最近、科学研究界の至る所で登場する「エクセレンス」という表現は、その意味が文脈で変わり、曖昧だ。

Science needs to redefine excellence p.403

The concept of research excellence is ubiquitous, but its meaning depends on context.

doi: 10.1038/d41586-018-02183-y

青年期に関連するさまざまな問題はもはや避けて通れない状況にあり、この誤解されやすい年齢層に焦点を合わせた研究や取り組みを世界的に急いで進める必要がある。

Adolescence research must grow up p.403

Young people get a raw deal from society. Targeted study and approaches as part of a new global effort are urgently needed to help them.

doi: 10.1038/d41586-018-02185-w

温暖化を緩和する「負の排出」対策は、現実には極めて困難なものである。

Why current negative-emissions strategies remain ‘magical thinking’ p.404

Work on how rocks draw carbon from the air shows the scale of the challenge.

doi: 10.1038/d41586-018-02184-x

イタリアの総選挙は、科学者にとっては期待の持てないものに。

Italian election leaves science out in the cold p.411

Researchers hold out little hope that the next government will improve their underfunded research system.

doi: 10.1038/d41586-018-02223-7

極めて不安定な反物質を制御してトラックで運び、それよりもさらに不安定な放射性原子核を調べるという実験計画が。

Physicists plan antimatter’s first outing — in a van p.412

Researchers intend to transport the elusive material between labs and use it to study the strange behaviour of rare radioactive nuclei.

doi: 10.1038/d41586-018-02221-9

北大西洋亜寒帯循環プログラム（OSNAP）が、世界の気候に大きく影響する北大西洋の複雑な潮流に関して新たな手掛かりを。

Ocean-wide sensor array provides new look at global ocean current p.413

Initial findings hint at the complexity of currents in the North Atlantic that drive the world's weather.

doi: 10.1038/d41586-018-02113-y

CRISPRを利用することで、細胞がイベントレコーダーに。

CRISPR hack transforms cells into data recorders p.414

Gene-editing tool can be harnessed to give a close-up view of life's most basic processes.

doi: 10.1038/d41586-018-02068-0

インドネシア初の科学助成機関が、資金不足に。

Indonesian scientists hamstrung by year-long funding delay p.415

The country's dedicated science fund has failed to raise enough money to finance projects.

doi: 10.1038/d41586-018-02118-7

セックスと薬物とセルフコントロール

Sex and drugs and self-control: how the teen brain navigates risk p.426

神経科学によって、青年期と危険な行動との間の微妙で深い関係が明らかになりつつある。

doi: 10.1038/d41586-018-02170-3

青年期の境界線の変化

Who exactly counts as an adolescent? p.429

子どもと大人の間である青年期を、どこからどこまでと定義すべきかに、研究者たちは悩まされている。

doi: 10.1038/d41586-018-02169-w

回顧：シナプス剪定仮説の成熟

In retrospect: Pruning hypothesis comes of age p.438

1983年、統合失調症の原因の1つは、青年期に神経接続の剪定が阻害されることだとする仮説が提唱された。その後の画像化研究、遺伝的研究、分子研究によって、この説の予見性が証明された。

doi: 10.1038/d41586-018-02053-7

メカノケミストリー：圧力を加えると反応する分子

Mechanochemistry: Molecules pressured to react p.468

圧縮されると反応する結晶が作られた。こうした過程のコンピューターシミュレーションによって、機械的に誘起される反応機構に関する切望されていた原子レベルの知見が得られた。

doi: 10.1038/d41586-018-02047-5

構造生物学：力によって活性化されるイオンチャンネルの詳細な構造

Structural biology: Force-activated ion channels in close-up p.469

ピエゾ（Piezo）タンパク質が機械的刺激に応答してイオンに細胞膜を通過させることによって、細胞は力を感知できる。今回得られたピエゾタンパク質の3つの構造は、この極めて重要な過程が機能する仕組みに光を当てる。

doi: 10.1038/d41586-018-01631-z

膵疾患：炎症性転写スイッチ

Pancreatic disease: An inflammatory transcriptional switch p.470

マウスの膵臓は、化学傷害や遺伝子Nr5a2の1つのコピーの欠損に応答して前炎症状態になる。この状態によって、マウスや（おそらくヒトも）膵炎や膵臓がんにかかりやすくなる可能性がある。

doi: 10.1038/d41586-018-01262-4

工学：ニューロンを模倣する電子デバイス

Engineering: Neurons mimicked by electronics p.472

現在の電子デバイスでは、生体ニューロンの基本的な機能しか模倣できない。今回、メモトランジスターと呼ばれるデバイスが、この限界を克服し、人工知能システムを改善する可能性があることが分かった。

doi: 10.1038/d41586-018-02025-x

青年期：発達科学の観点から見た青年期投資の重要性

Importance of investing in adolescence from a developmental science perspective p.441

doi: 10.1038/nature25770

青年期：青年期における身体時間、社会的時間、生活史の動態

Dynamics of body time, social time and life history at adolescence p.451

doi: 10.1038/nature25750

青年期：青年期と次世代

Adolescence and the next generation OPEN p.458

Investing in adolescents as the parents of the next generation is important for the wellbeing of current and future generations.

