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Editorials

科学界は、科学の進歩の恩恵が及んでいないと感じている人々の要望や雇用への期待に応えることを優先すべきだ。

Researchers should reach beyond the science bubble p.391

Scientists in the United States and elsewhere ought to address the needs and employment prospects of taxpayers who have seen little benefit from scientific advances.

doi: 10.1038/542391a

惑星の定義を、冥王星を含むような、より広いものに変えるという提案は、大変興味深い。

Pluto could be staging a comeback — and it’s not alone p.392

A proposal to massively expand the number of bodies called planets raises interesting questions.

doi: 10.1038/542392b

ヨーロッパの遺伝子編集に関するルール作りは遅れており、科学者は進展のために動くべきだ。

Gene editing in legal limbo in Europe p.392

The European Union is dragging its feet on gene-editing rules and scientists should push the issue.

doi: 10.1038/542392a

News

中国初のバイオセーフティレベル4(BSL-4)施設に期待と懸念が。

Inside the Chinese lab poised to study world's most dangerous pathogens p.399

Maximum-security biolab is part of plan to build network of BSL-4 facilities across China.

doi: 10.1038/nature.2017.21487

米国特許商標庁(USPTO)が、CRISPR関連技術の特許権はブロード研究所にあるとの判断を。

Broad Institute wins bitter battle over CRISPR patents p.401

The US Patent and Trademark Office issues a verdict in legal tussle over rights to genome-editing technology.

doi: 10.1038/nature.2017.21502

南極の巨大な棚氷ラーセンCの亀裂が急速に拡大し、崩壊が間近に。

Giant crack in Antarctic ice shelf spotlights advances in glaciology p.402

Rift through Larsen C ice shelf has grown to 175 kilometres, and collapse of nearby ice shelves could offer a glimpse of its future.

doi: 10.1038/nature.2017.21507

英国のEU離脱を担当する重要な2つの省で主席科学顧問がいまだ決まらず、離脱後の科学政策に悪影響を及ぼす可能性も。

Delay in hiring science advisers intensifies Brexit worries p.403

Policy experts want scientists at the table when government decides on environmental protection and membership of international collaborations.

doi: 10.1038/nature.2017.21511

16世紀にアステカ族を激減させた原因が、ヨーロッパから持ち込まれたチフス菌の大流行だった可能性が。

Collapse of Aztec society linked to catastrophic salmonella outbreak p.404

DNA of 500-year-old bacteria is first direct evidence of an epidemic — one of humanity's deadliest — that occurred after Spanish conquest.

doi: 10.1038/nature.2017.21485

がんやヒト組織の細胞レベルのアトラス作製が盛んに。

The race to map the human body — one cell at a time p.404

A host of detailed cell atlases could revolutionize understanding of cancer and other diseases.

doi: 10.1038/nature.2017.21508

News Features

エピジェネティクス:新たな展開

An epigenetics gold rush: new controls for gene expression p.406

DNAやRNAの見過ごされていた化学標識が、遺伝子発現に関するこれまでの見方を揺るがしている。

doi: 10.1038/542406a

News & Views

システム神経科学:視覚の多様性

Systems neuroscience: Diversity in sight p.418

網膜の信号伝達経路で中心的な役割を担っている双極細胞を系統的に分析した結果、このニューロンの光に対する多様な応答は、主に隣接するアマクリン細胞からのフィードバックによって生じていることが明らかになった。

doi: 10.1038/nature21498

気候科学:カオス的な惑星における予測可能な氷期

Climate science: Predictable ice ages on a chaotic planet p.419

統計解析によって、第四紀において温暖な期間が生じる単純な法則が明らかになったが、ずっと長い時間スケールでは、地質学的データから、太陽系がカオス的であることが確認された。

doi: 10.1038/542419a

分子生物学:2段階のRNA編集

Molecular biology: RNA editing packs a one-two punch p.420

最適なタンパク質合成には、転移RNAの塩基が修飾される必要がある。今回、2種の酵素の逐次的活性を伴う独特な2段階機構が、重要な修飾に関与していることが分かった。

doi: 10.1038/542420a

天文学:地球の7つの姉妹惑星

Astronomy: Earth's seven sisters p.421

表面に液体の水が存在している可能性のある7つの小さな惑星が、近傍の矮星の周囲に発見された。こうした配置がさまざまな惑星系で一般的だとすれば、銀河系は地球に似た惑星で満ちあふれている可能性がある。

