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71.
Bovee D Zhou Y Haugen E Wu Z Hayden HS Gillett W Tuzun E Cooper GM Sampas N Phelps K Levy R Morrison VA Sprague J Jewett D Buckley D Subramaniam S Chang J Smith DR Olson MV Eichler EE Kaul R 《Nature genetics》2008,40(1):96-101
The human genome sequence has been finished to very high standards; however, more than 340 gaps remained when the finished genome was published by the International Human Genome Sequencing Consortium in 2004. Using fosmid resources generated from multiple individuals, we targeted gaps in the euchromatic part of the human genome. Here we report 2,488,842 bp of previously unknown euchromatic sequence, 363,114 bp of which close 26 of 250 euchromatic gaps, or 10%, including two remaining euchromatic gaps on chromosome 19. Eight (30.7%) of the closed gaps were found to be polymorphic. These sequences allow complete annotation of several human genes as well as the assignment of mRNAs. The gap sequences are 2.3-fold enriched in segmentally duplicated sequences compared to the whole genome. Our analysis confirms that not all gaps within 'finished' genomes are recalcitrant to subcloning and suggests that the paired-end-sequenced fosmid libraries could prove to be a rich resource for completion of the human euchromatic genome. 相似文献
72.
1686年,莱布尼茨在他的《形而上学谈》中指出,如果某个任意复杂理论是被允许的话,那么"理论"的观念就是个空观念,因为总是会有一种理论存在的。这种思想现在被发展成现代的算法信息论,这种理论所涉及的是计算机程序的大小并为哥德尔不完全性工作以及图灵的不可计算性的工作提供了一个新视角。尤其重要的是,停机概率欧米茄数,其比特位是不可还原的,也就是说,其最大值是不可知的数学事实。更一般地说,这些思想构成了一类"数字哲学",由Edward Fredkin,Stephen Wolfram以及其他人所倡导的,他们将世界视为一台巨大的计算机。最近还有人将其进行"数字物理学"的思辨,认为宇宙实际上是离散的而非连续的。这一世界系统在作者本人的《元数学》一书中作了简要论述。 相似文献
73.
Sensorimotor coordination emerges early in development. The maturation period is characterized by the establishment of somatotopic cortical maps, the emergence of long-range cortical connections, heightened experience-dependent plasticity and spontaneous uncoordinated skeletal movement. How these various processes cooperate to allow the somatosensory system to form a three-dimensional representation of the body is not known. In the visual system, interactions between spontaneous network patterns and afferent activity have been suggested to be vital for normal development. Although several intrinsic cortical patterns of correlated neuronal activity have been described in developing somatosensory cortex in vitro, the in vivo patterns in the critical developmental period and the influence of physiological sensory inputs on these patterns remain unknown. We report here that in the intact somatosensory cortex of the newborn rat in vivo, spatially confined spindle bursts represent the first and only organized network pattern. The localized spindles are selectively triggered in a somatotopic manner by spontaneous muscle twitches, motor patterns analogous to human fetal movements. We suggest that the interaction between movement-triggered sensory feedback signals and self-organized spindle oscillations shapes the formation of cortical connections required for sensorimotor coordination. 相似文献
74.
Bakolitsa C Cohen DM Bankston LA Bobkov AA Cadwell GW Jennings L Critchley DR Craig SW Liddington RC 《Nature》2004,430(6999):583-586
Vinculin is a highly conserved intracellular protein with a crucial role in the maintenance and regulation of cell adhesion and migration. In the cytosol, vinculin adopts a default autoinhibited conformation. On recruitment to cell-cell and cell-matrix adherens-type junctions, vinculin becomes activated and mediates various protein-protein interactions that regulate the links between F-actin and the cadherin and integrin families of cell-adhesion molecules. Here we describe the crystal structure of the full-length vinculin molecule (1,066 amino acids), which shows a five-domain autoinhibited conformation in which the carboxy-terminal tail domain is held pincer-like by the vinculin head, and ligand binding is regulated both sterically and allosterically. We show that conformational changes in the head, tail and proline-rich domains are linked structurally and thermodynamically, and propose a combinatorial pathway to activation that ensures that vinculin is activated only at sites of cell adhesion when two or more of its binding partners are brought into apposition. 相似文献
75.
Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome 总被引:1,自引:0,他引:1
Parks AL Cook KR Belvin M Dompe NA Fawcett R Huppert K Tan LR Winter CG Bogart KP Deal JE Deal-Herr ME Grant D Marcinko M Miyazaki WY Robertson S Shaw KJ Tabios M Vysotskaia V Zhao L Andrade RS Edgar KA Howie E Killpack K Milash B Norton A Thao D Whittaker K Winner MA Friedman L Margolis J Singer MA Kopczynski C Curtis D Kaufman TC Plowman GD Duyk G Francis-Lang HL 《Nature genetics》2004,36(3):288-292
In fruit fly research, chromosomal deletions are indispensable tools for mapping mutations, characterizing alleles and identifying interacting loci. Most widely used deletions were generated by irradiation or chemical mutagenesis. These methods are labor-intensive, generate random breakpoints and result in unwanted secondary mutations that can confound phenotypic analyses. Most of the existing deletions are large, have molecularly undefined endpoints and are maintained in genetically complex stocks. Furthermore, the existence of haplolethal or haplosterile loci makes the recovery of deletions of certain regions exceedingly difficult by traditional methods, resulting in gaps in coverage. Here we describe two methods that address these problems by providing for the systematic isolation of targeted deletions in the D. melanogaster genome. The first strategy used a P element-based technique to generate deletions that closely flank haploinsufficient genes and minimize undeleted regions. This deletion set has increased overall genomic coverage by 5-7%. The second strategy used FLP recombinase and the large array of FRT-bearing insertions described in the accompanying paper to generate 519 isogenic deletions with molecularly defined endpoints. This second deletion collection provides 56% genome coverage so far. The latter methodology enables the generation of small custom deletions with predictable endpoints throughout the genome and should make their isolation a simple and routine task. 相似文献
76.
Applications are emerging that require the creation of fine-scale structures in three dimensions--examples include scaffolds for tissue engineering, micro-fluidic devices and photonic materials that control light propagation over a range of frequencies. But writing methods such as dip-pen nanolithography and ink-jet printing are either confined to two dimensions or beset by wetting and spreading problems. Here we use concentrated polyelectrolyte inks to write three-dimensional microperiodic structures directly without using masks. Our technique enables us to write arbitrary three-dimensional patterns whose features are nearly two orders of magnitude smaller than those attained with other multilayer printing techniques. 相似文献
77.
Scientists have sequenced the human genome and identified most of its genes. Now it is time to use these genomic data, and the high-throughput technology developed to generate them, to tackle major health problems such as cancer. To accelerate our understanding of this disease and to produce targeted therapies, further basic mutational and functional genomic information is required. A systematic and coordinated approach, with the results freely available, should speed up progress. This will best be accomplished through an international academic and pharmaceutical oncogenomics initiative. 相似文献
78.
79.
How evolutionary changes in body size are brought about by variance in developmental timing and/or growth rates (also known as heterochrony) is a topic of considerable interest in evolutionary biology. In particular, extreme size change leading to gigantism occurred within the dinosaurs on multiple occasions. Whether this change was brought about by accelerated growth, delayed maturity or a combination of both processes is unknown. A better understanding of relationships between non-avian dinosaur groups and the newfound capacity to reconstruct their growth curves make it possible to address these questions quantitatively. Here we study growth patterns within the Tyrannosauridae, the best known group of large carnivorous dinosaurs, and determine the developmental means by which Tyrannosaurus rex, weighing 5,000 kg and more, grew to be one of the most enormous terrestrial carnivorous animals ever. T. rex had a maximal growth rate of 2.1 kg d(-1), reached skeletal maturity in two decades and lived for up to 28 years. T. rex's great stature was primarily attained by accelerating growth rates beyond that of its closest relatives. 相似文献
80.
The Microprocessor complex mediates the genesis of microRNAs 总被引:5,自引:0,他引:5
Gregory RI Yan KP Amuthan G Chendrimada T Doratotaj B Cooch N Shiekhattar R 《Nature》2004,432(7014):235-240