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121.
It has been a long-standing goal to detect the effects of quantum mechanics on a macroscopic mechanical oscillator. Position measurements of an oscillator are ultimately limited by quantum mechanics, where 'zero-point motion' fluctuations in the quantum ground state combine with the uncertainty relation to yield a lower limit on the measured average displacement. Development of a position transducer, integrated with a mechanical resonator, that can approach this limit could have important applications in the detection of very weak forces, for example in magnetic resonance force microscopy and a variety of other precision experiments. One implementation that might allow near quantum-limited sensitivity is to use a single electron transistor (SET) as a displacement sensor: the exquisite charge sensitivity of the SET at cryogenic temperatures is exploited to measure motion by capacitively coupling it to the mechanical resonator. Here we present the experimental realization of such a device, yielding an unequalled displacement sensitivity of 2 x 10(-15) m x Hz(-1/2) for a 116-MHz mechanical oscillator at a temperature of 30 mK-a sensitivity roughly a factor of 100 larger than the quantum limit for this oscillator. 相似文献
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Read TD Peterson SN Tourasse N Baillie LW Paulsen IT Nelson KE Tettelin H Fouts DE Eisen JA Gill SR Holtzapple EK Okstad OA Helgason E Rilstone J Wu M Kolonay JF Beanan MJ Dodson RJ Brinkac LM Gwinn M DeBoy RT Madpu R Daugherty SC Durkin AS Haft DH Nelson WC Peterson JD Pop M Khouri HM Radune D Benton JL Mahamoud Y Jiang L Hance IR Weidman JF Berry KJ Plaut RD Wolf AM Watkins KL Nierman WC Hazen A Cline R Redmond C Thwaite JE White O Salzberg SL Thomason B Friedlander AM Koehler TM Hanna PC 《Nature》2003,423(6935):81-86
Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity--including haemolysins, phospholipases and iron acquisition functions--and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis. 相似文献
124.
The genome sequence of the filamentous fungus Neurospora crassa 总被引:1,自引:0,他引:1
Galagan JE Calvo SE Borkovich KA Selker EU Read ND Jaffe D FitzHugh W Ma LJ Smirnov S Purcell S Rehman B Elkins T Engels R Wang S Nielsen CB Butler J Endrizzi M Qui D Ianakiev P Bell-Pedersen D Nelson MA Werner-Washburne M Selitrennikoff CP Kinsey JA Braun EL Zelter A Schulte U Kothe GO Jedd G Mewes W Staben C Marcotte E Greenberg D Roy A Foley K Naylor J Stange-Thomann N Barrett R Gnerre S Kamal M Kamvysselis M Mauceli E Bielke C Rudd S Frishman D Krystofova S Rasmussen C Metzenberg RL 《Nature》2003,422(6934):859-868
Neurospora crassa is a central organism in the history of twentieth-century genetics, biochemistry and molecular biology. Here, we report a high-quality draft sequence of the N. crassa genome. The approximately 40-megabase genome encodes about 10,000 protein-coding genes--more than twice as many as in the fission yeast Schizosaccharomyces pombe and only about 25% fewer than in the fruitfly Drosophila melanogaster. Analysis of the gene set yields insights into unexpected aspects of Neurospora biology including the identification of genes potentially associated with red light photobiology, genes implicated in secondary metabolism, and important differences in Ca2+ signalling as compared with plants and animals. Neurospora possesses the widest array of genome defence mechanisms known for any eukaryotic organism, including a process unique to fungi called repeat-induced point mutation (RIP). Genome analysis suggests that RIP has had a profound impact on genome evolution, greatly slowing the creation of new genes through genomic duplication and resulting in a genome with an unusually low proportion of closely related genes. 相似文献
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Interaction of reelin signaling and Lis1 in brain development 总被引:1,自引:0,他引:1
Assadi AH Zhang G Beffert U McNeil RS Renfro AL Niu S Quattrocchi CC Antalffy BA Sheldon M Armstrong DD Wynshaw-Boris A Herz J D'Arcangelo G Clark GD 《Nature genetics》2003,35(3):270-276
Loss-of-function mutations in RELN (encoding reelin) or PAFAH1B1 (encoding LIS1) cause lissencephaly, a human neuronal migration disorder. In the mouse, homozygous mutations in Reln result in the reeler phenotype, characterized by ataxia and disrupted cortical layers. Pafah1b1(+/-) mice have hippocampal layering defects, whereas homozygous mutants are embryonic lethal. Reln encodes an extracellular protein that regulates layer formation by interacting with VLDLR and ApoER2 (Lrp8) receptors, thereby phosphorylating the Dab1 signaling molecule. Lis1 associates with microtubules and modulates neuronal migration. We investigated interactions between the reelin signaling pathway and Lis1 in brain development. Compound mutant mice with disruptions in the Reln pathway and heterozygous Pafah1b1 mutations had a higher incidence of hydrocephalus and enhanced cortical and hippocampal layering defects. Dab1 and Lis1 bound in a reelin-induced phosphorylation-dependent manner. These data indicate genetic and biochemical interaction between the reelin signaling pathway and Lis1. 相似文献
127.
