1. Nature Japan
  2. Nature
  3. v531 n7596

Volume 531 Number 7596

Nature 目次の表紙

2016年3月31日

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Editorials

多くのデジタル企業がインターネット上での有害な言動への対策に取り組んでおり、ネット市民の協力があれば、より使いやすく有益なネット空間につながるだろう。

Play nicely p.549

Attempts by digital companies to curb unpleasant behaviour online could make the Internet a more welcoming and useful space.

doi: 10.1038/531549a

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サマータイムのような時刻の人為的な変更は、恩恵よりも害が大きい恐れがある。

Time out p.549

Artificial fixes to make the most of summer time may do more harm than good.

doi: 10.1038/531549b

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心理学は、肥満や嗜癖などを引き起こすこともあるが、その解決につながる可能性もある。

Honey trap p.550

Psychology drives some overindulgence — and it could help us to resist.

doi: 10.1038/531550a

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News

米国の合成生物学者クレイグ・ベンターが人工の「最小ゲノム細胞」の作製を発表し、生命の設計に向けた競争が白熱を。

‘Minimal’ cell raises stakes in race to harness synthetic life p.557

Craig Venter’s creation comes as CRISPR gene-editing methods provide alternative ways to tinker with life’s building blocks.

doi: 10.1038/531557a

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Natureによる調査で、EUの科学者の大半が英国のEU脱退に反対との結果が。

Scientists say ‘no’ to UK exit from Europe in Nature poll p.559

Most researchers in Britain and the wider EU think that the union benefits science.

doi: 10.1038/531559a

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米国立衛生研究所（NIH）が、青年期のトランスジェンダーへの薬剤投与の影響について、長期追跡研究を。

Largest ever study of transgender teenagers kicks off p.560

Scientists will track psychological and medical outcomes of controversial treatments to help transgender adolescents transition.

doi: 10.1038/531560a

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全米科学財団（NSF）の助成凍結で、標本、試料などの生物学的収集物の維持に悪影響が。

Biological specimen troves threatened by funding pause p.561

Decision by US National Science Foundation could hamper research on conservation biology, climate change and invasive species.

doi: 10.1038/nature.2016.19599

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温室効果ガス排出が現状のペースで今後数十年増え続けると、南極の氷床崩壊が止められなくなる恐れが。

Antarctic model raises prospect of unstoppable ice collapse p.562

Sea levels could rise by more than 15 metres by 2500 if greenhouse-gas emissions continue to grow.

doi: 10.1038/531562a

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News Features

物理学：大型放射光発生施設の24時間

24 hours at the X-ray factory p.564

昼夜を分かたず働き続ける欧州シンクロトロン放射光研究所（ESRF）の1日を追う。

doi: 10.1038/531564a

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心理学：オンラインゲームでのマナー

Can a video game company tame toxic behaviour? p.568

プレーヤーの有害な言動を防ごうと、世界で最も人気の高いオンラインゲームで、科学者の助けを借りた取り組みが行われている。

doi: 10.1038/531568a

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News & Views

フォーラム：細胞生物学：繊毛でのカルシウムの働きについての反論

Cell biology: Calcium contradictions in cilia p.582

一次繊毛と呼ばれる、細胞から突き出た細胞小器官は、加えられた力に応答するカルシウムチャネルタンパク質を介して周囲環境を感知すると考えられてきた。この仮説に疑問を投げ掛けた研究が発生生物学と腎臓疾患研究に及ぼす影響を、2人の研究者が論じている。

doi: 10.1038/nature17313

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がん免疫療法：ステロールに乗った殺し屋細胞

Cancer immunotherapy: Killers on sterols p.583

マウスでキラーT細胞の細胞膜中のコレステロール濃度を上昇させてやると、この細胞の腫瘍細胞に対する免疫応答活性が増強されることが分かった。こうした戦略は抗がん免疫療法で有用となりそうだ。

doi: 10.1038/nature17310

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応用物理学：オンチップ重力測定

Applied physics: Gravity measurements on chips p.585

重力計は石油探査から地下トンネルの探知まで応用範囲が広いが、そのサイズと可搬性がないことが野外での使用を制限してきた。今回、郵便切手ほどの大きさの重力計が開発され、新しい使い道が生まれることが期待されている。

doi: 10.1038/531585a

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呼吸器疾患：喫煙に関連する気道疾患を鉄除去により回復させる

