查看完整版本: 《Nature》 vol.454 (7203), (24 Jul 2008)

《Nature》 vol.454 (7203), (24 Jul 2008)

《Nature》 vol.454 (7203), (24 Jul 2008)摘要
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酿酒酵母所有重组产物的高分辨率分布图
在减数分裂过程中，细胞分裂形成生殖配子，来自每个子染色单体的DNA链交换伙伴。这种重组有两种可能的遗传结果：Crossovers 和 Non-crossovers。Crossovers在整个基因组范围内的分布以前被测定过了，但关于Non-crossovers分布的数据却因在侧翼标记没有被交换时识别重组的DNA有困难而缺乏。现在，Mancera等人获得了酿酒酵母所有重组产物的高分辨率分布图。这一里程碑式的分布图显示，存在特定于Crossovers和 特定于Non-crossovers的热点。
Nature 454, 479-485 (24 July 2008) | doi:10.1038/nature07135; Received 10 March 2008; Accepted 30 May 2008; Published online 9 July 2008
High-resolution mapping of meiotic crossovers and non-crossovers in yeast
Eugenio Mancera1,3, Richard Bourgon2,3, Alessandro Brozzi2, Wolfgang Huber2 & Lars M. Steinmetz1
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge CB10 1SD, UK
These authors contributed equally to this work.
Correspondence to: Lars M. Steinmetz1 Correspondence and requests for materials should be addressed to L.M.S. (Email: [email]larsms@embl.de[/email]).
Top of pageAbstractMeiotic recombination has a central role in the evolution of sexually reproducing organisms. The two recombination outcomes, crossover and non-crossover, increase genetic diversity, but have the potential to homogenize alleles by gene conversion. Whereas crossover rates vary considerably across the genome, non-crossovers and gene conversions have only been identified in a handful of loci. To examine recombination genome wide and at high spatial resolution, we generated maps of crossovers, crossover-associated gene conversion and non-crossover gene conversion using dense genetic marker data collected from all four products of fifty-six yeast (Saccharomyces cerevisiae) meioses. Our maps reveal differences in the distributions of crossovers and non-crossovers, showing more regions where either crossovers or non-crossovers are favoured than expected by chance. Furthermore, we detect evidence for interference between crossovers and non-crossovers, a phenomenon previously only known to occur between crossovers. Up to 1% of the genome of each meiotic product is subject to gene conversion in a single meiosis, with detectable bias towards GC nucleotides. To our knowledge the maps represent the first high-resolution, genome-wide characterization of the multiple outcomes of recombination in any organism. In addition, because non-crossover hotspots create holes of reduced linkage within haplotype blocks, our results stress the need to incorporate non-crossovers into genetic linkage analysis.
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge CB10 1SD, UK
These authors contributed equally to this work.
Correspondence to: Lars M. Steinmetz1 Correspondence and requests for materials should be addressed to L.M.S. (Email: [email]larsms@embl.de[/email]).
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一种G-蛋白耦合受体的晶体结构
肾上腺素压力荷尔蒙受体（β肾上腺素受体或β-AR）调控心率和血压，是β阻断剂的作用目标。同G-蛋白耦合受体家族很多其他成员一样，它也难以纯化。但是，火鸡身上所发现的这种酶要比人体上尤为脆弱的这种酶更为稳定，利用这一点，同时利用突变来热稳定该受体，研究人员已经获得了结合到β阻断剂Cyanopindolol上的\"1AR的晶体。该结构显示了配体的结合模式，并且提供了G-蛋白结合界面的信息。
Nature 454, 486-491 (24 July 2008) | doi:10.1038/nature07101; Received 26 March 2008; Accepted 19 May 2008; Published online 25 June 2008
Structure of a 1-adrenergic G-protein-coupled receptor
Tony Warne1, Maria J. Serrano-Vega1, Jillian G. Baker2, Rouslan Moukhametzianov1, Patricia C. Edwards1, Richard Henderson1, Andrew G. W. Leslie1, Christopher G. Tate1 & Gebhard F. X. Schertler1
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
Institute of Cell Signalling, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
Correspondence to: Christopher G. Tate1Gebhard F. X. Schertler1 Correspondence and requests for materials should be addressed to C.G.T. (Email: [email]cgt@mrc-lmb.cam.ac.uk[/email]) or G.F.X.S. (Email: [email]gfx@mrc-lmb.cam.ac.uk[/email]).
