目次

Editorials

研究用原子炉JRR-3の運転再開の遅れが、日本の原子力科学を危うくしている。

Bureaucratic drag dents Japan’s nuclear science p.147

Japan needs a better way to assess whether research reactors are safe to re-open.

doi: 10.1038/d41586-017-08464-2

インターネットの速度に優先度を設けることは、科学の減速につながるだろう。

Loss of net neutrality could harm research p.147

Moves to create a multi-speed Internet could push science into the slow lane.

doi: 10.1038/d41586-017-07842-0

学際的研究は、互いの専門性に敬意を払いながら、時間をかけて行う必要がある。

How to avoid glib interdisciplinarity p.148

To make progress on the grand challenges, authors, reviewers and editors must take the time to respect each others’ expertise and blind spots.

doi: 10.1038/d41586-017-08465-1

News

セクハラ問題での対処が不適切だと、科学者たちが米国ロチェスター大学を相手取って訴訟を。

Nine researchers sue University of Rochester over sexual-harassment allegations p.155

Lawsuit alleges that the institution mishandled complaints about cognitive scientist Florian Jaeger.

doi: 10.1038/d41586-017-08235-z

絶滅したフクロオオカミのゲノム塩基配列解読により、絶滅やイヌとの類似についての遺伝的手掛かりが。

Tasmanian tiger genome offers clues to its extinction p.156

Geneticists analyse DNA from preserved pup, more than 80 years after the last of its kind died.

doi: 10.1038/d41586-017-08368-1

米国では、免除された大学の授業料も課税対象になる可能性が浮上し、激しい抗議の声が。

US graduate students in uproar over proposed tax hike p.157

Worries over the cost of an education spill over into protests.

doi: 10.1038/d41586-017-07879-1

鍼治療に鎮痛効果があることが、大規模臨床試験によって証明されたが、異論も。

Acupuncture in cancer study reignites debate about controversial technique p.157

Large study suggests acupuncture could help women stick with unpleasant cancer treatments.

doi: 10.1038/d41586-017-08309-y

政府の氷河調査の結果をゆがめたとして訴えられたアルゼンチンの地球科学者が、刑事責任を問われる危機に。

Argentinian geoscientist faces criminal charges over glacier survey p.158

Government researcher Ricardo Villalba stands accused of shaping a study to benefit mining interests.

doi: 10.1038/d41586-017-08236-y

News Features

出版:引用されない科学

The science that’s never been cited p.162

Natureは、出版後に1回も引用されることない論文がいったいどのくらいあって、その背景にはどのようなことがあるのかを調べた。

doi: 10.1038/d41586-017-08404-0

News & Views

発生生物学:抑制されている初期胚

Developmental biology: Early embryos kept in check p.178

多能性幹細胞は、全ての体細胞種を生み出す準備ができると、哺乳類の胎児が成長する羊膜腔の形成を始める。この遷移を制御するチェックポイントが、今回特定された。

doi: 10.1038/d41586-017-07436-w

天体物理学:間欠的な星の共食い

Astrophysics: Stellar cannibalism in fits and starts p.179

白色矮星と呼ばれる密度の高い星の残存物は、連星系によく見られる。今回、衛星観測によって、白色矮星が伴星から物質を引き出すこれまで知られていなかった機構が示唆された。

doi: 10.1038/d41586-017-08286-2

血管生物学:オメガ3脂肪酸の負の側面

Vascular biology: A dark side to omega-3 fatty acids p.180

正常な脳機能に関与する脂肪酸の代謝によって形成される19,20-ジヒドロキシドコサペンタエン酸分子が、マウスモデルで糖尿病に関連する失明の進行を促進することが、今回分かった。

doi: 10.1038/d41586-017-07678-8

加齢:ポリメラーゼIIIによる長寿

Ageing: Longer life through an odd Pol enzyme p.182

進化的に保存されたRNAポリメラーゼIII酵素は、タンパク質合成や細胞の成長を駆動する要因である。今回、この必須酵素を部分的に抑制すると、酵母、線虫、ハエの寿命が延びることが分かった。

doi: 10.1038/d41586-017-07435-x

古氷河学:温暖な気候における南極氷床のダイナミクス

Palaeoglaciology: Antarctic ice dynamics in warm climates p.183

地質記録から、オーロラ地域の南極氷床が、大気が暖かかった過去の複数の期間に対照的な応答をしていたことが明らかになった。この知見は、現在の温暖化に対する氷床の応答の予測に役立つ可能性がある。

doi: 10.1038/d41586-017-08285-3

感染:ウイルスが長鎖ノンコーディングを乗っ取る

Infection: Viruses hijack a long non-coding RNA p.184

宿主細胞の代謝の操作は、ウイルスの複製サイクルに不可欠な側面である。今回、ウイルスによる細胞の長鎖ノンコーディングRNAの吸収が、この過程の重要なステップであることが分かった。

doi: 10.1038/d41586-017-07692-w

Articles

細胞生物学:ミトコンドリアのタンパク質恒常性を高めることでアミロイドβのタンパク質毒性が低下する

Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity p.187

Amyloid-β peptide proteopathies disrupt mitochondria, and restoring mitochondrial proteostasis reduces protein aggregation in animal models of amyloid-β disease.

