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141.
Mutual synergistic folding in recruitment of CBP/p300 by p160 nuclear receptor coactivators 总被引:11,自引:0,他引:11
Demarest SJ Martinez-Yamout M Chung J Chen H Xu W Dyson HJ Evans RM Wright PE 《Nature》2002,415(6871):549-553
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143.
Ostertag EM DeBerardinis RJ Goodier JL Zhang Y Yang N Gerton GL Kazazian HH 《Nature genetics》2002,32(4):655-660
The L1 retrotransposon has had an immense impact on the size and structure of the human genome through a variety of mechanisms, including insertional mutagenesis. To study retrotransposition in a living organism, we created a mouse model of human L1 retrotransposition. Here we show that L1 elements can retrotranspose in male germ cells, and that expression of a human L1 element under the control of its endogenous promoter is restricted to testis and ovary. In the mouse line with the highest level of L1 expression, we found two de novo L1 insertions in 135 offspring. Both insertions were structurally indistinguishable from natural endogenous insertions. This suggests that an individual L1 element can have substantial mutagenic potential. In addition to providing a valuable in vivo model of retrotransposition in mammals, these mice are an important step in the development of a new random mutagenesis system. 相似文献
144.
Instant neural control of a movement signal 总被引:41,自引:0,他引:41
The activity of motor cortex (MI) neurons conveys movement intent sufficiently well to be used as a control signal to operate artificial devices, but until now this has called for extensive training or has been confined to a limited movement repertoire. Here we show how activity from a few (7-30) MI neurons can be decoded into a signal that a monkey is able to use immediately to move a computer cursor to any new position in its workspace (14 degrees x 14 degrees visual angle). Our results, which are based on recordings made by an electrode array that is suitable for human use, indicate that neurally based control of movement may eventually be feasible in paralysed humans. 相似文献
145.
The earliest known eutherian mammal 总被引:23,自引:0,他引:23
The skeleton of a eutherian (placental) mammal has been discovered from the Lower Cretaceous Yixian Formation of northeastern China. We estimate its age to be about 125 million years (Myr), extending the date of the oldest eutherian records with skull and skeleton by about 40 50 Myr. Our analyses place the new fossil at the root of the eutherian tree and among the four other known Early Cretaceous eutherians, and suggest an earlier and greater diversification of stem eutherians that occurred well before the molecular estimate for the diversification of extant placental superorders (104 64 Myr). The new eutherian has limb and foot features that are known only from scansorial (climbing) and arboreal (tree-living) extant mammals, in contrast to the terrestrial or cursorial (running) features of other Cretaceous eutherians. This suggests that the earliest eutherian lineages developed different locomotory adaptations, facilitating their spread to diverse niches in the Cretaceous. 相似文献
146.
Heterotrimeric G-proteins bind to cell-surface receptors and are integral in transmission of signals from outside the cell. Upon activation of the Galpha subunit by binding of GTP, the Galpha and Gbetagamma subunits dissociate and interact with effector proteins for signal transduction. Regulatory proteins with the 19-amino-acid GoLoco motif can bind to Galpha subunits and maintain G-protein subunit dissociation in the absence of Galpha activation. Here we describe the structural determinants of GoLoco activity as revealed by the crystal structure of Galpha(i1) GDP bound to the GoLoco region of the 'regulator of G-protein signalling' protein RGS14. Key contacts are described between the GoLoco motif and Galpha protein, including the extension of GoLoco's highly conserved Asp/Glu-Gln-Arg triad into the nucleotide-binding pocket of Galpha to make direct contact with the GDP alpha- and beta-phosphates. The structural organization of the GoLoco Galpha(i1) complex, when combined with supporting data from domain-swapping experiments, suggests that the Galpha all-helical domain and GoLoco-region carboxy-terminal residues control the specificity of GoLoco Galpha interactions. 相似文献
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148.
Chaudhari P Lacey J Doyle J Galligan E Lien SC Callegari A Hougham G Lang ND Andry PS John R Yang KH Lu M Cai C Speidell J Purushothaman S Ritsko J Samant M Stöhr J Nakagawa Y Katoh Y Saitoh Y Sakai K Satoh H Odahara S Nakano H Nakagaki J Shiota Y 《Nature》2001,411(6833):56-59
The technique used to align liquid crystals-rubbing the surface of a substrate on which a liquid crystal is subsequently deposited-has been perfected by the multibillion-dollar liquid-crystal display industry. However, it is widely recognized that a non-contact alignment technique would be highly desirable for future generations of large, high-resolution liquid-crystal displays. A number of alternative alignment techniques have been reported, but none of these have so far been implemented in large-scale manufacturing. Here, we report a non-contact alignment process, which uses low-energy ion beams impinging at a glancing angle on amorphous inorganic films, such as diamond-like carbon. Using this approach, we have produced both laptop and desktop displays in pilot-line manufacturing, and found that displays of higher quality and reliability could be made at a lower cost than the rubbing technique. The mechanism of alignment is explained by adopting a random network model of atomic arrangement in the inorganic films. Order is induced by exposure to an ion beam because unfavourably oriented rings of atoms are selectively destroyed. The planes of the remaining rings are predominantly parallel to the direction of the ion beam. 相似文献
149.
The composition of mid-ocean-ridge basalt is known to correlate with attributes such as ridge topography and seismic velocity in the underlying mantle, and these correlations have been interpreted to reflect variations in the average extent and mean pressures of melting during mantle upwelling. In this respect, the eastern extremity of the southwest Indian ridge is of special interest, as its mean depth of 4.7 km (ref. 4), high upper-mantle seismic wave velocities and thin oceanic crust of 4-5 km (ref. 6) suggest the presence of unusually cold mantle beneath the region. Here we show that basaltic glasses dredged in this zone, when compared to other sections of the global mid-ocean-ridge system, have higher Na(8.0), Sr and Al2O3 compositions, very low CaO/Al2O3 ratios relative to TiO2 and depleted heavy rare-earth element distributions. This signature cannot simply be ascribed to low-degree melting of a typical mid-ocean-ridge source mantle, as different geochemical indicators of the extent of melting are mutually inconsistent. Instead, we propose that the mantle beneath approximately 1,000 km of the southwest Indian ridge axis has a complex history involving extensive earlier melting events and interaction with partial melts of a more fertile source. 相似文献
150.
The Carnivora are one of only four orders of terrestrial mammals living in Madagascar today. All four (carnivorans, primates, rodents and lipotyphlan insectivores) are placental mammals with limited means for dispersal, yet they occur on a large island that has been surrounded by a formidable oceanic barrier for at least 88 million years, predating the age of origin for any of these groups. Even so, as many as four colonizations of Madagascar have been proposed for the Carnivora alone. The mystery of the island's mammalian origins is confounded by its poor Tertiary fossil record, which leaves us with no direct means for estimating dates of initial diversification. Here we use a multi-gene phylogenetic analysis to show that Malagasy carnivorans are monophyletic and thus the product of a single colonization of Madagascar by an African ancestor. Furthermore, a bayesian analysis of divergence ages for Malagasy carnivorans and lemuriforms indicates that their respective colonizations were temporally separated by tens of millions of years. We therefore conclude that a single event, such as vicariance or common dispersal, cannot explain the presence of both groups in Madagascar. 相似文献