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排序方式: 共有256条查询结果,搜索用时 468 毫秒
191.
192.
Wen JD Lancaster L Hodges C Zeri AC Yoshimura SH Noller HF Bustamante C Tinoco I 《Nature》2008,452(7187):598-603
We have followed individual ribosomes as they translate single messenger RNA hairpins tethered by the ends to optical tweezers. Here we reveal that translation occurs through successive translocation--and-pause cycles. The distribution of pause lengths, with a median of 2.8 s, indicates that at least two rate-determining processes control each pause. Each translocation step measures three bases--one codon-and occurs in less than 0.1 s. Analysis of the times required for translocation reveals, surprisingly, that there are three substeps in each step. Pause lengths, and thus the overall rate of translation, depend on the secondary structure of the mRNA; the applied force destabilizes secondary structure and decreases pause durations, but does not affect translocation times. Translocation and RNA unwinding are strictly coupled ribosomal functions. 相似文献
193.
Graupera M Guillermet-Guibert J Foukas LC Phng LK Cain RJ Salpekar A Pearce W Meek S Millan J Cutillas PR Smith AJ Ridley AJ Ruhrberg C Gerhardt H Vanhaesebroeck B 《Nature》2008,453(7195):662-666
Phosphoinositide 3-kinases (PI3Ks) signal downstream of multiple cell-surface receptor types. Class IA PI3K isoforms couple to tyrosine kinases and consist of a p110 catalytic subunit (p110alpha, p110beta or p110delta), constitutively bound to one of five distinct p85 regulatory subunits. PI3Ks have been implicated in angiogenesis, but little is known about potential selectivity among the PI3K isoforms and their mechanism of action in endothelial cells during angiogenesis in vivo. Here we show that only p110alpha activity is essential for vascular development. Ubiquitous or endothelial cell-specific inactivation of p110alpha led to embryonic lethality at mid-gestation because of severe defects in angiogenic sprouting and vascular remodelling. p110alpha exerts this critical endothelial cell-autonomous function by regulating endothelial cell migration through the small GTPase RhoA. p110alpha activity is particularly high in endothelial cells and preferentially induced by tyrosine kinase ligands (such as vascular endothelial growth factor (VEGF)-A). In contrast, p110beta in endothelial cells signals downstream of G-protein-coupled receptor (GPCR) ligands such as SDF-1alpha, whereas p110delta is expressed at low level and contributes only minimally to PI3K activity in endothelial cells. These results provide the first in vivo evidence for p110-isoform selectivity in endothelial PI3K signalling during angiogenesis. 相似文献
194.
Genes mirror geography within Europe 总被引:1,自引:0,他引:1
Novembre J Johnson T Bryc K Kutalik Z Boyko AR Auton A Indap A King KS Bergmann S Nelson MR Stephens M Bustamante CD 《Nature》2008,456(7218):98-101
Understanding the genetic structure of human populations is of fundamental interest to medical, forensic and anthropological sciences. Advances in high-throughput genotyping technology have markedly improved our understanding of global patterns of human genetic variation and suggest the potential to use large samples to uncover variation among closely spaced populations. Here we characterize genetic variation in a sample of 3,000 European individuals genotyped at over half a million variable DNA sites in the human genome. Despite low average levels of genetic differentiation among Europeans, we find a close correspondence between genetic and geographic distances; indeed, a geographical map of Europe arises naturally as an efficient two-dimensional summary of genetic variation in Europeans. The results emphasize that when mapping the genetic basis of a disease phenotype, spurious associations can arise if genetic structure is not properly accounted for. In addition, the results are relevant to the prospects of genetic ancestry testing; an individual's DNA can be used to infer their geographic origin with surprising accuracy-often to within a few hundred kilometres. 相似文献
195.
Warren WC Hillier LW Marshall Graves JA Birney E Ponting CP Grützner F Belov K Miller W Clarke L Chinwalla AT Yang SP Heger A Locke DP Miethke P Waters PD Veyrunes F Fulton L Fulton B Graves T Wallis J Puente XS López-Otín C Ordóñez GR Eichler EE Chen L Cheng Z Deakin JE Alsop A Thompson K Kirby P Papenfuss AT Wakefield MJ Olender T Lancet D Huttley GA Smit AF Pask A Temple-Smith P Batzer MA Walker JA Konkel MK Harris RS Whittington CM Wong ES Gemmell NJ Buschiazzo E Vargas Jentzsch IM Merkel A 《Nature》2008,453(7192):175-183
We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation. 相似文献
196.
