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31.
The minor spliceosome is a ribonucleoprotein complex that catalyses the removal of an atypical class of spliceosomal introns (U12-type) from eukaryotic messenger RNAs. It was first identified and characterized in animals, where it was found to contain several unique RNA constituents that share structural similarity with and seem to be functionally analogous to the small nuclear RNAs (snRNAs) contained in the major spliceosome. Subsequently, minor spliceosomal components and U12-type introns have been found in plants but not in fungi. Unlike that of the major spliceosome, which arose early in the eukaryotic lineage, the evolutionary history of the minor spliceosome is unclear because there is evidence of it in so few organisms. Here we report the identification of homologues of minor-spliceosome-specific proteins and snRNAs, and U12-type introns, in distantly related eukaryotic microbes (protists) and in a fungus (Rhizopus oryzae). Cumulatively, our results indicate that the minor spliceosome had an early origin: several of its characteristic constituents are present in representative organisms from all eukaryotic supergroups for which there is any substantial genome sequence information. In addition, our results reveal marked evolutionary conservation of functionally important sequence elements contained within U12-type introns and snRNAs. 相似文献
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2020 computing: science in an exponential world 总被引:2,自引:0,他引:2
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Pepys MB Hirschfield GM Tennent GA Gallimore JR Kahan MC Bellotti V Hawkins PN Myers RM Smith MD Polara A Cobb AJ Ley SV Aquilina JA Robinson CV Sharif I Gray GA Sabin CA Jenvey MC Kolstoe SE Thompson D Wood SP 《Nature》2006,440(7088):1217-1221
Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement, increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively. Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement. Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury. 相似文献
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Chin K de Solorzano CO Knowles D Jones A Chou W Rodriguez EG Kuo WL Ljung BM Chew K Myambo K Miranda M Krig S Garbe J Stampfer M Yaswen P Gray JW Lockett SJ 《Nature genetics》2004,36(9):984-988
Transition through telomere crisis is thought to be a crucial event in the development of most breast carcinomas. Our goal in this study was to determine where this occurs in the context of histologically defined breast cancer progression. To this end, we assessed genome instability (using fluorescence in situ hybridization) and other features associated with telomere crisis in normal ductal epithelium, usual ductal hyperplasia, ductal carcinoma in situ and invasive cancer. We modeled this process in vitro by measuring these same features in human mammary epithelial cell cultures during ZNF217-mediated transition through telomere crisis and immortalization. Taken together, the data suggest that transition through telomere crisis and immortalization in breast cancer occurs during progression from usual ductal hyperplasia to ductal carcinoma in situ. 相似文献
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Gray JM Karow DS Lu H Chang AJ Chang JS Ellis RE Marletta MA Bargmann CI 《Nature》2004,430(6997):317-322
Specialized oxygen-sensing cells in the nervous system generate rapid behavioural responses to oxygen. We show here that the nematode Caenorhabditis elegans exhibits a strong behavioural preference for 5-12% oxygen, avoiding higher and lower oxygen levels. 3',5'-cyclic guanosine monophosphate (cGMP) is a common second messenger in sensory transduction and is implicated in oxygen sensation. Avoidance of high oxygen levels by C. elegans requires the sensory cGMP-gated channel tax-2/tax-4 and a specific soluble guanylate cyclase homologue, gcy-35. The GCY-35 haem domain binds molecular oxygen, unlike the haem domains of classical nitric-oxide-regulated guanylate cyclases. GCY-35 and TAX-4 mediate oxygen sensation in four sensory neurons that control a naturally polymorphic social feeding behaviour in C. elegans. Social feeding and related behaviours occur only when oxygen exceeds C. elegans' preferred level, and require gcy-35 activity. Our results suggest that GCY-35 is regulated by molecular oxygen, and that social feeding can be a behavioural strategy for responding to hyperoxic environments. 相似文献
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D. P. Muehleisen E. J. Katahira R. S. Gray W. E. Bollenbacher 《Cellular and molecular life sciences : CMLS》1994,50(2):159-163
The prothoracicotropic hormones (PTTHs) are cerebral peptides that control insect postembryonic development by stimulating the prothoracic glands to synthesize ecdysteroids. InManduca sexta, the tobacco hornworm, two classes of PTTH are distinguished by their Mr, small (ca. 7 kDa) and big PTTH (ca. 25–30 kDa). Little is known about the physical nature of the PTTHs and this study takes a first step towards defining characteristics of theManduca big PTTH. The neurohormone has a Stokes radius of 2.59 nm and a sedimentation coefficient of 2.76 S. Based on these data, an Mr of 29,443.7 and anf/f
0 of 1.27 were calculated. Combined, the physical data revealManduca big PTTH is an asymmetrical acidic homodimeric peptide with intra- and intermolecular disulfide bonds. 相似文献
40.
A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse 总被引:37,自引:0,他引:37
Nolan PM Peters J Strivens M Rogers D Hagan J Spurr N Gray IC Vizor L Brooker D Whitehill E Washbourne R Hough T Greenaway S Hewitt M Liu X McCormack S Pickford K Selley R Wells C Tymowska-Lalanne Z Roby P Glenister P Thornton C Thaung C Stevenson JA Arkell R Mburu P Hardisty R Kiernan A Erven A Steel KP Voegeling S Guenet JL Nickols C Sadri R Nasse M Isaacs A Davies K Browne M Fisher EM Martin J Rastan S Brown SD Hunter J 《Nature genetics》2000,25(4):440-443
As the human genome project approaches completion, the challenge for mammalian geneticists is to develop approaches for the systematic determination of mammalian gene function. Mouse mutagenesis will be a key element of studies of gene function. Phenotype-driven approaches using the chemical mutagen ethylnitrosourea (ENU) represent a potentially efficient route for the generation of large numbers of mutant mice that can be screened for novel phenotypes. The advantage of this approach is that, in assessing gene function, no a priori assumptions are made about the genes involved in any pathway. Phenotype-driven mutagenesis is thus an effective method for the identification of novel genes and pathways. We have undertaken a genome-wide, phenotype-driven screen for dominant mutations in the mouse. We generated and screened over 26,000 mice, and recovered some 500 new mouse mutants. Our work, along with the programme reported in the accompanying paper, has led to a substantial increase in the mouse mutant resource and represents a first step towards systematic studies of gene function in mammalian genetics. 相似文献