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排序方式: 共有213条查询结果,搜索用时 15 毫秒
1.
Fibulin-5/DANCE is essential for elastogenesis in vivo. 总被引:19,自引:0,他引:19
Tomoyuki Nakamura Pilar Ruiz Lozano Yasuhiro Ikeda Yoshitaka Iwanaga Aleksander Hinek Susumu Minamisawa Ching-Feng Cheng Kazuhiro Kobuke Nancy Dalton Yoshikazu Takada Kei Tashiro John Ross Jr Tasuku Honjo Kenneth R Chien 《Nature》2002,415(6868):171-175
The elastic fibre system has a principal role in the structure and function of various types of organs that require elasticity, such as large arteries, lung and skin. Although elastic fibres are known to be composed of microfibril proteins (for example, fibrillins and latent transforming growth factor (TGF)-beta-binding proteins) and polymerized elastin, the mechanism of their assembly and development is not well understood. Here we report that fibulin-5 (also known as DANCE), a recently discovered integrin ligand, is an essential determinant of elastic fibre organization. fibulin-5-/- mice generated by gene targeting exhibit a severely disorganized elastic fibre system throughout the body. fibulin-5-/- mice survive to adulthood, but have a tortuous aorta with loss of compliance, severe emphysema, and loose skin (cutis laxa). These tissues contain fragmented elastin without an increase of elastase activity, indicating defective development of elastic fibres. Fibulin-5 interacts directly with elastic fibres in vitro, and serves as a ligand for cell surface integrins alphavbeta3, alphavbeta5 and alpha9beta1 through its amino-terminal domain. Thus, fibulin-5 may provide anchorage of elastic fibres to cells, thereby acting to stabilize and organize elastic fibres in the skin, lung and vasculature. 相似文献
2.
Summary In young spontaneously hypertensive rats (SHR), dopamine -hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) activities were examined in the brainstem nuclei. Activation of noradrenergic neurons in the locus coeruleus, A2 and spinal intermediolateral cell areas, resulting in enhanced sympathetic nervous activity in the periphery, initiates hypertension. Adrenergic neurons, unchanged in these and A1 cell areas of young SHR, are not involved in the development of hypertension in SHR. 相似文献
3.
A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage 总被引:18,自引:0,他引:18
Tanaka H Arakawa H Yamaguchi T Shiraishi K Fukuda S Matsui K Takei Y Nakamura Y 《Nature》2000,404(6773):42-49
The p53 gene is frequently inactivated in human cancers. Here we have isolated a p53-inducible gene, p53R2, by using differential display to examine messenger RNAs in a cancer-derived human cell line carrying a highly regulated wild-type p53 expression system. p53R2 contains a p53-binding sequence in intron 1 and encodes a 351-amino-acid peptide with striking similarity to the ribonucleotide reductase small subunit (R2), which is important in DNA synthesis during cell division. Expression of p53R2, but not R2, was induced by ultraviolet and gamma-irradiation and adriamycin treatment in a wild-type p53-dependent manner. Induction of p53R2 in p53-deficient cells caused G2/M arrest and prevented cells from death in response to adriamycin. Inhibition of endogenous p53R2 expression in cells that have an intact p53-dependent DNA damage checkpoint reduced ribonucleotide reductase activity, DNA repair and cell survival after exposure to various genotoxins. Our results indicate that p53R2 encodes a ribonucleotide reductase that is directly involved in the p53 checkpoint for repair of damaged DNA. The discovery of p53R2 clarifies a relationship between a ribonucleotide reductase activity involved in repair of damaged DNA and tumour suppression by p53. 相似文献
4.
XinMiao Lü LiPing Zhu Mitsugu Nishimura Yoshimune Morita Takahiro Watanabe Toshio Nakamura Yong Wang 《科学通报(英文版)》2011,56(27):2931-2940
A 380-cm-long sediment core was acquired from the deep water area of Pumoyum Co, southern Tibet. Twenty-five plant residue
samples were selected, and organic carbon stable isotopes were obtained using the AMS 14C chronological method. The 14C age and carbon reservoir effect were calibrated with surface sedimentation rate measurements using 210Pb dating. Results showed that the core sediment deposited over 19 cal ka BP. Based on a multi-proxy analysis of TOC and IC
contents, grain size and pollen assemblage data, the palaeoclimatic evolution of Pumoyum Co was reconstructed since the last
glacial. Pumoyum Co was a shallow lake prior to 16.2 cal ka BP; although the glacier around the lake began to melt due to
increasing temperatures, climate was still cold and dry. In the interval of 16.2–11.8 cal ka BP, the sedimentary environment
fluctuated drastically and frequently. Two cold-events occurred at 14.2 and 11.8 cal ka BP, and these may correspond to the
Older Dryas and the Younger Dryas events, respectively. After 11.8 cal ka BP, Pumoyun Co developed into the deep lake as it
is now. The lake water temperature was relatively lower at that time because of influx of cold water from glacial meltwater
entering the lake. As a result, the multi-proxy indicators showed no sign of warm conditions. Comparisons between the sedimentary
record of Pumoyum Co with that of other lakes of the same age in southern Tibet indicate a warmer climate following the last
deglaciation influenced the southeastern Tibetan Plateau. These results imply that the southwest Asian monsoon gradually became
stronger since the deglaciation during its expansion to the inner plateau. The glacial-supplied water of the lake responded
sensitively to cold-events. The entire southern Tibet region was dominantly influenced climatically by the southwest Asian
monsoon during the Holocene. 相似文献
5.