Respiratory disorders: Ironing out smoking-related airway disease p.586

ミトコンドリアと呼ばれる細胞小器官はタバコの煙に曝露されると有毒となるレベルの鉄を蓄積するようになるが、マウスでIRP2タンパク質を欠失させるとこのような蓄積が防止されることが分かった。この知見は、慢性肺疾患について環境内リスク因子と遺伝的リスク因子を結び付けるものである。

doi: 10.1038/nature17309

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物理化学：連動している分子のクローズアップ

Physical chemistry: A close-up view of coupled molecules p.587

光合成などの過程は、発色団分子の電気双極子間の相互作用に依存している。このような双極子間の相互作用は原子レベルで可視化されたことがまだなかったが、今回初めて画像化に成功した。

doi: 10.1038/531587a

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神経科学：冒険好きを落ち着かせる

Neuroscience: Making risk-takers settle p.588

リスクの選好性や損失に対する利得の感度には個体ごとにばらつきがある。今回ラットで、こうしたばらつきが特定の神経集団によって制御されていて、この神経集団を刺激するとリスクを求める行動が抑えられることが明らかになった。

doi: 10.1038/nature17314

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Articles

気候科学：過去と未来の海水準上昇に対する南極大陸の寄与

Contribution of Antarctica to past and future sea-level rise p.591

Climate and ice-sheet modelling that includes ice fracture dynamics reveals that Antarctica could contribute more than a metre of sea-level rise by 2100 and more than 15 metres by 2500, if greenhouse gas emissions continue unabated.

doi: 10.1038/nature17145

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細胞生物学：COP9シグナロソームによるcullin–RING型ユビキチンE3リガーゼの調節

Cullin–RING ubiquitin E3 ligase regulation by the COP9 signalosome p.598

Much of the intracellular protein degradation in eukaryotes is controlled by cullin–RING ubiquitin ligases (CRLs), a vast class of enzymes which are regulated by the COP9 signalosome (CSN); structural characterization of CSN–N8CRL4A complexes by cryo-electron microscopy reveals an induced-fit mechanism of CSN activation triggered only by catalytically activated CRLs without bound substrate, explaining how CSN acts as a global regulator of CRLs.

doi: 10.1038/nature17416

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構造生物学：プロモーターに結合したTFIIDの構造とヒト転写開始前複合体組み立てのモデル

Structure of promoter-bound TFIID and model of human pre-initiation complex assembly p.604

A sub-nanometre resolution cryo-EM structure of human TFIID bound to TFIIA and core promoter DNA and a model of the TFIID-based pre-initiation complex.

doi: 10.1038/nature17394

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Letters

宇宙物理学：年老いた矮小銀河における単一現象に由来するr過程による濃集

R-process enrichment from a single event in an ancient dwarf galaxy p.610

It has long been debated whether elements heavier than zinc are formed continually, for example in core-collapse supernovae, or in rare events, such as neutron star mergers; here, studies of element abundances in a local ultrafaint dwarf galaxy provide evidence that these elements are formed during rare yet prolific stellar events.

doi: 10.1038/nature17425

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固体地球科学：MEMS重力計による地球潮汐の測定

Measurement of the Earth tides with a MEMS gravimeter p.614

A light-weight, low-cost microelectromechanical system gravimeter is presented with sensitivity and stability high enough to measure the elastic deformation of the Earth’s crust as a result of tidal forces, enabling many applications.

doi: 10.1038/nature17397

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ナノスケール材料：ナノマテリアルの柔軟な表面が可能にする強いフォノン相互作用

Soft surfaces of nanomaterials enable strong phonon interactions p.618

A combined experimental and theoretical investigation of phononic properties in nanocrystal-based semiconductors reveals that unusually strong coupling between phonons and electrons originates from the mechanical softness of the surfaces of the nanocrystalline domains and sheds new light on charge carrier recombination in nanocrystal-based devices.