Top of pageAbstractG-protein-coupled receptors have a major role in transmembrane signalling in most eukaryotes and many are important drug targets. Here we report the 2.7 Å resolution crystal structure of a 1-adrenergic receptor in complex with the high-affinity antagonist cyanopindolol. The modified turkey (Meleagris gallopavo) receptor was selected to be in its antagonist conformation and its thermostability improved by earlier limited mutagenesis. The ligand-binding pocket comprises 15 side chains from amino acid residues in 4 transmembrane -helices and extracellular loop 2. This loop defines the entrance of the ligand-binding pocket and is stabilized by two disulphide bonds and a sodium ion. Binding of cyanopindolol to the 1-adrenergic receptor and binding of carazolol to the 2-adrenergic receptor involve similar interactions. A short well-defined helix in cytoplasmic loop 2, not observed in either rhodopsin or the 2-adrenergic receptor, directly interacts by means of a tyrosine with the highly conserved DRY motif at the end of helix 3 that is essential for receptor activation.
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“标准盘”模型被证明基本正确
多数活动星系核中的主要能量来源被认为是一个超大黑洞。对天文学家来说问题是，他们假设黑洞通过一个吸积盘来吸积周围气体，而迄今所获观测结果尚未证实这一模型。尤其是，“标准盘”（standard disk）模型预测存在一个从可见光到近红外的特定蓝色波形，但这个波形没有出现在光谱中。现在，Kishimoto等人报告了对几个类星体发射尘埃的区域内的偏振光的观测结果，这些结果在近红外波段显示了吸积盘的特征蓝色光谱。这表明，至少在外近红外发射半径内，对被本地加热的吸积盘的标准描绘基本上是正确的。
Nature 454, 492-494 (24 July 2008) | doi:10.1038/nature07114; Received 30 January 2008; Accepted 15 May 2008
The characteristic blue spectra of accretion disks in quasars as uncovered in the infrared
Makoto Kishimoto1,2, Robert Antonucci3, Omer Blaes3, Andy Lawrence2, Catherine Boisson4, Marcus Albrecht5 & Christian Leipski3
Max-Planck-Institut für Radioastronomie, Auf dem Hügel 69, 53121 Bonn, Germany
Scottish Universities Physics Alliance, Institute for Astronomy, University of Edinburgh, Royal Observatory, Blackford Hill, Edinburgh EH9 3HJ, UK
Physics Department, University of California, Santa Barbara, California 93106, USA
LUTH, FRE 2462 du CNRS, associée à l'Université Denis Diderot, Observatoire de Paris, Section de Meudon, F–92195 Meudon Cedex, France
Instituto de Astronomía, Universidad Católica del Norte, Avenida Angamos 0610, Antofagasta 1270709, Chile
Correspondence to: Makoto Kishimoto1,2 Correspondence and requests for materials should be addressed to M.K. (Email: [email]mk@mpifr-bonn.mpg.de[/email]).
Top of pageAbstractQuasars are thought to be powered by supermassive black holes accreting surrounding gas1, 2, 3. Central to this picture is a putative accretion disk which is believed to be the source of the majority of the radiative output2, 3, 4. It is well known, however, that the most extensively studied disk model5—an optically thick disk which is heated locally by the dissipation of gravitational binding energy—is apparently contradicted by observations in a few major respects6, 7. In particular, the model predicts a specific blue spectral shape asymptotically from the visible to the near-infrared5, 8, but this is not generally seen in the visible wavelength region where the disk spectrum is observable9, 10, 11, 12, 13. A crucial difficulty has been that, towards the infrared, the disk spectrum starts to be hidden under strong, hot dust emission from much larger but hitherto unresolved scales, and thus has essentially been impossible to observe. Here we report observations of polarized light interior to the dust-emitting region that enable us to uncover this near-infrared disk spectrum in several quasars. The revealed spectra show that the near-infrared disk spectrum is indeed as blue as predicted. This indicates that, at least for the outer near-infrared-emitting radii, the standard picture of the locally heated disk is approximately correct.
