Shiga toxin induces tubular membrane invaginations for its uptake into cells

Clathrin seems to be dispensable for some endocytic processes and, in several instances, no cytosolic coat protein complexes could be detected at sites of membrane invagination. Hence, new principles must in these cases be invoked to account for the mechanical force driving membrane shape changes. Here we show that the Gb3 (glycolipid)-binding B-subunit of bacterial Shiga toxin induces narrow tubular membrane invaginations in human and mouse cells and model membranes. In cells, tubule occurrence increases on energy depletion and inhibition of dynamin or actin functions. Our data thus demonstrate that active cellular processes are needed for tubule scission rather than tubule formation. We conclude that the B-subunit induces lipid reorganization that favours negative membrane curvature, which drives the formation of inward membrane tubules. Our findings support a model in which the lateral growth of B-subunit-Gb3 microdomains is limited by the invagination process, which itself is regulated by membrane tension. The physical principles underlying this basic cargo-induced membrane uptake may also be relevant to other internalization processes, creating a rationale for conceptualizing the perplexing diversity of endocytic routes.     

Hadean diamonds in zircon from Jack Hills, Western Australia

Detrital zircons more than 4 billion years old from the Jack Hills metasedimentary belt, Yilgarn craton, Western Australia, are the oldest identified fragments of the Earth's crust and are unique in preserving information on the earliest evolution of the Earth. Inclusions of quartz, K-feldspar and monazite in the zircons, in combination with an enrichment of light rare-earth elements and an estimated low zircon crystallization temperature, have previously been used as evidence for early recycling of continental crust, leading to the production of granitic melts in the Hadean era. Here we present the discovery of microdiamond inclusions in Jack Hills zircons with an age range from 3,058 +/- 7 to 4,252 +/- 7 million years. These include the oldest known diamonds found in terrestrial rocks, and introduce a new dimension to the debate on the origin of these zircons and the evolution of the early Earth. The spread of ages indicates that either conditions required for diamond formation were repeated several times during early Earth history or that there was significant recycling of ancient diamond. Mineralogical features of the Jack Hills diamonds-such as their occurrence in zircon, their association with graphite and their Raman spectroscopic characteristics-resemble those of diamonds formed during ultrahigh-pressure metamorphism and, unless conditions on the early Earth were unique, imply a relatively thick continental lithosphere and crust-mantle interaction at least 4,250 million years ago.     

Crystal structure of the human beta2 adrenergic G-protein-coupled receptor

Structural analysis of G-protein-coupled receptors (GPCRs) for hormones and neurotransmitters has been hindered by their low natural abundance, inherent structural flexibility, and instability in detergent solutions. Here we report a structure of the human beta2 adrenoceptor (beta2AR), which was crystallized in a lipid environment when bound to an inverse agonist and in complex with a Fab that binds to the third intracellular loop. Diffraction data were obtained by high-brilliance microcrystallography and the structure determined at 3.4 A/3.7 A resolution. The cytoplasmic ends of the beta2AR transmembrane segments and the connecting loops are well resolved, whereas the extracellular regions of the beta2AR are not seen. The beta2AR structure differs from rhodopsin in having weaker interactions between the cytoplasmic ends of transmembrane (TM)3 and TM6, involving the conserved E/DRY sequences. These differences may be responsible for the relatively high basal activity and structural instability of the beta2AR, and contribute to the challenges in obtaining diffraction-quality crystals of non-rhodopsin GPCRs.     

Links between erosion, runoff variability and seismicity in the Taiwan orogen

The erosion of mountain belts controls their topographic and structural evolution and is the main source of sediment delivered to the oceans. Mountain erosion rates have been estimated from current relief and precipitation, but a more complete evaluation of the controls on erosion rates requires detailed measurements across a range of timescales. Here we report erosion rates in the Taiwan mountains estimated from modern river sediment loads, Holocene river incision and thermochronometry on a million-year scale. Estimated erosion rates within the actively deforming mountains are high (3-6 mm yr(-1)) on all timescales, but the pattern of erosion has changed over time in response to the migration of localized tectonic deformation. Modern, decadal-scale erosion rates correlate with historical seismicity and storm-driven runoff variability. The highest erosion rates are found where rapid deformation, high storm frequency and weak substrates coincide, despite low topographic relief.     

Low European methyl chloroform emissions inferred from long-term atmospheric measurements

Methyl chloroform (CH3CCl3, 1,1,1,-trichloroethane) was used widely as a solvent before it was recognized to be an ozone-depleting substance and its phase-out was introduced under the Montreal Protocol. Subsequently, its atmospheric concentration has declined steadily and recent European methyl chloroform consumption and emissions were estimated to be less than 0.1 gigagrams per year. However, data from a short-term tropospheric measurement campaign (EXPORT) indicated that European methyl chloroform emissions could have been over 20 gigagrams in 2000 (ref. 6), almost doubling previously estimated global emissions. Such enhanced emissions would significantly affect results from the CH3CC13 method of deriving global abundances of hydroxyl radicals (OH) (refs 7-12)-the dominant reactive atmospheric chemical for removing trace gases related to air pollution, ozone depletion and the greenhouse effect. Here we use long-term, high-frequency data from Mace Head, Ireland and Jungfraujoch, Switzerland, to infer European methyl chloroform emissions. We find that European emission estimates declined from about 60 gigagrams per year in the mid-1990s to 0.3-1.4 and 1.9-3.4 gigagrams per year in 2000-03, based on Mace Head and Jungfraujoch data, respectively. Our European methyl chloroform emission estimates are therefore higher than calculated from consumption data, but are considerably lower than those derived from the EXPORT campaign in 2000 (ref. 6).     

The signature of orbital motion from the dayside of the planet τ Boötis b

The giant planet orbiting τ Bo?tis (named τ Bo?tis b) was amongst the first extrasolar planets to be discovered. It is one of the brightest exoplanets and one of the nearest to us, with an orbital period of just a few days. Over the course of more than a decade, measurements of its orbital inclination have been announced and refuted, and have hitherto remained elusive. Here we report the detection of carbon monoxide absorption in the thermal dayside spectrum of τ Bo?tis b. At a spectral resolution of ～100,000, we trace the change in the radial velocity of the planet over a large range in phase, determining an orbital inclination of 44.5°?±?1.5° and a mass 5.95?±?0.28 times that of Jupiter, demonstrating that atmospheric characterization is possible for non-transiting planets. The strong absorption signal points to an atmosphere with a temperature that is decreasing towards higher altitudes, in contrast to the temperature inversion inferred for other highly irradiated planets. This supports the hypothesis that the absorbing compounds believed to cause such atmospheric inversions are destroyed in τ Bo?tis b by the ultraviolet emission from the active host star.     

肿瘤放疗并发症概率预测模型参数拟合方法

为了建立具有群体特异性的肿瘤放疗NTCP预测模型,提出了一种模型参数拟合方法.首先,基于NTCP模型的特点构建最大似然函数;然后,分别采用确定性优化方法和随机性优化方法对最大似然函数进行优化,分析优化过程的时间成本及优化结果,探讨用于拟合NTCP模型参数的最优方法.实验结果表明,用于拟合NTCP模型参数的最大似然函数是非凸的,存在局部最优解;遗传算法是一种最稳定的最大似然函数优化方法,其运行时间比模拟退火算法短,而且可以在每次优化结束后给出全局最优解,以作为NTCP模型参数.所提方法可以帮助肿瘤放疗工作者在临床随访数据的基础上建立具有群体特异性的放疗并发症预测模型.