目次

Editorials

英国のEU離脱の是非を問う国民投票の結果は、世界にさまざまな影響を及ぼすだろう。

Turning point p.295

The result of next week’s crucial UK referendum on whether or not to remain in the European Union will have worldwide repercussions.

doi: 10.1038/534295a

Natureでは、研究をより分かりやすく伝える試みとして、著者による2ページの論文要約を実験的に掲載するので、感想を寄せてほしい。

Nature distilled p.296

We need your views on an experiment to convey the latest research in digestible form.

doi: 10.1038/534296b

海洋科学への人々の関心は、伝え方によってより大きなものへと変わるはずだ。

Under the sea p.296

If life in the oceans is to be preserved, people must get to know the wonders of the deep.

doi: 10.1038/534296a

News

ペットに対しても、抗体療法や細胞療法などを行う時代に。

Stem cells for Snoopy: pet medicines spark a biotech boom p.303

Firms chase a new breed of advanced veterinary care, from antibodies to cell therapies.

doi: 10.1038/534303a

フランスの大規模な隕石追跡プロジェクトFRIPONが、始動。

France launches massive meteor-spotting network p.304

Tracking space rocks that reach Earth will give insight into the early Solar System.

doi: 10.1038/nature.2016.20070

遺伝子治療をめぐり、巨額の費用を誰が負担するかという難しい問題が。

Promising gene therapies pose million-dollar conundrum p.305

Economists, investors and medical insurers can’t figure out how to pay for cutting-edge drugs.

doi: 10.1038/534305a

英国のEU離脱をめぐる国民投票を控え、EUがヨーロッパの科学にどう役立ってきたかを検証する。

Boon or burden: what has the EU ever done for science? p.307

More than 500 million people and 28 nations make up the European Union. It will lose one of its richest, most populous members, if the United Kingdom votes to leave on 23 June. Ahead of a possible ‘Brexit’, Nature examines five core ways that the EU shapes the course of research.

doi: 10.1038/534307a

News Features

幹細胞:iPS細胞の10年

How iPS cells changed the world p.310

医学に変革をもたらすと思われた誘導多能性幹(iPS)細胞は、今、生物学分野の研究を大きく変えつつある。

doi: 10.1038/534310a

ビジネス:古い薬に新たな効能を

Can you teach old drugs new tricks? p.314

新薬開発のコストが高騰する中、既存薬や治験初期に脱落した化合物を別の疾患に利用できないか検討する動きが強まっている。

doi: 10.1038/534314a

News & Views

ゲノミクス:花のゲノムが物語ること

Genomics: The language of flowers p.328

園芸種のペチュニアの親に当たる2つの野生種の完全なDNA塩基配列が解読され、このモデル植物に関する有用な遺伝的知見が得られた。この結果は他の栽培作物の最適化にも活用できそうだ。

doi: 10.1038/nature18445

免疫療法:抗ウイルス型の防御を誘導するがんワクチン

Immunotherapy: Cancer vaccine triggers antiviral-type defences p.329

ナノ粒子を免疫系の樹状細胞を標的として送達し、抗ウイルス応答に似た性質を持つ抗腫瘍免疫応答を誘導するという免疫療法が開発された。この手法を使った初期の臨床試験では有望な結果が得られている。

doi: 10.1038/nature18443

計算材料科学:特性のピンポイント予想

Computational materials science: Predictions of pinning p.331

電場中での強誘電性材料の挙動を正確に予測できるマルチスケールモデルが作られた。これはセンサーやデジタルメモリーのようなデバイスを設計する試みに役立つと考えられる。

doi: 10.1038/534331a

細胞の再プログラム化:脳か筋肉か

Cell reprogramming: Brain versus brawn p.332

成熟細胞の系譜を強制変更する際の基盤となる機序はよく分かっていない。ニューロンになるように誘導された1個の皮膚細胞のプロファイリングから、こうした細胞は筋肉細胞になることが多いという予想外の結果が明らかになった。

doi: 10.1038/nature18444

Articles

幹細胞:幹細胞機能とストレス応答はタンパク質合成によって制御される

Stem cell function and stress response are controlled by protein synthesis p.335

The protein translation rate is low in tissue stem cells and tumour-initiating cells, and genetically preventing cytosine-5 methylation on transfer RNA in skin tumours is shown to favour the maintenance of a state of translational inhibition in mice, with tumour-initiating cells in this state becoming more sensitive to cytotoxic stress.

doi: 10.1038/nature18282

がん:p53とc-MYCの両者を標的とすることで白血病幹細胞が選択的に除去される

Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells p.341

Leukaemic stem cells (LSCs) are responsible for BCR–ABL-driven chronic myeloid leukaemia relapse; here, p53 and MYC signalling networks are shown to regulate LSCs concurrently, and targeting both these pathways has a synergistic effect in managing the disease.