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新型柔性纳米管集成电路
在柔性塑料片上所形成的集成电路，会比用传统材料做成的集成电路更轻、更结实，同时又能根据需要弯曲。用有机小分子和聚合物做成的半导体在这类应用中已经显露了希望，但本期Nature上介绍的一种基于碳的新型纳米材料，据其发明者说，在电子应用中要比目前可以获得的材料性能更高。Cao等人研制出一种由塑料基质上的单壁碳纳米管构成的随机网络组成的中小尺度的集成电路。这种电路的布局既能实现高流动性，又能实现高开/关率，所获得的器件和电路（由多达100个晶体管组成）显示出极好的电子性能。这些新的薄膜在一系列不同应用中都应能够派上用场，如特殊消费电子设备、生物传感及光电子等。
Nature 454, 495-500 (24 July 2008) | doi:10.1038/nature07110; Received 29 January 2008; Accepted 20 May 2008
Medium-scale carbon nanotube thin-film integrated circuits on flexible plastic substrates
Qing Cao1, Hoon-sik Kim2, Ninad Pimparkar7, Jaydeep P. Kulkarni7, Congjun Wang2, Moonsub Shim2, Kaushik Roy7, Muhammad A. Alam7 & John A. Rogers1,6
Department of Chemistry,
Department of Materials Science and Engineering,
Department of Electrical and Computer Engineering,
Department of Mechanical Science and Engineering,
Frederick-Seitz Materials Research Laboratory,
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA
School of Electrical and Computer Engineering, Network for Computational Nanotechnology, Purdue University, West Lafayette, Indiana 47907, USA
Correspondence to: John A. Rogers1,6 Correspondence and requests for materials should be addressed to J.A.R. (Email: [email]jrogers@uiuc.edu[/email]).
Top of pageAbstractThe ability to form integrated circuits on flexible sheets of plastic enables attributes (for example conformal and flexible formats and lightweight and shock resistant construction) in electronic devices that are difficult or impossible to achieve with technologies that use semiconductor wafers or glass plates as substrates1. Organic small-molecule and polymer-based materials represent the most widely explored types of semiconductors for such flexible circuitry2. Although these materials and those that use films or nanostructures of inorganics have promise for certain applications, existing demonstrations of them in circuits on plastic indicate modest performance characteristics that might restrict the application possibilities. Here we report implementations of a comparatively high-performance carbon-based semiconductor consisting of sub-monolayer, random networks of single-walled carbon nanotubes to yield small- to medium-scale integrated digital circuits, composed of up to nearly 100 transistors on plastic substrates. Transistors in these integrated circuits have excellent properties: mobilities as high as 80 cm2 V-1 s-1, subthreshold slopes as low as 140 m V dec-1, operating voltages less than 5 V together with deterministic control over the threshold voltages, on/off ratios as high as 105, switching speeds in the kilohertz range even for coarse (100-m) device geometries, and good mechanical flexibility—all with levels of uniformity and reproducibility that enable high-yield fabrication of integrated circuits. Theoretical calculations, in contexts ranging from heterogeneous percolative transport through the networks to compact models for the transistors to circuit level simulations, provide quantitative and predictive understanding of these systems. Taken together, these results suggest that sub-monolayer films of single-walled carbon nanotubes are attractive materials for flexible integrated circuits, with many potential areas of application in consumer and other areas of electronics.
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东南亚地区的群体砷中毒事件,
也许是历史上最大的群体中毒事件目前正在整个东南亚发生，在那里，数百万人正在饮用被砷污染的井水。砷是从受到侵蚀的喜马拉雅沉积物中自然释放出来的，但控制砷释放进孔隙水中的过程仍然不清楚，部分原因是，我们对被广泛的灌溉抽水过程所改变的地下水流路径不是很了解。现在，Polizzotto等人利用水文和生物地化测量结果发现，在受到扰动很小的柬埔寨湄公河三角洲地区，砷是从近地表的、来自河流的沉积物中释放出来的，通过地下含水层又输送回河水中，这个过程发生在一个世纪的时间尺度上。这些结果为了解亚洲其他主要三角洲地区扰动前的状况提供了一个模型。
Nature 454, 505-508 (24 July 2008) | doi:10.1038/nature07093; Received 22 May 2007; Accepted 15 May 2008
Near-surface wetland sediments as a source of arsenic release to ground water in Asia
Matthew L. Polizzotto1, Benjamin D. Kocar1, Shawn G. Benner2, Michael Sampson3 & Scott Fendorf1
School of Earth Sciences, Stanford University, Stanford, California 94305, USA
Department of Geosciences, Boise State University, Boise, Idaho 83705, USA
Resource Development International – Cambodia, PO Box 494, Phnom Penh, Cambodia
Correspondence to: Scott Fendorf1 Correspondence and requests for materials should be addressed to S.F. (Email: [email]fendorf@stanford.edu[/email]).
