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991.
Bass AJ Lawrence MS Brace LE Ramos AH Drier Y Cibulskis K Sougnez C Voet D Saksena G Sivachenko A Jing R Parkin M Pugh T Verhaak RG Stransky N Boutin AT Barretina J Solit DB Vakiani E Shao W Mishina Y Warmuth M Jimenez J Chiang DY Signoretti S Kaelin WG Spardy N Hahn WC Hoshida Y Ogino S Depinho RA Chin L Garraway LA Fuchs CS Baselga J Tabernero J Gabriel S Lander ES Getz G Meyerson M 《Nature genetics》2011,43(10):964-968
Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.9× coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with β-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 β-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events. 相似文献
992.
我们利用月球侦察轨道器(LRO)的窄角相机(NAC)数据,使用一种新的光学遥感方法—相比率影像法,来评估月表亚分辨率尺度的粗糙度.我们用该方法对月面谷Vallis Schrteri地区的三维相比率影像进行分析后发现,在月面谷侧面上风化物的复杂运动模式与撞击坑并无关联,而是由风化物和岩屑形成的,而非冲击熔融. 相似文献
993.
The substrate- and inhibitor-related characteristics of monoamine oxidase (MAO) were studied on chick brain mitochondria. It was found that neither 5-hydroxytryptamine nor beta-phenylethylamine is the specific substrate for type A and type B MAO in chick brain. 相似文献
994.
995.
Peripheral blood samples from 52 women, including 16 with herpes genitalis and 36 healthy persons, were studied to enumerate subpopulations of lymphocytes. It was found that the mean percentage of 'active' T lymphocytes was significantly less in the patients with herpes genitalis than in the controls. 相似文献
996.
Under in vitro experimental conditions in which insulin increases adipose tissue lipoprotein lipase, cyclic GMP or dibutyryl cyclic GMP has no effect on this enzyme in rat adipose tissue fragments, or on either the intra- or extracellular forms of this enzyme in isolated fat cells. These results do not support the involvement of cyclic GMP in the insulin-stimulation of lipoprotein lipase in adipose tissue. 相似文献
997.
In the present paper we report examination of stereotypic hallmarks of apoptosis in heat-treated tobacco cells. Hyperthermia
(44 °C, 4 h) caused apoptosis in 53.6% of cells when assayed 24 h after heat treatment. The induction of apoptosis by heat
treatment was confirmed by flow cytometric assay. Cytological observations revealed condensation of the cytoplasm and nucleus,
as well as nuclear collapse. DNA ladders were observed in DNA extracted from heat-treated cells, whereas DNA from control
cells remained undegraded. The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay revealed
that 51.8% of the heat-treated cells (44 °C, 4 h) show positive reaction after a 24-h recovery. When cells were cultured in
a medium supplemented with 0.4–5.0 mM ZnSO4, internucleosomal DNA fragmentation induced by heat shock was completely negated. Strikingly, when cells were cultured in
Ca2+ and/or Mg2+ free medium for 44 h followed by heat treatment, DNA laddering was not observed. The results suggest hyperthermia-induced
apoptosis and a correlation between the regula tion of endonucleases and heat shock signal in apoptotic tobacco cells.
Received 17 September 1998; received after revision 4 January 1999; accepted 4 January 1999 相似文献
998.
It is easy to apply lines in design drawings to create different styles, however, there is no guarantee that all the style lines drawn are able to be manufactured. In this paper, we focus on one undeliverable style to enhance our understanding of the relationship between the design sketch and the pattern design process. In order to evidence that such style is unworkable, a systematic display of pattern development, and to be reinforced by mathematical evaluation, will be introduced and addressed. When one can easily detect design fault, waste of product development time can be minimized. 相似文献
999.
E A Lindsay A Botta V Jurecic S Carattini-Rivera Y C Cheah H M Rosenblatt A Bradley A Baldini 《Nature》1999,401(6751):379-383
The heterozygous chromosome deletion within the band 22q11 (del22q11) is an important cause of congenital cardiovascular defects. It is the genetic basis of DiGeorge syndrome and causes the most common deletion syndrome in humans. Because the deleted region is largely conserved in the mouse, we were able to engineer a chromosome deletion (Df1) spanning a segment of the murine region homologous to the human deleted region. Here we describe heterozygously deleted (Df1/+) mice with cardiovascular abnormalities of the same type as those associated with del22q11; we have traced the embryological origin of these abnormalities to defective development of the fourth pharyngeal arch arteries. Genetic complementation of the deletion using a chromosome duplicated for the Df1 DNA segment corrects the heart defects, indicating that they are caused by reduced dosage of genes located within Df1. The Df1/+ mouse model reveals the pathogenic basis of the most clinically severe aspect of DiGeorge syndrome and uncovers a new mechanism leading to aortic arch abnormalities. These mutants represent a mouse model of a human deletion syndrome generated by chromosome engineering. 相似文献
1000.
Dystrophin expression in the mdx mouse restored by stem cell transplantation. 总被引:180,自引:0,他引:180
E Gussoni Y Soneoka C D Strickland E A Buzney M K Khan A F Flint L M Kunkel R C Mulligan 《Nature》1999,401(6751):390-394
The development of cell or gene therapies for diseases involving cells that are widely distributed throughout the body has been severely hampered by the inability to achieve the disseminated delivery of cells or genes to the affected tissues or organ. Here we report the results of bone marrow transplantation studies in the mdx mouse, an animal model of Duchenne's muscular dystrophy, which indicate that the intravenous injection of either normal haematopoietic stem cells or a novel population of muscle-derived stem cells into irradiated animals results in the reconstitution of the haematopoietic compartment of the transplanted recipients, the incorporation of donor-derived nuclei into muscle, and the partial restoration of dystrophin expression in the affected muscle. These results suggest that the transplantation of different stem cell populations, using the procedures of bone marrow transplantation, might provide an unanticipated avenue for treating muscular dystrophy as well as other diseases where the systemic delivery of therapeutic cells to sites throughout the body is critical. Our studies also suggest that the inherent developmental potential of stem cells isolated from diverse tissues or organs may be more similar than previously anticipated. 相似文献