排序方式: 共有69条查询结果,搜索用时 15 毫秒
11.
Lobov IB Rao S Carroll TJ Vallance JE Ito M Ondr JK Kurup S Glass DA Patel MS Shu W Morrisey EE McMahon AP Karsenty G Lang RA 《Nature》2005,437(7057):417-421
Macrophages have a critical role in inflammatory and immune responses through their ability to recognize and engulf apoptotic cells. Here we show that macrophages initiate a cell-death programme in target cells by activating the canonical WNT pathway. We show in mice that macrophage WNT7b is a short-range paracrine signal required for WNT-pathway responses and programmed cell death in the vascular endothelial cells of the temporary hyaloid vessels of the developing eye. These findings indicate that macrophages can use WNT ligands to influence cell-fate decisions--including cell death--in adjacent cells, and raise the possibility that they do so in many different cellular contexts. 相似文献
12.
Pike-Overzet K de Ridder D Weerkamp F Baert MR Verstegen MM Brugman MH Howe SJ Reinders MJ Thrasher AJ Wagemaker G van Dongen JJ Staal FJ 《Nature》2006,443(7109):E5; discussion E6-E5; discussion E7
The gene IL2RG encodes the gamma-chain of the interleukin-2 receptor and is mutated in patients with X-linked severe combined immune deficiency (X-SCID). Woods et al. report the development of thymus tumours in a mouse model of X-SCID after correction by lentiviral overexpression of IL2RG and claim that these were caused by IL2RG itself. Here we find that retroviral overexpression of IL2RG in human CD34+ cells has no effect on T-cell development, whereas overexpression of the T-cell acute lymphoblastic leukaemia (T-ALL) oncogene LMO2 leads to severe abnormalities. Retroviral expression of IL2RG may therefore not be directly oncogenic--rather, the restoration of normal signalling by the interleukin-7 receptor to X-SCID precursor cells allows progression of T-cell development to stages that are permissive for the pro-leukaemic effects of ectopic LMO2. 相似文献
13.
Lianzhi Li Aixin Song Yi Xie Zhongxian Huang Ellen de Waal Kolczak Urszula Gerard W. Canters 《科学通报(英文版)》2001,46(19):1608-1611
The key subunit Ⅱ of cytochrome c oxidase (CcO) contains a soluble binuclear copper center (CuA) domain. The CuA domain of Paracoccus versutus was cloned, expressed, purified and characterized. The gene encoding the CuA domain in pET11d vector was expressed in E. coli BL21 (DE3). The results showed that the CuA domain was expressed mostly in inclusion bodies and the CuA domain protein synthesized in E. coli cells represents approximately 10 percent of the total cellular proteins. Dissolved in urea, dialyzed and recombined with Cu+/Cu2+ and purified by the Q-sepharose fast flow anion-exchange column and Sephadex G-75 gel filtration column, the soluble purple-colored protein, which shows a single band in electrophoresis, was obtained. The UV-visible absorption spectrum of CuA domain showed that there are intense band at 478 nm and a shoulder peak at 530 nm, and two weak bands at 360 and 806 nm respectively, which can be assigned to the charge transfer and the interactions of obitals of Cu—S and Cu——Cu in the mixed-valence binuclear metal center (Cu2S2R2). The far-UV CD spectrum indicated that this domain is predominantly in β-sheet structure. The fluorescence spectra showed that its maximal excitation wavelength and maximal emission wavelength are at 280 and 345 nm, respectively. 相似文献
14.
Wheeler DA Srinivasan M Egholm M Shen Y Chen L McGuire A He W Chen YJ Makhijani V Roth GT Gomes X Tartaro K Niazi F Turcotte CL Irzyk GP Lupski JR Chinault C Song XZ Liu Y Yuan Y Nazareth L Qin X Muzny DM Margulies M Weinstock GM Gibbs RA Rothberg JM 《Nature》2008,452(7189):872-876
The association of genetic variation with disease and drug response, and improvements in nucleic acid technologies, have given great optimism for the impact of 'genomic medicine'. However, the formidable size of the diploid human genome, approximately 6 gigabases, has prevented the routine application of sequencing methods to deciphering complete individual human genomes. To realize the full potential of genomics for human health, this limitation must be overcome. Here we report the DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels. This sequence was completed in two months at approximately one-hundredth of the cost of traditional capillary electrophoresis methods. Comparison of the sequence to the reference genome led to the identification of 3.3 million single nucleotide polymorphisms, of which 10,654 cause amino-acid substitution within the coding sequence. In addition, we accurately identified small-scale (2-40,000 base pair (bp)) insertion and deletion polymorphism as well as copy number variation resulting in the large-scale gain and loss of chromosomal segments ranging from 26,000 to 1.5 million base pairs. Overall, these results agree well with recent results of sequencing of a single individual by traditional methods. However, in addition to being faster and significantly less expensive, this sequencing technology avoids the arbitrary loss of genomic sequences inherent in random shotgun sequencing by bacterial cloning because it amplifies DNA in a cell-free system. As a result, we further demonstrate the acquisition of novel human sequence, including novel genes not previously identified by traditional genomic sequencing. This is the first genome sequenced by next-generation technologies. Therefore it is a pilot for the future challenges of 'personalized genome sequencing'. 相似文献
15.
