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31.
Maurer M Wedemeyer J Metz M Piliponsky AM Weller K Chatterjea D Clouthier DE Yanagisawa MM Tsai M Galli SJ 《Nature》2004,432(7016):512-516
Endothelin-1 (ET-1) is a 21-amino-acid peptide, derived from vascular endothelial cells, with potent vasoconstrictor activity. ET-1 has been implicated in diverse physiological or pathological processes, including the vascular changes associated with sepsis. However, the factors that regulate ET-1-associated toxicity during bacterial infections, or in other settings, are not fully understood. Both the pathology associated with certain allergic and autoimmune disorders, and optimal host defence against bacterial and parasitic infections are mediated by mast cells. In vitro, mast cells can produce ET-1 (ref. 11), undergo ET-1-dependent and endothelin-A receptor (ET(A))-dependent activation, and release proteases that degrade ET-1 (ref. 14). Although the potential relationships between mast cells and the ET-1 system thus may be complex, the importance of interactions between ET-1 and mast cells in vivo is obscure. Here we show that ET(A)-dependent mast-cell activation can diminish both ET-1 levels and ET-1-induced pathology in vivo, and also can contribute to optimal survival during acute bacterial peritonitis. These findings identify a new biological function for mast cells: promotion of homeostasis by limiting the toxicity associated with an endogenous mediator. 相似文献
32.
Following the demonstration of coherent control of the quantum state of a superconducting charge qubit, a variety of qubits based on Josephson junctions have been implemented. Although such solid-state devices are not currently as advanced as microscopic qubits based on nuclear magnetic resonance and ion trap technologies, the potential scalability of the former systems--together with progress in their coherence times and read-out schemes--makes them strong candidates for the building block of a quantum computer. Recently, coherent oscillations and microwave spectroscopy of capacitively coupled superconducting qubits have been reported; the next challenging step towards quantum computation is the realization of logic gates. Here we demonstrate conditional gate operation using a pair of coupled superconducting charge qubits. Using a pulse technique, we prepare different input states and show that their amplitude can be transformed by controlled-NOT (C-NOT) gate operation, although the phase evolution during the gate operation remains to be clarified. 相似文献
33.
促进型甲酸甲酯氢解制甲醇铜基催化剂的研究 总被引:2,自引:0,他引:2
研制开发了一种耐CO低温高效四组分(Cu-Cr-Mn-Ni)改进铜铬催化剂,其原料合成气中CO允许含量可高达13V%;在常压,413K,原料气H2/MF=4/1(v/v),流速为1800mL/hgcatal.的反应条件下,MF转化率高达99.8%,甲醇选择性为99.9%(在相同反应条件下二组分的Cu-Cr催化剂上MF转化率仅为73.1%,甲醇选择性为98.0%),当向原料气中添加13.1V%CO时,MF转化率仍可以稳定达到95.9%,甲醇选择性为96.3%.实验结果表明,CO导致催化剂失活的重要原因之一是CO导致Cu+深度还原为Cu0,减少催化剂的活性中心 相似文献
34.
The Dongcaohe ophiolite from the North Qilian Mountains: A fossil oceanic crust of the Paleo-Qilian ocean 总被引:9,自引:0,他引:9
Chien-Yuan TSENG Huai-Jen YANG Houng-Yi YANG LIU DunYi Ching-Lang TSAI WU HanQuan ZUO GuoChao 《科学通报(英文版)》2007,52(17):2390-2401
The Dongcaohe ophiolite, located at the south of the North Qilian subduction complexes, is a tectonic block with an exposed area of about 3 km×6 km. It consists of an intrusive section overlain by an ex- trusive section. The lower part of the intrusive section consists of cyclic layers of cumulate dunites, troctolites, anorthosites, anorthositic gabbros, and gabbros with small discordant dunite and troctolite bodies. This layered sequence grades upward to isotropic gabbros and gabbronorites, which are overlain by the extrusive sequence of diabasic sheeted dikes and basaltic lavas. The overall mineral crystallization sequence was olivine±Cr-spinel, plagioclase, clinopyroxene, orthopyroxene, and Fe-Ti oxides. The Cr-spinel (Mg#: 42-66, Cr#: 41-57) in these layered cumulates and present-day abyssal peridotites have similar compositions. Also, the compositional variations of the plagioclase and cli- nopyroxene in the intrusive section reflect crystallization from melts compositionally similar to the present-day ocean basalts. Moreover, the rare earth element (REE) and multi-element distribution pat- terns of the intrusive and extrusive lithologies in the Dongcaohe ophiolite are consistent with crystal- lization of mid-ocean ridge basalts. The zircon grains separated from the gabbronorite have an SHRIMP average 206Pb/238U weighted age of 497 ± 7 Ma, which is considered as the tectonic emplacement age of the Dongcaohe ophiolite. The field occurrence, mineral and whole-rock compositions indicate that the Dongcaohe ophiolite represents a well-persevered oceanic crustal fragment composed of a complete oceanic crustal section of layered cumulates at bottom upgrading through isotropic cumulates to sheeted dikes and lava flows. 相似文献
35.
攀西地区由于气候条件特殊,冬季光照充足,热量丰富,但降水量较少,干旱严重,影响作物生长和产量。通过免耕或少耕可以改善土壤物理化学性状,保护土壤,增加蓄水量,节省劳畜力,降低成本,而且还可以争取农时,及时播栽,扩大复种,提高产量,增加经济效益,该措施在攀西地区有着较大的发展潜力。 相似文献
36.
