目次

Editorials

反ユダヤ主義が大学などで再び見られるようになっているが、これは許してはならないことだ。

Challenge anti-Semitism p.407

A wave of anti-Jewish prejudice is once again washing over schools and universities. There is no excuse not to call out this vile behaviour.

doi: 10.1038/d41586-018-04926-3

気候変動に対する取り組みでは、温室効果ガス排出削減が何よりも重要であることは変わらない。

Climate talks are not enough p.407

As officials meet in Bonn to swap stories on progress towards the Paris goals, only emissions cuts will guarantee a happy ending.

doi: 10.1038/d41586-018-04925-4

Natureが開催した「#ScienceAtWork」写真コンテストは、画像の持つ力をはっきりと示している。

The science photos worth seeing p.408

Results from a Nature photo competition show the power of images.

doi: 10.1038/d41586-018-04924-5

News

気候変動による悪影響は、まず貧困国に現れることが明らかに。

Clear signs of global warming will hit poorer countries first p.415

New climate-inequality tool quantifies how quickly the weather will veer beyond normal in different regions.

doi: 10.1038/d41586-018-04854-2

研究資金獲得は、キャリアの早期に成功すれば、その後も順調であるという分析結果が。

Scientists’ early grant success fuels further funding p.416

Young researchers who narrowly miss out on postdoctoral grant struggle to compete with those who just qualify.

doi: 10.1038/d41586-018-04958-9

米国政府が、Landsatと全米農業画像プログラム(NAIP)の画像データの無償提供を見直しへ。

US government considers charging for popular Earth-observing data p.417

Images from Landsat satellites and agricultural-survey programme are freely available to scientists — but for how long?

doi: 10.1038/d41586-018-04874-y

英国のEU離脱に伴う欧州医薬品庁(EMA)の移転では、移転先のオランダ・アムステルダムでの家賃高騰が大きな障壁に。

Rent increase hits Europe’s drug regulator before Brexit move p.418

With a move from London to Amsterdam less than a year away, the European Medicines Agency is facing uncertainty.

doi: 10.1038/d41586-018-04917-4

ヨーロッパとロシアが共同で進める「エクソマーズ2016」ミッションの火星探査機トレース・ガス・オービター(TGO)が周回軌道に入り、観測を開始へ。

Mars probe poised to solve red planet’s methane mystery p.419

Researchers hope European–Russian Trace Gas Orbiter will end a long-running debate over source of the gas on Mars.

doi: 10.1038/d41586-018-04948-x

インフルエンザウイルスのゲノムを、RNAのままで解読することに成功。

Flu virus finally sequenced in its native form p.420

Direct sequencing of RNA molecules such as virus genomes should help to unpick role of mysterious chemical modifications.

doi: 10.1038/d41586-018-04908-5

News Features

エネルギー:炭素の未来の明暗

Can the world kick its fossil-fuel addiction fast enough? p.422

人間社会が化石燃料への依存を克服できる可能性は十分にあるが、そのために残された時間はわずかである。

doi: 10.1038/d41586-018-04931-6

神経科学:脳の「炎上」

Is ‘friendly fire’ in the brain provoking Alzheimer’s disease? p.426

アルツハイマー病などの神経変性疾患の原因が、脳の免疫系による「誤爆」によって引き起こされる炎症にある可能性が明らかになってきた。

doi: 10.1038/d41586-018-04930-7

News & Views

有機化学:分子の「顔認識」

Organic chemistry: Classic reaction re-engineered through molecular face recognition p.438

今回、平面状の反応中間体の1つの面だけのトポロジーを認識する触媒が開発された。注目すべきは、これによって反応生成物の鏡像異性体の片方だけを選択的に生成できるようになったことである。

doi: 10.1038/d41586-018-04684-2

疫学:小児HIV感染をより広く調べる

Epidemiology: A broader look at adolescents with perinatal HIV p.439

出生前後にHIVに感染した青年の疫学研究によって、全てのHIV感染小児の治療を出生後数年以内に開始できることが高所得国にどのような恩恵をもたらしているかが明らかになった。

doi: 10.1038/d41586-018-04476-8

海洋科学:動物プランクトンが起こす攪拌

Ocean science: Shrimp cause a stir p.440

ブラインシュリンプの移動が、水柱をかなり混合していることが、今回分かった。

doi: 10.1038/d41586-018-04673-5

生物工学:オルガノイドが明らかにしたがんのダイナミクス

Biotechnology: Organoids reveal cancer dynamics p.441

がんの単一細胞解析は、個々の細胞の生物量が少ないため限界がある。今回、単一の腫瘍由来細胞から3Dオルガノイド構造体をin vitroで作ることで、詳細に解析するのに十分な生物量が得られた。

doi: 10.1038/d41586-018-03841-x

腫瘍生物学:がんの転移を助ける移行状態

Tumour biology: Transition states that allow cancer to spread p.442

上皮細胞由来のがんには、間葉細胞の形質を獲得した数種の腫瘍細胞が含まれていることが多い。今回、このことががんの転移につながる仕組みがマウスモデルで明らかになった。