doi: 10.1038/nature18288

構造生物学:ナノディスク中のTRPV1構造から明らかになったリガンドと脂質の作用機構

TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action p.347

Cryo-electron microscopy has undergone a resolution revolution—here, this method has been combined with lipid nanodisc technology to solve structures of TRPV1, the receptor for capsaicin, in a membrane bilayer, revealing mechanisms of lipid and ligand regulation.

doi: 10.1038/nature17964

Letters

地形学:67P/チュリュモフ・ゲラシメンコ彗星によって明らかにされる馬蹄形状の彗星の分裂と再構成

Fission and reconfiguration of bilobate comets as revealed by 67P/Churyumov–Gerasimenko p.352

A modelling study of the bilobate nucleus of comet 67P/Churyumov–Gerasimenko reveals that it has spun much faster in the past, but that its chaotically changing spin rate has so far prevented it from splitting; eventually the two lobes will separate, but they will be unable to escape each other and will ultimately merge again—a situation that seems to be common among cometary nuclei.

doi: 10.1038/nature17670

統計物理学:閉じ込め中の非マルコフ酔歩者の平均初到達時間

Mean first-passage times of non-Markovian random walkers in confinement p.356

An analytical method of determining the mean first-passage time (the time taken by a random walker in confinement to reach a target point) is presented for a Gaussian non-Markovian random walker, thus revealing the importance of memory effects in first-passage statistics.

doi: 10.1038/nature18272

材料科学:第一原理による固有強誘電スイッチング

Intrinsic ferroelectric switching from first principles p.360

Molecular dynamics simulations of 90° domain walls in PbTiO3 are used to construct a nucleation-and-growth-based analytical model that quantifies the dynamics of many types of domain walls in various ferroelectrics, suggesting intrinsic domain-wall motion as a universal mechanism for ferroelectric switching.

doi: 10.1038/nature18286

材料科学:コロイド結合の混成と異方性を介したマイクロカプセルの自己集合

Self-assembly of microcapsules via colloidal bond hybridization and anisotropy p.364

The self-assembly of colloidal particles into hollow micrometre-scale capsules is achieved through the combination of anisotropic particle morphology, deformable surface ligands that re-distribute on binding and the mutual attraction between particles, suggesting a design strategy for colloidal self-assembly

doi: 10.1038/nature17956

有機化学:19Fおよび18Fによる協奏的求核芳香族置換

Concerted nucleophilic aromatic substitution with 19F and 18F p.369

Nucleophilic aromatic substitution (SNAr) is widely used by organic chemists to functionalize aromatic molecules, and it is the most commonly used method to generate arenes that contain 18F for use in positron-emission tomography (PET) imaging. A wide range of nucleophiles exhibit SNAr reactivity, and the operational simplicity of the reaction means that the transformation can be conducted reliably and on large scales. During SNAr, attack of a nucleophile at a carbon atom bearing a ‘leaving group’ leads to a negatively charged intermediate called a Meisenheimer complex. Only arenes with electron-withdrawing substituents can sufficiently stabilize the resulting build-up of negative charge during Meisenheimer complex formation, limiting the scope of SNAr reactions: the most common SNAr substrates contain strong π-acceptors in the ortho and/or para position(s). Here we present an unusual concerted nucleophilic aromatic substitution reaction (CSNAr) that is not limited to electron-poor arenes, because it does not proceed via a Meisenheimer intermediate. We show a phenol deoxyfluorination reaction for which CSNAr is favoured over a stepwise displacement. Mechanistic insights enabled us to develop a functional-group-tolerant 18F-deoxyfluorination reaction of phenols, which can be used to synthesize 18F-PET probes. Selective 18F introduction, without the need for the common, but cumbersome, azeotropic drying of 18F, can now be accomplished from phenols as starting materials, and provides access to 18F-labelled compounds not accessible through conventional chemistry.

doi: 10.1038/nature17667

テクトニクス:南海トラフ巨大地震震源域のプレート間固着に関する海底測地による絞り込み

Seafloor geodetic constraints on interplate coupling of the Nankai Trough megathrust zone p.374

Seafloor geodetic data from the Nankai Trough, off southwestern Japan, show that most offshore sites in this earthquake-prone region have high slip-deficit rates, revealing previously unknown locations that could be important for the mitigation of future earthquake- and tsunami-associated disasters.

doi: 10.1038/nature17632

神経科学:in vivoでの単一血管の血行動態応答の神経相関

Neural correlates of single-vessel haemodynamic responses in vivo p.378

Functional imaging techniques use changes in blood flow to infer neural activity, but how strongly the two are correlated is a subject of debate; here, vascular and neural responses to a range of visual stimuli are imaged in cat and rat primary visual cortex, revealing that vascular signals are partially decoupled from local neural signals.