doi: 10.1038/nature25143

創薬:アルコール依存症治療薬ジスルフィラムはp97セグレガーゼアダプターNPL4を介してがんを標的化する

Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4 p.194

Amyloid-β peptide proteopathies disrupt mitochondria, and restoring mitochondrial proteostasis reduces protein aggregation in animal models of amyloid-β disease.

doi: 10.1038/nature25016

構造生物学:ヒトTRPM4チャネルのクライオ電子顕微鏡構造

Electron cryo-microscopy structure of a human TRPM4 channel p.200

The structure of the Ca2+-activated, non-selective ion channel TRPM4 bound to the agonist Ca2+ and a modulator decavanadate, solved using electron cryo-microscopy.

doi: 10.1038/nature24674

構造生物学:カルシウム活性化型陽イオン非選択性チャネルTRPM4の構造

Structures of the calcium-activated, non-selective cation channel TRPM4 p.205

Electron cryo-microscopy structures of mouse TRPM4, a calcium-activated, non-selective cation channel, in the apo and ATP-bound states.

doi: 10.1038/nature24997

Letters

宇宙物理学:降着を受けている「非磁性」の白色矮星における磁気的にゲーティングされる降着現象

Magnetically gated accretion in an accreting ‘non-magnetic’ white dwarf p.210

A weak magnetic field regulates magnetically gated accretion of gas from a companion star onto the white dwarf in the binary system MV Lyrae, previously labelled as a ‘non-magnetic’ system.

doi: 10.1038/nature24653

生体エネルギー学:デンキウナギに着想を得た、積層されたヒドロゲルでできた柔らかい電源

An electric-eel-inspired soft power source from stacked hydrogels p.214

Miniature hydrogel compartments in scalable stacked and folded geometries were used to prepare a contact-activated artificial electric organ.

doi: 10.1038/nature24670

材料科学:力の印加によって説明される、細胞によるリガンドの空間センシング

Force loading explains spatial sensing of ligands by cells p.219

The formation of cellular adhesion complexes is important in normal and pathological cell activity, and is determined by the force imposed by the combined effect of the distribution of extracellular matrix molecules and substrate rigidity.

doi: 10.1038/nature24662

古氷河学:東南極氷床の始まりと長期的不安定性

Initiation and long-term instability of the East Antarctic Ice Sheet p.225

Geophysical and geological data reveal increased ice-sheet variability and surface meltwater—possibly analogous to future conditions—offshore of the Aurora subglacial basin of East Antarctica during warm climate intervals of the past 50 million years.

doi: 10.1038/nature25026

生物地球化学:氾濫原の樹木からの大量放出によってアマゾンにおけるメタン収支が完結する

Large emissions from floodplain trees close the Amazon methane budget p.230

Methane fluxes from the stems of Amazonian floodplain trees indicate that the escape of soil gas through wetland trees is the dominant source of methane emissions in the Amazon basin.

doi: 10.1038/nature24639

地球科学:流紋岩マグマの流動化と噴火様式を支配する組成上の転換点

A compositional tipping point governing the mobilization and eruption style of rhyolitic magma p.235

Measurements of the composition-dependent viscosity of rhyolitic magma reveal a tipping point that changes the physical properties of the melt and controls the transition between effusive and explosive eruptions.

doi: 10.1038/nature24488

発生生物学:多能性状態の移行がマウスおよびヒトの胚での形態形成を調整する

Pluripotent state transitions coordinate morphogenesis in mouse and human embryos p.239

Exit of epiblasts from an unrestricted naive pluripotent state is required for epithelialization and generation of the pro-amniotic cavity in mouse embryos and for amniotic cavity formation in human embryos and human embryonic stem cells.

doi: 10.1038/nature24675

微生物学:マイクロバイオーム規模の関連の域を超え原因微生物の特定へ

Moving beyond microbiome-wide associations to causal microbe identification p.244

Triangulation of microbe–phenotype relationships is an effective method for reducing the noise inherent in microbiota studies and enabling identification of causal microbes of disease, which may be applicable to human microbiome studies.

