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Editorials

米国政府は、北西部太平洋沿岸の大規模地震に対し、安全対策を整えるべきだ。

Protect funding for US earthquake early-warning system p.451

Donald Trump’s proposed cuts to ShakeAlert puts the west coast at risk.

doi: 10.1038/nature.2017.22162

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欧州委員会が推し進める「欧州オープンサイエンスクラウド」は素晴らしい計画であり、停滞させることなく進めなければならない。

Don’t let Europe’s open-science dream drift p.451

Now that the major players have agreed to the giant European Open Science Cloud, it’s time to get the project moving.

doi: 10.1038/546451a

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温暖化に伴う環境変化は現実に起きており、このまま策を講じなければ、将来の環境は脅威でしかなくなるだろう。

Heatwaves to soar above the hot air of climate politics p.452

Future generations will fear, rather than fend for, the global environment.

doi: 10.1038/546452a

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News

フランスの総選挙でマクロン新党が圧勝したことに対し、フランス国内外の科学者から歓迎の声が。

Macron consolidates electoral victory p.459

The party of France’s recently elected president won an absolute majority in its first general elections, with an agenda that included strong support for research.

doi: 10.1038/549459a

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樹齢234年の有名な古木「ナポレオン・オーク」のゲノム塩基配列解読により、この木では変異が驚くほど少ないことが明らかに。

Ancient oak's youthful genome surprises biologists p.460

DNA of 234-year-old tree has few mutations, giving weight to idea that plants protect their stem cells.

doi: 10.1038/546460a

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ゲノム塩基配列解析で有名な中国企業のBGIが上場し、プレシジョン・メディシン領域に参入を。

China’s genomics giant to make stock-market debut p.461

Once the world's biggest DNA sequencer for research, BGI is now looking to medical applications to boost profits.

doi: 10.1038/546461

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古代のカバの歯の化石から、カバがアフリカ全土に急激に広がった理由の手掛かりが。

Teeth tell tale of hippo’s quick spread across Africa p.462

Fossils from ancient hippo ancestor suggest that grass helped the animals to conquer a continent.

doi: 10.1038/nature.2017.22168

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ゲノム規模関連研究が、病気に関わる重要遺伝子の解明に本当に役立つか、疑問の声も。

New concerns raised over value of genome-wide disease studies p.463

Large analyses dredge up 'peripheral' genetic associations that offer little biological insight, researchers say.

doi: 10.1038/nature.2017.22152

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中国が、論文査読の不正に厳罰を定める方針を。

China cracks down on fake peer reviews p.464

Funding agencies announce harsh penalties and stronger policing efforts.

doi: 10.1038/546464a

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News Features

地球科学:地震探査

The fight to save thousands of lives with sea-floor sensors p.466

Jerry Parosが設立したParoscientific社は、巨大地震の前兆となる小さな変化を捉えることができる精密な海底センサー網の作成に長年取り組んできた。

doi: 10.1038/546466a

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News & Views

視覚:運動のために働く網膜細胞

Vision: These retinas are made for walkin' p.476

今回、マウスの網膜にある運動方向選択性神経節細胞と呼ばれるニューロンの活動を測定することによって、眼によって符号化された視覚的運動が、歩行などの体の動きをマッピングする仕組みが説明された。

doi: 10.1038/nature22505

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素粒子物理学:強い力の非対称性を示す証拠はない

Particle physics: No sign of asymmetry in the strong force p.477

強い力は、原子核の構成要素を結合している。力の基本相互作用とそれらの鏡像の違いが、重イオン衝突で観測されたと考えられていたが、新しいデータはこの見方に異議を唱えている。

doi: 10.1038/nature23086

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病原性細菌:スプーン1杯の糖が治療薬になる可能性

Bacterial pathogens: A spoonful of sugar could be the medicine p.479

線毛は、細菌表面にある繊維状構造で、宿主細胞への付着に用いられる。この付着を妨げる小分子によって、マウスで病原性細菌の腸内定着を防げることが、今回分かった。

doi: 10.1038/nature23084

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ゲノミクス:ネコのゲノム

Genomics: The feline line p.480

エジプトのネコのミイラや現代のヤマネコに由来する試料を含む、200を超えるさまざまなネコの標本から得られたサンプルのDNA解析によって、ネコの進化と世界的広がりに関する知見が得られた。

doi: 10.1038/546480a

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量子物理学:相互作用が磁気のダンスを生む

Quantum physics: Interactions propel a magnetic dance p.481

今回、最先端の技術を組み合わせて、極低温原子対の相互作用によって生じる磁気運動を観測できるようになった。これは、複雑な量子挙動のモデルの開発における大きな進歩である。

doi: 10.1038/546481a

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神経炎症:ループスにおけるシナプスの剪定

Neuroinflammation: Synapses pruned in lupus p.482

ループスは、脳機能障害を生じ得る自己免疫疾患である。今回、ループスのマウスモデルの研究から、インターフェロンタンパク質によって、脳の免疫細胞がニューロン間のシナプス結合を剪定するようになることが分かった。