doi: 10.1038/nature25759

神経科学：脳血管系における細胞タイプと空間的分離の分子アトラス

A molecular atlas of cell types and zonation in the brain vasculature p.475

Single-cell transcriptomic analysis of the murine blood–brain barrier provides molecular definitions of the main vascular cell types, classifies perivascular cell types and sheds light on the organization of the arteriovenous axis.

doi: 10.1038/nature25739

構造生物学：機械刺激によって活性化されたイオンチャネルピエゾ1の構造

Structure of the mechanically activated ion channel Piezo1 p.481

The cryo-electron microscopy structure of full-length mouse Piezo1 reveals six Piezo repeats, and 26 transmembrane helices per protomer, and shows that a kinked helical beam and anchor domain link the Piezo repeats to the pore and control gating allosterically.

doi: 10.1038/nature25453

構造生物学：ピエゾ1チャネルの構造と機械刺激によるゲート開閉機構

Structure and mechanogating mechanism of the Piezo1 channel p.487

The electron cryo-microscopy structure of full-length mouse Piezo1 reveals unique topological features such as the repetitive transmembrane helical units that constitute the highly curved transmembrane region, and identifies regions and single residues that are crucial for the mechanical activation of the channel.

doi: 10.1038/nature25743

天文学：重力アークトモグラフィーから分かった赤方偏移1にある塊状の異方的な銀河ハロー

A clumpy and anisotropic galaxy halo at redshift 1 from gravitational-arc tomography p.493

The halo of gas around a galaxy at redshift 1 is clumpy and anisotropic, with little variation in gas velocity, suggesting that it consists of entrained recycled material.

doi: 10.1038/nature25436

天文学：超新星の誕生時に起こる急激な増光

A surge of light at the birth of a supernova p.497

The discovery of a newly born type IIb supernova reveals a rapid brightening at optical wavelengths that corresponds to the shock-breakout phase of the explosion.

doi: 10.1038/nature25151

ナノスケール材料：多結晶単層二硫化モリブデンから作製される多端子メモトランジスター

Multi-terminal memtransistors from polycrystalline monolayer molybdenum disulfide p.500

Polycrystalline monolayer molybdenum disulfide is used to fabricate a multi-terminal device combining a memristor and a transistor, which can mimic biological neurons with multiple synapses for neuromorphic computing applications.

doi: 10.1038/nature25747

メカノケミストリー：静水圧下での立体的に制御されたメカノケミストリー

Sterically controlled mechanochemistry under hydrostatic pressure p.505

‘Molecular anvil’ molecules consisting of a compressible mechanophore and incompressible ligands react under hydrostatic pressure to produce elemental metal via an unexplored mechanism.

doi: 10.1038/nature25765

化学：パラジウムに触媒される求電子芳香族C–Hフッ素化

Palladium-catalysed electrophilic aromatic C–H fluorination p.511

An approach for the direct electrophilic C–H fluorination of arenes is reported, using a palladium catalyst and mild fluorinating reagents.

doi: 10.1038/nature25749

海洋科学：南北方向の鉛直循環は大西洋深部に速い酸性化をもたらす

Meridional overturning circulation conveys fast acidification to the deep Atlantic Ocean p.515

There has been a reduction of about forty per cent in the transport of carbonate ions to the deep North Atlantic Ocean since preindustrial times, severely endangering cold-water corals.

doi: 10.1038/nature25493

生態学：熱帯林の分断化の全球的なパターン

Global patterns of tropical forest fragmentation p.519

Satellite data and modelling reveal that tropical forest fragments have similar size distributions across continents, and that forest fragmentation is close to a critical point, beyond which fragment numbers will strongly increase.

doi: 10.1038/nature25508

細胞生物学：組織の硬化はin vivoで細胞の集団移動を引き起こすことにより形態形成を調整する

Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo p.523

Stiffening of the mesoderm owing to an accumulation of cells triggers collective migration of neural crest cells during morphogenesis.

doi: 10.1038/nature25742

微生物学：ペプチドグリカン合成は細胞質分裂のFtsZトレッドミリング非依存的な段階を促進する

Peptidoglycan synthesis drives an FtsZ-treadmilling-independent step of cytokinesis p.528

