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231.
232.
X-linked inheritance of Fanconi anemia complementation group B 总被引:20,自引:0,他引:20
Meetei AR Levitus M Xue Y Medhurst AL Zwaan M Ling C Rooimans MA Bier P Hoatlin M Pals G de Winter JP Wang W Joenje H 《Nature genetics》2004,36(11):1219-1224
Fanconi anemia is an autosomal recessive syndrome characterized by diverse clinical symptoms, hypersensitivity to DNA crosslinking agents, chromosomal instability and susceptibility to cancer. Fanconi anemia has at least 11 complementation groups (A, B, C, D1, D2, E, F, G, I, J, L); the genes mutated in 8 of these have been identified. The gene BRCA2 was suggested to underlie complementation group B, but the evidence is inconclusive. Here we show that the protein defective in individuals with Fanconi anemia belonging to complementation group B is an essential component of the nuclear protein 'core complex' responsible for monoubiquitination of FANCD2, a key event in the DNA-damage response pathway associated with Fanconi anemia and BRCA. Unexpectedly, the gene encoding this protein, FANCB, is localized at Xp22.31 and subject to X-chromosome inactivation. X-linked inheritance has important consequences for genetic counseling of families with Fanconi anemia belonging to complementation group B. Its presence as a single active copy and essentiality for a functional Fanconi anemia-BRCA pathway make FANCB a potentially vulnerable component of the cellular machinery that maintains genomic integrity. 相似文献
233.
Electrical detection of the spin resonance of a single electron in a silicon field-effect transistor
The ability to manipulate and monitor a single-electron spin using electron spin resonance is a long-sought goal. Such control would be invaluable for nanoscopic spin electronics, quantum information processing using individual electron spin qubits and magnetic resonance imaging of single molecules. There have been several examples of magnetic resonance detection of a single-electron spin in solids. Spin resonance of a nitrogen-vacancy defect centre in diamond has been detected optically, and spin precession of a localized electron spin on a surface was detected using scanning tunnelling microscopy. Spins in semiconductors are particularly attractive for study because of their very long decoherence times. Here we demonstrate electrical sensing of the magnetic resonance spin-flips of a single electron paramagnetic spin centre, formed by a defect in the gate oxide of a standard silicon transistor. The spin orientation is converted to electric charge, which we measure as a change in the source/drain channel current. Our set-up may facilitate the direct study of the physics of spin decoherence, and has the practical advantage of being composed of test transistors in a conventional, commercial, silicon integrated circuit. It is well known from the rich literature of magnetic resonance studies that there sometimes exist structural paramagnetic defects near the Si/SiO2 interface. For a small transistor, there might be only one isolated trap state that is within a tunnelling distance of the channel, and that has a charging energy close to the Fermi level. 相似文献
234.
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
235.
基于SVC的变电站中电磁辐射测试分析 总被引:3,自引:0,他引:3
安装新型静态无功补偿器(SVC)的变电站,其电磁兼容环境需要重新评估,以提出足够的电磁抗扰性措施。应用电磁场天线和光纤传输等技术,对4个不同类型的SVC变电站进行了现场测试和分析,结果表明SVC的高频电磁辐射集中在10kHz至3.5MHz,最大辐射强度为磁场0.87A/m和电场114V/m。将测量数据与当前国际电工委员会的IEC61000-4系列电磁兼容标准进行了相关比较,针对基于SVC的电磁辐射干扰提出两项抗扰性试验的具体改进建议。初步理论分析指出,晶闸管阀的开关特性和SVC结构的杂散参数是产生高频辐射干扰(谐波以上)的主要原因。 相似文献
236.
The 176Lu to 176Hf decay series has been widely used to understand the nature of Earth's early crust-mantle system. The interpretation, however, of Lu-Hf isotope data requires accurate knowledge of the radioactive decay constant of 176Lu (lambda176Lu), as well as bulk-Earth reference parameters. A recent calibration of the lambda176Lu value calls for the presence of highly unradiogenic hafnium in terrestrial zircons with ages greater than 3.9 Gyr, implying widespread continental crust extraction from an isotopically enriched mantle source more than 4.3 Gyr ago, but does not provide evidence for a complementary depleted mantle reservoir. Here we report Lu-Hf isotope measurements of different Solar System objects including chondrites and basaltic eucrites. The chondrites define a Lu-Hf isochron with an initial 176Hf/177Hf ratio of 0.279628 +/- 0.000047, corresponding to lambda176Lu = 1.983 +/- 0.033 x 10-11 yr-1 using an age of 4.56 Gyr for the chondrite-forming event. This lambda176Lu value indicates that Earth's oldest minerals were derived from melts of a mantle source with a time-integrated history of depletion rather than enrichment. The depletion event must have occurred no later than 320 Myr after planetary accretion, consistent with timing inferred from extinct radionuclides. 相似文献
237.