Lee K Jeong J Kwak I Yu CT Lanske B Soegiarto DW Toftgard R Tsai MJ Tsai S Lydon JP DeMayo FJ 《Nature genetics》2006,38(10):1204-1209
The hedgehog family of morphogens are regulators of cell proliferation, differentiation and cell-cell communication. These morphogens have been shown to have important roles in organogenesis, spermatogenesis, stem cell maintenance and oncogenesis. Indian hedgehog (encoded by Ihh) has been shown to be expressed in the uterine epithelium under the control of the steroid hormone, progesterone. Although in vivo and in vitro studies have shown that progesterone achieves its effects on uterine function through epithelial-stromal cross-talk, molecular mediator(s) for this cellular communication pathway have not been elucidated. Using new experimental approaches that ablate Ihh specifically in Pgr-positive uterine cells of the mouse, we demonstrate that Ihh is an essential mediator of Pgr action in the uterus, and expression of this factor is critical in mediating the communication between the uterine epithelium and stroma required for embryo implantation. 相似文献
37.
Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis
Lee YC Kuo HC Chang JS Chang LY Huang LM Chen MR Liang CD Chi H Huang FY Lee ML Huang YC Hwang B Chiu NC Hwang KP Lee PC Chang LC Liu YM Chen YJ Chen CH;Taiwan Pediatric ID Alliance Chen YT Tsai FJ Wu JY 《Nature genetics》2012,44(5):522-525
To find new candidate loci predisposing individuals to Kawasaki disease, an acute vasculitis that affects children, we conducted a genome-wide association study in 622 individuals with Kawasaki disease (cases) and 1,107 controls in a Han Chinese population residing in Taiwan, with replication in an independent Han Chinese sample of 261 cases and 550 controls. We report two new loci, one at BLK (encoding B-lymphoid tyrosine kinase) and one at CD40, that are associated with Kawasaki disease at genome-wide significance (P < 5 × 10(-8)). Our findings may lead to a better understanding of the role of immune activation and inflammation in Kawasaki disease pathogenesis. 相似文献
38.
Y Okada X Sim MJ Go JY Wu D Gu F Takeuchi A Takahashi S Maeda T Tsunoda P Chen SC Lim TY Wong J Liu TL Young T Aung M Seielstad YY Teo YJ Kim JY Lee BG Han D Kang CH Chen FJ Tsai LC Chang SJ Fann H Mei DC Rao JE Hixson S Chen T Katsuya M Isono T Ogihara JC Chambers W Zhang JS Kooner;KidneyGen Consortium;CKDGen Consortium E Albrecht;GUGC consortium K Yamamoto M Kubo Y Nakamura N Kamatani N Kato J He YT Chen YS Cho ES Tai T Tanaka 《Nature genetics》2012,44(8):904-909
Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ~110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function. 相似文献
39.
Arteries and veins are anatomically, functionally and molecularly distinct. The current model of arterial-venous identity proposes that binding of vascular endothelial growth factor to its heterodimeric receptor--Flk1 and neuropilin 1 (NP-1; also called Nrp1)--activates the Notch signalling pathway in the endothelium, causing induction of ephrin B2 expression and suppression of ephrin receptor B4 expression to establish arterial identity. Little is known about vein identity except that it involves ephrin receptor B4 expression, because Notch signalling is not activated in veins; an unresolved question is how vein identity is regulated. Here, we show that COUP-TFII (also known as Nr2f2), a member of the orphan nuclear receptor superfamily, is specifically expressed in venous but not arterial endothelium. Ablation of COUP-TFII in endothelial cells enables veins to acquire arterial characteristics, including the expression of arterial markers NP-1 and Notch signalling molecules, and the generation of haematopoietic cell clusters. Furthermore, ectopic expression of COUP-TFII in endothelial cells results in the fusion of veins and arteries in transgenic mouse embryos. Thus, COUP-TFII has a critical role in repressing Notch signalling to maintain vein identity, which suggests that vein identity is under genetic control and is not derived by a default pathway. 相似文献
40.
Neurotoxicity induces cleavage of p35 to p25 by calpain 总被引:52,自引:0,他引:52
Cyclin-dependent kinase 5 (cdk5) and its neuron-specific activator p35 are required for neurite outgrowth and cortical lamination. Proteolytic cleavage of p35 produces p25, which accumulates in the brains of patients with Alzheimer's disease. Conversion of p35 to p25 causes prolonged activation and mislocalization of cdk5. Consequently, the p25/cdk5 kinase hyperphosphorylates tau, disrupts the cytoskeleton and promotes the death (apoptosis) of primary neurons. Here we describe the mechanism of conversion of p35 to p25. In cultured primary cortical neurons, excitotoxins, hypoxic stress and calcium influx induce the production of p25. In fresh brain lysates, addition of calcium can stimulate cleavage of p35 to p25. Specific inhibitors of calpain, a calcium-dependent cysteine protease, effectively inhibit the calcium-induced cleavage of p35. In vitro, calpain directly cleaves p35 to release a fragment with relative molecular mass 25,000. The sequence of the calpain cleavage product corresponds precisely to that of p25. Application of the amyloid beta-peptide A beta(1-42) induces the conversion of p35 to p25 in primary cortical neurons. Furthermore, inhibition of cdk5 or calpain activity reduces cell death in A beta-treated cortical neurons. These observations indicate that cleavage of p35 to p25 by calpain may be involved in the pathogenesis of Alzheimer's disease. 相似文献