doi: 10.1038/nature23087

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気候科学:雲はエアロゾルに屈しない

Climate science: Clouds unfazed by haze p.483

エアロゾルが気候にどの程度の影響を及ぼすかは、極めて不確かである。今回、火山噴火で生じたエアロゾルと相互作用する雲の観測結果から、その影響は、これまで懸念されていたよりずっと小さいことが示された。

doi: 10.1038/546483a

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Articles

気候科学:火山噴火に起因するエアロゾルと雲の相互作用に関する強い制約条件

Strong constraints on aerosol–cloud interactions from volcanic eruptions p.485

Investigations of an Icelandic volcanic eruption confirm that sulfate aerosols caused a discernible yet transient brightening effect, as predicted, but their effect on the liquid water path was unexpectedly negligible.

doi: 10.1038/nature22974

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視覚:重力軸と体軸に沿った運動の網膜での符号化

A retinal code for motion along the gravitational and body axes p.492

Global mapping shows that mouse retinal neurons prefer visual motion produced when the animal moves along two behaviourally relevant axes, allowing the encoding of the animal’s every translation and rotation.

doi: 10.1038/nature22818

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がん:エキソソームは膵臓がんで発がん性KRASの治療標的化を促進する

Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer p.498

Exosomes improve the delivery of siRNA to mutant KRAS in the pancreatic tumours and bypass immune clearance better than artificial liposomes, probably owing to enhanced macropinocytocis and presence of CD47 on exosomes, respectively.

doi: 10.1038/nature22341

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構造生物学:ヒト多剤輸送体ABCG2の構造

Structure of the human multidrug transporter ABCG2 p.504

The structure of human ABCG2 bound to an inhibitory antibody using cryo-electron microscopy, representing the first high-resolution structural data of a human multidrug transporter.

doi: 10.1038/nature22345

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Letters

天文学:初期宇宙において活動をやめた大質量の円盤銀河

A massive, dead disk galaxy in the early Universe p.510

When the Universe was just 3 billion years old, half of the most massive galaxies had already ceased star formation, and such a galaxy has now been observed using gravitational lensing, unexpectedly turning out to be a compact, fast-spinning disk galaxy rather than a proto-bulge galaxy.

doi: 10.1038/nature22388

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天文学:大質量高温中心星からの極端紫外線照射を受けている巨大惑星

A giant planet undergoing extreme-ultraviolet irradiation by its hot massive-star host p.514

The giant planet KELT-9b has a dayside temperature of about 4,600 K, which is sufficiently high to dissociate molecules and to evaporate its atmosphere, owing to its hot stellar host.

doi: 10.1038/nature22392

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量子物理学:二体極限におけるハーパー・ホフスタッター相互作用モデルの顕微鏡観察

Microscopy of the interacting Harper–Hofstadter model in the two-body limit p.519

The combination of interparticle interactions and a synthetic gauge field leads to chirality in the propagation dynamics of particles in a ladder-like lattice.

doi: 10.1038/nature22811

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植物科学:単一分子技術によって改良されたトウモロコシの参照ゲノム

Improved maize reference genome with single-molecule technologies OPEN p.524

An improved reference genome for maize, using single-molecule sequencing and high-resolution optical mapping, enables characterization of structural variation and repetitive regions, and identifies lineage expansions of transposable elements that are unique to maize.

doi: 10.1038/nature22971

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病原性細菌:FimHアンタゴニストによる腸内の尿路病原性大腸菌の選択的除去

Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist p.528

Both F17-like and type 1 pili promote intestinal colonization in mouse colonic crypts, and the high-affinity mannoside M4284 reduces intestinal colonization of uropathogenic Escherichia coli while simultaneously treating urinary tract infections without disrupting the composition of the gut microbiota.

doi: 10.1038/nature22972

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発生生物学:多細胞系譜間の相互作用が多能性状態からのヒト肝芽発生を調節する

Multilineage communication regulates human liver bud development from pluripotency p.533

Single-cell RNA sequencing analysis of two- and three-dimensional hepatic differentiation reveals that both systems recapitulate certain transcriptomic features of human hepatogenesis.

doi: 10.1038/nature22796

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神経炎症:I型インターフェロンが介在するループスにおけるミクログリア依存的なシナプス消失

Microglia-dependent synapse loss in type I interferon-mediated lupus p.539

Abnormal behavioural phenotypes and synapse loss in the brain of lupus-prone mice are prevented by blocking type I interferon signalling, which is further shown to stimulate microglial phagocytosis of neuronal material in the brains of these mice.

doi: 10.1038/nature22821

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分子生物学:ヒストンデアセチラーゼ3は急な熱産生誘発に対して褐色脂肪組織に準備をさせる

Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge p.544

Histone deacetylase 3 (HDAC3) is required to activate brown adipose tissue enhancers to ensure thermogenic aptitude.

