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Editorials

増え続ける博士課程学生に対し、大学は、学術研究以外の職種に備えた教育も考える必要がある。

There is life after academia p.5

With high numbers of postdocs emerging from universities, prospective PhD students must be prepared for the fact that they will probably not end up with a career in research.

doi: 10.1038/513005a

新たな超銀河団を定義することで、宇宙における地球の位置付けがさらに詳しく示せるようになった。

Heavenly homes p.6

The discovery of our Galaxy’s place in the Universe adds detail to our address.

doi: 10.1038/513006a

Natureでは、研究に役立つソフトウエアやウェブサイトを紹介するToolbox欄を新たに設ける。

The digital toolbox p.6

A new section of Nature examines the software and websites that make research easier.

doi: 10.1038/513006b

News

エボラ出血熱流行の拡大が止まらず、新薬やワクチンが急いで臨床試験に。

Ebola drug trials set to begin amid crisis p.13

Testing drugs in the middle of deadly disease outbreak is challenging but can be done.

doi: 10.1038/513013a

兆候がありながらなかなか起こらないエルニーニョ現象から、研究者たちが多くの有用な知見を。

Stalled El Niño poised to resurge p.15

Studies of brewing weather event test understanding of past and future climate.

doi: 10.1038/513015a

スイスで、高山湖の津波も考慮に入れた災害対策が。

Switzerland braces for Alpine lake tsunami p.16

Authorities in Swiss canton blaze a trail by factoring the risk into hazard planning.

doi: 10.1038/513016a

米国カリフォルニア州で8月24日に起きたマグニチュード6.0の地震で、警報システムの実用性の問題点が明らかに。

California quake puts warning system in the spotlight p.18

Scientists, politicians and business leaders will discuss practicalities of a regional network.

doi: 10.1038/513018a

News Features

逃した人材:研究室を離れて

Life outside the lab: The ones who got away p.20

将来を嘱望される科学者が、研究生活に見切りをつけて向かう先は、どこなのだろうか。

doi: 10.1038/513020a

電子たばこ:消えない疑問

E-cigarettes: The lingering questions p.24

電子たばこの効果と危険性については、データが不十分で、科学者の間でも意見が分かれている。

doi: 10.1038/513024a

News & Views

地球ダイナミクス:プリュームがプレート破壊を助ける仕組み

Geodynamics: How plumes help to break plates p.36

コンピューターモデルによって、地球内部から生じた高温の物質にプレートテクトニクスが影響を与え、地球の地形に予想外の不規則性を生じさせ、また大陸プレートの破壊を助ける仕組みが明らかにされた。

doi: 10.1038/513036a

進化発生生物学:可塑性を持つ魚の遺産

Evolutionary developmental biology: Dynasty of the plastic fish p.37

現生魚類についての大がかりな実験と形態学的研究から、初期の「四肢魚」が鰭のある水生動物から陸上を歩行する四肢動物に移行するのを、発生可塑性が助けた仕組みと考えられるものが明らかになった。

doi: 10.1038/nature13743

細胞生物学:細胞の完全性を守るRIPK1

Cell biology: A guardian angel of cell integrity p.38

細胞死経路に必須のタンパク質であるRIPK1が、体の上皮細胞障壁の維持にも関わっていることが分かった。この知見は、細胞の死と生存は別々の因子によって調節されているという考え方に疑問を投じるものだ。

doi: 10.1038/513038a

生物学的手法:ゲノムを編集によって解明する

Biological techniques: Edit the genome to understand it p.40

ゲノム編集を行ってから塩基配列を解読する方法を使って、生細胞中のヒトDNAの複数の領域の全変異が操作・解析され、それぞれの構成成分であるヌクレオチド分子の機能に関する手がかりが得られた。

