The stress kinase MKK7 couples oncogenic stress to p53 stability and tumor suppression

Most preneoplastic lesions are quiescent and do not progress to form overt tumors. It has been proposed that oncogenic stress activates the DNA damage response and the key tumor suppressor p53, which prohibits tumor growth. However, the molecular pathways by which cells sense a premalignant state in vivo are largely unknown. Here we report that tissue-specific inactivation of the stress signaling kinase MKK7 in KRas(G12D)-driven lung carcinomas and NeuT-driven mammary tumors markedly accelerates tumor onset and reduces overall survival. Mechanistically, MKK7 acts through the kinases JNK1 and JNK2, and this signaling pathway directly couples oncogenic and genotoxic stress to the stability of p53, which is required for cell cycle arrest and suppression of epithelial cancers. These results show that MKK7 functions as a major tumor suppressor in lung and mammary cancer in mouse and identify MKK7 as a vital molecular sensor to set a cellular anti-cancer barrier.     

陈国达矿(Ag9FeTe2S4): 胶东地区金矿床中发现的硫碲化物新矿物

陈国达矿(Ag9FeTe₂S₄), 产于中国胶东金矿区埠南金矿的含金-银的黄铜矿-石英脉中, 呈5~70 μm的半自形-他形粒状与方铅矿、黄铜矿、碲银矿、银金矿、自然银、未定名的Ag₆TeS₂, Ag₁₆FeBiTe₃S₈共生, 并被自然银和螺状硫银矿包围交代. 其平均化学成分(16个EPMA分析值)为Ag_8.97Fe_1.00Te_1.99S_4.04, 理想化学式Ag₉FeTe₂S₄. 利用甘多菲照相及同步辐射迴摆照相技术, 获得陈国达矿的67个衍射线, 主要衍射强线的d值和相对强度(括号中)为: 6.742(69), 6.416(39), 5.951(33), 3.265(100), 2.981(24), 2.649(22), 2.25(24), 2.188(71), 2.142(22), 2.123(31), 2.044(23), 1.949(33). 该衍射数据指标化为斜方晶系, a = 12.769 (2) Å, b = 14.814(2) Å, c = 16.233 (1) Å, V = 3070.6 ų, Z = 9, d_cal = 6.85 g/cm³. 反光显微镜下, 陈国达矿的光学性质与硫银锡矿接近, 浅灰色, 无明显非均质性, 摩氏硬度2~3, 颜色指数: x = 0.3027, y = 0.3076, Y = 25.78%, λ_d = 474 nm, Pe = 3.68%. 该矿物以中国地质学家、地洼学说的创立人陈国达教授的姓名命名. 该矿物及命名经IMA-CNMMN于2004年投票通过. 2005年作者补充数据后, 由CNMMN主席正式公布, 批准号2004-042a.     

Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4

Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns, and members of the pro-inflammatory interleukin-1 receptor (IL-1R) family, share homologies in their cytoplasmic domains called Toll/IL-1R/plant R gene homology (TIR) domains. Intracellular signalling mechanisms mediated by TIRs are similar, with MyD88 (refs 5-8) and TRAF6 (refs 9, 10) having critical roles. Signal transduction between MyD88 and TRAF6 is known to involve the serine-threonine kinase IL-1 receptor-associated kinase 1 (IRAK-1) and two homologous proteins, IRAK-2 (ref. 12) and IRAK-M. However, the physiological functions of the IRAK molecules remain unclear, and gene-targeting studies have shown that IRAK-1 is only partially required for IL-1R and TLR signalling. Here we show by gene-targeting that IRAK-4, an IRAK molecule closely related to the Drosophila Pelle protein, is indispensable for the responses of animals and cultured cells to IL-1 and ligands that stimulate various TLRs. IRAK-4-deficient animals are completely resistant to a lethal dose of lipopolysaccharide (LPS). In addition, animals lacking IRAK-4 are severely impaired in their responses to viral and bacterial challenges. Our results indicate that IRAK-4 has an essential role in innate immunity.     

