目次

Editorials

医薬品の適応外使用は科学の軽視であり、患者に被害が及ばぬよう、規制する必要がある。

The limits of free speech p.311

Unregulated drug marketing stifles science and harms patients. To suggest otherwise is an affront to liberty — not a protection of it.

doi: 10.1038/492311a

世界各国の保健指標を調べた大規模研究GBD2010には、不十分な点もあるが、高く評価すべきだ。

A burden weighed p.311

Despite some shortcomings, a global study of health metrics should be applauded.

doi: 10.1038/492311b

世界的な金融危機の中で、夢の大型加速器、国際リニアコライダー(ILC)計画を推進する日本の科学者たちを支援すべきだ。

Head of the line p.312

Japanese scientists deserve support in their bid for the next big collider.

doi: 10.1038/492312a

News

ALMA(アタカマ大型ミリ波サブミリ波干渉計)の初期の観測で、星の誕生の手がかりとなる成果が。

Mega-array reveals birthplace of giant stars p.319

Early results from Atacama telescope signal the opening of a scientific frontier.

doi: 10.1038/492319a

ロシアが、優れた研究所に予算を重点的に配分し、不振な研究所は閉鎖するという、思い切った大学改革を。

Russia shakes up its universities p.320

Government plans to close struggling institutions and increase funding to the best.

doi: 10.1038/492320a

バイオ医薬品大手のアムジェン社が、デコード・ジェネティクス社を買収へ。

Big biotech buys iconic genetics firm p.321

Amgen’s deal with deCODE Genetics shows value of combined medical and genetic data.

doi: 10.1038/492321a

世界的な調査で、寿命や健康状態の実態と変化が明らかに。

Global survey reveals impact of disability p.322

Study tracks changes in life expectancy and health burdens.

doi: 10.1038/492322a

中国で特許の急増に伴い、訴訟も増えているが、司法が追いついていない面も。

China’s patent boom brings legal wrangles p.323

Court decision sets precedent for protecting intellectual property.

doi: 10.1038/492323a

生物学分野、素粒子物理学分野で、ビッグデータから画期的成果が生まれた。

2012 in review p.324

This epic year for science saw the discovery of the Higgs boson and Curiosity’s arrival on Mars, but researchers also felt the sting of austerity.

doi: 10.1038/492324a

写真で見る2012年

Images of the year p.328

Disintegrating ice, spectacular sunbursts and minuscule lizards are among 2012’s most striking pictures.

doi: 10.1038/492328a

News Features

Natureが選ぶ今年の10人

Nature's 10 p.335

この1年間、最も注目を浴びた10人とは、どんな顔ぶれだろうか。

doi: 10.1038/492335a

News & Views

熱物理学:いちだんと熱が入る量子干渉

Thermal physics: Quantum interference heats up p.358

40年以上前に存在が予測されたある熱効果は、それに似たもう1つ別の現象が代わって脚光を浴びたためにほとんど忘れ去られていた。今回、実験的に確認されたこの効果は、熱制御デバイスの開発を後押しするものとなりそうだ。

doi: 10.1038/492358a

神経発達障害:脆弱X症候群でのシグナル伝達経路

Neurodevelopmental disorders: Signalling pathways of fragile X syndrome p.359

RNA結合タンパク質のFMR1は神経発達障害である脆弱X症候群に重要な役割を果たしているが、このタンパク質が標的とするRNAについてはほとんどわかっていなかった。今回行われた解析によって、非常に多数の標的候補が見つかった。

doi: 10.1038/nature11764

心血管生物学:心臓再生を後押しする

Cardiovascular biology: A boost for heart regeneration p.360

心筋細胞は傷害を受けると大量に死ぬが、哺乳類成体の心臓にはこうした細胞を再生する能力がほとんどない。調節性マイクロRNA配列はこのような心筋細胞の自己複製を促進する可能性がある。

