Single-molecule DNA sequencing of a viral genome   总被引：4，自引：0，他引：4  

Harris TD  Buzby PR  Babcock H  Beer E  Bowers J  Braslavsky I  Causey M  Colonell J  Dimeo J  Efcavitch JW  Giladi E  Gill J  Healy J  Jarosz M  Lapen D  Moulton K  Quake SR  Steinmann K  Thayer E  Tyurina A  Ward R  Weiss H  Xie Z 《Science (New York, N.Y.)》2008,320(5872):106-109

The full promise of human genomics will be realized only when the genomes of thousands of individuals can be sequenced for comparative analysis. A reference sequence enables the use of short read length. We report an amplification-free method for determining the nucleotide sequence of more than 280,000 individual DNA molecules simultaneously. A DNA polymerase adds labeled nucleotides to surface-immobilized primer-template duplexes in stepwise fashion, and the asynchronous growth of individual DNA molecules was monitored by fluorescence imaging. Read lengths of >25 bases and equivalent phred software program quality scores approaching 30 were achieved. We used this method to sequence the M13 virus to an average depth of >150x and with 100% coverage; thus, we resequenced the M13 genome with high-sensitivity mutation detection. This demonstrates a strategy for high-throughput low-cost resequencing.  相似文献   

Neuroscience. Axons seek neighborly advice     

Murai KK  Pasquale EB 《Science (New York, N.Y.)》2008,320(5873):185-186

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Cell migration: integrating signals from front to back   总被引：2，自引：0，他引：2  

Ridley AJ  Schwartz MA  Burridge K  Firtel RA  Ginsberg MH  Borisy G  Parsons JT  Horwitz AR 《Science (New York, N.Y.)》2003,302(5651):1704-1709

Cell migration is a highly integrated multistep process that orchestrates embryonic morphogenesis; contributes to tissue repair and regeneration; and drives disease progression in cancer, mental retardation, atherosclerosis, and arthritis. The migrating cell is highly polarized with complex regulatory pathways that spatially and temporally integrate its component processes. This review describes the mechanisms underlying the major steps of migration and the signaling pathways that regulate them, and outlines recent advances investigating the nature of polarity in migrating cells and the pathways that establish it.  相似文献   

Hierarchical structure in polymeric materials   总被引：4，自引：0，他引：4  

E Baer  A Hiltner  H D Keith 《Science (New York, N.Y.)》1987,235(4792):1015-1022

The diversity of monomers available for synthesis of high polymers makes it possible to prepare a wide variety of long-chain macromolecular compounds. It is instructive to consider a hierarchical organization of structure in polymers at four successive levels--the molecular, nano-, micro-, and macrolevels--and to examine how interactions at and between these various levels of structure have important and often quite specific influences. Examples are drawn from semicrystalline polymers with flexible chains, liquid-crystalline polymers composed of rigid macromolecules, and amorphous polymers. Structural hierarchies in biocomposite systems are also discussed, particularly in soft connective tissues such as tendon and intervertebral disk.  相似文献   

Biofuels: effects on land and fire     

Kline KL  Dale VH 《Science (New York, N.Y.)》2008,321(5886):199-201; author reply 199-201

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Tyrosinase reactivity in a model complex: an alternative hydroxylation mechanism   总被引：1，自引：0，他引：1  

Mirica LM  Vance M  Rudd DJ  Hedman B  Hodgson KO  Solomon EI  Stack TD 《Science (New York, N.Y.)》2005,308(5730):1890-1892

The binuclear copper enzyme tyrosinase activates O2 to form a mu-eta2:eta2-peroxodicopper(II) complex, which oxidizes phenols to catechols. Here, a synthetic mu-eta2:eta2-peroxodicopper(II) complex, with an absorption spectrum similar to that of the enzymatic active oxidant, is reported to rapidly hydroxylate phenolates at -80 degrees C. Upon phenolate addition at extreme temperature in solution (-120 degrees C), a reactive intermediate consistent with a bis-mu-oxodicopper(III)-phenolate complex, with the O-O bond fully cleaved, is observed experimentally. The subsequent hydroxylation step has the hallmarks of an electrophilic aromatic substitution mechanism, similar to tyrosinase. Overall, the evidence for sequential O-O bond cleavage and C-O bond formation in this synthetic complex suggests an alternative intimate mechanism to the concerted or late stage O-O bond scission generally accepted for the phenol hydroxylation reaction performed by tyrosinase.  相似文献   

Ecology: managing evolving fish stocks     

Jørgensen C  Enberg K  Dunlop ES  Arlinghaus R  Boukal DS  Brander K  Ernande B  Gardmark A  Johnston F  Matsumura S  Pardoe H  Raab K  Silva A  Vainikka A  Dieckmann U  Heino M  Rijnsdorp AD 《Science (New York, N.Y.)》2007,318(5854):1247-1248

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Mathematical modeling of planar cell polarity to understand domineering nonautonomy     

Amonlirdviman K  Khare NA  Tree DR  Chen WS  Axelrod JD  Tomlin CJ 《Science (New York, N.Y.)》2005,307(5708):423-426

Planar cell polarity (PCP) signaling generates subcellular asymmetry along an axis orthogonal to the epithelial apical-basal axis. Through a poorly understood mechanism, cell clones that have mutations in some PCP signaling components, including some, but not all, alleles of the receptor frizzled, cause polarity disruptions of neighboring wild-type cells, a phenomenon referred to as domineering nonautonomy. Here, a contact-dependent signaling hypothesis, derived from experimental results, is shown by reaction-diffusion, partial differential equation modeling and simulation to fully reproduce PCP phenotypes, including domineering nonautonomy, in the Drosophila wing. The sufficiency of this model and the experimental validation of model predictions reveal how specific protein-protein interactions produce autonomy or domineering nonautonomy.  相似文献   

Atmospheric science. CO2 is not the only gas     

Shine KP  Sturges WT 《Science (New York, N.Y.)》2007,315(5820):1804-1805

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Studies of the human c-myb gene and its product in human acute leukemias   总被引：23，自引：0，他引：23  

D J Slamon  T C Boone  D C Murdock  D E Keith  M F Press  R A Larson  L M Souza 《Science (New York, N.Y.)》1986,233(4761):347-351

The myb gene is the transforming oncogene of the avian myeloblastosis virus (AMV); its normal cellular homolog, c-myb, is conserved across a broad span of evolution. In humans, c-myb is expressed in malignant hematopoietic cell lines and in primary hematopoietic tumors. Partial complementary DNA clones were generated from blast cells of patients with acute myelogenous leukemia. The sequences of the clones were compared to the c-myb of other species, as well as the v-myb of AMV. In addition, the carboxyl terminal region of human c-myb was placed in an expression vector to obtain protein for the generation of antiserum, which was used to identify the human c-myb gene product. Like v-myb, this protein was found within the nucleus of leukemic cells where it was associated with the nuclear matrix. These studies provide further evidence that c-myb might be involved in human leukemia.  相似文献