排序方式: 共有69条查询结果,搜索用时 15 毫秒
21.
Michele Bertacchi Luca Pandolfini Elisa Murenu Alessandro Viegi Simona Capsoni Alessandro Cellerino Andrea Messina Simona Casarosa Federico Cremisi 《Cellular and molecular life sciences : CMLS》2013,70(6):1095-1111
We investigated the effects of bone morphogenetic proteins (BMPs) in determining the positional identity of neurons generated in vitro from mouse embryonic stem cells (ESCs), an aspect that has been neglected thus far. Classical embryological studies in lower vertebrates indicate that BMPs inhibit the default fate of pluripotent embryonic cells, which is both neural and anterior. Moreover, mammalian ESCs generate neurons more efficiently when cultured in a minimal medium containing BMP inhibitors. In this paper, we show that mouse ESCs produce, secrete, and respond to BMPs during in vitro neural differentiation. After neuralization in a minimal medium, differentiated ESCs show a gene expression profile consistent with a midbrain identity, as evaluated by the analysis of a number of markers of anterior–posterior and dorsoventral identity. We found that BMPs endogenously produced during neural differentiation mainly act by inhibiting the expression of a telencephalic gene profile, which was revealed by the treatment with Noggin or with other BMP inhibitors. To better characterize the effect of BMPs on positional fate, we compared the global gene expression profiles of differentiated ESCs with those of embryonic forebrain, midbrain, and hindbrain. Both Noggin and retinoic acid (RA) support neuronal differentiation of ESCs, but they show different effects on their positional identity: whereas RA supports the typical gene expression profile of hindbrain neurons, Noggin induces a profile characteristic of dorsal telencephalic neurons. Our findings show that endogenously produced BMPs affect the positional identity of the neurons that ESCs spontaneously generate when differentiating in vitro in a minimal medium. The data also support the existence of an intrinsic program of neuronal differentiation with dorsal telencephalic identity. Our method of ESC neuralization allows for fast differentiation of neural cells via the same signals found during in vivo embryonic development and for the acquisition of cortical identity by the inhibition of BMP alone. 相似文献
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Kopp JB Smith MW Nelson GW Johnson RC Freedman BI Bowden DW Oleksyk T McKenzie LM Kajiyama H Ahuja TS Berns JS Briggs W Cho ME Dart RA Kimmel PL Korbet SM Michel DM Mokrzycki MH Schelling JR Simon E Trachtman H Vlahov D Winkler CA 《Nature genetics》2008,40(10):1175-1184
The increased burden of chronic kidney and end-stage kidney diseases (ESKD) in populations of African ancestry has been largely unexplained. To identify genetic variants predisposing to idiopathic and HIV-1-associated focal segmental glomerulosclerosis (FSGS), we carried out an admixture-mapping linkage-disequilibrium genome scan on 190 African American individuals with FSGS and 222 controls. We identified a chromosome 22 region with a genome-wide logarithm of the odds (lod) score of 9.2 and a peak lod of 12.4 centered on MYH9, a functional candidate gene expressed in kidney podocytes. Multiple MYH9 SNPs and haplotypes were recessively associated with FSGS, most strongly a haplotype spanning exons 14 through 23 (OR = 5.0, 95% CI = 3.5-7.1; P = 4 x 10(-23), n = 852). This association extended to hypertensive ESKD (OR = 2.2, 95% CI = 1.5-3.4; n = 433), but not type 2 diabetic ESKD (n = 476). Genetic variation at the MYH9 locus substantially explains the increased burden of FSGS and hypertensive ESKD among African Americans. 相似文献
23.
A major obstacle to creating precisely expressed transgenes lies in the epigenetic effects of the host chromatin that surrounds them. Here we present a strategy to overcome this problem, employing a Gal4-inducible luciferase assay to systematically quantify position effects of host chromatin and the ability of insulators to counteract these effects at phiC31 integration loci randomly distributed throughout the Drosophila genome. We identify loci that can be exploited to deliver precise doses of transgene expression to specific tissues. Moreover, we uncover a previously unrecognized property of the gypsy retrovirus insulator to boost gene expression to levels severalfold greater than at most or possibly all un-insulated loci, in every tissue tested. These findings provide the first opportunity to create a battery of transgenes that can be reliably expressed at high levels in virtually any tissue by integration at a single locus, and conversely, to engineer a controlled phenotypic allelic series by exploiting several loci. The generality of our approach makes it adaptable to other model systems to identify and modify loci for optimal transgene expression. 相似文献
24.
Second-generation shRNA libraries covering the mouse and human genomes 总被引:23,自引:0,他引:23
25.