doi: 10.1038/nature25019

血管生物学:可溶性エポキシドヒドロラーゼの阻害は糖尿病性網膜症を防止する

Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy p.248

A product of the soluble epoxide hydrolase enzyme, 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP), is implicated in the pathogenesis of diabetic retinopathy; levels of 19,20-DHDP increase in the retinas of mice and humans with diabetes, and inhibition of its production can rescue vascular abnormalities in a mouse model of the disease.

doi: 10.1038/nature25013

免疫学:Runx3は非リンパ組織と腫瘍におけるCD8+ T細胞常在性をプログラムする

Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours p.253

Tissue-resident memory CD8+ T (TRM) cells are found at common sites of pathogen exposure, where they elicit rapid and robust protective immune responses. However, the molecular signals that control TRM cell differentiation and homeostasis are not fully understood. Here we show that mouse TRM precursor cells represent a unique CD8+ T cell subset that is distinct from the precursors of circulating memory cell populations at the levels of gene expression and chromatin accessibility. Using computational and pooled in vivo RNA interference screens, we identify the transcription factor Runx3 as a key regulator of TRM cell differentiation and homeostasis. Runx3 was required to establish TRM cell populations in diverse tissue environments, and supported the expression of crucial tissue-residency genes while suppressing genes associated with tissue egress and recirculation. Furthermore, we show that human and mouse tumour-infiltrating lymphocytes share a core tissue-residency gene-expression signature with TRM cells that is associated with Runx3 activity. In a mouse model of adoptive T cell therapy for melanoma, Runx3-deficient CD8+ tumour-infiltrating lymphocytes failed to accumulate in tumours, resulting in greater rates of tumour growth and mortality. Conversely, overexpression of Runx3 enhanced tumour-specific CD8+ T cell abundance, delayed tumour growth, and prolonged survival. In addition to establishing Runx3 as a central regulator of TRM cell differentiation, these results provide insight into the signals that promote T cell residency in non-lymphoid sites, which could be used to enhance vaccine efficacy or adoptive cell therapy treatments that target cancer.

doi: 10.1038/nature24993

細胞生物学:非カノニカルなNotch複合体が、アドヘレンスジャンクションと血管のバリア機能を調節する

A non-canonical Notch complex regulates adherens junctions and vascular barrier function p.258

The transmembrane domain of NOTCH1 plays a key role in the assembly of adherens junctions and the non-transcriptional regulation of vascular permeability that links transcriptional programs with adhesive and cytoskeletal remodelling.

doi: 10.1038/nature24998

加齢:RNAポリメラーゼIIIはTORC1の下流で寿命を制限する

RNA polymerase III limits longevity downstream of TORC1 p.263

RNA polymerase III is a key evolutionarily conserved regulator of longevity that may have potential as a therapeutic target for age-related conditions.

doi: 10.1038/nature25007

遺伝:体細胞および生殖細胞系列におけるトランスポゾンの選択的スプライシングのpiRNAを介した調節

piRNA-mediated regulation of transposon alternative splicing in the soma and germ line p.268

A new mechanism of pre-mRNA splicing regulation is revealed that is mediated by piRNA pathway components and is dependent on heterochromatin histone modifications.

doi: 10.1038/nature25018

分子生物学:α-KGDH複合体と共役したKAT2AはヒストンH3スクシニルトランスフェラーゼとして働く

KAT2A coupled with the α-KGDH complex acts as a histone H3 succinyltransferase p.273

Histone modifications, such as the frequently occurring lysine succinylation, are central to the regulation of chromatin-based processes. However, the mechanism and functional consequences of histone succinylation are unknown. Here we show that the α-ketoglutarate dehydrogenase (α-KGDH) complex is localized in the nucleus in human cell lines and binds to lysine acetyltransferase 2A (KAT2A, also known as GCN5) in the promoter regions of genes. We show that succinyl-coenzyme A (succinyl-CoA) binds to KAT2A. The crystal structure of the catalytic domain of KAT2A in complex with succinyl-CoA at 2.3 Å resolution shows that succinyl-CoA binds to a deep cleft of KAT2A with the succinyl moiety pointing towards the end of a flexible loop 3, which adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Site-directed mutagenesis indicates that tyrosine 645 in this loop has an important role in the selective binding of succinyl-CoA over acetyl-CoA. KAT2A acts as a succinyltransferase and succinylates histone H3 on lysine 79, with a maximum frequency around the transcription start sites of genes. Preventing the α-KGDH complex from entering the nucleus, or expression of KAT2A(Tyr645Ala), reduces gene expression and inhibits tumour cell proliferation and tumour growth. These findings reveal an important mechanism of histone modification and demonstrate that local generation of succinyl-CoA by the nuclear α-KGDH complex coupled with the succinyltransferase activity of KAT2A is instrumental in histone succinylation, tumour cell proliferation, and tumour development.

doi: 10.1038/nature25003

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