Onouchi Y Gunji T Burns JC Shimizu C Newburger JW Yashiro M Nakamura Y Yanagawa H Wakui K Fukushima Y Kishi F Hamamoto K Terai M Sato Y Ouchi K Saji T Nariai A Kaburagi Y Yoshikawa T Suzuki K Tanaka T Nagai T Cho H Fujino A Sekine A Nakamichi R Tsunoda T Kawasaki T Nakamura Y Hata A 《Nature genetics》2008,40(1):35-42
Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children. Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis. 相似文献
6.
Miki D Ochi H Hayes CN Abe H Yoshima T Aikata H Ikeda K Kumada H Toyota J Morizono T Tsunoda T Kubo M Nakamura Y Kamatani N Chayama K 《Nature genetics》2011,43(8):797-800
Chronic viral hepatitis is the most important risk factor for progression to hepatocellular carcinoma (HCC). To identify genetic risk factors for progression to HCC in individuals with chronic hepatitis C virus (HCV), we analyzed 467,538 SNPs in 212 Japanese individuals with chronic HCV with HCC and 765 individuals with chronic HCV without HCC. We identified one intronic SNP in the DEPDC5 locus on chromosome 22 associated with HCC risk and confirmed the association using an independent case-control population (710 cases and 1,625 controls). The association was highly significant when we analyzed the stages separately as well as together (rs1012068, P(combined) = 1.27 × 10(-13), odds ratio = 1.75). The significance level of the association further increased after adjustment for gender, age and platelet count (P = 1.35 × 10(-14), odds ratio = 1.96). Our findings suggest that common variants within the DEPDC5 locus affect susceptibility to HCC in Japanese individuals with chronic HCV infection. 相似文献
7.
为获得眼镜王蛇(Ophiophagus hannah,简称Oh)蛇毒α-神经毒素(α-NT)的基因序列,依据眼镜蛇科不同毒蛇种类来源的α-NT基因有较高的同源性,设计1对上下游引物,为克服引物带来模糊扩增,在蛋白编码部分再设计1对上下游特异引物,用Nacleospin RNA Kit法从3条活眼镜王蛇毒腺中提取mRNA,以3′端引物合成的cDNA作为模板进行PCR扩增反应,测定产物的核苷酸序列,得到全长474bp的眼镜王蛇cDNA基因核苷酸序列。该核苷酸序列的信号肽与眼镜蛇树属Pseudonnaja textilis(Pt)、海蛇Laticauda semifasciata(Ls)100%同源,与眼镜蛇南洋亚种Naja sputatrix (Ns)、银环蛇(Bungarus multicinctus)(Bm)96.8%同源;蛋白密码部分有83.3%与Ns、79.2%与Pt、76.4%与Ls、74.1%与Bm同源。信号肽后紧接着的72个氨基酸有90.3%与已发现的眼镜王蛇毒长链α-NT Toxin a同源,大约有73.6%与Toxin b、69.7%与Oh-4、66.7%与Oh-5、56.9%与Oh-6A和6B同源,并与α-银环蛇毒素54.2%同源。说明新发现的眼镜王蛇cDNA是一条长链α-NT基因。 相似文献
8.
9.
Ultrahigh-quality silicon carbide single crystals 总被引:1,自引:0,他引:1
Nakamura D Gunjishima I Yamaguchi S Ito T Okamoto A Kondo H Onda S Takatori K 《Nature》2004,430(7003):1009-1012
Silicon carbide (SiC) has a range of useful physical, mechanical and electronic properties that make it a promising material for next-generation electronic devices. Careful consideration of the thermal conditions in which SiC [0001] is grown has resulted in improvements in crystal diameter and quality: the quantity of macroscopic defects such as hollow core dislocations (micropipes), inclusions, small-angle boundaries and long-range lattice warp has been reduced. But some macroscopic defects (about 1-10 cm(-2)) and a large density of elementary dislocations (approximately 10(4) cm(-2)), such as edge, basal plane and screw dislocations, remain within the crystal, and have so far prevented the realization of high-efficiency, reliable electronic devices in SiC (refs 12-16). Here we report a method, inspired by the dislocation structure of SiC grown perpendicular to the c-axis (a-face growth), to reduce the number of dislocations in SiC single crystals by two to three orders of magnitude, rendering them virtually dislocation-free. These substrates will promote the development of high-power SiC devices and reduce energy losses of the resulting electrical systems. 相似文献
10.
RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta 总被引:18,自引:0,他引:18
Takayanagi H Kim S Matsuo K Suzuki H Suzuki T Sato K Yokochi T Oda H Nakamura K Ida N Wagner EF Taniguchi T 《Nature》2002,416(6882):744-749