Volume 434 Number 7033 pp545-680封面故事：DNA与酶之间的相互作用
在复制和转录过程中发生的各种变化导致DNA分子中扭曲张力的积累，而这种张力的释放要靠“拓朴异构酶”来完成。IB-型“拓朴异构酶”（TopIB）先是将一个DNA链切开，然后再重新连接起来，并将正、负“超螺旋”都去除掉。现在，对单独一个TopIB所做的直接监测表明，与其他“拓朴异构酶”不同的是，它并不去除固定数量的“超螺旋”，被去除的“超螺旋”的数量取决于DNA中储存的扭矩，它们是通过一个旋转机制被去除的，该机制涉及旋转的DNA和酶空腔之间的摩擦力。将摩擦力作为一个因素引入DNA与“拓朴异构酶”之间的相互作用中，对于研究DNA与酶之间相互作用的普遍规律具有重要意义。封面图片所示为正在发挥作用的TopIB。
千年生态系统评估
“千年生态系统评估”是一个为期四年的雄心勃勃的研究项目，旨在评估地球的人类支持系统的状态，本期Nature报告了该项目的结果。资助该项目的有“世界银行”、联合国和很多大学等，它们希望该项目对决策者们能够有所帮助，因为该项目将生物多样性等生态数据放进了生态系统变化过去是怎样影响人类生存条件的、以及生态系统变化今后将怎样影响人类生存条件等背景中。虽然现在没有重复进行这种研究的计划，但在本期Nature的Commentary栏目中，三位参加该项目研究的科学家提出，这样的评估工作应当是一个持续的过程。
“后生遗传”与生殖健康
生殖细胞的生产是一个独特的过程，涉及将基因组大小减小一半的细胞分裂。然而，所产生的DNA中的遗传密码并不是对精子和卵子成熟过程的唯一影响，还涉及一系列可遗传的“后生遗传”修正，它们通过染色质和组蛋白所发生的变化及DNA甲基化来控制基因表达，但却使DNA密码保持原样。生殖细胞的“后生遗传”是本期Nature上Review Article所讨论的主题。了解其中所涉及的酶和信号分子，可能会有助于新的生殖技术的开发和防止遗传疾病的发生。
与乳腺癌有关的分子开关
有BRCA2突变者易患乳腺癌，后者被认为是由于DNA双链断裂在修复中产生缺陷引起的。研究人员知道，BRCA2蛋白与重组蛋白RAD51发生相互作用，调节这一相互作用的一个关键步骤现在已被识别出来。Cdk1改变BRCA2中一个丝氨酸的磷酸化状态，而这种作用就像一个分子开关一样，控制BRCA2的C-端点与RAD51之间的相互作用。BRCA2的C-端点发生突变或被删除者会因不能促进有效的DNA修复而患乳腺癌。
酶在DNA修复过程中的作用
氧化性DNA损伤被认为参与了肿瘤发生过程，具体来讲，能识别8-oxoguanine（与正常“鸟嘌呤”只有两个原子不同）的酶“hOGG1”已被与肺癌、还可能有肾癌联系了起来。在一项结构研究中，“hOGG1”（全名为8-oxoguanine DNA glycosylase 1）被束缚在测试正常DNA、看是否存在缺陷的操作过程中。该研究结果显示了这种酶是如何扮演其重要的“守门员”角色的。奇怪的是，“鸟嘌呤”残体没有被插入病灶识别槽中，而是位于另一个在DNA螺旋外的点上。该结果有助于解释DNA修复蛋白为什么能找出嵌入在大量过剩的正常DNA中的病灶，为什么能从DNA螺旋上去除核苷而不破坏正常的碱基。
原始太阳系的气体组成
在原始陨石中氧同位素含量存在很大变化的发现呈现给我们这样一个难解之谜：要么太阳系的来源物质在同位素组成上不是均匀的，要么构成陨石和行星的含氧构造单元是通过尚未被识别出来的反应通道产生的。为了弄清到底是哪种情况，我们需要知道原始太阳系的气体的组成，这种气体可能保存在太阳外层中。“创世纪”探测器在美国犹他州沙漠坠毁时所损坏的样品收集装置也许能提供太阳材料，但现在关于这个问题的一种间接方法也产生了结果。月球暴露于太阳风已有很多世纪了，对束缚在由“阿波罗”登月行动带回的来自月球的颗粒材料外壳中的太阳材料所做的分析表明，太阳富含氧-16，其含量比地球和大块陨石中多1/3。这意味着原始太阳系的气体也有类似的组成，太阳系的大多数固体经历了使它们当中氧-17和氧化-18浓度增大的反应。
基于钚的超导体PuCoGa5