128.
Rawat UB Zavialov AV Sengupta J Valle M Grassucci RA Linde J Vestergaard B Ehrenberg M Frank J 《Nature》2003,421(6918):87-90
Protein synthesis takes place on the ribosome, where genetic information carried by messenger RNA is translated into a sequence of amino acids. This process is terminated when a stop codon moves into the ribosomal decoding centre (DC) and is recognized by a class-1 release factor (RF). RFs have a conserved GGQ amino-acid motif, which is crucial for peptide release and is believed to interact directly with the peptidyl-transferase centre (PTC) of the 50S ribosomal subunit. Another conserved motif of RFs (SPF in RF2) has been proposed to interact directly with stop codons in the DC of the 30S subunit. The distance between the DC and PTC is approximately 73 A. However, in the X-ray structure of RF2, SPF and GGQ are only 23 A apart, indicating that they cannot be at DC and PTC simultaneously. Here we show that RF2 is in an open conformation when bound to the ribosome, allowing GGQ to reach the PTC while still allowing SPF-stop-codon interaction. The results indicate new interpretations of accuracy in termination, and have implications for how the presence of a stop codon in the DC is signalled to PTC. 相似文献
129.
130.
Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans 总被引:18,自引:0,他引:18
Robertson SP Twigg SR Sutherland-Smith AJ Biancalana V Gorlin RJ Horn D Kenwrick SJ Kim CA Morava E Newbury-Ecob R Orstavik KH Quarrell OW Schwartz CE Shears DJ Suri M Kendrick-Jones J Wilkie AO;OPD-spectrum Disorders Clinical Collaborative Group 《Nature genetics》2003,33(4):487-491
Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. Filamin A, encoded by the gene FLNA, is a widely expressed protein that regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second messengers. We identified localized mutations in FLNA that conserve the reading frame and lead to a broad range of congenital malformations, affecting craniofacial structures, skeleton, brain, viscera and urogenital tract, in four X-linked human disorders: otopalatodigital syndrome types 1 (OPD1; OMIM 311300) and 2 (OPD2; OMIM 304120), frontometaphyseal dysplasia (FMD; OMIM 305620) and Melnick-Needles syndrome (MNS; OMIM 309350). Several mutations are recurrent, and all are clustered into four regions of the gene: the actin-binding domain and rod domain repeats 3, 10 and 14/15. Our findings contrast with previous observations that loss of function of FLNA is embryonic lethal in males but manifests in females as a localized neuronal migration disorder, called periventricular nodular heterotopia (PVNH; refs. 3-6). The patterns of mutation, X-chromosome inactivation and phenotypic manifestations in the newly described mutations indicate that they have gain-of-function effects, implicating filamin A in signaling pathways that mediate organogenesis in multiple systems during embryonic development. 相似文献