FK506 sensitizes mammalian cells to high osmolarity by modulating p38 MAP kinase activation

The immunosuppressants tacrolimus (FK506) and cyclosporin A (CsA) have increased the survival rates in organ transplantation. Both drugs inhibit the protein phosphatase calcineurin (CaN) in activated T cells, exhibiting similar side-effects. Diabetes is observed more often in FK506 than CsA therapy, probably due to inhibition of new molecular targets other than CaN. We studied FK506 toxicity in mammalian cells. FK506, but not CsA, regulated p38 activation by osmotic stress, and decreased viability in osmostressed cells. In addition, FK506 treatment strongly increased the phosphorylation of the eukaryotic initiation factor-2a (eIF-2a) subunit. eIF-2a phosphorylation, p38 inhibition and cell lethality were relieved by addition of excess amino acids to the medium, suggesting that amino acid availability mediated FK506 toxicity. Therefore, these FK506-dependent responses could be relevant to the non-therapeutic effects of FK506 therapy.Received 16 October 2003; received after revision 8 January 2004; accepted 14 January 2004     

深海中的歌手——座头鲸

我清楚地记得去年夏季的某一天那不平凡的经历. 黄昏中我坐在我们那条小帆船的尾部,倚靠着一段木桩,借助落日的余辉又朝百慕大吉伯斯山灯塔看了一眼…离开陆地已经很远,今晚赶回去已来不及.我妻子凯蒂和我只好在海上过夜.即使在大白天驶过百慕大那变幻莫测的礁石也是够困难的,夜里那就简直是不可能的事了.     

Coulomb blockade and the Kondo effect in single-atom transistors

Using molecules as electronic components is a powerful new direction in the science and technology of nanometre-scale systems. Experiments to date have examined a multitude of molecules conducting in parallel, or, in some cases, transport through single molecules. The latter includes molecules probed in a two-terminal geometry using mechanically controlled break junctions or scanning probes as well as three-terminal single-molecule transistors made from carbon nanotubes, C(60) molecules, and conjugated molecules diluted in a less-conducting molecular layer. The ultimate limit would be a device where electrons hop on to, and off from, a single atom between two contacts. Here we describe transistors incorporating a transition-metal complex designed so that electron transport occurs through well-defined charge states of a single atom. We examine two related molecules containing a Co ion bonded to polypyridyl ligands, attached to insulating tethers of different lengths. Changing the length of the insulating tether alters the coupling of the ion to the electrodes, enabling the fabrication of devices that exhibit either single-electron phenomena, such as Coulomb blockade, or the Kondo effect.     

Large Cretaceous sphenodontian from Patagonia provides insight into lepidosaur evolution in Gondwana

Sphenodontian reptiles successfully radiated during Triassic and Jurassic times, but were driven almost to extinction during the Cretaceous period. The sparse Early Cretaceous record of sphenodontians has been interpreted as reflecting the decline of the group in favour of lizards, their suspected ecological successors. However, recent discoveries in Late Cretaceous beds in Patagonia partially modify this interpretation. Numerous skeletons of a new sphenodontian, Priosphenodon avelasi gen. et sp. nov., were collected from a single locality in the Cenomanian-Turonian Candeleros Formation, where it is more abundant than any other tetrapod group recorded in the quarry (for example, Crocodyliformes, Serpentes, Dinosauria and Mammalia). Adult specimens of Priosphenodon reached one metre in length, larger than any previously known terrestrial sphenodontian. Here we propose, using available evidence, that sphenodontians were not a minor component of the Cretaceous terrestrial ecosystems of South America, and that their ecological replacement by squamates was delayed until the early Tertiary. The new discovery helps to bridge the considerable gap in the fossil record (around 120 million years) that separates the Early Cretaceous sphenodontians from their living relatives (Sphenodon).     

Application of ICP-MS trace element analysis in study of ancient Chinese ceramics

Chemical analysis plays a significant role in the study of ancient ceramics[1,2]. Most ancient Chinese kilns used clays mined from the local areas and differences in the geochemistry and mineralogy of these raw materials may be expected. The chemical composition of ceramics may also be influenced by production techniques, such as processing by washing and mixing of different sorts of raw materials. These may also vary from kiln to kiln and even change over time. Thus the raw materials and pro…     

Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28

Linkage disequilibrium (LD), or the non-random association of alleles, is poorly understood in the human genome. Population genetic theory suggests that LD is determined by the age of the markers, population history, recombination rate, selection and genetic drift. Despite the uncertainties in determining the relative contributions of these factors, some groups have argued that LD is a simple function of distance between markers. Disease-gene mapping studies and a simulation study gave differing predictions on the degree of LD in isolated and general populations. In view of the discrepancies between theory and experimental observations, we constructed a high-density SNP map of the Xq25-Xq28 region and analysed the male genotypes and haplotypes across this region for LD in three populations. The populations included an outbred European sample (CEPH males) and isolated population samples from Finland and Sardinia. We found two extended regions of strong LD bracketed by regions with no evidence for LD in all three samples. Haplotype analysis showed a paucity of haplotypes in regions of strong LD. Our results suggest that, in this region of the X chromosome, LD is not a monotonic function of the distance between markers, but is more a property of the particular location in the human genome.     

Fe3+掺杂TiO2薄膜的制备和光催化性能研究

以钛酸正丁酯、无水乙醇和冰醋酸为原料,采用溶胶—凝胶法制备了Fe^3＋掺杂的TiO2纳米薄膜。考察了其催化降解甲基蓝实验中的光催化活性和杀菌性能。并通过XRD、SEM等手段分析了Fe^3＋掺杂TiO2样品的相组成和表面形貌。在450℃时最佳反应物配比浓度为钛酸正丁酯：无水乙醇：冰醋酸：蒸馏水=1：4：1．5：0．2 （摩尔比）,Fe^3＋掺杂对TiO2薄膜光催化性有着重要的影响。     

拨开云雾看埃及之变——阿拉伯学者怎么看伊斯兰政治力量执政

当地时间7月3日晚,在埃及军方为支持和反对现任总统穆尔西的两大阵营设置的48小时解决危机最后期限到期后,埃及军方发表声明称,穆尔西已经下台,埃及将提前举行总统选举,总统职权暂时由最高宪法法院院长代行。历史是何其相似。2011年2月11日,穆巴拉克也是在开罗解放广场一浪高过一浪的抗议声中下台。区别在于,穆巴拉克是军人出身的强势总统;穆尔西则是埃及现代历史上第一位民选总统,同时还是埃及穆斯林兄弟会的成员。毫无疑问,在"阿拉伯之春"的影响下,西亚北非的政治生态发生了巨大变化,最明显的表现就是一些伊斯兰政治力量短期内迅速合法化、政党化,一些伊斯兰政党甚至进入了权力的中心。自2012年年中以来,埃及穆兄会、突尼斯复兴运动、摩洛哥公正与发展党相继上台执政,利比亚公正与建设党在议会