Gómez-Consarnau L González JM Coll-Lladó M Gourdon P Pascher T Neutze R Pedrós-Alió C Pinhassi J 《Nature》2007,445(7124):210-213
Proteorhodopsins are bacterial light-dependent proton pumps. Their discovery within genomic material from uncultivated marine bacterioplankton caused considerable excitement because it indicated a potential phototrophic function within these organisms, which had previously been considered strictly chemotrophic. Subsequent studies established that sequences encoding proteorhodopsin are broadly distributed throughout the world's oceans. Nevertheless, the role of proteorhodopsins in native marine bacteria is still unknown. Here we show, from an analysis of the complete genomes of three marine Flavobacteria, that cultivated bacteria in the phylum Bacteroidetes, one of the principal components of marine bacterioplankton, contain proteorhodopsin. Moreover, growth experiments in both natural and artificial seawater (low in labile organic matter, which is typical of the world's oceans) establish that exposure to light results in a marked increase in the cell yield of one such bacterium (Dokdonia sp. strain MED134) when compared with cells grown in darkness. Thus, our results show that the phototrophy conferred by proteorhodopsin can provide critical amounts of energy, not only for respiration and maintenance but also for active growth of marine bacterioplankton in their natural environment. 相似文献
197.
198.
The d-enantiomers of amino acids have been thought to have relatively minor functions in biological processes. While l-amino acids clearly predominate in nature, d-amino acids are sometimes found in proteins that are not synthesized by ribosomes, and d-Ala and d-Glu are routinely found in the peptidoglycan cell wall of bacteria. Here, we review recent findings showing that d-amino acids have previously unappreciated regulatory roles in the bacterial kingdom. Many diverse bacterial phyla synthesize
and release d-amino acids, including d-Met and d-Leu, which were not previously known to be made. These noncanonical d-amino acids regulate cell wall remodeling in stationary phase and cause biofilm dispersal in aging bacterial communities.
Elucidating the mechanisms by which d-amino acids govern cell wall remodeling and biofilm disassembly will undoubtedly reveal new paradigms for understanding how
extracytoplasmic processes are regulated as well as lead to development of novel therapeutics. 相似文献
199.
Hu TT Pattyn P Bakker EG Cao J Cheng JF Clark RM Fahlgren N Fawcett JA Grimwood J Gundlach H Haberer G Hollister JD Ossowski S Ottilar RP Salamov AA Schneeberger K Spannagl M Wang X Yang L Nasrallah ME Bergelson J Carrington JC Gaut BS Schmutz J Mayer KF Van de Peer Y Grigoriev IV Nordborg M Weigel D Guo YL 《Nature genetics》2011,43(5):476-481
We report the 207-Mb genome sequence of the North American Arabidopsis lyrata strain MN47 based on 8.3× dideoxy sequence coverage. We predict 32,670 genes in this outcrossing species compared to the 27,025 genes in the selfing species Arabidopsis thaliana. The much smaller 125-Mb genome of A. thaliana, which diverged from A. lyrata 10 million years ago, likely constitutes the derived state for the family. We found evidence for DNA loss from large-scale rearrangements, but most of the difference in genome size can be attributed to hundreds of thousands of small deletions, mostly in noncoding DNA and transposons. Analysis of deletions and insertions still segregating in A. thaliana indicates that the process of DNA loss is ongoing, suggesting pervasive selection for a smaller genome. The high-quality reference genome sequence for A. lyrata will be an important resource for functional, evolutionary and ecological studies in the genus Arabidopsis. 相似文献
200.
Functional interplay between tetraspanins and proteases 总被引:1,自引:1,他引:0
Yáñez-Mó M Gutiérrez-López MD Cabañas C 《Cellular and molecular life sciences : CMLS》2011,68(20):3323-3335
Several recent publications have described examples of physical and functional interations between tetraspanins and specific
membrane proteases belonging to the TM-MMP and α-(ADAMs) and γ-secretases families. Collectively, these examples constitute
an emerging body of evidence supporting the notion that tetraspanin-enriched microdomains (TEMs) represent functional platforms
for the regulation of key cellular processes including the release of surface protein ectodomains ("shedding"), regulated
intramembrane proteolysis ("RIPing") and matrix degradation and assembly. These cellular processes in turn play a crucial
role in an array of physiological and pathological phenomena. Thus, TEMs may represent new therapeutical targets that may
simultaneously affect the proteolytic activity of different enzymes and their substrates. Agonistic or antagonistic antibodies
and blocking soluble peptides corresponding to tetraspanin functional regions may offer new opportunities in the treatment
of pathologies such as chronic inflammation, cancer, or Alzheimer's disease. In this review article, we will discuss all these
aspects of functional regulation of protease activities by tetraspanins. 相似文献