Top of pageAbstractTens of millions of people in south and southeast Asia routinely consume ground water that has unsafe arsenic levels1, 2. Arsenic is naturally derived from eroded Himalayan sediments, and is believed to enter solution following reductive release from solid phases under anaerobic conditions. However, the processes governing aqueous concentrations and locations of arsenic release to pore water remain unresolved, limiting our ability to predict arsenic concentrations spatially (between wells) and temporally (future concentrations) and to assess the impact of human activities on the arsenic problem3, 4, 5, 6, 7, 8, 9. This uncertainty is partly attributed to a poor understanding of groundwater flow paths altered by extensive irrigation pumping in the Ganges-Brahmaputra delta10, where most research has focused. Here, using hydrologic and (bio)geochemical measurements, we show that on the minimally disturbed Mekong delta of Cambodia, arsenic is released from near-surface, river-derived sediments and transported, on a centennial timescale, through the underlying aquifer back to the river. Owing to similarities in geologic deposition, aquifer source rock and regional hydrologic gradients11, 12, 13, 14, 15, our results represent a model for understanding pre-disturbance conditions for other major deltas in Asia. Furthermore, the observation of strong hydrologic influence on arsenic behaviour indicates that release and transport of arsenic are sensitive to continuing and impending anthropogenic disturbances. In particular, groundwater pumping for irrigation, changes in agricultural practices, sediment excavation, levee construction and upstream dam installations will alter the hydraulic regime and/or arsenic source material and, by extension, influence groundwater arsenic concentrations and the future of this health problem.
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四川地震后震区应力分布的变化  
今年5月12日在中国四川省发生的7.9级破坏性地震，可能已使该地区地壳中的应力分布发生了极大变化。在7月6日在网上提前发表、并在上周Nature杂志新闻版块中（第148页）作为封面文章发表的一篇论文中，Tom Parsons、 Chen Ji 和Eric Kirby报告了对四川盆地及其周边地区应力变化的计算结果，这些结果表明，该地区的活动走滑地带和逆冲断层上的应力显著增加。在一次诱发的大震之后，余震可持续几年到几十年时间；鉴于这些活动断层上有几个大城市，未来潜在断裂区的识别对于减灾工作将会是有价值的。
Nature 454, 509-510 (24 July 2008) | doi:10.1038/nature07177; Received 16 May 2008; Accepted 19 June 2008; Published online 6 July 2008
Stress changes from the 2008 Wenchuan earthquake and increased hazard in the Sichuan basin
Tom Parsons1, Chen Ji2 & Eric Kirby3
US Geological Survey, MS-999, 345 Middlefield Road, Menlo Park, California 94025, USA
Department of Geological Sciences, University of California, Santa Barbara, California 93106, USA
Department of Geosciences, Penn State University, University Park, Pennsylvania 16802, USA
Correspondence to: Tom Parsons1 Correspondence and requests for materials should be addressed to T.P. (Email: [email]tparsons@usgs.gov[/email]).
Top of pageAbstractOn 12 May 2008, the devastating magnitude 7.9 (Wenchuan) earthquake struck the eastern edge of the Tibetan plateau, collapsing buildings and killing thousands in major cities aligned along the western Sichuan basin in China. After such a large-magnitude earthquake, rearrangement of stresses in the crust commonly leads to subsequent damaging earthquakes1, 2, 3, 4, 5. The mainshock of the 12 May earthquake ruptured with as much as 9 m of slip along the boundary between the Longmen Shan and Sichuan basin, and demonstrated the complex strike–slip and thrust motion6 that characterizes the region7, 8. The Sichuan basin and surroundings are also crossed by other active strike–slip and thrust faults. Here we present calculations of the coseismic stress changes that resulted from the 12 May event using models of those faults, and show that many indicate significant stress increases. Rapid mapping of such stress changes can help to locate fault sections with relatively higher odds of producing large aftershocks.