doi: 10.1038/nature11763

がん:ドライバー変異での代謝

Cancer: Metabolism in 'the driver's seat p.362

がん細胞における代謝の変化は腫瘍形成を後押しすることがあるという説は、徐々に受け入れられつつある。SIRT6タンパク質が代謝の調節によって腫瘍形成を抑制するという知見は、この説に重みを加えるものだ。

doi: 10.1038/492362a

エピジェネティクス:新たなスタートのための消去

Epigenetics: Erase for a new start p.363

Tetタンパク質はDNA中の塩基からメチル基を除去することにより遺伝子発現を調節している。この活性は、精子や卵の細胞を形成するための細胞分裂経路を開始させる促進段階なのかもしれない。

doi: 10.1038/492363a

低温物理学:クールな分子たち

Low-temperature physics: Cool molecules p.364

ヒドロキシルラジカルの1つが数ミリケルビンという温度まで冷却された。この結果は、分子の基底状態におけるボース・アインシュタイン凝縮のような現象の観察へつながる扉を開くものである。

doi: 10.1038/492364a

地球科学:ポーラーロウとともに行かん

Earth science: Go with the lows p.365

ポーラーロウ(polar low、極低気圧)として知られる強力な暴風の影響は、普通は気象モデルに取り込まれない。だが、ポーラーロウの海洋循環への影響を評価するシミュレーションは、これをモデルに取り込むべきであることを示唆している。

doi: 10.1038/492365a

編集部のお勧めNews & Views

2012 Editors' choice p.366

今年掲載されたNews & Viewsの中から編集部が選んだ記事の抜粋を集めた。

doi: 10.1038/492366a

Articles

遺伝:ヒト赤血球に影響を与える75か所の遺伝子座

Seventy-five genetic loci influencing the human red blood cell p.369

Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10−8, which together explain 4–9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.

doi: 10.1038/nature11677

再生医学:心臓再生を誘導するmiRNAを機能的スクリーニングによって同定

Functional screening identifies miRNAs inducing cardiac regeneration p.376

In mammals, enlargement of the heart during embryonic development is primarily dependent on the increase in cardiomyocyte numbers. Shortly after birth, however, cardiomyocytes stop proliferating and further growth of the myocardium occurs through hypertrophic enlargement of the existing myocytes. As a consequence of the minimal renewal of cardiomyocytes during adult life, repair of cardiac damage through myocardial regeneration is very limited. Here we show that the exogenous administration of selected microRNAs (miRNAs) markedly stimulates cardiomyocyte proliferation and promotes cardiac repair. We performed a high-content microscopy, high-throughput functional screening for human miRNAs that promoted neonatal cardiomyocyte proliferation using a whole-genome miRNA library. Forty miRNAs strongly increased both DNA synthesis and cytokinesis in neonatal mouse and rat cardiomyocytes. Two of these miRNAs (hsa-miR-590 and hsa-miR-199a) were further selected for testing and were shown to promote cell cycle re-entry of adult cardiomyocytes ex vivo and to promote cardiomyocyte proliferation in both neonatal and adult animals. After myocardial infarction in mice, these miRNAs stimulated marked cardiac regeneration and almost complete recovery of cardiac functional parameters. The miRNAs identified hold great promise for the treatment of cardiac pathologies consequent to cardiomyocyte loss.

doi: 10.1038/nature11739

医学:FMRPは異なったmRNA配列要素を標的としてタンパク質の発現を調節する

FMRP targets distinct mRNA sequence elements to regulate protein expression p.382