doi: 10.1038/nature13659

宇宙論:こちらがラニアケア超銀河団

Cosmology: Meet the Laniakea supercluster p.41

銀河とその運動速度の三次元マップの解析によって、我々が暮らしている大規模な銀河系の、これまで不明だった境界が明らかにされ、ラニアケア超銀河団と名付けられた。

doi: 10.1038/513041a

構造生物学:蛍光タグを付けたRNAが光る仕組み

Structural biology: How fluorescent RNA gets its glow p.42

蛍光標識は細胞内でRNA分子を追跡するのに非常に有用であることが分かっている。そのような標識の1つ、つまり色素と結合すると蛍光を出すようなRNAモチーフについて、2組の結晶構造が明らかにされた。これは、もっと有用なマーカーの開発を助けると考えられる。

doi: 10.1038/513042a

Review

気候:熱帯収束帯の移動とダイナミクス

Migrations and dynamics of the intertropical convergence zone p.45

The intertropical convergence zone, where global rainfall is greatest, is a narrow belt of clouds usually centred about six degrees north of the Equator; this Review links its migrations on various timescales to the atmospheric energy balance.

doi: 10.1038/nature13636

Articles

実験進化学:発生可塑性と四肢類の出現

Developmental plasticity and the origin of tetrapods p.54

The most primitive extant bony fish, Polypterus, exhibits adaptive plasticity for life on land when raised on land rather than in water, suggesting that environmentally induced phenotypic plasticity might have facilitated the macroevolutionary transition to life on land.

doi: 10.1038/nature13708

微生物学:肝硬変におけるヒト腸内マイクロバイオームの変化

Alterations of the human gut microbiome in liver cirrhosis p.59

Invasion of the gut by oral bacteria in liver cirrhosis.

doi: 10.1038/nature13568

がん:RNAのグアニン四重鎖はがんでeIF4A依存性がん遺伝子の翻訳を引き起こす

RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer p.65

The translation of many messenger RNAs that encode important oncogenes and transcription factors depends on the eIF4A RNA helicase to resolve G-quadruplex structures, implying eIF4A inhibition as an effective cancer therapy.

doi: 10.1038/nature13485

Letters

宇宙:ラニアケア超銀河団

The Laniakea supercluster of galaxies p.71

Examination of a three-dimensional map of galaxies and their velocities shows a surface bounding the motions of galaxies that are inward after removal of the mean cosmic expansion and long-range flows; the galaxies within this surface lie within our home supercluster.

doi: 10.1038/nature13674

宇宙:銀河M82にある太陽の400倍の質量を持つブラックホール

A 400-solar-mass black hole in the galaxy M82 p.74

The discovery of two stable peaks at frequencies with a ratio of 3:2 in the power spectrum of X-ray emission from the brightest X-ray source in galaxy M82 suggests that, if the relationship between frequency and mass that holds for stellar-mass black holes can be extended to intermediate masses, the black hole believed to be the source of the emission has a mass approximately 400 times that of the Sun.

doi: 10.1038/nature13710

材料:コロイド膜におけるキラルなラフト構造体の階層的組織化

Hierarchical organization of chiral rafts in colloidal membranes p.77

Inclusions dissolved in a colloidal membrane assemble into highly uniform finite-sized liquid droplets or rafts consisting of thousands of molecules.

doi: 10.1038/nature13694

生物地球化学:微生物群集の応答が高める土壌呼吸速度の温度感受性

Temperature sensitivity of soil respiration rates enhanced by microbial community response p.81

Microbial community responses in soils from the Arctic to the Amazon often enhance the longer-term temperature sensitivity of respiration, particularly in soils with high carbon-to-nitrogen ratios and in soils from cold regions, suggesting that carbon stored in Arctic and boreal soils could be more vulnerable to climate warming than currently predicted.

doi: 10.1038/nature13604

地球物理学:マントル・プリュームの上の非対称三次元的地形

Asymmetric three-dimensional topography over mantle plumes p.85

Three-dimensional numerical models of the interaction of a mantle plume with a rheologically realistic lithosphere predict complex surface evolution very different from the smooth, radially symmetric patterns usually assumed to be the signature of a mantle upwelling, with strongly asymmetric small-scale three-dimensional features such as rifts and linear fault structures.

doi: 10.1038/nature13703

免疫:RIPK1はアポトーシスとネクロトーシスの阻害により上皮の恒常性を維持する

RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis p.90

RIPK1 is shown to have a crucial role—independent of its known kinase function—in suppressing epithelial cell apoptosis and necroptosis in mice, thereby regulating homeostasis and preventing inflammation in barrier tissues.

