目次

Editorials

米国の次期トランプ政権には大きな不安が伴うが、科学者たちは、冷静に動向を見守り、科学に立脚した政策がとられるよう全力で働きかける必要がある。

Reality must trump rhetoric after US election shock p.329

It is time for scientists and politicians alike to constructively engage with core issues — from climate change and energy independence to social inequality.

doi: 10.1038/539329a

科学を一般の人々に正確に伝えることは重要だが、非常に難しい。

Being able to explain your work to passers-by is laudable — but not always possible p.330

The first person to invoke the ‘man on the street’ has been identified, but sometimes maths is just too difficult to make simple.

doi: 10.1038/539330a

火星への移住に関する計画や将来の予測を見ると、そこはまるで地球のようだ。

Fed up of Earth? Try Mars p.330

Establishing a Martian outpost is likely to bring many of the same societal problems we face on Earth.

doi: 10.1038/539330b

News

ドナルド・トランプ米国次期大統領の科学に関連する政策の展望に、多くの人々が固唾を。

The ultimate experiment: How Trump will handle science p.337

Climate-change and immigration policies raise alarm, but much of the incoming US president's agenda is simply unknown.

doi: 10.1038/nature.2016.20971

世論調査ではトランプ氏勝利を予測できなかったことに、調査会社も困惑を。

Pollsters struggle to explain failures of US presidential forecasts p.339

Most surveys did not predict Donald Trump’s victory over Hillary Clinton.

doi: 10.1038/nature.2016.20968

禁止された幹細胞療法を実施して有罪判決を受けたイタリアの医師が、その後国外で活動を。

Disgraced stem-cell entrepreneur under fresh investigation p.340

Davide Vannoni is barred from offering a controversial stem-cell therapy in Italy but may be continuing his work abroad.

doi: 10.1038/539340a

ユニコードコンソーシアムに提出された、科学をテーマにした新しい絵文字を紹介。

I can haz more science emoji? Host of nerd icons proposed p.341

At a conference in San Francisco, a group drafted proposals to add more planets, instruments and other science icons to the keyboard.

doi: 10.1038/nature.2016.20960

ルワンダは、国民の健康が増進したため先進国からの資金援助が縮小してしまい、対応に苦慮を。

Rwanda feels the pinch as donors slash health aid p.342

Country's progress on public health and science prompts funding shift to more-troubled nations.

doi: 10.1038/539342a

オープン査読の試験的実施の結果、その支持者が60%にも達することが明らかに。

Open peer review finds more takers p.343

Journal experiments and surveys suggest scientists are coming round to the idea of publishing review reports.

doi: 10.1038/nature.2016.20969

News Features

気候問題:過酷な海の恩恵

How much longer can Antarctica’s hostile ocean delay global warming? p.346

南大洋の海水は、人間活動によって生じた熱と炭素の大部分を吸収して地球温暖化を遅らせてきたが、この機能は長くは続かないかもしれない。

doi: 10.1038/539346a

News & Views

光物理学:ランダムレーザーの明るい未来

Optical physics: Clear directions for random lasers p.360

ランダムレーザーは無秩序な構造を使って光を発生させる装置で、通常は光を多方向へ放射する。平行ビームを生成できるランダムレーザーは、画像化からセキュリティースキャンまで、さまざまな応用が可能である。

doi: 10.1038/nature20477

分子生物学:シャペロンによって安定化される成熟タンパク質

Molecular biology: Mature proteins braced by a chaperone p.361

他のタンパク質が折りたたまれるのを助けるシャペロンのHsp70分子は、主に折りたたまれていないタンパク質に結合すると考えられていた。だが今回、Hsp70はほとんど完全に折りたたまれたタンパク質も安定化することが、1分子実験によって示唆された。

doi: 10.1038/nature20470

地球化学:地球深部の流体はイオンに敏感

Geochemistry: Ions surprise in Earth's deep fluids p.362

地球深部の主要な不連続帯であるスラブ・マントル境界では、流体の元素濃度とpHに強い勾配が存在することがモデルによって示された。この変化は全球規模での地球化学的輸送に関する我々の理解を変えるものだ。

doi: 10.1038/539362a

神経科学:眠くて夢を見ない変異マウス

Neuroscience: Sleepy and dreamless mutant mice p.364

哺乳類の睡眠は、ノンレム睡眠とレム睡眠の2相から構成されている。大規模な遺伝学的スクリーニングによって、マウスではこれら2種類の睡眠状態のバランスがSleepyDreamlessと命名された変異によって変化することが明らかにされた。