Gerard de Zeeuw 《Foundations of Science》2001,6(1-3):77-98
Radical Constructivism has been defined as an‘unconventional approach to the problem ofknowledge and knowing’. Its unconventionalityis summarised by its claim that it isimpossible to attribute unique meaning toexperience – as no mind-independent yardstick canbe assumed to exist against which to identifyuniqueness, and hence to produce knowledge andknowing. In other words, it is claimed thatthere is no ‘reality’ that is knowable to allindividual knowers. This claim appearsindefensible by itself, as it does not explainwhy the successes of traditional science appearas such. However, it is defensible in thecontext of numerous failures to achieve uniqueattributions, or of the history of science.Even so, what is missing are concrete methodsand research designs. This often leaves RadicalConstructivism to be critical only, toconcentrate on justifying the impossibility ofsuccess without contributing itself.Where this is the case it reduces scientiststo individuals considered unable to communicatewith others on public (and unique)attributions-who may do so only by borrowingmethods from previous approaches. It is arguedthat a more valuable contribution is possibleif Radical Constructivism is seen as a responseto the challenge defined by frequent failuresof traditional approaches. The latter may beextended such that the extensions converge toRadical Constructivism. Such extensions arebased on reported observations, rather than onexperiences in general, and are to beattributed meanings – uniquely as well asnon-uniquely – by way of a collective. The lattershould allow its ‘actors’ to restrict whatmaintains the collective to what is observableto others, as well as use the collective torestrict their own observations. The study ofcollectives thus allows for the study ofrestrictions or values, and hence for includingsubjective or constructivist experiences beyond(reportable) observations. 相似文献
16.
Gerard Jagers op Akkerhuis 《Foundations of Science》2011,16(4):327-329
The comments focus on a presumed circular reasoning in the operator hierarchy and the necessity of understanding life’s origin for defining life. Below it is shown that its layered structure prevents the operator hierarchy from circular definitions. It is argued that the origin of life is an insufficient basis for a definition of life that includes multicellular and neural network organisms. 相似文献
17.
Evolution of the chalcone-isomerase fold from fatty-acid binding to stereospecific catalysis 总被引:1,自引:0,他引:1
Ngaki MN Louie GV Philippe RN Manning G Pojer F Bowman ME Li L Larsen E Wurtele ES Noel JP 《Nature》2012,485(7399):530-533
Specialized metabolic enzymes biosynthesize chemicals of ecological importance, often sharing a pedigree with primary metabolic enzymes. However, the lineage of the enzyme chalcone isomerase (CHI) remained unknown. In vascular plants, CHI-catalysed conversion of chalcones to chiral (S)-flavanones is a committed step in the production of plant flavonoids, compounds that contribute to attraction, defence and development. CHI operates near the diffusion limit with stereospecific control. Although associated primarily with plants, the CHI fold occurs in several other eukaryotic lineages and in some bacteria. Here we report crystal structures, ligand-binding properties and in vivo functional characterization of a non-catalytic CHI-fold family from plants. Arabidopsis thaliana contains five actively transcribed genes encoding CHI-fold proteins, three of which additionally encode amino-terminal chloroplast-transit sequences. These three CHI-fold proteins localize to plastids, the site of de novo fatty-acid biosynthesis in plant cells. Furthermore, their expression profiles correlate with those of core fatty-acid biosynthetic enzymes, with maximal expression occurring in seeds and coinciding with increased fatty-acid storage in the developing embryo. In vitro, these proteins are fatty-acid-binding proteins (FAPs). FAP knockout A. thaliana plants show elevated α-linolenic acid levels and marked reproductive defects, including aberrant seed formation. Notably, the FAP discovery defines the adaptive evolution of a stereospecific and catalytically 'perfected' enzyme from a non-enzymatic ancestor over a defined period of plant evolution. 相似文献
18.
André B.de Haan 《清华大学学报》2006,11(2):222-227
Introduction Oxygenates like carboxylic acids, aldehydes/ketones, and alcohols are often present in less than 10 wt.% concentrations in apolar organic solvents from which they are industrially recovered by a highly energy-consuming distillation in which t… 相似文献
19.
Proteome survey reveals modularity of the yeast cell machinery 总被引:4,自引:0,他引:4
Gavin AC Aloy P Grandi P Krause R Boesche M Marzioch M Rau C Jensen LJ Bastuck S Dümpelfeld B Edelmann A Heurtier MA Hoffman V Hoefert C Klein K Hudak M Michon AM Schelder M Schirle M Remor M Rudi T Hooper S Bauer A Bouwmeester T Casari G Drewes G Neubauer G Rick JM Kuster B Bork P Russell RB Superti-Furga G 《Nature》2006,440(7084):631-636
Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry. Through systematic tagging of open reading frames (ORFs), the majority of complexes were purified several times, suggesting screen saturation. The richness of the data set enabled a de novo characterization of the composition and organization of the cellular machinery. The ensemble of cellular proteins partitions into 491 complexes, of which 257 are novel, that differentially combine with additional attachment proteins or protein modules to enable a diversification of potential functions. Support for this modular organization of the proteome comes from integration with available data on expression, localization, function, evolutionary conservation, protein structure and binary interactions. This study provides the largest collection of physically determined eukaryotic cellular machines so far and a platform for biological data integration and modelling. 相似文献
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