Initial sequencing and comparative analysis of the mouse genome 总被引:2,自引:0,他引:2
Mouse Genome Sequencing Consortium Waterston RH Lindblad-Toh K Birney E Rogers J Abril JF Agarwal P Agarwala R Ainscough R Alexandersson M An P Antonarakis SE Attwood J Baertsch R Bailey J Barlow K Beck S Berry E Birren B Bloom T Bork P Botcherby M Bray N Brent MR Brown DG Brown SD Bult C Burton J Butler J Campbell RD Carninci P Cawley S Chiaromonte F Chinwalla AT Church DM Clamp M Clee C Collins FS Cook LL Copley RR Coulson A Couronne O Cuff J Curwen V Cutts T Daly M David R Davies J 《Nature》2002,420(6915):520-562
The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism. 相似文献
26.
Pryor WR Rymer AM Mitchell DG Hill TW Young DT Saur J Jones GH Jacobsen S Cowley SW Mauk BH Coates AJ Gustin J Grodent D Gérard JC Lamy L Nichols JD Krimigis SM Esposito LW Dougherty MK Jouchoux AJ Stewart AI McClintock WE Holsclaw GM Ajello JM Colwell JE Hendrix AR Crary FJ Clarke JT Zhou X 《Nature》2011,472(7343):331-333
Although there are substantial differences between the magnetospheres of Jupiter and Saturn, it has been suggested that cryovolcanic activity at Enceladus could lead to electrodynamic coupling between Enceladus and Saturn like that which links Jupiter with Io, Europa and Ganymede. Powerful field-aligned electron beams associated with the Io-Jupiter coupling, for example, create an auroral footprint in Jupiter's ionosphere. Auroral ultraviolet emission associated with Enceladus-Saturn coupling is anticipated to be just a few tenths of a kilorayleigh (ref. 12), about an order of magnitude dimmer than Io's footprint and below the observable threshold, consistent with its non-detection. Here we report the detection of magnetic-field-aligned ion and electron beams (offset several moon radii downstream from Enceladus) with sufficient power to stimulate detectable aurora, and the subsequent discovery of Enceladus-associated aurora in a few per cent of the scans of the moon's footprint. The footprint varies in emission magnitude more than can plausibly be explained by changes in magnetospheric parameters--and as such is probably indicative of variable plume activity. 相似文献
27.
Peptidoglycan is the major structural constituent of the bacterial cell wall, forming a meshwork outside the cytoplasmic membrane that maintains cell shape and prevents lysis. In Gram-negative bacteria, peptidoglycan is located in the periplasm, where it is protected from exogenous lytic enzymes by the outer membrane. Here we show that the type VI secretion system of Pseudomonas aeruginosa breaches this barrier to deliver two effector proteins, Tse1 and Tse3, to the periplasm of recipient cells. In this compartment, the effectors hydrolyse peptidoglycan, thereby providing a fitness advantage for P. aeruginosa cells in competition with other bacteria. To protect itself from lysis by Tse1 and Tse3, P. aeruginosa uses specific periplasmically localized immunity proteins. The requirement for these immunity proteins depends on intercellular self-intoxication through an active type VI secretion system, indicating a mechanism for export whereby effectors do not access donor cell periplasm in transit. 相似文献
28.
创造在人类所有活动中扮演着一个重要的角色。本书是《数学与文化》丛书中的第二本,着重介绍数学、文化与众多领域的创造之间的紧密联系,这些领域包括建筑、当代艺术、地理、计算机绘图、文艺、戏剧和电影。近年来,得益于计算机绘图的出现,可视化在数学的某些部分中的角色越来越引人注目。这类新“可视化数学”必然会为艺术创造与数学之间的联系打开新路,本书收集了关于这些问题的论文。 相似文献
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Mikkelsen TS Wakefield MJ Aken B Amemiya CT Chang JL Duke S Garber M Gentles AJ Goodstadt L Heger A Jurka J Kamal M Mauceli E Searle SM Sharpe T Baker ML Batzer MA Benos PV Belov K Clamp M Cook A Cuff J Das R Davidow L Deakin JE Fazzari MJ Glass JL Grabherr M Greally JM Gu W Hore TA Huttley GA Kleber M Jirtle RL Koina E Lee JT Mahony S Marra MA Miller RD Nicholls RD Oda M Papenfuss AT Parra ZE Pollock DD Ray DA Schein JE Speed TP Thompson K VandeBerg JL Wade CM Walker JA Waters PD Webber C 《Nature》2007,447(7141):167-177
We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation. 相似文献