doi: 10.1038/542421a

材料科学:グラフェンに類似した有機物

Materials science: Organic analogues of graphene p.423

化学の分野では、完全共役した、つまり有用な性質をもたらす可能性のある属性を持つ二次元ポリマーの合成が切望されていた。今回まさにそうした材料が、固体重合反応を用いて作製された。

doi: 10.1038/nature21503

がん:オフターゲットリスクを伴う標的治療

Cancer: A targeted treatment with off-target risks p.424

腫瘍生存経路を阻害する血液がん標的薬がマウス細胞とヒト細胞の突然変異を生じさせる酵素も活性化することが、今回明らかになった。この結果は、こうした薬剤の臨床用途に影響を与える可能性がある。

doi: 10.1038/nature21504

Articles

気候科学:日射量のどの変動周期が間氷期をもたらしたかを決める単純な法則

A simple rule to determine which insolation cycles lead to interglacials p.427

A simple model, based on only summer insolation energy and time since the previous deglaciation, correctly predicts the deglaciation history of the past 2.6 million years, including the change in frequency of glacial–interglacial cycles about one million years ago.

doi: 10.1038/nature21364

遺伝学:発達障害におけるde novo変異の保有率と構造

Prevalence and architecture of de novo mutations in developmental disorders p.433

Whole-exome analysis of individuals with developmental disorders shows that de novo mutations can equally cause loss or altered protein function, but that most mutations causing altered protein function have not yet been described.

doi: 10.1038/nature21062

神経科学:網膜内の複数の視覚特徴表現は抑制によって脱相関される

Inhibition decorrelates visual feature representations in the inner retina p.439

The functional diversity of bipolar cells, which split visual inputs into different excitatory channels within the retina, arises from centre–surround interactions in their receptive fields that tune both spatial and temporal signalling.

doi: 10.1038/nature21394

免疫学:化学弱毒化PfSPZワクチンによるヒトマラリアに対する完全な予防

Sterile protection against human malaria by chemoattenuated PfSPZ vaccine p.445

Immunization with Plasmodium falciparum sporozoites under chemoprophylaxis can protect against controlled human malaria infection with the same strain for at least 10 weeks, and protection correlates with polyfunctional T-cell memory.

doi: 10.1038/nature21060

生理学:脂肪由来循環miRNAは他の組織の遺伝子発現を調節する

Adipose-derived circulating miRNAs regulate gene expression in other tissues p.450

Adipose tissue is a major source of circulating exosomal miRNAs, which contribute to the regulation of gene expression in distant tissues and organs.

doi: 10.1038/nature21365

Letters

天文学:近傍にある超低温矮星TRAPPIST-1の周囲にある7個の温暖な地球型惑星

Seven temperate terrestrial planets around the nearby ultracool dwarf star TRAPPIST-1 p.456

Last year, three Earth-sized planets were discovered to be orbiting the nearby Jupiter-sized star TRAPPIST-1; now, follow-up photometric observations from the ground and from space show that there are at least seven Earth-sized planets in this star system, and that they might be the right temperature to harbour liquid water on their surfaces.

doi: 10.1038/nature21360

材料科学:機械メタマテリアルにおける静的な非相反性

Static non-reciprocity in mechanical metamaterials p.461

Suitably engineered mechanical metamaterials show static non-reciprocity—that is, the transmission of motion from one side to the other depends on the direction of that motion.

doi: 10.1038/nature21044

地球科学:大酸化事変時における好気的な窒素循環の開始

Onset of the aerobic nitrogen cycle during the Great Oxidation Event p.465

Nitrogen isotope data from sediments deposited during the earliest stage of the Great Oxidation Event show evidence for the emergence of a pervasive aerobic marine nitrogen cycle.

doi: 10.1038/nature20826

地球科学:白亜紀の地質学的証拠によって確証されたカオス的軌道変動理論

Theory of chaotic orbital variations confirmed by Cretaceous geological evidence p.468

Cretaceous astrochronologic evidence reveals a resonance transition associated with the orbits of Mars and the Earth, confirming predicted chaotic Solar System behaviour and enabling an improvement in the geological timescale.

doi: 10.1038/nature21402

進化学:オルドビス紀の新たなステム群Aculifera類から明らかになったクラウン群軟体動物の祖先的形態

Ancestral morphology of crown-group molluscs revealed by a new Ordovician stem aculiferan p.471

Presence of a radula in Calvapilosa kroegeri confirms the molluscan affinity of sachitids, and the single shell plate reveals the ancestral condition for all crown molluscs and early evolution of the multi-plated body plan characteristic of Aculifera.

