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931.
A naturally occurring MTA1 variant sequesters oestrogen receptor-alpha in the cytoplasm 总被引:13,自引:0,他引:13
Kumar R Wang RA Mazumdar A Talukder AH Mandal M Yang Z Bagheri-Yarmand R Sahin A Hortobagyi G Adam L Barnes CJ Vadlamudi RK 《Nature》2002,418(6898):654-657
Oestrogen receptor (ER) is a good prognostic marker for the treatment of breast cancers. Upregulation of metastatic tumour antigen 1 (MTA1) is associated with the invasiveness and metastatic potential of several human cancers and acts as a co-repressor of nuclear ER-alpha. Here we identify a naturally occurring short form of MTA1 (MTA1s) that contains a previously unknown sequence of 33 amino acids with an ER-binding motif, Leu-Arg-Ile-Leu-Leu (LRILL). MTA1s localizes in the cytoplasm, sequesters ER in the cytoplasm, and enhances non-genomic responses of ER. Deleting the LRILL motif in MTA1s abolishes its co-repressor function and its interaction with ER, and restores nuclear localization of ER. Dysregulation of human epidermal growth factor receptor-2 in breast cancer cells enhances the expression of MTA1s and the cytoplasmic sequestration of ER. Expression of MTA1s in breast cancer cells prevents ligand-induced nuclear translocation of ER and stimulates malignant phenotypes. MTA1s expression is increased in human breast tumours with no or low nuclear ER. The regulation of the cellular localization of ER by MTA1s represents a mechanism for redirecting nuclear receptor signalling by nuclear exclusion. 相似文献
932.
Rapid accretion and early core formation on asteroids and the terrestrial planets from Hf-W chronometry 总被引:2,自引:0,他引:2
The timescales and mechanisms for the formation and chemical differentiation of the planets can be quantified using the radioactive decay of short-lived isotopes. Of these, the (182)Hf-to-(182)W decay is ideally suited for dating core formation in planetary bodies. In an earlier study, the W isotope composition of the Earth's mantle was used to infer that core formation was late (> or = 60 million years after the beginning of the Solar System) and that accretion was a protracted process. The correct interpretation of Hf-W data depends, however, on accurate knowledge of the initial abundance of (182)Hf in the Solar System and the W isotope composition of chondritic meteorites. Here we report Hf-W data for carbonaceous and H chondrite meteorites that lead to timescales of accretion and core formation significantly different from those calculated previously. The revised ages for Vesta, Mars and Earth indicate rapid accretion, and show that the timescale for core formation decreases with decreasing size of the planet. We conclude that core formation in the terrestrial planets and the formation of the Moon must have occurred during the first approximately 30 million years of the life of the Solar System. 相似文献
933.
934.
A key question in ecology is which factors control species diversity in a community. Two largely separate groups of ecologists have emphasized the importance of productivity or resource supply, and consumers or physical disturbance, respectively. These variables show unimodal relationships with diversity when manipulated in isolation. Recent multivariate models, however, predict that these factors interact, such that the disturbance diversity relationship depends on productivity, and vice versa. We tested these models in marine food webs, using field manipulations of nutrient resources and consumer pressure on rocky shores of contrasting productivity. Here we show that the effects of consumers and nutrients on diversity consistently depend on each other, and that the direction of their effects and peak diversity shift between sites of low and high productivity. Factorial meta-analysis of published experiments confirms these results across widely varying aquatic communities. Furthermore, our experiments demonstrate that these patterns extend to important ecosystem functions such as carbon storage and nitrogen retention. This suggests that human impacts on nutrient supply and food-web structure have strong and interdependent effects on species diversity and ecosystem functioning, and must therefore be managed together. 相似文献
935.
VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism 总被引:49,自引:0,他引:49
Gerber HP Malik AK Solar GP Sherman D Liang XH Meng G Hong K Marsters JC Ferrara N 《Nature》2002,417(6892):954-958
Vascular endothelial growth factor (VEGF) is a principal regulator of blood vessel formation and haematopoiesis, but the mechanisms by which VEGF differentially regulates these processes have been elusive. Here we describe a regulatory loop by which VEGF controls survival of haematopoietic stem cells (HSCs). We observed a reduction in survival, colony formation and in vivo repopulation rates of HSCs after ablation of the VEGF gene in mice. Intracellularly acting small-molecule inhibitors of VEGF receptor (VEGFR) tyrosine kinase dramatically reduced colony formation of HSCs, thus mimicking deletion of the VEGF gene. However, blocking VEGF by administering a soluble VEGFR-1, which acts extracellularly, induced only minor effects. These findings support the involvement in HSC survival of a VEGF-dependent internal autocrine loop mechanism (that is, the mechanism is resistant to inhibitors that fail to penetrate the intracellular compartment). Not only ligands selective for VEGF and VEGFR-2 but also VEGFR-1 agonists rescued survival and repopulation of VEGF-deficient HSCs, revealing a function for VEGFR-1 signalling during haematopoiesis. 相似文献
936.
The T-box genes Tbx4 and Tbx5 have been shown to have key functions in the specification of the identity of the vertebrate forelimb (Tbx5) and hindlimb (Tbx4). Here we show that in zebrafish, Tbx5 has an additional early function that precedes the formation of the limb bud itself. Functional knockdown of zebrafish tbx5 through the use of an antisense oligonucleotide resulted in a failure to initiate fin bud formation, leading to the complete loss of pectoral fins. The function of the tbx5 gene in the development of zebrafish forelimbs seems to involve the directed migration of individual lateral-plate mesodermal cells into the future limb-bud-producing region. The primary defect seen in the tbx5-knockdown phenotype is similar to the primary defects described in known T-box-gene mutants such as the spadetail mutant of zebrafish and the Brachyury mutant of the mouse, which both similarly exhibit an altered migration of mesodermal cells. A common function for many of the T-box genes might therefore be in mediating the proper migration and/or changes in adhesive properties of early embryonic cells. 相似文献
937.
938.
Qiuli?Li Shuguang?LiEmail author Hongying?Zhou Huimin?Li Ji’an?Hong Qingchen?Wang H.?J.?Massonne 《科学通报(英文版)》2002,47(1):62-65
The U-Pb isotope compositions of rutile, omphacite and garnet in the eclogite from the Jinheqiao area in the Southern Dabie ultrahigh-pressure metamorphic zone were analyzed. The consistent high precision U-Pb age (218 ± 1.2) Ma of rutile in eclogite from the Dabie Mountains was obtained by two ways of isochron and common Pb correction based on the composition of omphacite. This proves that the omphacite in eclogite has a U/Pb ratio (m = 2.8) low enough to be used for common Pb correction in the analyses of rutile. Under the rapid cooling condition (40℃/Ma) the closure temperature for U-Pb diffusion in rutile is about 470℃. Thus, this U-Pb age of rutile proves that 218 Ma should be the cooling age of eclogite at 470℃ instead of the peak metamorphic age. 相似文献
939.
Calcineurin (CN) is thought to play a role in the synaptic plastivity and long-term potentiation (LTP) in the hippocampus.
Based on two LTP models in vivo, a specific inhibitor cyclosporin A (CsA) of CN was observed, which affected LTP in the hippocampal dentate gyrus of the
rats. The results indicated that CsA blocked LTP induced by high frequency stimulation (HFS) partly, but it had no effect
on the decrease of the onset and peak latency of population spikes (PS) except that it reduced the increase of the amplitude
after HFS. On the other hand, CsA blocked LTP induced by ginsenosides (GSS) completely. It suppressed the GSS-enhanced amplitude
of PS reversibly and blocked the decrease of the peak latency of PS induced by the GSS. These results suggest that the postsynaptic
CN plays a role in the induction of LTP in the hippocampus of the rats. 相似文献
940.
Zhuo?XuEmail author Shuguang?Zheng Zhenxing?Yue Yujun?Feng An?Jin Xi?Yao 《科学通报(英文版)》2002,47(6):513-518
The dielectric properties of Pb(Zn11/3Nb2/3)O3− BaTiO3−PbTiO3 relaxor ferroelectric ceramics near the rhombohedral and tetragonal phase boundary were investigated under hydrostatic pressure.
It was found that hydrostatic pressure made their phase transition temperature T
c and the peak temperature T
m decreased, and the frequency dispersion and relaxor behavior enhanced. In these disorder systems of composite pervoskite
structures, there appeared polar clusters or nanodomains. The unique physical characteristics, which made the relaxor behavior
enhanced, is that the correlation length among these nanodomains decreases greatly with the pressure increasing. 相似文献