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1.
Stark A Lin MF Kheradpour P Pedersen JS Parts L Carlson JW Crosby MA Rasmussen MD Roy S Deoras AN Ruby JG Brennecke J;Harvard FlyBase curators;Berkeley Drosophila Genome Project Hodges E Hinrichs AS Caspi A Paten B Park SW Han MV Maeder ML Polansky BJ Robson BE Aerts S van Helden J Hassan B Gilbert DG Eastman DA Rice M Weir M Hahn MW Park Y Dewey CN Pachter L Kent WJ Haussler D Lai EC Bartel DP Hannon GJ Kaufman TC Eisen MB Clark AG Smith D Celniker SE Gelbart WM Kellis M 《Nature》2007,450(7167):219-232
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Horvath A Boikos S Giatzakis C Robinson-White A Groussin L Griffin KJ Stein E Levine E Delimpasi G Hsiao HP Keil M Heyerdahl S Matyakhina L Libè R Fratticci A Kirschner LS Cramer K Gaillard RC Bertagna X Carney JA Bertherat J Bossis I Stratakis CA 《Nature genetics》2006,38(7):794-800
Phosphodiesterases (PDEs) regulate cyclic nucleotide levels. Increased cyclic AMP (cAMP) signaling has been associated with PRKAR1A or GNAS mutations and leads to adrenocortical tumors and Cushing syndrome. We investigated the genetic source of Cushing syndrome in individuals with adrenocortical hyperplasia that was not caused by known defects. We performed genome-wide SNP genotyping, including the adrenocortical tumor DNA. The region with the highest probability to harbor a susceptibility gene by loss of heterozygosity (LOH) and other analyses was 2q31-2q35. We identified mutations disrupting the expression of the PDE11A isoform-4 gene (PDE11A) in three kindreds. Tumor tissues showed 2q31-2q35 LOH, decreased protein expression and high cyclic nucleotide levels and cAMP-responsive element binding protein (CREB) phosphorylation. PDE11A codes for a dual-specificity PDE that is expressed in adrenal cortex and is partially inhibited by tadalafil and other PDE inhibitors; its germline inactivation is associated with adrenocortical hyperplasia, suggesting another means by which dysregulation of cAMP signaling causes endocrine tumors. 相似文献
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J F Catterall J P Stein E C Lai S L Woo A Dugaiczyk M L Mace A R Means B W O'Malley 《Nature》1979,278(5702):323-327
A 15-kilobase pair EcoRI chick DNA fragment, containing both the termination codon UGA and the 5'-portion of the structural ovomucoid gene, has been cloned in lambda phage Charon 4A by in vitro packaging. Restriction mapping and electron microscopic analyses of this cloned DNA have revealed that the structural ovomucoid gene sequences are separated by at least six intervening sequences. 相似文献
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Lincoln AJ Wickramasinghe D Stein P Schultz RM Palko ME De Miguel MP Tessarollo L Donovan PJ 《Nature genetics》2002,30(4):446-449
In a wide variety of animal species, oocyte maturation is arrested temporarily at prophase of meiosis I (ref. 1). Resumption of meiosis requires activation of cyclin-dependent kinase-1 (CDK1, p34cdc2), one component of maturation-promoting factor (MPF). The dual specificity phosphatases Cdc25a, Cdc25b and Cdc25c are activators of cyclin-dependent kinases; consequently, they are postulated to regulate cell-cycle progression in meiosis and mitosis as well as the DNA-damage response. We generated Cdc25b-deficient (Cdc25b-/-) mice and found that they are viable. As compared with wildtype cells, fibroblasts from Cdc25b-/- mice grew vigorously in culture and arrested normally in response to DNA damage. Female Cdc25b-/- mice were sterile, and Cdc25b-/- oocytes remained arrested at prophase with low MPF activity. Microinjection of wildtype Cdc25b mRNA into Cdc25b-/- oocytes caused activation of MPF and resumption of meiosis. Thus, Cdc25b-/- female mice are sterile because of permanent meiotic arrest resulting from the inability to activate MPF. Cdc25b is therefore essential for meiotic resumption in female mice. Mice lacking Cdc25b provide the first genetic model for studying the mechanisms regulating prophase arrest in vertebrates. 相似文献
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Variations in the isotopic composition of some components in primitive meteorites demonstrate that the pre-solar material was not completely homogenized, nor was it processed at sufficiently high temperatures to erase the signatures of the diverse stellar sources. This is in accord with the observation that accretion disks of young stellar objects are at relatively low temperatures. Carbonaceous chondrites are considered to represent the 'average' Solar System composition; the rare pre-solar grains in the matrixes of carbonaceous chondrites have been used to identify some sources of the pre-solar material. Here we report that the molybdenum isotopic composition of bulk carbonaceous chondrites is distinctly different from the accepted average solar value. We show that the Mo data require the presence of material produced in at least two different r-processes, and that the contribution from the p-process material is decoupled from the r-process, all occurring in supernova explosions. This is consistent with the emerging picture of diverse sources inferred from short-lived isotopes in the early Solar System and elemental analyses of metal-poor stars. 相似文献
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R.S.斯特恩 《国外科技新书评介》2006,(12):18-19
高分子概念的形成和高分子科学的出现始于20世纪20年代。当时有些有机化学家开展了缩聚反应及其自由基聚合反应的研究,并通过这些反应相继开发出尼龙(聚酰胺)66、氯丁橡胶、丁苯橡胶和聚甲基丙烯酸甲酯等一大批高分子材料,从而形成了“高分子化学”的研究领域。随着这些合成高分子的出现,解决这些高分子的性能和表征:以及了解其结构对性能的影响等问题也随之变得很必要了。因此从20世纪40年代至50年代,一批化学家、物理学家投入这方面的研究,渐渐形成了“高分子物理”这门新兴的学科。 相似文献
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E. Stein Cornelia Iditoiu M. Deleanu 《Cellular and molecular life sciences : CMLS》1969,25(9):916-917
Zusammenfassung JanusgrÜn B mit oxidativen Fermenten, insbesondere mit dem FAD, geht eine Komplexverbindung ein, die eine Syndaktylie zur Folge hat. Die Abbauprodukte des JanusgrÜn B (Diäthylsafranin undp-Dimethylanilin) wirken zwar gleich toxisch wie das JanusgrÜn B, haben aber keinen Syndaktylie-Effekt.
We are indebted to Prof. B.Menkes for his advice and generous aid in our problems. 相似文献
We are indebted to Prof. B.Menkes for his advice and generous aid in our problems. 相似文献