doi: 10.1038/d41586-018-04403-x

量子物理学:機械振動子のエンタングルした振動

Quantum physics: Entangled vibrations in mechanical oscillators p.444

今回2つの実験によって、無数の原子からなる遠く離れた機械系の間のエンタングルメント(非古典的相関)が実証された。この結果によって、量子物理学の理解が前進すると思われる。

doi: 10.1038/d41586-018-04827-5

神経科学:飢えは痛みを管理する

Neuroscience: Hunger is a gatekeeper of pain in the brain p.445

今回、ある神経集団が、飢えと痛みという競合する要求を調節していることが分かった。切迫した痛みは飢えに優先するが、食欲によって生じる神経活動によって長期にわたる疼痛応答が低下し、摂食が可能になるのである。

doi: 10.1038/d41586-018-04759-0

Articles

有機化学:エナンチオ収束的な触媒的SN1反応による第四級立体中心の構築

Quaternary stereocentres via an enantioconvergent catalytic SN1 reaction p.447

The unimolecular nucleophilic substitution (SN1) mechanism features prominently in every introductory organic chemistry course. In principle, stepwise displacement of a leaving group by a nucleophile via a carbocationic intermediate enables the construction of highly congested carbon centres. However, the intrinsic instability and high reactivity of the carbocationic intermediates make it very difficult to control product distributions and stereoselectivity in reactions that proceed via SN1 pathways. Here we report asymmetric catalysis of an SN1-type reaction mechanism that results in the enantioselective construction of quaternary stereocentres from racemic precursors. The transformation relies on the synergistic action of a chiral hydrogen-bond-donor catalyst with a strong Lewis-acid promoter to mediate the formation of tertiary carbocationic intermediates at low temperature and to achieve high levels of control over reaction enantioselectivity and product distribution. This work provides a foundation for the enantioconvergent synthesis of other fully substituted carbon stereocentres.

doi: 10.1038/s41586-018-0042-1

進化学:ビッグデータの時代にフェルゼンシュタインのブートストラップ法による系統発生学的解析を更新する

Renewing Felsenstein’s phylogenetic bootstrap in the era of big data p.452

A new version of the phylogenetic bootstrap method enables assessment of the robustness of phylogenies that are based on large datasets of hundreds or thousands of taxa.

doi: 10.1038/s41586-018-0043-0

生物工学:大腸がんにおける単一細胞レベルでの腫瘍内多様化

Intra-tumour diversification in colorectal cancer at the single-cell level p.457

Organoids derived from individual cells from colorectal cancers and adjacent normal tissue are used to investigate intra-tumour diversification at the genomic, epigenetic and functional levels.

doi: 10.1038/s41586-018-0024-3

腫瘍生物学:EMTの際に起こる、腫瘍の複数の移行状態の特定

Identification of the tumour transition states occurring during EMT p.463

Epithelial-to-mesenchymal transition in tumour cells occurs through distinct intermediate states, associated with different metastatic potential, cellular properties, gene expression, and chromatin landscape

doi: 10.1038/s41586-018-0040-3

Letters

天文学:赤方偏移4.3の位置にある銀河団の大質量コア

A massive core for a cluster of galaxies at a redshift of 4.3 p.469

Observations of carbon monoxide and ionized carbon lines from the source SPT2349-56 show it to contain a cluster of at least fourteen gas-rich galaxies with redshifts of 4.31, in a highly dense core region.

doi: 10.1038/s41586-018-0025-2

量子物理学:2つの微小機械振動子の間の遠隔量子エンタングルメント

Remote quantum entanglement between two micromechanical oscillators p.473

Remote quantum entanglement is demonstrated in a micromachined solid-state system comprising two optomechanical oscillators across two chips physically separated by 20 cm and with an optical separation of around 70 m.

doi: 10.1038/s41586-018-0036-z

量子物理学:大きな機械振動子の安定化されたエンタングルメント

Stabilized entanglement of massive mechanical oscillators p.478

Quantum entanglement is demonstrated in a system of massive micromechanical oscillators coupled to a microwave-frequency electromagnetic cavity by driving the devices into a steady state that is entangled.

doi: 10.1038/s41586-018-0038-x

光材料学:低損失プラズモン支援電気光学変調器

Low-loss plasmon-assisted electro-optic modulator p.483

Ohmic losses in plasmonic devices can be reduced by exploiting ‘resonant switching’, in which light couples to surface plasmon polaritons only when in resonance and bypasses them otherwise.

doi: 10.1038/s41586-018-0031-4

地球科学:地震によって生じる下部地殻の変化

Earthquake-induced transformation of the lower crust p.487

During continent collision and associated mountain building, a surprisingly large volume of the lower crust is shown to be affected by earthquake aftershocks, producing a top-down effect on crustal geodynamics.

doi: 10.1038/s41586-018-0045-y

気候変動生態学:地球温暖化により変容するサンゴ礁群集

Global warming transforms coral reef assemblages p.492

Acute heat stress from the extended marine heatwave of 2016 is a potent driver of the transformation of coral assemblages, which affects even the most remote and well-protected reefs of the Great Barrier Reef.