doi: 10.1038/nature16977

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光物性：コヒーレントな分子間双極子–双極子カップリングを実空間で可視化する

Visualizing coherent intermolecular dipole–dipole coupling in real space p.623

Luminescence induced by highly localized excitations that are produced by electrons tunnelling from the tip of a scanning tunnelling microscope is used to map the spatial distribution of the excitonic coupling in well-defined arrangements of a few zinc-phthalocyanine molecules and the dependence of this spatial distribution on the relative orientation and phase of the transition dipoles of the individual molecules.

doi: 10.1038/nature17428

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地球化学：コマチアイトが明らかにした水を含む始生代の深部マントル貯蔵庫

Komatiites reveal a hydrous Archaean deep-mantle reservoir p.628

Archaean komatiites are shown to originate in hot mantle plumes that entrained hydrous material from deep in the mantle.

doi: 10.1038/nature17152

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気候変動生態学：北方帯および温帯の高木は呼吸において温暖化への強い順化を示す

Boreal and temperate trees show strong acclimation of respiration to warming p.633

Acclimation of leaf respiration to a 3–5-year period of warming by 3.4 °C for 10 North American tree species in forest conditions eliminated 80% of the increase in leaf respiration expected of non-acclimated trees; this suggests that the increase in respiration rates of terrestrial plants from climate warming, and the associated increase in atmospheric CO2 levels, may be less than anticipated.

doi: 10.1038/nature17142

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進化生物学：mid-developmental transitionと動物のボディープランの進化

The mid-developmental transition and the evolution of animal body plans p.637

Embryos in a particular phylum of the animal kingdom tend to most resemble one another at a stage in the middle of embryogenesis known as the phylotypic period; a transcriptional analysis of embryogenesis from single embryos of ten different phyla reveals that the transcripts expressed at the phylotypic stage (or mid-developmental transition) differ greatly between phyla, and a ‘phylum’ may be defined as a set of species sharing the same signals and transcription factor networks during the mid-developmental transition.

doi: 10.1038/nature16994

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認知神経科学：側坐核D2Rは以前の結果を符号化して危険な意思決定を制御する

Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making p.642

Increased activity of dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens of rats during a ‘decision’ period reflects a ‘loss’ outcome of the previous decision and predicts a subsequent safe choice; by artificially increasing the activity of D2R neurons during the decision period, risk-seeking rats could be converted to risk-avoiding rats.

doi: 10.1038/nature17400

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内分泌学：視床下部の双方向性電磁制御によって摂食と代謝が調節される

Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism p.647

Activation of glucose-sensing neurons in the ventromedial hypothalamic nucleus using radio waves or magnetic fields remotely and non-invasively in vivo increases plasma glucose and glucagon, and suppresses plasma insulin; conversely, remote inhibition of glucose-sensing neurons decreased blood glucose and increased plasma insulin.

doi: 10.1038/nature17183

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がん免疫療法：コレステロール代謝を調整することでCD8+ T細胞の抗腫瘍応答を増強する

Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism p.651

CD8+ T cells have a central role in antitumour immunity, but their activity is suppressed in the tumour microenvironment. Reactivating the cytotoxicity of CD8+ T cells is of great clinical interest in cancer immunotherapy. Here we report a new mechanism by which the antitumour response of mouse CD8+ T cells can be potentiated by modulating cholesterol metabolism. Inhibiting cholesterol esterification in T cells by genetic ablation or pharmacological inhibition of ACAT1, a key cholesterol esterification enzyme, led to potentiated effector function and enhanced proliferation of CD8+ but not CD4+ T cells. This is due to the increase in the plasma membrane cholesterol level of CD8+ T cells, which causes enhanced T-cell receptor clustering and signalling as well as more efficient formation of the immunological synapse. ACAT1-deficient CD8+ T cells were better than wild-type CD8+ T cells at controlling melanoma growth and metastasis in mice. We used the ACAT inhibitor avasimibe, which was previously tested in clinical trials for treating atherosclerosis and showed a good human safety profile, to treat melanoma in mice and observed a good antitumour effect. A combined therapy of avasimibe plus an anti-PD-1 antibody showed better efficacy than monotherapies in controlling tumour progression. ACAT1, an established target for atherosclerosis, is therefore also a potential target for cancer immunotherapy.

