Mutational analysis of the tyrosine phosphatome in colorectal cancers   总被引：1，自引：0，他引：1  

Wang Z  Shen D  Parsons DW  Bardelli A  Sager J  Szabo S  Ptak J  Silliman N  Peters BA  van der Heijden MS  Parmigiani G  Yan H  Wang TL  Riggins G  Powell SM  Willson JK  Markowitz S  Kinzler KW  Vogelstein B  Velculescu VE 《Science (New York, N.Y.)》2004,304(5674):1164-1166

Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or splice-site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRT) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the mutated tyrosine phosphatases are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.  相似文献   

Computational improvements reveal great bacterial diversity and high metal toxicity in soil   总被引：4，自引：0，他引：4  

Gans J  Wolinsky M  Dunbar J 《Science (New York, N.Y.)》2005,309(5739):1387-1390

The complexity of soil bacterial communities has thus far confounded effective measurement. However, with improved analytical methods, we show that the abundance distribution and total diversity can be deciphered. Reanalysis of reassociation kinetics for bacterial community DNA from pristine and metal-polluted soils showed that a power law best described the abundance distributions. More than one million distinct genomes occurred in the pristine soil, exceeding previous estimates by two orders of magnitude. Metal pollution reduced diversity more than 99.9%, revealing the highly toxic effect of metal contamination, especially for rare taxa.  相似文献   

Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of CCR5   总被引：1，自引：0，他引：1  

Lederman MM  Veazey RS  Offord R  Mosier DE  Dufour J  Mefford M  Piatak M  Lifson JD  Salkowitz JR  Rodriguez B  Blauvelt A  Hartley O 《Science (New York, N.Y.)》2004,306(5695):485-487

Topical agents, such as microbicides, that can protect against human immunodeficiency virus (HIV) transmission are urgently needed. Using a chimeric simian/human immunodeficiency virus (SHIV SF162), which is tropic for the chemokine receptor CCR5, we report that topical application of high doses of PSC-RANTES, an amino terminus-modified analog of the chemokine RANTES, provided potent protection against vaginal challenge in rhesus macaques. These experimental findings have potentially important implications for understanding vaginal transmission of HIV and the design of strategies for its prevention.  相似文献   

Requirement of mammalian Timeless for circadian rhythmicity     

Barnes JW  Tischkau SA  Barnes JA  Mitchell JW  Burgoon PW  Hickok JR  Gillette MU 《Science (New York, N.Y.)》2003,302(5644):439-442

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Harnessing chaperones to generate small-molecule inhibitors of amyloid beta aggregation     

Gestwicki JE  Crabtree GR  Graef IA 《Science (New York, N.Y.)》2004,306(5697):865-869

Protein aggregation is involved in the pathogenesis of neurodegenerative diseases and hence is considered an attractive target for therapeutic intervention. However, protein-protein interactions are exceedingly difficult to inhibit. Small molecules lack sufficient steric bulk to prevent interactions between large peptide surfaces. To yield potent inhibitors of beta-amyloid (Abeta) aggregation, we synthesized small molecules that increase their steric bulk by binding to chaperones but also have a moiety available for interaction with Abeta. This strategy yields potent inhibitors of Abeta aggregation and could lead to therapeutics for Alzheimer's disease and other forms of neurodegeneration.  相似文献   

Informatics and quantitative analysis in biological imaging     

Swedlow JR  Goldberg I  Brauner E  Sorger PK 《Science (New York, N.Y.)》2003,300(5616):100-102

Biological imaging is now a quantitative technique for probing cellular structure and dynamics and is increasingly used for cell-based screens. However, the bioinformatics tools required for hypothesis-driven analysis of digital images are still immature. We are developing the Open Microscopy Environment (OME) as an informatics solution for the storage and analysis of optical microscope image data. OME aims to automate image analysis, modeling, and mining of large sets of images and specifies a flexible data model, a relational database, and an XML-encoded file standard that is usable by potentially any software tool. With this design, OME provides a first step toward biological image informatics.  相似文献   

Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling     

Major MB  Camp ND  Berndt JD  Yi X  Goldenberg SJ  Hubbert C  Biechele TL  Gingras AC  Zheng N  Maccoss MJ  Angers S  Moon RT 《Science (New York, N.Y.)》2007,316(5827):1043-1046

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Purkinje cell degeneration (pcd) phenotypes caused by mutations in the axotomy-induced gene, Nna1     

Fernandez-Gonzalez A  La Spada AR  Treadaway J  Higdon JC  Harris BS  Sidman RL  Morgan JI  Zuo J 《Science (New York, N.Y.)》2002,295(5561):1904-1906

The classical recessive mouse mutant, Purkinje cell degeneration (pcd), exhibits adult-onset degeneration of cerebellar Purkinje neurons, retinal photoreceptors, olfactory bulb mitral neurons, and selected thalamic neurons, and has defective spermatogenesis. Here we identify Nna1 as the gene mutated in the original pcd and two additional pcd alleles (pcd2J and pcd3J). Nna1 encodes a putative nuclear protein containing a zinc carboxypeptidase domain initially identified by its induction in spinal motor neurons during axonal regeneration. The present study suggests an unexpected molecular link between neuronal degeneration and regeneration, and its results have potential implications for neurodegenerative diseases and male infertility.  相似文献   

The Miller volcanic spark discharge experiment     

Johnson AP  Cleaves HJ  Dworkin JP  Glavin DP  Lazcano A  Bada JL 《Science (New York, N.Y.)》2008,322(5900):404

Miller's 1950s experiments used, besides the apparatus known in textbooks, one that generated a hot water mist in the spark flask, simulating a water vapor-rich volcanic eruption. We found the original extracts of this experiment in Miller's material and reanalyzed them. The volcanic apparatus produced a wider variety of amino acids than the classic one. Release of reduced gases in volcanic eruptions accompanied by lightning could have been common on the early Earth. Prebiotic compounds synthesized in these environments could have locally accumulated, where they could have undergone further processing.  相似文献   

Origin and evolution of prebiotic organic matter as inferred from the Tagish Lake meteorite     

Herd CD  Blinova A  Simkus DN  Huang Y  Tarozo R  Alexander CM  Gyngard F  Nittler LR  Cody GD  Fogel ML  Kebukawa Y  Kilcoyne AL  Hilts RW  Slater GF  Glavin DP  Dworkin JP  Callahan MP  Elsila JE  De Gregorio BT  Stroud RM 《Science (New York, N.Y.)》2011,332(6035):1304-1307

The complex suite of organic materials in carbonaceous chondrite meteorites probably originally formed in the interstellar medium and/or the solar protoplanetary disk, but was subsequently modified in the meteorites' asteroidal parent bodies. The mechanisms of formation and modification are still very poorly understood. We carried out a systematic study of variations in the mineralogy, petrology, and soluble and insoluble organic matter in distinct fragments of the Tagish Lake meteorite. The variations correlate with indicators of parent body aqueous alteration. At least some molecules of prebiotic importance formed during the alteration.  相似文献