Peptidoglycan is the main component of the bacterial wall and protects cells from the mechanical stress that results from high intracellular turgor. Peptidoglycan biosynthesis is very similar in all bacteria; bacterial shapes are therefore mainly determined by the spatial and temporal regulation of peptidoglycan synthesis rather than by the chemical composition of peptidoglycan. The form of rod-shaped bacteria, such as Bacillus subtilis or Escherichia coli, is generated by the action of two peptidoglycan synthesis machineries that act at the septum and at the lateral wall in processes coordinated by the cytoskeletal proteins FtsZ and MreB, respectively. The tubulin homologue FtsZ is the first protein recruited to the division site, where it assembles in filaments—forming the Z ring—that undergo treadmilling and recruit later divisome proteins. The rate of treadmilling in B. subtilis controls the rates of both peptidoglycan synthesis and cell division. The actin homologue MreB forms discrete patches that move circumferentially around the cell in tracks perpendicular to the long axis of the cell, and organize the insertion of new cell wall during elongation. Cocci such as Staphylococcus aureus possess only one type of peptidoglycan synthesis machinery, which is diverted from the cell periphery to the septum in preparation for division. The molecular cue that coordinates this transition has remained elusive. Here we investigate the localization of S. aureus peptidoglycan biosynthesis proteins and show that the recruitment of the putative lipid II flippase MurJ to the septum, by the DivIB–DivIC–FtsL complex, drives peptidoglycan incorporation to the midcell. MurJ recruitment corresponds to a turning point in cytokinesis, which is slow and dependent on FtsZ treadmilling before MurJ arrival but becomes faster and independent of FtsZ treadmilling after peptidoglycan synthesis activity is directed to the septum, where it provides additional force for cell envelope constriction.

doi: 10.1038/nature25506

炎症：NR5A2による転写調節が膵臓の分化と炎症を結び付ける

Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas p.533

In mouse pancreas cells with only one copy of the Nr5a2 gene, the orphan nuclear receptor NR5A2 undergoes a marked transcriptional shift from differentiation-specific to inflammatory genes, which results in an epithelial-cell-autonomous basal pre-inflammatory state.

doi: 10.1038/nature25751

がん：遺伝学的に再構築された大腸がん転移ではTGFβが免疫回避を促進する

TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis p.538

Most patients with colorectal cancer die as a result of the disease spreading to other organs. However, no prevalent mutations have been associated with metastatic colorectal cancers. Instead, particular features of the tumour microenvironment, such as lack of T-cell infiltration, low type 1 T-helper cell (T_H1) activity and reduced immune cytotoxicity or increased TGFβ levels predict adverse outcomes in patients with colorectal cancer. Here we analyse the interplay between genetic alterations and the tumour microenvironment by crossing mice bearing conditional alleles of four main colorectal cancer mutations in intestinal stem cells. Quadruple-mutant mice developed metastatic intestinal tumours that display key hallmarks of human microsatellite-stable colorectal cancers, including low mutational burden, T-cell exclusion and TGFβ-activated stroma. Inhibition of the PD-1–PD-L1 immune checkpoint provoked a limited response in this model system. By contrast, inhibition of TGFβ unleashed a potent and enduring cytotoxic T-cell response against tumour cells that prevented metastasis. In mice with progressive liver metastatic disease, blockade of TGFβ signalling rendered tumours susceptible to anti-PD-1–PD-L1 therapy. Our data show that increased TGFβ in the tumour microenvironment represents a primary mechanism of immune evasion that promotes T-cell exclusion and blocks acquisition of the T_H1-effector phenotype. Immunotherapies directed against TGFβ signalling may therefore have broad applications in treating patients with advanced colorectal cancer.

doi: 10.1038/nature25492

がん：TGFβはT細胞の排除に関与してPD-L1阻害に対する腫瘍応答を減弱させる

TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells p.544

Therapeutic antibodies that block the programmed death-1 (PD-1)–programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here we examined tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response to treatment was associated with CD8+ T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden. Lack of response was associated with a signature of transforming growth factor β (TGFβ) signalling in fibroblasts. This occurred particularly in patients with tumours, which showed exclusion of CD8+ T cells from the tumour parenchyma that were instead found in the fibroblast- and collagen-rich peritumoural stroma; a common phenotype among patients with metastatic urothelial cancer. Using a mouse model that recapitulates this immune-excluded phenotype, we found that therapeutic co-administration of TGFβ-blocking and anti-PD-L1 antibodies reduced TGFβ signalling in stromal cells, facilitated T-cell penetration into the centre of tumours, and provoked vigorous anti-tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding patient outcome in this setting and suggests that TGFβ shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T-cell infiltration.

doi: 10.1038/nature25501

細胞生物学：MEKはKSRタンパク質のアロステリック制御を介してBRAF活性化を促進する

MEK drives BRAF activation through allosteric control of KSR proteins p.549

KSR–MEK complexes allosterically activate BRAF through the action of N-terminal regulatory region and kinase domain contacts, thus challenging the accepted role of KSR as a scaffold for MEK recruitment to RAF.

doi: 10.1038/nature25478