doi: 10.1038/s41586-018-0041-2

海洋科学:鉛直移動する遊泳動物は成層水柱中に集合体スケールの渦を生じる

Vertically migrating swimmers generate aggregation-scale eddies in a stratified column p.497

Laboratory experiments with the brine shrimp Artemia salina illustrate the potential for turbulence generated by the diurnal vertical migrations of aggregations of centimetre-scale zooplankton to affect the physical and biogeochemical structure of oceanic water columns.

doi: 10.1038/s41586-018-0044-z

免疫学:イタコン酸とその誘導体の求電子的な性質はIκBζ–ATF3炎症軸を調節する

Electrophilic properties of itaconate and derivatives regulate the IκBζ–ATF3 inflammatory axis p.501

Metabolic regulation has been recognized as a powerful principle guiding immune responses. Inflammatory macrophages undergo extensive metabolic rewiring1 marked by the production of substantial amounts of itaconate, which has recently been described as an immunoregulatory metabolite2. Itaconate and its membranepermeable derivative dimethyl itaconate (DI) selectively inhibit a subset of cytokines2, including IL-6 and IL-12 but not TNF. The major effects of itaconate on cellular metabolism during macrophage activation have been attributed to the inhibition of succinate dehydrogenase2,3, yet this inhibition alone is not sufficient to account for the pronounced immunoregulatory effects observed in the case of DI. Furthermore, the regulatory pathway responsible for such selective effects of itaconate and DI on the inflammatory program has not been defined. Here we show that itaconate and DI induce electrophilic stress, react with glutathione and subsequently induce both Nrf2 (also known as NFitalicL2)-dependent and -independent responses. We find that electrophilic stress can selectively regulate secondary, but not primary, transcriptional responses to toll-like receptor stimulation via inhibition of IκBζ protein induction. The regulation of IκBζ is independent of Nrf2, and we identify ATF3 as its key mediator. The inhibitory effect is conserved across species and cell types, and the in vivo administration of DI can ameliorate IL-17–IκBζ- driven skin pathology in a mouse model of psoriasis, highlighting the therapeutic potential of this regulatory pathway. Our results demonstrate that targeting the DI–IκBζ regulatory axis could be an important new strategy for the treatment of IL-17–IκBζ-mediated autoimmune diseases.

doi: 10.1038/s41586-018-0052-z

神経科学:エネルギー恒常性とグルコース恒常性のレプチン神経回路の遺伝的特定

Genetic identification of leptin neural circuits in energy and glucose homeostases p.505

A subset of neurons in the hypothalamus is identified as the primary site of action for regulating energy balance and glucose homeostasis by leptin.

doi: 10.1038/s41586-018-0049-7

幹細胞:ES細胞では多能性因子が細胞タイプに限定されたエンハンサーを機能的に先行標識する

Pluripotency factors functionally premark cell-type-restricted enhancers in ES cells p.510

Binding of an ES cell-specific transcription factor pre-marks cell-type-restricted enhancers in ES cells, and this premarking is required for the robustness of enhancer activation in differentiated cells.

doi: 10.1038/s41586-018-0048-8

構造生物学:MK-801およびメマンチンによるNMDA受容体チャネル遮断の機構

Mechanism of NMDA receptor channel block by MK-801 and memantine p.515

A high-resolution X-ray structure and molecular dynamics simulations of the N-methyl-d-aspartate receptor in complexes with channel-blocking ligands reveals the molecular basis of the ligand binding and channel block.

doi: 10.1038/s41586-018-0039-9

構造生物学:神経ペプチドYのY1受容体におけるリガンド結合様式の構造基盤

Structural basis of ligand binding modes at the neuropeptide Y Y1 receptor p.520

Neuropeptide Y (NPY) receptors belong to the G-protein-coupled receptor superfamily and have important roles in food intake, anxiety and cancer biology1,2. The NPY–Y receptor system has emerged as one of the most complex networks with three peptide ligands (NPY, peptide YY and pancreatic polypeptide) binding to four receptors in most mammals, namely the Y1, Y2, Y4 and Y5 receptors, with different affinity and selectivity3. NPY is the most powerful stimulant of food intake and this effect is primarily mediated by the Y1 receptor (Y1R)4. A number of peptides and small-molecule compounds have been characterized as Y1R antagonists and have shown clinical potential in the treatment of obesity4, tumour1 and bone loss5. However, their clinical usage has been hampered by low potency and selectivity, poor brain penetration ability or lack of oral bioavailability6. Here we report crystal structures of the human Y1R bound to the two selective antagonists UR-MK299 and BMS-193885 at 2.7 and 3.0 Å resolution, respectively. The structures combined with mutagenesis studies reveal the binding modes of Y1R to several structurally diverse antagonists and the determinants of ligand selectivity. The Y1R structure and molecular docking of the endogenous agonist NPY, together with nuclear magnetic resonance, photo-crosslinking and functional studies, provide insights into the binding behaviour of the agonist and for the first time, to our knowledge, determine the interaction of its N terminus with the receptor. These insights into Y1R can enable structure-based drug discovery that targets NPY receptors.

doi: 10.1038/s41586-018-0046-x

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