data are also discussed.     

中美科学合作:文献计量学分析

利用SCI论文中作者间的国际合作信息,分析了纳米科技、化学、遗传学和细胞生物学领域44个研究方向中国和美国在1996年至2005年10年间的科学合作发展态势.从中美合作论文的数量增长、合作强度的趋强、中国和美国各自最重要的合作伙伴以及与科技发达国家的国际合作等方面证明中美在重要研究方向上的合作发展迅速,成效显著.结果表明,中美合作之所以发展迅速,在美国的中国学者和华人发挥了重要作用.     

Three-dimensional brittle shear fracturing by tensile crack interaction

Faults in brittle rock are shear fractures formed through the interaction and coalescence of many tensile microcracks. The geometry of these microcracks and their surrounding elastic stress fields control the orientation of the final shear fracture surfaces. The classic Coulomb-Mohr failure criterion predicts the development of two conjugate (bimodal) shear planes that are inclined at an acute angle to the axis of maximum compressive stress. This criterion, however, is incapable of explaining the three-dimensional polymodal fault patterns that are widely observed in rocks. Here we show that the elastic stress around tensile microcracks in three dimensions promotes a mutual interaction that produces brittle shear planes oriented obliquely to the remote principal stresses, and can therefore account for observed polymodal fault patterns. Our microcrack interaction model is based on the three-dimensional solution of Eshelby, unlike previous models that employed two-dimensional approximations. Our model predicts that shear fractures formed by the coalescence of interacting mode I cracks will be inclined at a maximum of 26 degrees to the axes of remote maximum and intermediate compression. An improved understanding of brittle shear failure in three dimensions has important implications for earthquake seismology and rock-mass stability, as well as fluid migration in fractured rocks.     

Dynamics of seismogenic volcanic extrusion at Mount St Helens in 2004-05

The 2004-05 eruption of Mount St Helens exhibited sustained, near-equilibrium behaviour characterized by relatively steady extrusion of a solid dacite plug and nearly periodic shallow earthquakes. Here we present a diverse data set to support our hypothesis that these earthquakes resulted from stick-slip motion along the margins of the plug as it was forced incrementally upwards by ascending, solidifying, gas-poor magma. We formalize this hypothesis with a dynamical model that reveals a strong analogy between behaviour of the magma-plug system and that of a variably damped oscillator. Modelled stick-slip oscillations have properties that help constrain the balance of forces governing the earthquakes and eruption, and they imply that magma pressure never deviated much from the steady equilibrium pressure. We infer that the volcano was probably poised in a near-eruptive equilibrium state long before the onset of the 2004-05 eruption.