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Mutations in the gene encoding the retinoblastoma tumor suppressor predispose humans and mice to tumor development. Here we have assessed the effect of Nras loss on tumor development in Rb1 heterozygous mice. Loss of one or two Nras alleles is shown to significantly reduce the severity of pituitary tumors arising in Rb1(+/-) animals by enhancing their differentiation. By contrast, C-cell thyroid adenomas occurring in Rb1(+/-) mice progress to metastatic medullary carcinomas after loss of Nras. In Rb1(+/-)Nras(+/-) animals, distant medullary thyroid carcinoma metastases are associated with loss of the remaining wild-type Nras allele. Loss of Nras in Rb1-deficient C cells results in elevated Ras homolog family A (RhoA) activity, and this is causally linked to the invasiveness and metastatic behavior of these cells. These findings suggest that the loss of the proto-oncogene Nras in certain cellular contexts can promote malignant tumor progression.  相似文献   
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A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy   总被引:19,自引:0,他引:19  
Spinal muscular atrophy (SMA) is a relatively common neurodegenerative disease caused by homozygous loss of the survival motor neuron 1 (SMN1) gene. Humans possess a linked, nearly identical gene, SMN2, which produces a functional SMN protein but at levels insufficient to compensate for loss of SMN1 (refs. 1,2). A C/T transition at position +6 in exon 7 is all that differentiates the two genes, but this is sufficient to prevent efficient exon 7 splicing in SMN2 (refs. 2,3). Here we show that the C/T transition functions not to disrupt an exonic splicing enhancer (ESE) in SMN1 (ref. 4), as previously suggested, but rather to create an exonic splicing silencer (ESS) in SMN2. We show that this ESS functions as a binding site for a known repressor protein, hnRNP A1, which binds to SMN2 but not SMN1 exon 7 RNA. We establish the physiological importance of these results by using small interfering RNAs to reduce hnRNP A protein levels in living cells and show that this results in efficient SMN2 exon 7 splicing. Our findings not only define a new mechanism underlying the inefficient splicing of SMN2 exon 7 but also illustrate more generally the remarkable sensitivity and precision that characterizes control of mRNA splicing.  相似文献   
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Summary The induction of unresponsiveness to mycobacterial adjuvant took a longer time in male DA rats than in female rats. A shift in the induction time of unresponsiveness in males toward the female type was brought about by castration, but could be reverted to the male type by the application of testosterone. The transfer study revealed that cells capable of preventing arthritis required a longer incubation time for their development in males than in females. This suggests that testosterone inhibits the development of suppressor cells in adjuvant arthritis.Acknowledgments. We are grateful to The Naito Foundation Research Grant for 1983.  相似文献   
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Zusammenfassung Subkutane Einspritzung von Kalium- oder Natriumzyanid in die Zehenballen der Katze führt über einen Axonreflex zu merklichem Schwitzen. Dieser Effekt von Kaliumzyanid wird durch Procain und Atropin gehemmt, nicht aber durch Hexamethonium. Auch beim Menschen ruft intrakutan eingeführtes Natriumzyanid eine entsprechende Schweissabsonderung hervor.  相似文献   
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Photocatalyst releasing hydrogen from water   总被引:4,自引:0,他引:4  
Maeda K  Teramura K  Lu D  Takata T  Saito N  Inoue Y  Domen K 《Nature》2006,440(7082):295
Direct splitting of water using a particulate photocatalyst would be a good way to produce clean and recyclable hydrogen on a large scale, and in the past 30 years various photocatalysts have been found that function under visible light. Here we describe an advance in the catalysis of the overall splitting of water under visible light: the new catalyst is a solid solution of gallium and zinc nitrogen oxide, (Ga(1-x)Zn(x))(N(1-x)O(x)), modified with nanoparticles of a mixed oxide of rhodium and chromium. The mixture functions as a promising and efficient photocatalyst in promoting the evolution of hydrogen gas.  相似文献   
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Organic solar cells based on copper naphthalocyanine(CuNc) and fullerene(C60) were fabricated, and their photovoltaic properties were investigated. C60 and CuNc were used as n-type and p-type semiconductors, respectively. In addition, the effect of Au nanoparticle addition on a hole transfer layer was investigated, and the power conversion efficiency of the devices was improved after blending the Au nanoparticles into the hole transport layer. Nanostructures of Au nanoparticles were investigated by transmission electron microscopy and X-ray diffraction. Energy levels of molecules were calculated by molecular orbital calculations, and the nanostructure and electronic properties were discussed.& 2014 Chinese Materials Research Society. Production and hosting by Elsevier B.V. All rights reserved.  相似文献   
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Haploinsufficiency of NSD1 causes Sotos syndrome   总被引:14,自引:0,他引:14  
We isolated NSD1 from the 5q35 breakpoint in an individual with Sotos syndrome harboring a chromosomal translocation. We identified 1 nonsense, 3 frameshift and 20 submicroscopic deletion mutations of NSD1 among 42 individuals with sporadic cases of Sotos syndrome. The results indicate that haploinsufficiency of NSD1 is the major cause of Sotos syndrome.  相似文献   
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产甲烷阶段季铵化合物的厌氧生物降解性研究(英文)   总被引:1,自引:1,他引:0  
基于厌氧序批式测试系统,研究了一组季铵化合物的最终生物降解性和对生物气产生过程的毒性效果.四个测试物中每个化合物均带有四个相同的烷基,通式为R4N+Br-(TEAB,TPAB,TOAB和TODAB分别对应R=C2,C5,C8,C18,).测试物的矿化程度被用来评估其最终厌氧生物降解性;对碳源D-葡萄糖代谢过程的毒性可以利用测试物对生物气生成过程的抑制效果来指示.研究结果表明:带有偶碳数烷基链的季铵化合物,即TEAB、TOAB和TODAB在20 mg/L(以C计)能够被很容易地降解为CO2和CH4,它们对生物气生成过程的毒性随着所带烷基链长的增长而减小.测试物中带有最长碳链的TODAB,即使碳浓度提高到100 mg/L也可以顺利降解;并且在200 mg/L的高浓度条件下也没有发现其对代谢过程的毒性证据.相反,带有奇数碳链的TPAB很难被厌氧生物降解,而且在所有测试物中显示出最强的厌氧毒性,200 mg/L时的生物气抑制率高达69%.  相似文献   
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