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不同地方的树叶温度几乎相同  
植物没有热血动物所形成的维持其体温的机制，所以人们自然而然地假设叶子是在环境温度下进行光合作用的。但根据对由木质纤维素的氧18/氧16比例（该比例是对碳吸收过程中温度和湿度的一个度量）所确定的39个树种中树冠叶子温度所做的一项研究，事实并非如此。令人吃惊的是，叶子温度在取样的所有地点几乎都是恒定的。在植物吸收碳期间，叶子的温度约为21.4 ˚C，不管是亚热带的叶子还是极地的叶子。这一发现的意义之一是，叶子温度也许是决定树种分布的一个因素，因为在低温环境中所形成的用来提高温度的树枝在环境温度升高时可能会成为累赘。
Nature 454, 511-514 (24 July 2008) | doi:10.1038/nature07031; Received 10 March 2008; Accepted 28 April 2008; Published online 11 June 2008
Subtropical to boreal convergence of tree-leaf temperatures
Brent R. Helliker1 & Suzanna L. Richter2
Department of Biology,
Department of Earth and Environmental Science, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Correspondence to: Brent R. Helliker1 Correspondence and requests for materials should be addressed to B.R.H (Email: [email]helliker@sas.upenn.edu[/email]).
Top of pageAbstractThe oxygen isotope ratio (18O) of cellulose is thought to provide a record of ambient temperature and relative humidity during periods of carbon assimilation1, 2. Here we introduce a method to resolve tree-canopy leaf temperature with the use of 18O of cellulose in 39 tree species. We show a remarkably constant leaf temperature of 21.4  2.2 °C across 50° of latitude, from subtropical to boreal biomes. This means that when carbon assimilation is maximal, the physiological and morphological properties of tree branches serve to raise leaf temperature above air temperature to a much greater extent in more northern latitudes. A main assumption underlying the use of 18O to reconstruct climate history is that the temperature and relative humidity of an actively photosynthesizing leaf are the same as those of the surrounding air3, 4. Our data are contrary to that assumption and show that plant physiological ecology must be considered when reconstructing climate through isotope analysis. Furthermore, our results may explain why climate has only a modest effect on leaf economic traits5 in general.
Department of Biology,
Department of Earth and Environmental Science, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Correspondence to: Brent R. Helliker1 Correspondence and requests for materials should be addressed to B.R.H (Email: [email]helliker@sas.upenn.edu[/email]).
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寄生虫在生态系统中的地位举足轻重
寄生虫和其他传染性媒体会对一个生态系统产生重大影响，其影响的方式是以某种显著的猎物或捕食者为目标。但对加利福尼亚和下加利福尼亚太平洋沿岸三个河口地区自由生活物种及寄生物种的生物量所做的一项研究表明，今后在食物链分析和生态系统模拟研究中，应当对寄生生态给予更多考虑。一个令人吃惊的发现是，寄生虫在这些生态系统中有相当大的生物量，甚至超过顶级捕食者的生物量。例如，与鸟类、鱼类吸虫、掘洞虾和多毛目环节动物的生物量相比，吸虫的生物量尤其高。
Nature 454, 515-518 (24 July 2008) | doi:10.1038/nature06970; Received 3 January 2008; Accepted 2 April 2008
Ecosystem energetic implications of parasite and free-living biomass in three estuaries
Armand M. Kuris1,12, Ryan F. Hechinger1,12, Jenny C. Shaw1, Kathleen L. Whitney1, Leopoldina Aguirre-Macedo2, Charlie A. Boch1, Andrew P. Dobson3, Eleca J. Dunham4, Brian L. Fredensborg5, Todd C. Huspeni6, Julio Lorda1, Luzviminda Mababa1, Frank T. Mancini7, Adrienne B. Mora8, Maria Pickering9, Nadia L. Talhouk1, Mark E. Torchin10 & Kevin D. Lafferty11
Department of Ecology, Evolution and Marine Biology and Marine Science Institute, University of California, Santa Barbara, California 93106, USA
Centro de Investigación y Estudios Avanzados del IPN, C.P. 97310, Mérida, Mexico
Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey 08544-1003, USA
Center for Infectious Disease Dynamics, Department of Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA
Department of Biology, University of Texas Pan-American, Edinburg, Texas 78539, USA
Department of Biology, University of Wisconsin–Stevens Point, Stevens Point, Wisconsin 54481, USA
Pacific Islands Fisheries Research Center, National Marine Fisheries Service, Honolulu, Hawaii 96822, USA
Department of Biology, University of California, Riverside, California 92521, USA
Ecology and Evolutionary Biology, University of Connecticut, Storrs, 75 North Eagleville Rd. Unit 3043, Storrs, Connecticut 06269, USA
Smithsonian Tropical Research Institute, Apartado 0843, Ancon, Balboa 03092, Panama, Republic of Panama
Western Ecological Research Center, US Geological Survey, Marine Science Institute, University of California, Santa Barbara, California 93106, USA
These authors contributed equally to this work.