装配式预制混凝土结构在日本的应用

装配式预制混凝土结构具有构件加工精度高、混凝土浇筑质量好、施工速度快、建筑物使用寿命长、节省大量模板材料及省略支模工序等主要优点,在欧美及日本等发达国家得到了广泛的应用与推广.其中,各种预制件间的连接抗震设计是保证结构整体抗震性能的关键所在.介绍了日本在该结构体系上的实际应用情况及主要连接抗震设计的基本内容,为该结构体系在我国的推广应用提供一定的参考资料.     

框架边节点斜压机构混凝土强度有效因数解析

利用斜压-桁架模型对以往35个剪切破坏型以及6个梁屈服后剪切破坏型钢筋混凝土框架边节点试件抗剪强度进行解析.探讨了混凝土抗压强度、柱轴压比、节点水平箍筋量、节点竖向箍筋量以及斜压机构倾角等参数对斜压机构混凝土强度有效因数p的影响.研究结果表明,混凝土强度越高,最大荷载时p值衰减率越大;普通强度混凝土时节点箍筋对p值衰减的抑制效果比高强度混凝土时明显;节点箍筋配箍率小于0.3%范围内斜压机构承担总剪力的80%以上.根据对p值的解析结果提出了针对节点强度的计算式,计算值与试验结果吻合.     

Regulation of cancer cell migration and bone metastasis by RANKL

Bone metastases are a frequent complication of many cancers that result in severe disease burden and pain. Since the late nineteenth century, it has been thought that the microenvironment of the local host tissue actively participates in the propensity of certain cancers to metastasize to specific organs, and that bone provides an especially fertile 'soil'. In the case of breast cancers, the local chemokine milieu is now emerging as an explanation for why these tumours preferentially metastasize to certain organs. However, as the inhibition of chemokine receptors in vivo only partially blocks metastatic behaviour, other factors must exist that regulate the preferential metastasis of breast cancer cells. Here we show that the cytokine RANKL (receptor activator of NF-kappaB ligand) triggers migration of human epithelial cancer cells and melanoma cells that express the receptor RANK. RANK is expressed on cancer cell lines and breast cancer cells in patients. In a mouse model of melanoma metastasis, in vivo neutralization of RANKL by osteoprotegerin results in complete protection from paralysis and a marked reduction in tumour burden in bones but not in other organs. Our data show that local differentiation factors such as RANKL have an important role in cell migration and the tissue-specific metastatic behaviour of cancer cells.     

Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN

Wound healing is essential for maintaining the integrity of multicellular organisms. In every species studied, disruption of an epithelial layer instantaneously generates endogenous electric fields, which have been proposed to be important in wound healing. The identity of signalling pathways that guide both cell migration to electric cues and electric-field-induced wound healing have not been elucidated at a genetic level. Here we show that electric fields, of a strength equal to those detected endogenously, direct cell migration during wound healing as a prime directional cue. Manipulation of endogenous wound electric fields affects wound healing in vivo. Electric stimulation triggers activation of Src and inositol-phospholipid signalling, which polarizes in the direction of cell migration. Notably, genetic disruption of phosphatidylinositol-3-OH kinase-gamma (PI(3)Kgamma) decreases electric-field-induced signalling and abolishes directed movements of healing epithelium in response to electric signals. Deletion of the tumour suppressor phosphatase and tensin homolog (PTEN) enhances signalling and electrotactic responses. These data identify genes essential for electrical-signal-induced wound healing and show that PI(3)Kgamma and PTEN control electrotaxis.     

K-type breakdown process of intracloud discharge in Chinese

Some special features of lightning discharges in the eastern area of Qinghai-Tibetan Plateau have been investigated through multi-station measurements of wide-band slow antenna systems synchronized by Global Positioning System (GPS) with a time resolution of 1 jis. The K-type breakdown processes during one intracloud (1C) discharge were analyzed using the time differences of radiation pulses arriving at different stations. It was found that K-type breakdown processes during IC discharge started from a negative charge region and propagated downward to the lower positive charge region with an average speed of 1.5 x 10 m/s. The altitude of negative charge region was between 5.0 and 6.0 km above ground, while that of positive charge region was between 2 .5 and 3 .5 km above ground.     

为后世生活—汉族的生死观与死的条件

汉族理想的死亡是在“后世”(阴间)幸福生活的条件。理想的死,需要具备生前长寿、临终前的必要准备、寿终的正常死亡及成为被子孙祭祀的祖先等必要条件。