自从基于钚的超导体PuCoGa5几年前被发现以来，便存在这么一个热门问题：它是一种非常普通的BCS超导体，还是一种由磁波动调节的非传统的超导体？这个问题的答案是，它有一个奇异的机制，超导体分子中钚部分的“f”电子提供超导性，而不是由“CoGa5”提供超导性，否则它就更可能遵从人们熟悉的Bardeen-Copper-Schrieffer机制。这一发现将会引发的一个问题是，人们对其他也可能具有这种新型超导性的材料的性质会有更多猜测。
AMO消失了会怎样？
“全球海洋翻腾环流”的大西洋部分（即“大西洋经向翻腾”，英文简称为AMO）曾被与上个冰期气候突变联系起来。曾有人提出，全球变暖可能会增强淡水向北大西洋中的排放，终止AMO，从而导致明显变冷。人们对这些可能的气候效应给予很多关注，但却几乎没有想过如果AMO减弱或消失时海洋生态系统会发生什么。Andreas Schmittner进行了一次详细的模拟，发现AMO消失会使全球生产力降低约20%。这一模拟结果与可从过去获得的生产力记录是一致的。与那么大规模的气候变化相伴随的浮游生物存量的大幅度减少，可能会对受害区域的渔业生产产生影响。
性的成因
性的演化长期以来使生物学家感到困惑。它似乎是浪费时间和精力，还会打破有利的基因组成。那么为什么还要有性的演化呢？关于这个问题有大量理论解释，但分辨这些理论所需的数据却很缺乏，因为难以设计能将不想要的变量排除在外的实验。现在，利用一种用基因工程方法获得的、只包括性繁殖基本内容的无性酵母菌种，可将外来因素排除掉。很多现代理论都是以性能够增加遗传变异、从而能使自然选择更为有效的思想为基础的，研究发现，处在严酷环境中的具有最低组成的酵母体系属于这种情况。但在很少有或没有选择的良好环境中，性没有生存优势。
“家族性提早睡眠综合症”
直到不久前，了解人类睡眠还因在人类睡眠模式中缺乏遗传变异而受阻。但在1999年，一个家庭被诊断出患有“家族性提早睡眠综合症”（FASPS），关于睡眠遗传学的研究工作便在进行中。患者都是“早醒者”，睡眠、体温和黑色素的节律提早4小时。现在，研究人员在酪蛋白激酶1-“德尔塔”基因中已经识别出了引起FASPS的一种突变，它存在于一个从人类到果蝇都保留下来的残体中。在果蝇和小鼠模型中，该突变都引起生理节奏的破坏，因此它们也许可成为开发治疗睡眠失调症的药物的有用的实验模型。
治疗骨关节炎的分子手段
关节中软骨的退化与Aggrecan的损失有关，后者是一种大型的、能聚集的蛋白聚糖。多年来，研究人员一直在寻找造成该物质损失的“蛋白聚糖酶”。现在，两个小组报告了他们所取得的成功：名为ADAMTS-5的酶（也称为aggrecanase-2）在小鼠骨关节炎模型中被发现是主要的“蛋白聚糖酶”。还需要更多研究工作才能将该物质与人类的这种疾病联系起来，但现在抑制ADAMTS-5 成为人类骨关节炎的一种候选治疗手段。
本期目录：
Editorials
Drug safety on trial p545
The current US system for checking the safety of drugs already on the market is toothless. Why isn't the government doing more to strengthen it?
doi: 10.1038/434545a
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A state of ignorance p545
Severe brain damage attracts little research attention, yet science could help inform the decisions of doctors and families.
doi: 10.1038/434545b
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Top of pageNews
Millennium group nails down the financial value of ecosystems p547
Governments need to stop taking environmental benefits for granted, report says.