Correspondence to: Armand M. Kuris1,12 Correspondence and requests for materials should be addressed to A.M.K. (Email: [email]kuris@lifesci.ucsb.edu[/email]).
Top of pageAbstractParasites can have strong impacts but are thought to contribute little biomass to ecosystems1, 2, 3. We quantified the biomass of free-living and parasitic species in three estuaries on the Pacific coast of California and Baja California. Here we show that parasites have substantial biomass in these ecosystems. We found that parasite biomass exceeded that of top predators. The biomass of trematodes was particularly high, being comparable to that of the abundant birds, fishes, burrowing shrimps and polychaetes. Trophically transmitted parasites and parasitic castrators subsumed more biomass than did other parasitic functional groups. The extended phenotype biomass controlled by parasitic castrators sometimes exceeded that of their uninfected hosts. The annual production of free-swimming trematode transmission stages was greater than the combined biomass of all quantified parasites and was also greater than bird biomass. This biomass and productivity of parasites implies a profound role for infectious processes in these estuaries.
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决定蜜蜂性别的一个新基因
蜜蜂的性别由一个单一基因上的等位基因（变体）的组合决定，这与由性染色体决定性别的体系形成对比。在蜜蜂种群中，在“主调控因子”csd基因上已知有15种不同的等位基因。雄蜂由对csd来说属于纯合性的卵发育，携带同一变体的两个版本；雌蜂由对csd来说属于杂合性的卵发育。现在，蜜蜂性别决定通道中的一个新成分已经被识别出来。被称为Feminizer的这个基因实施雄性和雌性通道的转换，从而将csd上等位基因多样性与发育程序联系起来。对5种蜜蜂的基因序列所做对比表明，今天的“主调控因子”csd是最近通过基因复制从其“从属基因”（fem gene）演变来的，通过适应性达尔文演化形成了其新的功能。
Nature 454, 519-522 (24 July 2008) | doi:10.1038/nature07052; Received 5 November 2007; Accepted 1 May 2008; Published online 25 June 2008
Evidence for the evolutionary nascence of a novel sex determination pathway in honeybees
Martin Hasselmann1,4, Tanja Gempe1,4, Morten Schiøtt1,2, Carlos Gustavo Nunes-Silva3, Marianne Otte1 & Martin Beye1
Department of Genetics, Heinrich Heine University Duesseldorf, Universitaetsstrasse 1, 40225 Duesseldorf, Germany
Centre for Social Evolution, Department of Biology, University of Copenhagen, Universitetsparken 15, 2100 Copenhagen, Denmark
Grupo de Pesquisas em Abelhas (GPA), Instituto Nacional de Pesquisas da Amazônia (INPA) Avenida André Araújo 2936, 69060-001 Manaus, AM, Brazil
These authors contributed equally to this work.
Correspondence to: Martin Beye1 Correspondence and requests for materials should be addressed to M.B. (Email: [email]martin.beye@uni-duesseldorf.de[/email]).
Top of pageAbstractSex determination in honeybees (Apis mellifera) is governed by heterozygosity at a single locus harbouring the complementary sex determiner (csd) gene1, in contrast to the well-studied sex chromosome system of Drosophila melanogaster2. Bees heterozygous at csd are females, whereas homozygotes and hemizygotes (haploid individuals) are males. Although at least 15 different csd alleles are known among natural bee populations3, the mechanisms linking allelic interactions to switching of the sexual development programme are still obscure. Here we report a new component of the sex-determining pathway in honeybees, encoded 12 kilobases upstream of csd. The gene feminizer (fem) is the ancestrally conserved progenitor gene from which csd arose and encodes an SR-type protein, harbouring an Arg/Ser-rich domain. Fem shares the same arrangement of Arg/Ser- and proline-rich-domain with the Drosophila principal sex-determining gene transformer (tra), but lacks conserved motifs except for a 30-amino-acid motif that Fem shares only with Tra of another fly, Ceratitis capitata4. Like tra, the fem transcript is alternatively spliced. The male-specific splice variant contains a premature stop codon and yields no functional product, whereas the female-specific splice variant encodes the functional protein. We show that RNA interference (RNAi)-induced knockdowns of the female-specific fem splice variant result in male bees, indicating that the fem product is required for entire female development. Furthermore, RNAi-induced knockdowns of female allelic csd transcripts result in the male-specific fem splice variant, suggesting that the fem gene implements the switch of developmental pathways controlled by heterozygosity at csd. Comparative analysis of fem and csd coding sequences from five bee species indicates a recent origin of csd in the honeybee lineage from the fem progenitor and provides evidence for positive selection at csd accompanied by purifying selection at fem. The fem locus in bees uncovers gene duplication and positive selection as evolutionary mechanisms underlying the origin of a novel sex determination pathway.