Self-organization of dissolved organic matter to micelle-like microparticles in river water 总被引:1,自引:0,他引:1
In aquatic systems, the concept of the 'microbial loop' is invoked to describe the conversion of dissolved organic matter to particulate organic matter by bacteria. This process mediates the transfer of energy and matter from dissolved organic matter to higher trophic levels, and therefore controls (together with primary production) the productivity of aquatic systems. Here we report experiments on laboratory incubations of sterile filtered river water in which we find that up to 25% of the dissolved organic carbon (DOC) aggregates abiotically to particles of diameter 0.4-0.8 micrometres, at rates similar to bacterial growth. Diffusion drives aggregation of low- to high-molecular-mass DOC and further to larger micelle-like microparticles. The chemical composition of these microparticles suggests their potential use as food by planktonic bacterivores. This pathway is apparent from differences in the stable carbon isotope compositions of picoplankton and the microparticles. A large fraction of dissolved organic matter might therefore be channelled through microparticles directly to higher trophic levels--bypassing the microbial loop--suggesting that current concepts of carbon conversion in aquatic systems require revision. 相似文献
238.
Stable isotopic evidence for methane seeps in Neoproterozoic postglacial cap carbonates 总被引:3,自引:0,他引:3
The Earth's most severe glaciations are thought to have occurred about 600 million years ago, in the late Neoproterozoic era. A puzzling feature of glacial deposits from this interval is that they are overlain by 1-5-m-thick 'cap carbonates' (particulate deep-water marine carbonate rocks) associated with a prominent negative carbon isotope excursion. Cap carbonates have been controversially ascribed to the aftermath of almost complete shutdown of the ocean ecosystems for millions of years during such ice ages--the 'snowball Earth' hypothesis. Conversely, it has also been suggested that these carbonate rocks were the result of destabilization of methane hydrates during deglaciation and concomitant flooding of continental shelves and interior basins. The most compelling criticism of the latter 'methane hydrate' hypothesis has been the apparent lack of extreme isotopic variation in cap carbonates inferred locally to be associated with methane seeps. Here we report carbon isotopic and petrographic data from a Neoproterozoic postglacial cap carbonate in south China that provide direct evidence for methane-influenced processes during deglaciation. This evidence lends strong support to the hypothesis that methane hydrate destabilization contributed to the enigmatic cap carbonate deposition and strongly negative carbon isotopic anomalies following Neoproterozoic ice ages. This explanation requires less extreme environmental disturbance than that implied by the snowball Earth hypothesis. 相似文献
239.
240.
Walther TC Askjaer P Gentzel M Habermann A Griffiths G Wilm M Mattaj IW Hetzer M 《Nature》2003,424(6949):689-694
In metazoa, the nuclear envelope breaks down and reforms during each cell cycle. Nuclear pore complexes (NPCs), which serve as channels for transport between the nucleus and cytoplasm, assemble into the reforming nuclear envelope in a sequential process involving association of a subset of NPC proteins, nucleoporins, with chromatin followed by the formation of a closed nuclear envelope fenestrated by NPCs. How chromatin recruitment of nucleoporins and NPC assembly are regulated is unknown. Here we demonstrate that RanGTP production is required to dissociate nucleoporins Nup107, Nup153 and Nup358 from Importin beta, to target them to chromatin and to induce association between separate NPC subcomplexes. Additionally, either an excess of RanGTP or removal of Importin beta induces formation of NPC-containing membrane structures--annulate lamellae--both in vitro in the absence of chromatin and in vivo. Annulate lamellae formation is strongly and specifically inhibited by an excess of Importin beta. The data demonstrate that RanGTP triggers distinct steps of NPC assembly, and suggest a mechanism for the spatial restriction of NPC assembly to the surface of chromatin. 相似文献