doi: 10.1038/nature20471

材料科学:伸縮性と修復性のある半導体

Materials science: Semiconductors that stretch and heal p.365

構成分子の性質によって伸縮性と修復性を持つようになったポリマー半導体が作られた。これは人間の皮膚を模倣した精巧な有機電子表面の開発に向けた第一段階といえる。

doi: 10.1038/539365a

微生物学:深海に潜むブタン代謝の秘密

Microbiology: Deep-sea secrets of butane metabolism p.367

嫌気性微生物が、炭化水素のブタンを、嫌気的メタン酸化に一部が似ている経路によって分解していることが明らかになった。このブタン分解経路の利用によってバイオ燃料の生産が可能になるかもしれない。

doi: 10.1038/539367a

Review

神経科学:Δ9-テトラヒドロカンナビノールがドーパミン系に及ぼす影響

The effects of Δ9-tetrahydrocannabinol on the dopamine system p.369

A review into the complex effects of Δ9-tetrahydrocannabinol on the dopamine system, examining data from animal and human studies and discussing the necessary future direction of research.

doi: 10.1038/nature20153

Articles

神経科学:ランダムに変異を起こさせたマウスにおける睡眠の順遺伝学的解析

Forward-genetics analysis of sleep in randomly mutagenized mice p.378

Two mutations affecting the sleep–wakefulness balance in mice are detected, showing that the SIK3 protein kinase is essential for determining daily wake time, and the NALCN cation channel regulates the duration of rapid eye movement sleep.

doi: 10.1038/nature20142

幹細胞生物工学:ヒト造血幹細胞でのCRISPR/Cas9によるβグロビン遺伝子ターゲッティング

CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells p.384

These preclinical studies outline a CRISPR-based methodology for correcting β-globin gene mutations in haematopoietic stem cells to advance the development of next-generation therapies for β-haemoglobinopathies.

doi: 10.1038/nature20134

がんの代謝:LKB1の喪失はセリン代謝をDNAメチル化と腫瘍発生に結び付ける

LKB1 loss links serine metabolism to DNA methylation and tumorigenesis p.390

Human tumours with mutations in LKB1 and Kras have a specific hypermetabolic state associated with increased DNA methylation, pointing to potential metabolic and epigenetic vulnerabilities of specific tumours.

doi: 10.1038/nature20132

微生物学:好熱性アーキアはアルキル補酵素Mの形成を介してブタンを活性化する

Thermophilic archaea activate butane via alkyl-coenzyme M formation p.396

Anaerobic archaea enriched in thermophilic microbial consortia completely degrade butane by modifying mechanisms which were hitherto thought to be specific to methane metabolism.

doi: 10.1038/nature20152

Letters

惑星科学:角運動量の大きな高傾斜角の地球によって生じた月の潮汐進化

Tidal evolution of the Moon from a high-obliquity, high-angular-momentum Earth p.402

A model of the Moon’s tidal evolution, starting from the fast-spinning, high-obliquity Earth that would be expected after a giant impact, reveals that solar perturbations on the Moon’s orbit naturally produce the current lunar inclination and Earth’s low obliquity.

doi: 10.1038/nature19846

材料学:量子系の散逸に対するナノスケールの熱画像化法

Nanoscale thermal imaging of dissipation in quantum systems p.407

A cryogenic thermal imaging technique that uses a superconducting quantum interference device fabricated on the tip of a sharp pipette can be used to image the thermal signature of extremely low power nanometre-scale dissipation processes.

doi: 10.1038/nature19843

高分子:固有伸縮性と固有修復性を有する有機トランジスター用半導体ポリマー

Intrinsically stretchable and healable semiconducting polymer for organic transistors p.411

Introducing non-covalent crosslinking moieties to polymer semiconductors produces a stretchable and healable material suitable for wearable electronics.

doi: 10.1038/nature20102

大気科学:降雨時の鉛直輸送によって維持されるアマゾン境界層のエアロゾル濃度

Amazon boundary layer aerosol concentration sustained by vertical transport during rainfall p.416

Rapid vertical transport of small aerosol particles from the free troposphere to the atmospheric boundary layer occurs during precipitation and maintains the population of aerosol particles over Amazonia.

doi: 10.1038/nature19819

地球化学:沈み込み帯流体のpHから得られた金属の循環と揮発性物質の循環の関連

Implications for metal and volatile cycles from the pH of subduction zone fluids p.420

A thermodynamic model of fluid pH and its variability in Earth’s mantle and subducting crust highlights chemical feedbacks that connect deep Earth to surface processes.

doi: 10.1038/nature20103

生態学:植物における栄養素の変動は植食性昆虫のパフォーマンスを低下させる

Variability in plant nutrients reduces insect herbivore performance p.425

Variation in plant nutrient levels suppresses insect herbivore populations and the homogenous nutrient content of modern agricultural crops could be contributing to insect pest outbreaks.

doi: 10.1038/nature20140

神経科学:アストロサイトを介する神経調節物質の信号が神経回路活動と行動を変化させる

Neuromodulators signal through astrocytes to alter neural circuit activity and behaviour p.428

