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31.
MicroRNAs are key regulators of gene expression, but the precise mechanisms underlying their interaction with their mRNA targets are still poorly understood. Here, we systematically investigate the role of target-site accessibility, as determined by base-pairing interactions within the mRNA, in microRNA target recognition. We experimentally show that mutations diminishing target accessibility substantially reduce microRNA-mediated translational repression, with effects comparable to those of mutations that disrupt sequence complementarity. We devise a parameter-free model for microRNA-target interaction that computes the difference between the free energy gained from the formation of the microRNA-target duplex and the energetic cost of unpairing the target to make it accessible to the microRNA. This model explains the variability in our experiments, predicts validated targets more accurately than existing algorithms, and shows that genomes accommodate site accessibility by preferentially positioning targets in highly accessible regions. Our study thus demonstrates that target accessibility is a critical factor in microRNA function. 相似文献
32.
David H. Hubel 《自然科学进展(英文版)》2007,17(13):1-3
The visual field is topographically mapped onto the primary visual cortex (V1), forming a retinotopic map which is far more detailed for the foveal regions than for the periphery. We found that receptive field (RF) size in monkey V1 increases with eccentricity, and that a 1—2 m2 V1 region contains roughly a complete set of machinery necessary to analyze a visual-field area whose size is about that of the RFs of the cells. This allows V1 to be anatomically uniform, and is in sharp contrast with the retina. 相似文献
33.
Rogaeva E Meng Y Lee JH Gu Y Kawarai T Zou F Katayama T Baldwin CT Cheng R Hasegawa H Chen F Shibata N Lunetta KL Pardossi-Piquard R Bohm C Wakutani Y Cupples LA Cuenco KT Green RC Pinessi L Rainero I Sorbi S Bruni A Duara R Friedland RP Inzelberg R Hampe W Bujo H Song YQ Andersen OM Willnow TE Graff-Radford N Petersen RC Dickson D Der SD Fraser PE Schmitt-Ulms G Younkin S Mayeux R Farrer LA St George-Hyslop P 《Nature genetics》2007,39(2):168-177
The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease. 相似文献
34.
The interleukin 1β (IL-1β) cDNA was cloned from the red seabream (Pagrus major) by homology cloning strategy. A cDNA fragment was amplified by PCR using two degenerated primers, which were designed according to the conserved regions of other known IL-1β sequences, and elongated by 3' ends and 5' ends RACE PCR to get the full length coding sequence of red seabream IL-1β (RS IL-1β). The sequence contained 1252 nucleotides that included a 5' untranslated region (UTR) of 84bp, a 3' UTR of 410 bp and an open reading frame (ORF) of 759 nucleotides which could be translated into a putative peptide of 253 amino acids with molecular weight of 28.6 kD and putative isoelectric point pI of 5.29. The deduced peptide contained two potential N-glycosylation sites and an identifiable IL1 family signature, but lacked the signal peptide and the clear ICE cut site, which were common in other nonmammalian IL-1β genes. The RS IL-1β had the highest homology with piscine IL-1β according to phylogenetic tree analysis. 相似文献
35.
在《魔兽争霸3》中,Human一直是以防御见长的种族。Footman抵挡穿刺攻击的Defense技能,Paladin的防御光环和Priest的Inner Fire魔法都是用以加强部队防御力量的。而且Human是《魔兽争霸3》中综合移动速度最慢的种族。不但只有Knight具有比较快的移动速度,而且没有任何加速的光环和魔法加以辅助。基于Human的这种特点,以 相似文献
37.
GIS-Based Mapping and Zonation of Landslide Hazards in Xiaojiang Valley of Southwestern China 总被引:3,自引:0,他引:3
MaZe-zhong HeYi-ping XieHong CuiPeng ZhongDun-lun JamesS.Gardner 《武汉大学学报:自然科学英文版》2003,8(3B):1021-1028
Through the field survey, previous researches and interpretation of aerial photos, a landslide information database of Xiaojiang Valley, Yurman Province was set up based on the remote sensing (RS) and geographic information system (GIS) technologies. In the paper, a quantitative model for the landslide hazard assessment and zoning was presented,in which the potential energy could be obtained on basis of thorough analysis of the potential sliding volume, distance and direction of the landslide body. Taking landslide potential energy as the index of the hazard severity zonation, the study area was divided into severe, heavy, medium and light hazard zones. 相似文献
38.
一度是数学中死水一潭的纽结理论,其应用已向临床医学广泛延伸。我们都知道什么是个结--如果没有它,我们的鞋就会掉下来。但对于数学家而言,纽结与我们所描绘的稍有些不同——更像一根电线,能缠在一起并插回其自身中。电线如何婉蜒地穿过空间并在找到正确的空位以再度插入之前缠绕自身即是对数学家而言所有的区别——而且也正日益为考虑实用性东西的研究人员所关注。 相似文献
39.
Itknownthatsmallamountsoffluxonthesurfaceofstainlesssteelcanincreasethedepthofweldpene trationinTIGweldingbyafactorofthree[1] .Thisprocessisreferredtoas”ATIG”orTIGweldingacti vatedbyflux .Therehavebeenthreepublishedphys icalmechanismsthatarepossiblecontri… 相似文献
40.
生物序列分析 总被引:1,自引:0,他引:1
这次演讲将回顾近 1 0多年来应用某些随机模型于生物序列分析的研究工作 .这些模型本身有很长的历史 ,可追溯到 3 0多年以前 ,尽管从那时起 ,这些模型已经产生了很多新的变种 .在生物序列分析中模型的作用是归总那些涉及到在生物信息学中已知的模体 (motif)或域 (domain)的信息 ,并且提供一种工具在另一序列片段中寻找模体或域的实例 (instance) .我们将逐步介绍模体模型 ,从非常简单的 ,非随机情况开始 ,进而是更复杂的情况 ,直至近来的关于模体的剖面隐马氏模型 .第二个例子是来自利用一个或两个物种的序列数据进行基因发现 ,其中广义隐马氏模型或广义成对 (pair)隐马氏模型已被证实非常有效 相似文献