doi: 10.1038/nature13608

免疫:RIPK1は上皮をアポトーシスから保護することによって腸の恒常性を確保する

RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis p.95

This study provides evidence for a critical role of RIPK1 in suppressing caspase-8-mediated cell death and maintaining intestinal homeostasis independently of its kinase activity.

doi: 10.1038/nature13706

がん:腫瘍由来PTH関連タンパク質が脂肪組織の褐色化とがん悪液質を誘導する

Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia p.100

Many patients with cancer experience cachexia, a wasting disorder of adipose tissue and skeletal muscle that leads to weight loss and frailty; now, tumour-derived parathyroid-hormone-related protein has been shown to stimulate the expression of genes involved in heat production in adipose tissues and to have an important role in tissue wasting.

doi: 10.1038/nature13528

がん:eIF4FはがんBRAF阻害/MEK阻害療法に対する耐性の中核である

eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies p.105

BRAF mutations occur frequently in melanomas, but patients generally develop resistance to agents targeting mutant BRAF; now, the persistent formation of the translation initiation complex eIF4F has been described as an indicator of multiple mechanisms of resistance that arise in BRAF-mutated tumours and as a promising therapeutic target.

doi: 10.1038/nature13572

がん:変異型IDHはHNF-4αを抑制して肝細胞の分化を阻害し胆道がんを促進する

Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer p.110

Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are among the most common genetic alterations in intrahepatic cholangiocarcinoma (IHCC), a deadly liver cancer. Mutant IDH proteins in IHCC and other malignancies acquire an abnormal enzymatic activity allowing them to convert α-ketoglutarate (αKG) to 2-hydroxyglutarate (2HG), which inhibits the activity of multiple αKG-dependent dioxygenases, and results in alterations in cell differentiation, survival, and extracellular matrix maturation. However, the molecular pathways by which IDH mutations lead to tumour formation remain unclear. Here we show that mutant IDH blocks liver progenitor cells from undergoing hepatocyte differentiation through the production of 2HG and suppression of HNF-4α, a master regulator of hepatocyte identity and quiescence. Correspondingly, genetically engineered mouse models expressing mutant IDH in the adult liver show an aberrant response to hepatic injury, characterized by HNF-4α silencing, impaired hepatocyte differentiation, and markedly elevated levels of cell proliferation. Moreover, IDH and Kras mutations, genetic alterations that co-exist in a subset of human IHCCs, cooperate to drive the expansion of liver progenitor cells, development of premalignant biliary lesions, and progression to metastatic IHCC. These studies provide a functional link between IDH mutations, hepatic cell fate, and IHCC pathogenesis, and present a novel genetically engineered mouse model of IDH-driven malignancy.

doi: 10.1038/nature13441

細胞:多能性細胞と体細胞におけるエピジェネティック記憶の動的維持と静的維持

Dynamic and static maintenance of epigenetic memory in pluripotent and somatic cells p.115

Using a new method to estimate DNA methylation turnover rate, embryonic stem cells are shown to lack clonal transmission of methylation but still maintain a stable epigenetic state, whereas somatic cells transmit methylation clonally but lose epigenetic state coherence owing to the persistence of accumulated methylation errors.

doi: 10.1038/nature13458

ゲノミクス:多重相同組換え修復によるゲノム領域の飽和編集

Saturation editing of genomic regions by multiplex homology-directed repair p.120

The authors perform saturation mutagenesis of genomic regions in their native endogenous chromosomal context by using CRISPR/Cas9 RNA-guided cleavage and multiplex homology-directed repair; its utility is demonstrated by measuring the effects of hundreds to thousands of genomic edits to BRCA1 and DBR1 on splicing and cellular fitness, respectively.

doi: 10.1038/nature13695

構造生物学:アロステリックアゴニストTAK-875と結合したヒトGPR40受容体の高分解能構造

High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875 p.124

The X-ray crystal structure of human GPR40 receptor in the presence of TAK-875, an orally available, potent and selective human GPR40 agonist.

doi: 10.1038/nature13494

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