Jim Giles
doi: 10.1038/434547a
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Indonesia spared tsunami as disaster quake strikes p547
Seismologists say fault line was likely to slip, but puzzle over lack of waves.
Michael Hopkin
doi: 10.1038/434547b
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Stray seeds had antibiotic-resistance genes p548
Accidental release of genetically modified crops sparks new worries.
Colin Macilwain
doi: 10.1038/434548a
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Deal paves way for Congress vote on stem-cell rules p548
US restrictions on human embryonic research may loosen.
Erika Check
doi: 10.1038/434548b
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Journals lack explicit policies for separating eds from ads p549
Ethics committee suggests rules for internal conflicts of interest.
Jim Giles
doi: 10.1038/434549a
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WWF warns that China's forests are not out of the woods p549
Incentives to restore tree cover are harming environment, report says.
Rachael Williams
doi: 10.1038/434549b
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Biologists snub 'kangaroo court' for Darwin p550
Kansas scientists protest revisions to how evolution is taught.
Geoff Brumfiel
doi: 10.1038/434550a
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Viennese lab renovations stall as cash goes unspent p550
Ethology institute hamstrung as half the annual budget is returned.
Quirin Schiermeier
doi: 10.1038/434550b
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Space agencies mull over mutual mission to Europa p551
US and Europe could join forces to reach Jupiter's moon.
Tony Reichhardt
doi: 10.1038/434551a
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Political aide sails into top job at maritime institute p551
Finance adviser winds up in science slot after scandal.
Declan Butler
doi: 10.1038/434551b
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news in brief p552
doi: 10.1038/434552a
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Top of pageNews Features
Drug safety special: The safety catch p554
The past year has seen a beleaguered Food and Drug Administration publicly denounced as unable to protect the US public. As the political pressure mounts, Meredith Wadman joins the agency's hunt for a remedy to its ills.
doi: 10.1038/434554a
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Drug safety special: Chasing shadows p557
Why do current safety systems sometimes fail to notice that approved drugs are causing serious adverse effects? And can surveillance methods be improved? Simon Frantz investigates.
doi: 10.1038/434557a
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Top of pageCorrespondence
Time to speak up for climate-change science p559
If debate is left to greens and sceptics, people think the evidence is equal on each side.
doi: 10.1038/434559a
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We Africans must take our future in our hands p559
Justin Hategekimana
doi: 10.1038/434559b
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Driving passion brought rare bird to the masses p559
Rupert C. Marshall and Helen E. Nice
doi: 10.1038/434559c
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Authors say that they prefer online submission p559
Mark Ware
doi: 10.1038/434559d
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Top of pageCommentary
Confronting the human dilemma p561
How can ecosystems provide sustainable services to benefit society?
doi: 10.1038/434561a
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Top of pageBooks and Arts
Words of wisdom p563
A scholarly selection of scientific soundbites and sayings.
Steven Shapin reviews Oxford Dictionary of Scientific Quotations
doi: 10.1038/434563a
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A natural history of India p564
Deepak Apte reviews Inventing Global Ecology: Tracking the Biodiversity Ideal in India, 1947?1997 by Michael L. Lewis
doi: 10.1038/434564a
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Science in culture p565
Thomas Heatherwick's sculpture for the Wellcome Trust's new building in London.
Martin Kemp reviews
doi: 10.1038/434565a
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Erratum p565
doi: 10.1038/434565b
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Top of pageEssay
Concept
The Janus face of Mnemosyne p567
Memory: some systems in the brain may be better equipped to handle the future than the past.