Fragile X syndrome (FXS) is a multi-organ disease that leads to mental retardation, macro-orchidism in males and premature ovarian insufficiency in female carriers. FXS is also a prominent monogenic disease associated with autism spectrum disorders (ASDs). FXS is typically caused by the loss of fragile X mental retardation 1 (FMR1) expression, which codes for the RNA-binding protein FMRP. Here we report the discovery of distinct RNA-recognition elements that correspond to the two independent RNA-binding domains of FMRP, in addition to the binding sites within the messenger RNA targets for wild-type and I304N mutant FMRP isoforms and the FMRP paralogues FXR1P and FXR2P (also known as FXR1 and FXR2). RNA-recognition-element frequency, ratio and distribution determine target mRNA association with FMRP. Among highly enriched targets, we identify many genes involved in ASD and show that FMRP affects their protein levels in human cell culture, mouse ovaries and human brain. Notably, we discovered that these targets are also dysregulated in Fmr1−/− mouse ovaries showing signs of premature follicular overdevelopment. These results indicate that FMRP targets share signalling pathways across different cellular contexts. As the importance of signalling pathways in both FXS and ASD is becoming increasingly apparent, our results provide a ranked list of genes as basis for the pursuit of new therapeutic targets for these neurological disorders.

doi: 10.1038/nature11737

構造生物学:ヒトのプロテアーゼ活性化受容体1の高分解能結晶構造

High-resolution crystal structure of human protease-activated receptor 1 p.387

Protease-activated receptor 1 (PAR1) is the prototypical member of a family of G-protein-coupled receptors that mediate cellular responses to thrombin and related proteases. Thrombin irreversibly activates PAR1 by cleaving the amino-terminal exodomain of the receptor, which exposes a tethered peptide ligand that binds the heptahelical bundle of the receptor to affect G-protein activation. Here we report the 2.2-Å-resolution crystal structure of human PAR1 bound to vorapaxar, a PAR1 antagonist. The structure reveals an unusual mode of drug binding that explains how a small molecule binds virtually irreversibly to inhibit receptor activation by the tethered ligand of PAR1. In contrast to deep, solvent-exposed binding pockets observed in other peptide-activated G-protein-coupled receptors, the vorapaxar-binding pocket is superficial but has little surface exposed to the aqueous solvent. Protease-activated receptors are important targets for drug development. The structure reported here will aid the development of improved PAR1 antagonists and the discovery of antagonists to other members of this receptor family.

doi: 10.1038/nature11701

Letters

宇宙:青色はぐれ星によって明らかにされた同年代の星団の間の力学的年齢の違い

Dynamical age differences among coeval star clusters as revealed by blue stragglers p.393

Globular clusters can be grouped into a few distinct families on the basis of the radial distribution of ‘blue stragglers’, stars with masses greater than those at the turn-off point on the main sequence; this grouping can yield a direct measure of the cluster’s dynamical age purely from observed properties.

doi: 10.1038/nature11686

物理:双極子ヒドロキシルラジカルの蒸発冷却

Evaporative cooling of the dipolar hydroxyl radical p.396

Evaporative cooling of molecules has not been achieved so far, owing to unfavourable collision properties and trap losses; microwave-forced evaporative cooling of hydroxyl molecules loaded in a magnetic quadrupole trap is now reported.

doi: 10.1038/nature11718

物理:ジョセフソン熱干渉計

The Josephson heat interferometer p.401

A thermal analogue of a superconducting quantum interference device (SQUID, widely used to measure small magnetic fields) is realized, in which the flow of heat between the superconductors is dependent on the quantum phase difference between them.

doi: 10.1038/nature11702

物性:カゴメ格子反強磁性体のスピン液体状態における分数励起

Fractionalized excitations in the spin-liquid state of a kagome-lattice antiferromagnet p.406

Neutron scattering measurements on single-crystal samples of the mineral herbertsmithite, which is a spin-1/2 kagome-lattice antiferromagnet, provide evidence of fractionalized spin excitations at low temperatures, indicating that the ground state of herbertsmithite may be a quantum spin liquid.

doi: 10.1038/nature11659

光学:異常光透過の実験における準円筒波の寄与

Quasi-cylindrical wave contribution in experiments on extraordinary optical transmission p.411

Results on light scattering from metal hole arrays show the relative importance of surface plasmon polaritons and quasi-cylindrical waves in extraordinary optical transmission.