Calcium signalling in astrocytes, driven through the octopamine/tyramine receptor and the TRP channel Water witch, is essential for neuromodulation and sensory responses in Drosophila larvae.

doi: 10.1038/nature20145

発生生物学:非コードRNAであるupperhandの転写はHand2の発現と心臓発生を制御する

Transcription of the non-coding RNA upperhand controls Hand2 expression and heart development p.433

Transcription of a long non-coding RNA, known as upperhand (Uph) located upstream of the HAND2 transcription factor is required to maintain transcription of the Hand2 gene by RNA polymerase, and blockade of Uph expression leads to heart defects and embryonic lethality in mice.

doi: 10.1038/nature20128

免疫学:PI3Kγは免疫抑制を制御する分子スイッチである

PI3Kγ is a molecular switch that controls immune suppression p.437

Macrophages play critical, but opposite, roles in acute and chronic inflammation and cancer. In response to pathogens or injury, inflammatory macrophages express cytokines that stimulate cytotoxic T cells, whereas macrophages in neoplastic and parasitic diseases express anti-inflammatory cytokines that induce immune suppression and may promote resistance to T cell checkpoint inhibitors. Here we show that macrophage PI 3-kinase γ controls a critical switch between immune stimulation and suppression during inflammation and cancer. PI3Kγ signalling through Akt and mTor inhibits NFκB activation while stimulating C/EBPβ activation, thereby inducing a transcriptional program that promotes immune suppression during inflammation and tumour growth. By contrast, selective inactivation of macrophage PI3Kγ stimulates and prolongs NFκB activation and inhibits C/EBPβ activation, thus promoting an immunostimulatory transcriptional program that restores CD8+ T cell activation and cytotoxicity. PI3Kγ synergizes with checkpoint inhibitor therapy to promote tumour regression and increased survival in mouse models of cancer. In addition, PI3Kγ-directed, anti-inflammatory gene expression can predict survival probability in cancer patients. Our work thus demonstrates that therapeutic targeting of intracellular signalling pathways that regulate the switch between macrophage polarization states can control immune suppression in cancer and other disorders.

doi: 10.1038/nature19834

免疫学:チェックポイント阻害療法に対する耐性を骨髄細胞でのPI3Kγ標的化によって克服する

Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells p.443

Recent clinical trials using immunotherapy have demonstrated its potential to control cancer by disinhibiting the immune system. Immune checkpoint blocking (ICB) antibodies against cytotoxic-T-lymphocyte-associated protein 4 or programmed cell death protein 1/programmed death-ligand 1 have displayed durable clinical responses in various cancers. Although these new immunotherapies have had a notable effect on cancer treatment, multiple mechanisms of immune resistance exist in tumours. Among the key mechanisms, myeloid cells have a major role in limiting effective tumour immunity. Growing evidence suggests that high infiltration of immune-suppressive myeloid cells correlates with poor prognosis and ICB resistance. These observations suggest a need for a precision medicine approach in which the design of the immunotherapeutic combination is modified on the basis of the tumour immune landscape to overcome such resistance mechanisms. Here we employ a pre-clinical mouse model system and show that resistance to ICB is directly mediated by the suppressive activity of infiltrating myeloid cells in various tumours. Furthermore, selective pharmacologic targeting of the gamma isoform of phosphoinositide 3-kinase (PI3Kγ), highly expressed in myeloid cells, restores sensitivity to ICB. We demonstrate that targeting PI3Kγ with a selective inhibitor, currently being evaluated in a phase 1 clinical trial (NCT02637531), can reshape the tumour immune microenvironment and promote cytotoxic-T-cell-mediated tumour regression without targeting cancer cells directly. Our results introduce opportunities for new combination strategies using a selective small molecule PI3Kγ inhibitor, such as IPI-549, to overcome resistance to ICB in patients with high levels of suppressive myeloid cell infiltration in tumours.

doi: 10.1038/nature20554

分子生物学:Hsp70の機能的可塑性は相手によって異なる結合方式をとることで可能となっている

Alternative modes of client binding enable functional plasticity of Hsp70 p.448

Hsp70 binds unfolded protein segments in its groove, but can also bind and stabilize folded protein structures, owing to its moveable lid, with ATP hydrolysis and co-chaperones allowing control of these contrasting effects.

doi: 10.1038/nature20137

遺伝子調節:lncRNAのプロモーター、転写、スプライシングによる遺伝子発現の局所的調節

Local regulation of gene expression by lncRNA promoters, transcription and splicing p.452

Various cis-regulatory functions of genomic loci that produce long non-coding RNAs are revealed, including instances where their promoters have enhancer-like activity and the lncRNA transcripts themselves are not required for activity.

doi: 10.1038/nature20149

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