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191.
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Classical studies show that for many proteins, the information required for specifying the tertiary structure is contained in the amino acid sequence. Here, we attempt to define the sequence rules for specifying a protein fold by computationally creating artificial protein sequences using only statistical information encoded in a multiple sequence alignment and no tertiary structure information. Experimental testing of libraries of artificial WW domain sequences shows that a simple statistical energy function capturing coevolution between amino acid residues is necessary and sufficient to specify sequences that fold into native structures. The artificial proteins show thermodynamic stabilities similar to natural WW domains, and structure determination of one artificial protein shows excellent agreement with the WW fold at atomic resolution. The relative simplicity of the information used for creating sequences suggests a marked reduction to the potential complexity of the protein-folding problem. 相似文献
193.
Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics 总被引:1,自引:0,他引:1
Biochemical networks are perturbed both by fluctuations in environmental conditions and genetic variation. These perturbations must be compensated for, especially when they occur during embryonic pattern formation. Complex chemical reaction networks displaying spatiotemporal dynamics have been controlled and understood by perturbing their environment in space and time. Here, we apply this approach using microfluidics to investigate the robust network in Drosophila melanogaster that compensates for variation in the Bicoid morphogen gradient. We show that the compensation system can counteract the effects of extremely unnatural environmental conditions--a temperature step--in which the anterior and posterior halves of the embryo are developing at different temperatures and thus at different rates. Embryonic patterning was normal under this condition, suggesting that a simple reciprocal gradient system is not the mechanism of compensation. Time-specific reversals of the temperature step narrowed down the critical period for compensation to between 65 and 100 min after onset of embryonic development. The microfluidic technology used here may prove useful to future studies, as it allows spatial and temporal regulation of embryonic development. 相似文献
194.
Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs 总被引:11,自引:0,他引:11
Lim LP Lau NC Garrett-Engele P Grimson A Schelter JM Castle J Bartel DP Linsley PS Johnson JM 《Nature》2005,433(7027):769-773
195.
Suppression of Polycomb group proteins by JNK signalling induces transdetermination in Drosophila imaginal discs 总被引:1,自引:0,他引:1
During the regeneration of Drosophila imaginal discs, cellular identities can switch fate in a process known as transdetermination. For leg-to-wing transdetermination, the underlying mechanism involves morphogens such as Wingless that, when activated outside their normal context, induce ectopic expression of the wing-specific selector gene vestigial. Polycomb group (PcG) proteins maintain cellular fates by controlling the expression patterns of homeotic genes and other developmental regulators. Here we report that transdetermination events are coupled to PcG regulation. We show that the frequency of transdetermination is enhanced in PcG mutant flies. Downregulation of PcG function, as monitored by the reactivation of a silent PcG-regulated reporter gene, is observed in transdetermined cells. This downregulation is directly controlled by the Jun amino-terminal kinase (JNK) signalling pathway, which is activated in cells undergoing regeneration. Accordingly, transdetermination frequency is reduced in a JNK mutant background. This regulatory interaction also occurs in mammalian cells, indicating that the role of this signalling cascade in remodelling cellular fates may be conserved. 相似文献
196.
1IntroductionLiquefactionof saturatedgranules(e.g.brokenrocks,sandy soils and tailings,etc)is aphenomenon that granules show similar liquidcharacter and lose carrying capacity completelyunderthe actionof dynamical load[1-5].There aresome behaviors about liquefaction,such as theeruption of water and sands fromthe ground,theinstability of foundation,the large area landslip,the building falling by vibration,etc.Theproblemof liquefactionis aremarkable questioningeotechnical engineering.In the past… 相似文献
197.
氧化锌避雷器的一种在线测试仪的研制 总被引:1,自引:0,他引:1
阐明了区分氧化锌避雷器性能不降的原因,介绍了一种应用单片计算机和配套的软件系统构成的氧化锌避雷器阻性电流在线测试仪,通过实验室和现场测试结果表明:在信号采集、处理和抗电磁干扰能力方面具有优良的特性,且能较灵敏地反映阻性电流的高次谐波分量,同时,还介绍了一种只从氧化锌避雷器取信号测量阻性电流的新方法。 相似文献
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Variability of DNA content of murine fibrosarcoma cells 总被引:1,自引:0,他引:1