doi: 10.1038/nature11669

地球:カンラン石集合体の粘性異方性の室内測定

Laboratory measurements of the viscous anisotropy of olivine aggregates p.415

Measurements of the viscous anisotropy of highly deformed polycrystalline olivine find it to be approximately an order of magnitude larger than that predicted by grain-scale simulations; the maximum degree of anisotropy is reached at geologically low shear strain, such that deforming regions of the Earth’s upper mantle should exhibit significant viscous anisotropy.

doi: 10.1038/nature11671

環境:フリッカー現象は湖沼の富栄養状態への臨界遷移の早期警告シグナルとなる

Flickering gives early warning signals of a critical transition to a eutrophic lake state p.419

Critical transitions in experimental and theoretical systems can be anticipated on the basis of specific warning signs, with ‘critical slowing down’ being the best studied; long-term data from a real system, a Chinese lake, now show that a flickering phenomenon can be observed up to 20 years before the critical transition to a eutrophic state.

doi: 10.1038/nature11655

遺伝:ワタ属ゲノムで繰り返された倍数化と、紡績可能なワタ繊維の進化

Repeated polyploidization of Gossypium genomes and the evolution of spinnable cotton fibres p.423

The Gossypium genus is used to investigate emergent consequences of polyploidy in cotton species; comparative genomic analyses reveal a complex evolutionary history including interactions among subgenomes that result in genetic novelty in elite cottons and provide insight into the evolution of spinnable fibres.

doi: 10.1038/nature11798

脳:行動負荷への応答を制御する、前頭前皮質から脳幹への投射

A prefrontal cortex–brainstem neuronal projection that controls response to behavioural challenge p.428

High-speed tracking of effortful responses and neuronal activity in rats during a forced swim test identifies medial prefrontal cortex (mPFC) neurons that respond during escape-related swimming but not normal locomotion, and optogenetics shows that mPFC neurons projecting to the brainstem dorsal raphe nucleus, which is implicated in depression, modulate this behavioural response to challenge.

doi: 10.1038/nature11617

神経:ショウジョウバエにおけるオクトパミン、ドーパミンを介した重層的な報酬シグナル伝達

Layered reward signalling through octopamine and dopamine in Drosophila p.433

Dopamine is synonymous with reward in mammals but associated with aversive reinforcement in insects, where reward seems to be signalled by octopamine; here it is shown that flies have discrete populations of dopamine neurons representing positive or negative values that are coordinately regulated by octopamine.

doi: 10.1038/nature11614

細胞:人工多能性幹細胞によって明らかになったヒト皮膚での体細胞性コピー数モザイク現象

Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells p.438

A whole-genome and transcriptome analysis of 20 human induced pluripotent stem-cell lines shows that reprogramming does not necessarily add de novo copy number variants to what is already present in the somatic cells from which they originated.

doi: 10.1038/nature11629

発生:Tet1は減数分裂関連遺伝子の発現調節により減数分裂を制御する

Tet1 controls meiosis by regulating meiotic gene expression p.443

A loss-of-function approach in mice is used to show that the methylcytosine dioxygenase Tet1 has a role in regulating meiosis and meiotic gene activation in female germ cells; Tet1 deficiency does not greatly affect genome-wide demethylation but has a more specific effect on the expression of a subset of meiotic genes.

doi: 10.1038/nature11709

構造生物学:転写メディエーター複合体のヘッドモジュールの構造

Structure of the Mediator head module p.448

The crystal structure of the Mediator head module from the fission yeast Schizosaccharomyces pombe is solved at 3.4 Å resolution.

doi: 10.1038/nature11670

脳:腹側被蓋野のGABA性投射は側坐核のコリン性介在ニューロンを停止させて連合学習を強化する

Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning p.452

GABA-releasing neurons from the ventral tegmental area that project to the nucleus accumbens are shown to block the firing of cholinergic accumbal interneurons, affecting learning in mice.

doi: 10.1038/nature11657

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