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丙肝病毒的识别 .
先天免疫是防止病毒感染的一个重要机制，由宿主对PAMPS（与病原体相关的分子模式）的识别触发。现在，Saito等人识别出，丙肝病毒基因组的3´非转录区中的一个保留下来的多尿苷主题是可被RNA解旋酶RIG-I检测到的相关PAMP。以前的研究表明，该解旋酶是在双链RNA诱导的先天抗病毒反应中发挥重要功能的一种蛋白.
Nature 454, 523-527 (24 July 2008) | doi:10.1038/nature07106; Received 13 February 2008; Accepted 23 May 2008; Published online 11 June 2008
Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA
Takeshi Saito1, David M. Owen1,2, Fuguo Jiang3, Joseph Marcotrigiano3 & Michael Gale Jr.1
Department of Immunology, University of Washington School of Medicine, Seattle, Washington 98195-7650, USA
Department of Microbiology, UT Southwestern Medical Center, Dallas, Texas 75235-9048, USA
Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, USA
Correspondence to: Michael Gale Jr.1 Correspondence and requests for materials should be addressed to M.G. (Email: [email]mgale@u.washington.edu[/email]).
Top of pageAbstractInnate immune defences are essential for the control of virus infection and are triggered through host recognition of viral macromolecular motifs known as pathogen-associated molecular patterns (PAMPs)1. Hepatitis C virus (HCV) is an RNA virus that replicates in the liver, and infects 200 million people worldwide2. Infection is regulated by hepatic immune defences triggered by the cellular RIG-I helicase. RIG-I binds PAMP RNA and signals interferon regulatory factor 3 activation to induce the expression of interferon-/ and antiviral/interferon-stimulated genes (ISGs) that limit infection3, 4, 5, 6, 7, 8, 9, 10. Here we identify the polyuridine motif of the HCV genome 3' non-translated region and its replication intermediate as the PAMP substrate of RIG-I, and show that this and similar homopolyuridine or homopolyriboadenine motifs present in the genomes of RNA viruses are the chief feature of RIG-I recognition and immune triggering in human and murine cells8. 5' terminal triphosphate on the PAMP RNA was necessary but not sufficient for RIG-I binding, which was primarily dependent on homopolymeric ribonucleotide composition, linear structure and length. The HCV PAMP RNA stimulated RIG-I-dependent signalling to induce a hepatic innate immune response in vivo, and triggered interferon and ISG expression to suppress HCV infection in vitro. These results provide a conceptual advance by defining specific homopolymeric RNA motifs within the genome of HCV and other RNA viruses as the PAMP substrate of RIG-I, and demonstrate immunogenic features of the PAMP–RIG-I interaction that could be used as an immune adjuvant for vaccine and immunotherapy approaches.
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让肌肉变年轻的可能性
老化肌肉组织自身再生及修复能力的降低，被发现是由于肌肉干细胞或卫星细胞中TGF-\"水平高。将2岁小鼠的（相当于75岁至80岁的人）肌肉再生能力与2个月大小鼠（相当于20岁至25岁的人）的肌肉再生能力所做对比表明，肌肉修复的成功与失败是由TGF-\"/pSmad信号作用的水平与Notch通道的激发水平之间的平衡决定的。这项工作提出了用治疗干预来恢复衰老肌肉中干细胞微环境的可能性。
Nature 454, 528-532 (24 July 2008) | doi:10.1038/nature07034; Received 6 November 2007; Accepted 28 April 2008; Published online 15 June 2008
Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells
Morgan E. Carlson1, Michael Hsu1 & Irina M. Conboy1
Department of Bioengineering, University of California, Berkeley, California 94720, USA
Correspondence to: Irina M. Conboy1 Correspondence and requests for materials should be addressed to I.M.C. (Email: [email]iconboy@berkeley.edu[/email]).
