排序方式: 共有58条查询结果,搜索用时 171 毫秒
31.
Bong June Yoon Herry Herman Aimee Sikora Laura T Smith Christoph Plass Paul D Soloway 《Nature genetics》2002,30(1):92-96
In mammals, DNA is methylated at cytosines within CpG dinucleotides. Properly regulated methylation is crucial for normal development. Inappropriate methylation may contribute to tumorigenesis by silencing tumor-suppressor genes or by activating growth-stimulating genes. Although many genes have been identified that acquire methylation and whose expression is methylation-sensitive, little is known about how DNA methylation is controlled. We have identified a DNA sequence that regulates establishment of DNA methylation in the male germ line at Rasgrf1. In mice, the imprinted Rasgrf1 locus is methylated on the paternal allele within a differentially methylated domain (DMD) 30 kbp 5' of the promoter. Expression is exclusively from the paternal allele in neonatal brain. Methylation is regulated by a repeated sequence, consisting of a 41-mer repeated 40 times, found immediately 3' of the DMD. This sequence is present in organisms in which Rasgrf1 is imprinted. In addition, DMD methylation is required for imprinted Rasgrf1 expression. Together the DMD and repeat element constitute a binary switch that regulates imprinting at the locus. 相似文献
32.
斯蒂芬·杰伊·古尔德 (StephenJayGould ,见上图 )是哈佛大学生物进化论科学家 ,他的研究、演讲以及大量科学散文作品给古生物学研究领域注入了新的内涵。 2 0 0 2年 5月 2 0日 ,他在曼哈顿的家中去世 ,癌症夺去了他的生命 ,享年 60岁。古尔德博士可以说是 2 0世纪最有影响的进化生物学家之一 ,也可以说是自查尔斯·达尔文 (CharlesDarwin)以来最知名的生物学家。他引发了多场争论 ,时而迫使科学家们重新考虑已成定论的有关进化模式和进化过程的观点。他最有名的理论之一是与奈尔斯·埃尔德雷奇(NilesE… 相似文献
33.
Mills RE Walter K Stewart C Handsaker RE Chen K Alkan C Abyzov A Yoon SC Ye K Cheetham RK Chinwalla A Conrad DF Fu Y Grubert F Hajirasouliha I Hormozdiari F Iakoucheva LM Iqbal Z Kang S Kidd JM Konkel MK Korn J Khurana E Kural D Lam HY Leng J Li R Li Y Lin CY Luo R Mu XJ Nemesh J Peckham HE Rausch T Scally A Shi X Stromberg MP Stütz AM Urban AE Walker JA Wu J Zhang Y Zhang ZD Batzer MA Ding L Marth GT McVean G Sebat J Snyder M Wang J Ye K Eichler EE Gerstein MB Hurles ME Lee C McCarroll SA 《Nature》2011,470(7332):59-65
Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies. 相似文献
34.
Cho YS Chen CH Hu C Long J Ong RT Sim X Takeuchi F Wu Y Go MJ Yamauchi T Chang YC Kwak SH Ma RC Yamamoto K Adair LS Aung T Cai Q Chang LC Chen YT Gao Y Hu FB Kim HL Kim S Kim YJ Lee JJ Lee NR Li Y Liu JJ Lu W Nakamura J Nakashima E Ng DP Tay WT Tsai FJ Wong TY Yokota M Zheng W Zhang R Wang C So WY Ohnaka K Ikegami H Hara K Cho YM Cho NH Chang TJ Bao Y Hedman ÅK Morris AP McCarthy MI;DIAGRAM Consortium;MuTHER Consortium Takayanagi R Park KS Jia W Chuang LM Chan JC Maeda S Kadowaki T Lee JY Wu JY 《Nature genetics》2012,44(1):67-72
We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D. 相似文献
35.
This paper explains the unpredictability of exchange rate movements at short horizons and provides a plausible answer on the exchange rate disconnect puzzle. By generalizing Chaboud and Wright's (Journal of International Economics 2005; 66 : 349–362) work, it is shown that exchange rates follow a martingale process at short horizons but over long horizons may contain some predictable structure. The empirical results applied to several major currencies of the US dollar support our hypothesis. This evidence is not coincided with the explanation of the inefficient market hypothesis under which exchange rate movements can be predictable in both short and long horizons. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
36.
Metamaterials with negative refractive indices can manipulate electromagnetic waves in unusual ways, and can be used to achieve, for example, sub-diffraction-limit focusing, the bending of light in the 'wrong' direction, and reversed Doppler and Cerenkov effects. These counterintuitive and technologically useful behaviours have spurred considerable efforts to synthesize a broad array of negative-index metamaterials with engineered electric, magnetic or optical properties. Here we demonstrate another route to negative refraction by exploiting the inertia of electrons in semiconductor two-dimensional electron gases, collectively accelerated by electromagnetic waves according to Newton's second law of motion, where this acceleration effect manifests as kinetic inductance. Using kinetic inductance to attain negative refraction was theoretically proposed for three-dimensional metallic nanoparticles and seen experimentally with surface plasmons on the surface of a three-dimensional metal. The two-dimensional electron gas that we use at cryogenic temperatures has a larger kinetic inductance than three-dimensional metals, leading to extraordinarily strong negative refraction at gigahertz frequencies, with an index as large as -700. This pronounced negative refractive index and the corresponding reduction in the effective wavelength opens a path to miniaturization in the science and technology of negative refraction. 相似文献
37.
