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排序方式: 共有141条查询结果,搜索用时 125 毫秒
81.
82.
Angela Dittmer Kristina Hohlfeld Jana Lützkendorf Lutz P. Müller Jürgen Dittmer 《Cellular and molecular life sciences : CMLS》2009,66(18):3053-3065
Mesenchymal stem cells (MSCs) have been shown to communicate with tumor cells. We analyzed the effect of human MSCs (hMSCs)
on breast cancer cells in three-dimensional cultures. By using GFP expression and immunohistochemistry, we show that hMSCs
invade 3D breast cancer cell aggregates. hMSCs caused breast cancer spheroids to become disorganized which was accompanied
by a disruption of cell–cell adhesion, E-cadherin cleavage, and nuclear translocation of E-cadherin, but not by epithelial/mesenchymal
transition or by an increase in ERK1/2 activity. In addition, hMSCs enhanced the motility of breast cancer cells. Inhibition
of ADAM10 (a disintegrin and metalloprotease 10), known to cleave E-cadherin, prevented both hMSC-mediated E-cadherin cleavage
and enhanced migration. Our data suggest that hMSCs interfere with cell–cell adhesion and enhance migration of breast cancer
cells by activating ADAM10. 相似文献
83.
Disruption of P2RY5, an orphan G protein-coupled receptor, underlies autosomal recessive woolly hair
Shimomura Y Wajid M Ishii Y Shapiro L Petukhova L Gordon D Christiano AM 《Nature genetics》2008,40(3):335-339
The genetic determinants of hair texture in humans are largely unknown. Several human syndromes exist in which woolly hair comprises a part of the phenotype; however, simple autosomal recessive inheritance of isolated woolly hair has only rarely been reported. To identify a gene involved in controlling hair texture, we performed genetic linkage analysis in six families of Pakistani origin with autosomal recessive woolly hair (ARWH; OMIM 278150). All six families showed linkage to chromosome 13q14.2-14.3 (Z = 17.97). In all cases, we discovered pathogenic mutations in P2RY5, which encodes a G protein-coupled receptor and is a nested gene residing within intron 17 of the retinoblastoma 1 (RB1) gene. P2RY5 is expressed in both Henle's and Huxley's layers of the inner root sheath of the hair follicle. Our findings indicate that disruption of P2RY5 underlies ARWH and, more broadly, uncover a new gene involved in determining hair texture in humans. 相似文献
84.
Krishnamurthy J Ramsey MR Ligon KL Torrice C Koh A Bonner-Weir S Sharpless NE 《Nature》2006,443(7110):453-457
85.
Roberts DM Nanda A Havenga MJ Abbink P Lynch DM Ewald BA Liu J Thorner AR Swanson PE Gorgone DA Lifton MA Lemckert AA Holterman L Chen B Dilraj A Carville A Mansfield KG Goudsmit J Barouch DH 《Nature》2006,441(7090):239-243
A common viral immune evasion strategy involves mutating viral surface proteins in order to evade host neutralizing antibodies. Such immune evasion tactics have not previously been intentionally applied to the development of novel viral gene delivery vectors that overcome the critical problem of anti-vector immunity. Recombinant, replication-incompetent adenovirus serotype 5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens have proved highly immunogenic in preclinical studies but will probably be limited by the high prevalence of pre-existing anti-Ad5 immunity in human populations, particularly in the developing world. Here we show that rAd5 vectors can be engineered to circumvent anti-Ad5 immunity. We constructed novel chimaeric rAd5 vectors in which the seven short hypervariable regions (HVRs) on the surface of the Ad5 hexon protein were replaced with the corresponding HVRs from the rare adenovirus serotype Ad48. These HVR-chimaeric rAd5 vectors were produced at high titres and were stable through serial passages in vitro. HVR-chimaeric rAd5 vectors expressing simian immunodeficiency virus Gag proved comparably immunogenic to parental rAd5 vectors in naive mice and rhesus monkeys. In the presence of high levels of pre-existing anti-Ad5 immunity, the immunogenicity of HVR-chimaeric rAd5 vectors was not detectably suppressed, whereas the immunogenicity of parental rAd5 vectors was abrogated. These data demonstrate that functionally relevant Ad5-specific neutralizing antibodies are focused on epitopes located within the hexon HVRs. Moreover, these studies show that recombinant viral vectors can be engineered to circumvent pre-existing anti-vector immunity by removing key neutralizing epitopes on the surface of viral capsid proteins. Such chimaeric viral vectors may have important practical implications for vaccination and gene therapy. 相似文献
86.