Top of pageAbstractAdult skeletal muscle robustly regenerates throughout an organism's life, but as the muscle ages, its ability to repair diminishes and eventually fails1, 2. Previous work suggests that the regenerative potential of muscle stem cells (satellite cells) is not triggered in the old muscle because of a decline in Notch activation, and that it can be rejuvenated by forced local activation of Notch3. Here we report that, in addition to the loss of Notch activation, old muscle produces excessive transforming growth factor (TGF)- (but not myostatin), which induces unusually high levels of TGF- pSmad3 in resident satellite cells and interferes with their regenerative capacity. Importantly, endogenous Notch and pSmad3 antagonize each other in the control of satellite-cell proliferation, such that activation of Notch blocks the TGF--dependent upregulation of the cyclin-dependent kinase (CDK) inhibitors p15, p16, p21 and p27, whereas inhibition of Notch induces them. Furthermore, in muscle stem cells, Notch activity determines the binding of pSmad3 to the promoters of these negative regulators of cell-cycle progression. Attenuation of TGF-/pSmad3 in old, injured muscle restores regeneration to satellite cells in vivo. Thus a balance between endogenous pSmad3 and active Notch controls the regenerative competence of muscle stem cells, and deregulation of this balance in the old muscle microniche interferes with regeneration.
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[[i] 本帖最后由 kawapu007 于 2008-7-24 08:25 编辑 [/i]]

体细胞变成干细胞所存在的障碍
如果能够让完全差异化的人体细胞可靠地变成多能干细胞，那将是再生医学领域的一大进步。最近用人类和小鼠细胞所做研究表明，这种重组是有可能的，但当前获取诱导多能干细胞（iPS细胞）的路径效率不高，所涉及的机制也不清楚。现在，对老鼠成纤维细胞和B-淋巴细胞的重组所做的一项基因组分析及对染色质状态和DNA甲基化所做的一项分析，为了解阻止大多数细胞进行重组的障碍提供了线索：由于转录因子的不完全抑制，一些细胞可能会被束缚在部分重组的状态；转录因子的瞬间RNA抑制也许能够帮助重组；用DNA甲基转移酶抑制成分处理，也许能够提高重组过程的效率。
Nature 454, 49-55 (3 July 2008) | doi:10.1038/nature07056; Received 20 March 2008; Accepted 8 May 2008; Published online 28 May 2008
Dissecting direct reprogramming through integrative genomic analysis
Tarjei S. Mikkelsen1,2, Jacob Hanna4, Xiaolan Zhang1, Manching Ku5, Marius Wernig4, Patrick Schorderet4, Bradley E. Bernstein1,5,6, Rudolf Jaenisch3,4, Eric S. Lander1,3,4,7 & Alexander Meissner1,8
Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Division of Health Sciences and Technology,
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02114, USA
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Correspondence to: Alexander Meissner1,8 Correspondence and requests for materials should be addressed to A.M. (Email: [email]alex@broad.mit.edu[/email]).
Top of pageAbstractSomatic cells can be reprogrammed to a pluripotent state through the ectopic expression of defined transcription factors. Understanding the mechanism and kinetics of this transformation may shed light on the nature of developmental potency and suggest strategies with improved efficiency or safety. Here we report an integrative genomic analysis of reprogramming of mouse fibroblasts and B lymphocytes. Lineage-committed cells show a complex response to the ectopic expression involving induction of genes downstream of individual reprogramming factors. Fully reprogrammed cells show gene expression and epigenetic states that are highly similar to embryonic stem cells. In contrast, stable partially reprogrammed cell lines show reactivation of a distinctive subset of stem-cell-related genes, incomplete repression of lineage-specifying transcription factors, and DNA hypermethylation at pluripotency-related loci. These observations suggest that some cells may become trapped in partially reprogrammed states owing to incomplete repression of transcription factors, and that DNA de-methylation is an inefficient step in the transition to pluripotency. We demonstrate that RNA inhibition of transcription factors can facilitate reprogramming, and that treatment with DNA methyltransferase inhibitors can improve the overall efficiency of the reprogramming process.
Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Division of Health Sciences and Technology,
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02114, USA
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Correspondence to: Alexander Meissner1,8 Correspondence and requests for materials should be addressed to A.M. (Email: [email]alex@broad.mit.edu[/email]).
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