doi: 10.1038/nature22819

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がん:BAP1は、ミトコンドリアへのIP3R3を介したCa2+流入量を調節して細胞の形質転換を抑制する

BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation p.549

BRCA1-associated protein 1 (BAP1) is a potent tumour suppressor gene that modulates environmental carcinogenesis1–3. All carriers of inherited heterozygous germline BAP1-inactivating mutations (BAP1+/-) developed one and often several BAP1-/- malignancies in their lifetime4, mostly malignant mesothelioma, uveal melanoma2,5, and so on6–10. Moreover, BAP1-acquired biallelic mutations are frequent in human cancers8,11–14. BAP1 tumour suppressor activity has been attributed to its nuclear localization, where it helps to maintain genome integrity15–17. The possible activity of BAP1 in the cytoplasm is unknown. Cells with reduced levels of BAP1 exhibit chromosomal abnormalities and decreased DNA repair by homologous recombination18, indicating that BAP1 dosage is critical. Cells with extensive DNA damage should die and not grow into malignancies. Here we discover that BAP1 localizes at the endoplasmic reticulum. Here, it binds, deubiquitylates, and stabilizes type 3 inositol-1,4,5-trisphosphate receptor (IP3R3), modulating calcium (Ca2+) release from the endoplasmic reticulum into the cytosol and mitochondria, promoting apoptosis. Reduced levels of BAP1 in BAP1+/- carriers cause reduction both of IP3R3 levels and of Ca2+ flux, preventing BAP1+/- cells that accumulate DNA damage from executing apoptosis. A higher fraction of cells exposed to either ionizing or ultraviolet radiation, or to asbestos, survive genotoxic stress, resulting in a higher rate of cellular transformation. We propose that the high incidence of cancers in BAP1+/- carriers results from the combined reduced nuclear and cytoplasmic activities of BAP1. Our data provide a mechanistic rationale for the powerful ability of BAP1 to regulate gene–environment interaction in human carcinogenesis.

doi: 10.1038/nature22798

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がん:PTENはFBXL2に対抗してIP3R3とCa2+が仲介するアポトーシスを促進し、腫瘍増殖を制限する

PTEN counteracts FBXL2 to promote IP3R3- and Ca2+-mediated apoptosis limiting tumour growth p.554

In response to environmental cues that promote IP3 (inositol 1,4,5-trisphosphate) generation, IP3 receptors (IP3Rs) located on the endoplasmic reticulum allow the ‘quasisynaptical’ feeding of calcium to the mitochondria to promote oxidative phosphorylation. However, persistent Ca2+ release results in mitochondrial Ca2+ overload and consequent apoptosis. Among the three mammalian IP3Rs, IP3R3 appears to be the major player in Ca2+-dependent apoptosis. Here we show that the F-box protein FBXL2 (the receptor subunit of one of 69 human SCF (SKP1, CUL1, F-box protein) ubiquitin ligase complexes) binds IP3R3 and targets it for ubiquitin-, p97- and proteasome-mediated degradation to limit Ca2+ influx into mitochondria. FBXL2-knockdown cells and FBXL2-insensitive IP3R3 mutant knock-in clones display increased cytosolic Ca2+ release from the endoplasmic reticulum and sensitization to Ca2+-dependent apoptotic stimuli. The phosphatase and tensin homologue (PTEN) gene is frequently mutated or lost in human tumours and syndromes that predispose individuals to cancer. We found that PTEN competes with FBXL2 for IP3R3 binding, and the FBXL2-dependent degradation of IP3R3 is accelerated in Pten/ mouse embryonic fibroblasts and PTEN-null cancer cells. Reconstitution of PTEN-null cells with either wild-type PTEN or a catalytically dead mutant stabilizes IP3R3 and induces persistent Ca2+ mobilization and apoptosis. IP3R3 and PTEN protein levels directly correlate in human prostate cancer. Both in cell culture and xenograft models, a non-degradable IP3R3 mutant sensitizes tumour cells with low or no PTEN expression to photodynamic therapy, which is based on the ability of photosensitizer drugs to cause Ca2+-dependent cytotoxicity after irradiation with visible light. Similarly, disruption of FBXL2 localization with GGTi-2418, a geranylgeranyl transferase inhibitor, sensitizes xenotransplanted tumours to photodynamic therapy. In summary, we identify a novel molecular mechanism that limits mitochondrial Ca2+ overload to prevent cell death. Notably, we provide proof-of-principle that inhibiting IP3R3 degradation in PTEN-deregulated cancers represents a valid therapeutic strategy.

doi: 10.1038/nature22965

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構造生物学:標的DNA切断後に形成されたCpf1エンドヌクレアーゼ–Rループ複合体の構造

Structure of the Cpf1 endonuclease R-loop complex after target DNA cleavage p.559

The structure of Cpf1, a CRISPR–Cas/RNA-guided nuclease, is presented with a three-stranded RNA–DNA loop after cleavage, providing insight into its working mechanism.

doi: 10.1038/nature22398

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