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121.
Hao HX Xie Y Zhang Y Charlat O Oster E Avello M Lei H Mickanin C Liu D Ruffner H Mao X Ma Q Zamponi R Bouwmeester T Finan PM Kirschner MW Porter JA Serluca FC Cong F 《Nature》2012,485(7397):195-200
R-spondin proteins strongly potentiate Wnt signalling and function as stem-cell growth factors. Despite the biological and therapeutic significance, the molecular mechanism of R-spondin action remains unclear. Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. Inhibition of ZNRF3 enhances Wnt/β-catenin signalling and disrupts Wnt/planar cell polarity signalling in vivo. Notably, R-spondin mimics ZNRF3 inhibition by increasing the membrane level of Wnt receptors. Mechanistically, R-spondin interacts with the extracellular domain of ZNRF3 and induces the association between ZNRF3 and LGR4, which results in membrane clearance of ZNRF3. These data suggest that R-spondin enhances Wnt signalling by inhibiting ZNRF3. Our study provides new mechanistic insights into the regulation of Wnt receptor turnover, and reveals ZNRF3 as a tractable target for therapeutic exploration. 相似文献
122.
Among vertebrates, only microchiropteran bats, cetaceans and some rodents are known to produce and detect ultrasounds (frequencies greater than 20 kHz) for the purpose of communication and/or echolocation, suggesting that this capacity might be restricted to mammals. Amphibians, reptiles and most birds generally have limited hearing capacity, with the ability to detect and produce sounds below approximately 12 kHz. Here we report evidence of ultrasonic communication in an amphibian, the concave-eared torrent frog (Amolops tormotus) from Huangshan Hot Springs, China. Males of A. tormotus produce diverse bird-like melodic calls with pronounced frequency modulations that often contain spectral energy in the ultrasonic range. To determine whether A. tormotus communicates using ultrasound to avoid masking by the wideband background noise of local fast-flowing streams, or whether the ultrasound is simply a by-product of the sound-production mechanism, we conducted acoustic playback experiments in the frogs' natural habitat. We found that the audible as well as the ultrasonic components of an A. tormotus call can evoke male vocal responses. Electrophysiological recordings from the auditory midbrain confirmed the ultrasonic hearing capacity of these frogs and that of a sympatric species facing similar environmental constraints. This extraordinary upward extension into the ultrasonic range of both the harmonic content of the advertisement calls and the frog's hearing sensitivity is likely to have co-evolved in response to the intense, predominantly low-frequency ambient noise from local streams. Because amphibians are a distinct evolutionary lineage from microchiropterans and cetaceans (which have evolved ultrasonic hearing to minimize congestion in the frequency bands used for sound communication and to increase hunting efficacy in darkness), ultrasonic perception in these animals represents a new example of independent evolution. 相似文献
123.
Continental runoff has increased through the twentieth century despite more intensive human water consumption. Possible reasons for the increase include: climate change and variability, deforestation, solar dimming, and direct atmospheric carbon dioxide (CO2) effects on plant transpiration. All of these mechanisms have the potential to affect precipitation and/or evaporation and thereby modify runoff. Here we use a mechanistic land-surface model and optimal fingerprinting statistical techniques to attribute observational runoff changes into contributions due to these factors. The model successfully captures the climate-driven inter-annual runoff variability, but twentieth-century climate alone is insufficient to explain the runoff trends. Instead we find that the trends are consistent with a suppression of plant transpiration due to CO2-induced stomatal closure. This result will affect projections of freshwater availability, and also represents the detection of a direct CO2 effect on the functioning of the terrestrial biosphere. 相似文献
124.
针对低渗油气田开发中存在的应力敏感性损害,选取天然储层岩心,开展不同渗透率储层应力敏感性试验对比研究,建立渗透率与有效应力之间的数学关系。对应力敏感性损害机制进行分析。基于平面径向流渗流理论,计算应力敏感性损害对低渗油田产能的影响。结果表明:随有效应力增加,中、高渗储层属于"缓慢下降"型应力敏感性损害模式,储层损害程度较弱;低渗、超低渗储层则属于"先快后慢"型应力敏感性损害模式,储层损害程度较强;储层孔喉结构特征及其尺寸分布是储层应力敏感性损害的主要控制因素;在油井井壁附近存在"渗透率漏斗",一定程度上影响了油井产能。 相似文献
125.
以锈损率较低的钢筋混凝土简支梁为对象,在平截面假定基础上,提出考虑钢筋、混凝土材料性能劣化和几何尺寸变化的受弯承载力计算公式;采用换算截面法计算锈蚀钢筋混凝土梁的等效刚度,给出考虑锈蚀钢筋、混凝土二者间黏结性能退化的有效刚度计算公式,建议锈蚀钢筋混凝土简支梁在集中荷载作用下跨中挠度的计算方法,并通过39根锈蚀钢筋混凝土梁的试验数据对建议受弯分析模型验证。研究结果表明:锈蚀钢筋混凝土梁受弯承载力试验值与计算值之比的平均值为1.100,方差为0.041,二者吻合较好;多数锈蚀试件按受弯分析模型计算得到的荷载-跨中挠度曲线与试验曲线吻合较好,变化趋势相当,建议受弯分析模型可为锈蚀钢筋混凝土梁的全过程受力分析提供参考。 相似文献
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128.
【目的】研究红树蚬(Polymesoda erosa)分布密度与潮高、底质和红树根际等环境因子的关系。【方法】在广西廉州湾和珍珠湾红树林设置5条断面25个取样站进行采样调查,运用单因素方差分析(one-way ANOVA)和主成分分析的统计方法对数据进行分析。【结果】红树蚬多见于高潮带而鲜见于低潮带,红树蚬分布密度从高潮位向低潮位递减。红树根际与林内空地红树蚬分布密度差异不明显(P0.05),不同红树植物树种根际红树蚬的分布密度差异不明显(P0.05)。【结论】沉积物紧实度和盐度是红树蚬分布的影响因素。 相似文献
129.
采用非线性有限元方法研究除尘器壳体承受板顶竖向均布荷载作用的墙板发挥受力蒙皮作用时的破坏形式和承载能力,分析墙板厚度、墙板宽度、加劲肋间距、立柱横向支撑间距、立柱截面尺寸等因素对墙板承载能力的影响。结果表明:立柱受载水平较低时,墙板发生受剪屈服破坏;立柱受载水平中等时,墙板同时发生受压和受剪屈服破坏;立柱受载水平较高时,墙板发生受压屈服破坏。在同等立柱受载水平情况时,墙板承载能力随着墙板厚度增加、墙板宽度减小、加劲肋间距减小或者立柱支撑间距减小而增大。立柱截面尺寸增大使得立柱刚度增大时,立柱稳定性提高,墙板承载力增大。 相似文献
130.
柱形件液态模锻中缩孔的计算机模拟研究 总被引:4,自引:1,他引:3
通过数学建模对柱形件液态模锻的温度场进行了研究,计算了凝固过程中在凝固收缩和加压补缩作用下的缩孔体积,建立了差分方程,编制了通用性软件,并以高锰钢为例进行了工艺研究。结果表明,液态模锻中比压、保压时间和压下速度是控制铸件不产生缩孔的三个重要因素,该软件对于液态模锻铸件缩孔的防止具有指导作用。 相似文献