Yadin Dudai and Mary Carruthers
doi: 10.1038/434567a
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Top of pageNews and Views
Structural biology: DNA search and rescue p569
How do DNA-repair enzymes find aberrant nucleotides among the myriad of normal ones? One enzyme has been caught in the act of checking for damage, providing clues to its quality-control process.
Sheila S. David
doi: 10.1038/434569a
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Techniques: Spectroscopy at a stretch p570
Two-dimensional spectroscopy can now be done using visible light. This allows the electronic couplings between energy levels to be measured directly and sheds new light on how molecules function in photosynthesis.
Robin M. Hochstrasser
doi: 10.1038/434570a
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Evolutionary biology: Why sex is good p571
According to a proposal put forward many years ago, sexual reproduction makes natural selection more effective because it increases genetic variation. Experiments now verify that idea — at least in yeast.
Rolf F. Hoekstra
doi: 10.1038/434571a
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Aceh?Andaman earthquake: What happened and what's next? p573
The huge earthquake of 26 December 2004 and ensuing tsunami were caused by a submarine rupture running from offshore Aceh, Indonesia, to the Andaman Islands. A clearer picture of events is starting to emerge.
Kerry Sieh
doi: 10.1038/434573a
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100 and 50 years ago p573
doi: 10.1038/434573b
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Cell biology: The more MAD, the merrier p575
Cells must pass the correct number of chromosomes to their progeny through the complex ballet of cell division. An unusual conformation-sensitive switch seems to maintain accurate chromosome segregation.
Robert S. Hagan and Peter K. Sorger
doi: 10.1038/434575a
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Cosmochemistry: A breath of solar air p577
The abundance of different isotopes of oxygen provides clues to the origin of matter in the Solar System. Hence the importance of studies of oxygen atoms from the Sun trapped in metal grains on the Moon.
Andrew M. Davis
doi: 10.1038/434577a
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Biochemistry: A pore way to die p578
Like Jekyll to Hyde, mitochondria can change from acting as the cell's powerhouses to become merciless killers. Mice lacking this mechanism develop normally, and their hearts are resistant to pathological damage.
Andrew Halestrap
doi: 10.1038/434578a
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research highlights p580
doi: 10.1038/434580a
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Top of pageBrief Communications
Seismology: Speed and size of the Sumatra earthquake p581
We now have a clearer picture of the seismic features of last year's gigantic event.
Seth Stein and Emile A. Okal
doi: 10.1038/434581a
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Seismology: Energy radiation from the Sumatra earthquake p582
Sidao Ni, Hiroo Kanamori and Don Helmberger
doi: 10.1038/434582a
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Top of pageReview Article
Chromatin remodelling and epigenetic features of germ cells p583
Sarah Kimmins and Paolo Sassone-Corsi
doi: 10.1038/nature03368
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Top of pageArticles
An olivine-free mantle source of Hawaiian shield basalts p590
Alexander V. Sobolev, Albrecht W. Hofmann, Stephan V. Sobolev and Igor K. Nikogosian
doi: 10.1038/nature03411
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CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair p598
Fumiko Esashi, Nicole Christ, Julian Gannon, Yilun Liu, Tim Hunt, Maria Jasin and Stephen C. West
doi: 10.1038/nature03404
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Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage p605
Jacob Falck, Julia Coates and Stephen P. Jackson
doi: 10.1038/nature03442
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Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA p612
Anirban Banerjee, Wei Yang, Martin Karplus and Gregory L. Verdine
doi: 10.1038/nature03458
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Top of pageLetters to Nature
A non-terrestrial 16O-rich isotopic composition for the protosolar nebula p619
Ko Hashizume and Marc Chaussidon
doi: 10.1038/nature03432