Beaulieu JP Bennett DP Fouqué P Williams A Dominik M Jørgensen UG Kubas D Cassan A Coutures C Greenhill J Hill K Menzies J Sackett PD Albrow M Brillant S Caldwell JA Calitz JJ Cook KH Corrales E Desort M Dieters S Dominis D Donatowicz J Hoffman M Kane S Marquette JB Martin R Meintjes P Pollard K Sahu K Vinter C Wambsganss J Woller K Horne K Steele I Bramich DM Burgdorf M Snodgrass C Bode M Udalski A Szymański MK Kubiak M Wieckowski T Pietrzyński G Soszyński I Szewczyk O Wyrzykowski L 《Nature》2006,439(7075):437-440
In the favoured core-accretion model of formation of planetary systems, solid planetesimals accumulate to build up planetary cores, which then accrete nebular gas if they are sufficiently massive. Around M-dwarf stars (the most common stars in our Galaxy), this model favours the formation of Earth-mass (M(o)) to Neptune-mass planets with orbital radii of 1 to 10 astronomical units (au), which is consistent with the small number of gas giant planets known to orbit M-dwarf host stars. More than 170 extrasolar planets have been discovered with a wide range of masses and orbital periods, but planets of Neptune's mass or less have not hitherto been detected at separations of more than 0.15 au from normal stars. Here we report the discovery of a 5.5(+5.5)(-2.7) M(o) planetary companion at a separation of 2.6+1.5-0.6 au from a 0.22+0.21-0.11 M(o) M-dwarf star, where M(o) refers to a solar mass. (We propose to name it OGLE-2005-BLG-390Lb, indicating a planetary mass companion to the lens star of the microlensing event.) The mass is lower than that of GJ876d (ref. 5), although the error bars overlap. Our detection suggests that such cool, sub-Neptune-mass planets may be more common than gas giant planets, as predicted by the core accretion theory. 相似文献
87.
A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response 总被引:1,自引:0,他引:1
L Kruidenier CW Chung Z Cheng J Liddle K Che G Joberty M Bantscheff C Bountra A Bridges H Diallo D Eberhard S Hutchinson E Jones R Katso M Leveridge PK Mander J Mosley C Ramirez-Molina P Rowland CJ Schofield RJ Sheppard JE Smith C Swales R Tanner P Thomas A Tumber G Drewes U Oppermann DJ Patel K Lee DM Wilson 《Nature》2012,488(7411):404-408
88.
The developmental transcriptome of Drosophila melanogaster 总被引:2,自引:0,他引:2
Graveley BR Brooks AN Carlson JW Duff MO Landolin JM Yang L Artieri CG van Baren MJ Boley N Booth BW Brown JB Cherbas L Davis CA Dobin A Li R Lin W Malone JH Mattiuzzo NR Miller D Sturgill D Tuch BB Zaleski C Zhang D Blanchette M Dudoit S Eads B Green RE Hammonds A Jiang L Kapranov P Langton L Perrimon N Sandler JE Wan KH Willingham A Zhang Y Zou Y Andrews J Bickel PJ Brenner SE Brent MR Cherbas P Gingeras TR Hoskins RA Kaufman TC Oliver B Celniker SE 《Nature》2011,471(7339):473-479
89.
Independent genome-wide scans identify a chromosome 18 quantitative-trait locus influencing dyslexia. 总被引:23,自引:0,他引:23
Simon E Fisher Clyde Francks Angela J Marlow I Laurence MacPhie Dianne F Newbury Lon R Cardon Yumiko Ishikawa-Brush Alex J Richardson Joel B Talcott Javier Gayán Richard K Olson Bruce F Pennington Shelley D Smith John C DeFries John F Stein Anthony P Monaco 《Nature genetics》2002,30(1):86-91
Developmental dyslexia is defined as a specific and significant impairment in reading ability that cannot be explained by deficits in intelligence, learning opportunity, motivation or sensory acuity. It is one of the most frequently diagnosed disorders in childhood, representing a major educational and social problem. It is well established that dyslexia is a significantly heritable trait with a neurobiological basis. The etiological mechanisms remain elusive, however, despite being the focus of intensive multidisciplinary research. All attempts to map quantitative-trait loci (QTLs) influencing dyslexia susceptibility have targeted specific chromosomal regions, so that inferences regarding genetic etiology have been made on the basis of very limited information. Here we present the first two complete QTL-based genome-wide scans for this trait, in large samples of families from the United Kingdom and United States. Using single-point analysis, linkage to marker D18S53 was independently identified as being one of the most significant results of the genome in each scan (P< or =0.0004 for single word-reading ability in each family sample). Multipoint analysis gave increased evidence of 18p11.2 linkage for single-word reading, yielding top empirical P values of 0.00001 (UK) and 0.0004 (US). Measures related to phonological and orthographic processing also showed linkage at this locus. We replicated linkage to 18p11.2 in a third independent sample of families (from the UK), in which the strongest evidence came from a phoneme-awareness measure (most significant P value=0.00004). A combined analysis of all UK families confirmed that this newly discovered 18p QTL is probably a general risk factor for dyslexia, influencing several reading-related processes. This is the first report of QTL-based genome-wide scanning for a human cognitive trait. 相似文献
90.
Oceanography: a marine nitrogen cycle fix? 总被引:2,自引:0,他引:2