doi: 10.1038/nature17965

発生学:ミトコンドリアDNA病を防ぐための前核移植の臨床応用に向けて

Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease p.383

Preclinical evaluation and optimization of mitochondrial replacement therapy reveals that a modified form of pronuclear transfer is likely to give rise to normal pregnancies with a reduced risk of mitochondrial DNA disease, but may need further modification to eradicate the disease in all cases.

doi: 10.1038/nature18303

幹細胞:コリプレッサーCBFA2T2は多能性と生殖系列の発生を調節する

Co-repressor CBFA2T2 regulates pluripotency and germline development p.387

A co-repressor protein, CBFA2T2, oligomerizes to stabilize its binding partner PRDM14 and the pluripotency factor OCT4 on chromatin, thus facilitating the transcriptional landscape underpinning the germline and pluripotent fate.

doi: 10.1038/nature18004

幹細胞:単一細胞RNA-seqを用いた繊維芽細胞からニューロンへの直接的再プログラム化の分析

Dissecting direct reprogramming from fibroblast to neuron using single-cell RNA-seq p.391

The transcriptome changes driving the conversion of fibroblasts to neurons at the single-cell level are reported, revealing that early neuronal reprogramming steps are homogenous, driven by the proneural pioneer factor Ascl1; the expression of myogenic genes then has a dampening effect on efficiency, which needs to be counteracted by the neuronal factors Myt1l and Brn2 for more efficient reprogramming.

doi: 10.1038/nature18323

がん免疫学:樹状細胞への全身的RNA送達は抗ウイルス防御を利用したがん免疫療法である

Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy p.396

The development of a nanoparticle RNA vaccine is reported that preferentially targets dendritic cells after systemic administration, and is shown to provide durable interferon-α-dependent antigen-specific immunity in mouse tumour models; initial results in advanced melanoma patients indicate potential efficacy in humans.

doi: 10.1038/nature18300

がん免疫学:多様ながん種においてPD-L1遺伝子の過剰発現を誘導する3′-UTRの構造異常

Aberrant PD-L1 expression through 3′-UTR disruption in multiple cancers p.402

Successful treatment of many patients with advanced cancer using antibodies against programmed cell death 1 (PD-1; also known as PDCD1) and its ligand (PD-L1; also known as CD274) has highlighted the critical importance of PD-1/PD-L1-mediated immune escape in cancer development. However, the genetic basis for the immune escape has not been fully elucidated, with the exception of elevated PD-L1 expression by gene amplification and utilization of an ectopic promoter by translocation, as reported in Hodgkin and other B-cell lymphomas, as well as stomach adenocarcinoma. Here we show a unique genetic mechanism of immune escape caused by structural variations (SVs) commonly disrupting the 3′ region of the PD-L1 gene. Widely affecting multiple common human cancer types, including adult T-cell leukaemia/lymphoma (27%), diffuse large B-cell lymphoma (8%), and stomach adenocarcinoma (2%), these SVs invariably lead to a marked elevation of aberrant PD-L1 transcripts that are stabilized by truncation of the 3′-untranslated region (UTR). Disruption of the Pd-l1 3′-UTR in mice enables immune evasion of EG7-OVA tumour cells with elevated Pd-l1 expression in vivo, which is effectively inhibited by Pd-1/Pd-l1 blockade, supporting the role of relevant SVs in clonal selection through immune evasion. Our findings not only unmask a novel regulatory mechanism of PD-L1 expression, but also suggest that PD-L1 3′-UTR disruption could serve as a genetic marker to identify cancers that actively evade anti-tumour immunity through PD-L1 overexpression.

doi: 10.1038/nature18294

がん:膵臓腺がんの画像を利用した検出と抵抗性に対抗する治療標的

Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma p.407

The stem cell determinant Musashi (Msi) is a key mediator of pancreatic cancer progression and therapy resistance.

doi: 10.1038/nature17988

分子生物学:細菌の複製起点エレメントDnaA-trioはイニシエーターの一本鎖DNAへの結合を確実にする

The bacterial DnaA-trio replication origin element specifies single-stranded DNA initiator binding p.412

The bacterial chromosome replication origin contains an indispensable element composed of a repeating trinucleotide motif, termed the DnaA-trio, that stabilizes DnaA binding on single-stranded DNA.

doi: 10.1038/nature17962

構造生物学:DMTスーパーファミリーの輸送体YddGによるアミノ酸排出の構造基盤

Structural basis for amino acid export by DMT superfamily transporter YddG p.417

The X-ray structure of the drug/metabolite transporter (DMT) protein YddG from Starkeya novella reveals a new membrane transport topology, with ten transmembrane segments in an outward-facing state and two pseudo-symmetric inverted structural repeats.

doi: 10.1038/nature17991

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