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Unconventional superconductivity in PuCoGa5 p622
N. J. Curro, T. Caldwell, E. D. Bauer, L. A. Morales, M. J. Graf, Y. Bang, A. V. Balatsky, J. D. Thompson and J. L. Sarrao
doi: 10.1038/nature03428
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Two-dimensional spectroscopy of electronic couplings in photosynthesis p625
Tobias Brixner, Jens Stenger, Harsha M. Vaswani, Minhaeng Cho, Robert E. Blankenship and Graham R. Fleming
doi: 10.1038/nature03429
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Decline of the marine ecosystem caused by a reduction in the Atlantic overturning circulation p628
Andreas Schmittner
doi: 10.1038/nature03476
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Structural and temporal requirements for geomagnetic field reversal deduced from lava flows p633
Brad S. Singer, Kenneth A. Hoffman, Robert S. Coe, Laurie L. Brown, Brian R. Jicha, Malcolm S. Pringle and Annick Chauvin
doi: 10.1038/nature03431
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Sex increases the efficacy of natural selection in experimental yeast populations p636
Matthew R. Goddard, H. Charles J. Godfray and Austin Burt
doi: 10.1038/nature03405
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Functional consequences of a CKI mutation causing familial advanced sleep phase syndrome p640
Ying Xu, Quasar S. Padiath, Robert E. Shapiro, Christopher R. Jones, Susan C. Wu, Noriko Saigoh, Kazumasa Saigoh, Louis J. Ptáek and Ying-Hui Fu
doi: 10.1038/nature03453
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Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis p644
Sonya S. Glasson, Roger Askew, Barbara Sheppard, Brenda Carito, Tracey Blanchet, Hak-Ling Ma, Carl R. Flannery, Diane Peluso, Kim Kanki, Zhiyong Yang, Manas K. Majumdar and Elisabeth A. Morris
doi: 10.1038/nature03369
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ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro p648
Heather Stanton, Fraser M. Rogerson, Charlotte J. East, Suzanne B. Golub, Kate E. Lawlor, Clare T. Meeker, Christopher B. Little, Karena Last, Pamela J. Farmer, Ian K. Campbell, Anne M. Fourie and Amanda J. Fosang
doi: 10.1038/nature03417
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Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death p652
Takashi Nakagawa, Shigeomi Shimizu, Tetsuya Watanabe, Osamu Yamaguchi, Kinya Otsu, Hirotaka Yamagata, Hidenori Inohara, Takeshi Kubo and Yoshihide Tsujimoto
doi: 10.1038/nature03317
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Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death p658
Christopher P. Baines, Robert A. Kaiser, Nicole H. Purcell, N. Scott Blair, Hanna Osinska, Michael A. Hambleton, Eric W. Brunskill, M. Richard Sayen, Roberta A. Gottlieb, Gerald W. Dorn, II, Jeffrey Robbins and Jeffery D. Molkentin
doi: 10.1038/nature03434
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Structural insights into mRNA recognition from a PIWI domain?siRNA guide complex p663
James S. Parker, S. Mark Roe and David Barford
doi: 10.1038/nature03462
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Structural basis for 5'-end-specific recognition of guide RNA by the A. fulgidus Piwi protein p666
Jin-Biao Ma, Yu-Ren Yuan, Gunter Meister, Yi Pei, Thomas Tuschl and Dinshaw J. Patel
doi: 10.1038/nature03514
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Friction and torque govern the relaxation of DNA supercoils by eukaryotic topoisomerase IB p671
Daniel A. Koster, Vincent Croquette, Cees Dekker, Stewart Shuman and Nynke H. Dekker
doi: 10.1038/nature03395
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Top of pageNaturejobs
Prospects
Sizing up the odds p675
Paul Smaglik
doi: 10.1038/nj7033-675a
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Regions
Ontario p676
Messages from MaRS
Hannah Hoag
doi: 10.1038/nj7033-676a
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Career View
Graduate Journal: International aid to pay the rent p678
Karolina Tkaczuk
doi: 10.1038/nj7033-678a
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Recruiters & Industry p678
Roger Bezdek and Robert Wendling
doi: 10.1038/nj7033-678b
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Movers p678
doi: 10.1038/nj7033-678c
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Top of pageFutures
Dreadnought p680
All for one ... and one for all.
Justina Robson
doi: 10.1038/434680a
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