doi: 10.1038/nature17412

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細胞生物学：一次繊毛はカルシウム応答性メカノセンサーではない

Primary cilia are not calcium-responsive mechanosensors p.656

Mechanosensation, if it originates in primary cilia, is not via calcium signalling.

doi: 10.1038/nature17426

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細胞生物学：βアレスチンバイオセンサーにより明らかになった受容体依存性の迅速な活性化/脱活性化サイクル

β-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle p.661

(β-)Arrestins are important regulators of G-protein-coupled receptors (GPCRs). They bind to active, phosphorylated GPCRs and thereby shut off ‘classical’ signalling to G proteins, trigger internalization of GPCRs via interaction with the clathrin machinery and mediate signalling via ‘non-classical’ pathways. In addition to two visual arrestins that bind to rod and cone photoreceptors (termed arrestin1 and arrestin4), there are only two (non-visual) β-arrestin proteins (β-arrestin1 and β-arrestin2, also termed arrestin2 and arrestin3), which regulate hundreds of different (non-visual) GPCRs. Binding of these proteins to GPCRs usually requires the active form of the receptors plus their phosphorylation by G-protein-coupled receptor kinases (GRKs). The binding of receptors or their carboxy terminus as well as certain truncations induce active conformations of (β-)arrestins that have recently been solved by X-ray crystallography. Here we investigate both the interaction of β-arrestin with GPCRs, and the β-arrestin conformational changes in real time and in living human cells, using a series of fluorescence resonance energy transfer (FRET)-based β-arrestin2 biosensors. We observe receptor-specific patterns of conformational changes in β-arrestin2 that occur rapidly after the receptor–β-arrestin2 interaction. After agonist removal, these changes persist for longer than the direct receptor interaction. Our data indicate a rapid, receptor-type-specific, two-step binding and activation process between GPCRs and β-arrestins. They further indicate that β-arrestins remain active after dissociation from receptors, allowing them to remain at the cell surface and presumably signal independently. Thus, GPCRs trigger a rapid, receptor-specific activation/deactivation cycle of β-arrestins, which permits their active signalling.

doi: 10.1038/nature17198

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細胞生物学：βアレスチン2のコンホメーショナルシグネチャーからは転送機能とシグナル伝達機能が予測される

The conformational signature of β-arrestin2 predicts its trafficking and signalling functions p.665

Arrestins are cytosolic proteins that regulate G-protein-coupled receptor (GPCR) desensitization, internalization, trafficking and signalling. Arrestin recruitment uncouples GPCRs from heterotrimeric G proteins, and targets the proteins for internalization via clathrin-coated pits. Arrestins also function as ligand-regulated scaffolds that recruit multiple non-G-protein effectors into GPCR-based ‘signalsomes’. Although the dominant function(s) of arrestins vary between receptors, the mechanism whereby different GPCRs specify these divergent functions is unclear. Using a panel of intramolecular fluorescein arsenical hairpin (FlAsH) bioluminescence resonance energy transfer (BRET) reporters to monitor conformational changes in β-arrestin2, here we show that GPCRs impose distinctive arrestin ‘conformational signatures’ that reflect the stability of the receptor–arrestin complex and role of β-arrestin2 in activating or dampening downstream signalling events. The predictive value of these signatures extends to structurally distinct ligands activating the same GPCR, such that the innate properties of the ligand are reflected as changes in β-arrestin2 conformation. Our findings demonstrate that information about ligand–receptor conformation is encoded within the population average β-arrestin2 conformation, and provide insight into how different GPCRs can use a common effector for different purposes. This approach may have application in the characterization and development of functionally selective GPCR ligands and in identifying factors that dictate arrestin conformation and function.

doi: 10.1038/nature17154

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