doi: 10.1038/nature21055

発生生物学:m6A依存的な母性mRNAの除去が、ゼブラフィッシュの母性・胚性転移を促進する

m6A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition p.475

The maternal-to-zygotic transition (MZT) is one of the most profound and tightly orchestrated processes during the early life of embryos, yet factors that shape the temporal pattern of vertebrate MZT are largely unknown. Here we show that over one-third of zebrafish maternal messenger RNAs (mRNAs) can be N6-methyladenosine (m6A) modified, and the clearance of these maternal mRNAs is facilitated by an m6A-binding protein, Ythdf2. Removal of Ythdf2 in zebrafish embryos decelerates the decay of m6A-modified maternal mRNAs and impedes zygotic genome activation. These embryos fail to initiate timely MZT, undergo cell-cycle pause, and remain developmentally delayed throughout larval life. Our study reveals m6A-dependent RNA decay as a previously unidentified maternally driven mechanism that regulates maternal mRNA clearance during zebrafish MZT, highlighting the critical role of m6A mRNA methylation in transcriptome switching and animal development.

doi: 10.1038/nature21355

がん:Bリンパ球系転写因子の代謝ゲートキーパー機能

Metabolic gatekeeper function of B-lymphoid transcription factors p.479

The B-lymphoid transcription factors PAX5 and IKZF1 restrict the supply of glucose and energy to B cells to levels that are not enough to fuel a driver-oncogene, thereby acting as tumour suppressors and sensitizing acute lymphoblastic leukaemia B cells to glucocorticoid therapy.

doi: 10.1038/nature21076

がん:PTEN欠失がんにおけるクロマチンリモデリング因子CHD1の合成必須性

Synthetic essentiality of chromatin remodelling factor CHD1 in PTEN-deficient cancer p.484

The gene CHD1 is synthetic essential in PTEN-deficient prostate and breast cancers.

doi: 10.1038/nature21357

がん:B細胞でのホスファチジルイノシトール 3-キナーゼδの遮断はゲノム不安定性を上昇させる

Phosphatidylinositol 3-kinase δ blockade increases genomic instability in B cells p.489

Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglobulin genes to initiate class switch recombination and somatic hypermutation. In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. AID expression is tightly regulated in B cells and its overexpression leads to enhanced genomic instability and lymphoma formation. The phosphatidylinositol 3-kinase δ (PI3Kδ) pathway regulates AID by suppressing its expression in B cells. Drugs for leukaemia or lymphoma therapy such as idelalisib, duvelisib and ibrutinib block PI3Kδ activity directly or indirectly, potentially affecting AID expression and, consequently, genomic stability in B cells. Here we show that treatment of primary mouse B cells with idelalisib or duvelisib, and to a lesser extent ibrutinib, enhanced the expression of AID and increased somatic hypermutation and chromosomal translocation frequency to the Igh locus and to several AID off-target sites. Both of these effects were completely abrogated in AID-deficient B cells. PI3Kδ inhibitors or ibrutinib increased the formation of AID-dependent tumours in pristane-treated mice. Consistently, PI3Kδ inhibitors enhanced AID expression and translocation frequency to IGH and AID off-target sites in human chronic lymphocytic leukaemia and mantle cell lymphoma cell lines, and patients treated with idelalisib, but not ibrutinib, showed increased somatic hypermutation in AID off-targets. In summary, we show that PI3Kδ or Bruton’s tyrosine kinase inhibitors increase genomic instability in normal and neoplastic B cells by an AID-dependent mechanism. This effect should be carefully considered, as such inhibitors can be administered to patients for years.

doi: 10.1038/nature21406

分子生物学:機能的に相互依存する活性による同一部位の編集とメチル化

Editing and methylation at a single site by functionally interdependent activities p.494

The C-to-U deamination at position 32 of tRNAThr in Trypanosoma brucei requires two enzymatic activities and proceeds via formation of a 3-methylcytosine intermediate, supporting the notion of a coupled modification system.

doi: 10.1038/nature21396

細胞生物学:有糸分裂チェックポイント複合体の触媒反応的な速い会合の基盤

Basis of catalytic assembly of the mitotic checkpoint complex p.498

The near-complete in vitro reconstitution of the mitotic spindle assembly checkpoint reveals how the assembly of its effector, the mitotic checkpoint complex, is catalysed.

doi: 10.1038/nature21384

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