Amorphous metal-oxide semiconductors have emerged as potential replacements for organic and silicon materials in thin-film electronics. The high carrier mobility in the amorphous state, and excellent large-area uniformity, have extended their applications to active-matrix electronics, including displays, sensor arrays and X-ray detectors. Moreover, their solution processability and optical transparency have opened new horizons for low-cost printable and transparent electronics on plastic substrates. But metal-oxide formation by the sol-gel route requires an annealing step at relatively high temperature, which has prevented the incorporation of these materials with the polymer substrates used in high-performance flexible electronics. Here we report a general method for forming high-performance and operationally stable metal-oxide semiconductors at room temperature, by deep-ultraviolet photochemical activation of sol-gel films. Deep-ultraviolet irradiation induces efficient condensation and densification of oxide semiconducting films by photochemical activation at low temperature. This photochemical activation is applicable to numerous metal-oxide semiconductors, and the performance (in terms of transistor mobility and operational stability) of thin-film transistors fabricated by this route compares favourably with that of thin-film transistors based on thermally annealed materials. The field-effect mobilities of the photo-activated metal-oxide semiconductors are as high as 14 and 7?cm(2)?V(-1)?s(-1) (with an Al(2)O(3) gate insulator) on glass and polymer substrates, respectively; and seven-stage ring oscillators fabricated on polymer substrates operate with an oscillation frequency of more than 340?kHz, corresponding to a propagation delay of less than 210?nanoseconds per stage. 相似文献
38.
Neale BM Kou Y Liu L Ma'ayan A Samocha KE Sabo A Lin CF Stevens C Wang LS Makarov V Polak P Yoon S Maguire J Crawford EL Campbell NG Geller ET Valladares O Schafer C Liu H Zhao T Cai G Lihm J Dannenfelser R Jabado O Peralta Z Nagaswamy U Muzny D Reid JG Newsham I Wu Y Lewis L Han Y Voight BF Lim E Rossin E Kirby A Flannick J Fromer M Shakir K Fennell T Garimella K Banks E Poplin R Gabriel S DePristo M Wimbish JR Boone BE Levy SE Betancur C Sunyaev S Boerwinkle E Buxbaum JD Cook EH Devlin B 《Nature》2012,485(7397):242-245
Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified. To identify further genetic risk factors, here we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n = 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant, and the overall rate of mutation is only modestly higher than the expected rate. In contrast, the proteins encoded by genes that harboured de novo missense or nonsense mutations showed a higher degree of connectivity among themselves and to previous ASD genes as indexed by protein-protein interaction screens. The small increase in the rate of de novo events, when taken together with the protein interaction results, are consistent with an important but limited role for de novo point mutations in ASD, similar to that documented for de novo copy number variants. Genetic models incorporating these data indicate that most of the observed de novo events are unconnected to ASD; those that do confer risk are distributed across many genes and are incompletely penetrant (that is, not necessarily sufficient for disease). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5- to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favour of CHD8 and KATNAL2 as genuine autism risk factors. 相似文献
39.
本文证明了公式β(n)=σ(n-1)+1其中α(n-1)是n-1次多项式微分系统的不为直线的最多条数,βn)是n次多项式微分系统的不变直线的不同斜率的最大个数。这里假设所讨论的多项式系统只有限条不变直线。 相似文献
40.
Hellström M Phng LK Hofmann JJ Wallgard E Coultas L Lindblom P Alva J Nilsson AK Karlsson L Gaiano N Yoon K Rossant J Iruela-Arispe ML Kalén M Gerhardt H Betsholtz C 《Nature》2007,445(7129):776-780
In sprouting angiogenesis, specialized endothelial tip cells lead the outgrowth of blood-vessel sprouts towards gradients of vascular endothelial growth factor (VEGF)-A. VEGF-A is also essential for the induction of endothelial tip cells, but it is not known how single tip cells are selected to lead each vessel sprout, and how tip-cell numbers are determined. Here we present evidence that delta-like 4 (Dll4)-Notch1 signalling regulates the formation of appropriate numbers of tip cells to control vessel sprouting and branching in the mouse retina. We show that inhibition of Notch signalling using gamma-secretase inhibitors, genetic inactivation of one allele of the endothelial Notch ligand Dll4, or endothelial-specific genetic deletion of Notch1, all promote increased numbers of tip cells. Conversely, activation of Notch by a soluble jagged1 peptide leads to fewer tip cells and vessel branches. Dll4 and reporters of Notch signalling are distributed in a mosaic pattern among endothelial cells of actively sprouting retinal vessels. At this location, Notch1-deleted endothelial cells preferentially assume tip-cell characteristics. Together, our results suggest that Dll4-Notch1 signalling between the endothelial cells within the angiogenic sprout serves to restrict tip-cell formation in response to VEGF, thereby establishing the adequate ratio between tip and stalk cells required for correct sprouting and branching patterns. This model offers an explanation for the dose-dependency and haploinsufficiency of the Dll4 gene, and indicates that modulators of Dll4 or Notch signalling, such as gamma-secretase inhibitors developed for Alzheimer's disease, might find usage as pharmacological regulators of angiogenesis. 相似文献