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Editorials

嗜癖の研究では、資金提供者が介入するケースが多く見られることが明らかとなったが、資金提供に研究の自由を奪うような条項を設けるべきではない。

Censorship of addiction research is an abuse of science p.133

Researchers must stand up to funders that insist on gagging clauses.

doi: 10.1038/nature.2017.21948

科学は「真実と無知との闘い」という単純なものではなく、政治にアンチ科学のレッテル貼りをするのはよくない。

Beware the anti-science label p.133

Presenting science as a battle for truth against ignorance is an unhelpful exaggeration.

doi: 10.1038/545133b

ブレインストーミングは、科学問題の議論には最適の方法ではない。

Brainstorming is not the way to discuss scientific issues p.134

An intellectual free-for-all doesn’t lead to the common ground on which research can build.

doi: 10.1038/545134a

News

衛星写真から、発展途上国の詳しい居住状況を明らかにすることが可能に。

Satellite images reveal gaps in global population data p.141

Algorithms help to produce precise maps of where people in developing countries live and work.

doi: 10.1038/545141a

米国立衛生研究所(NIH)が、個々の研究者の助成に限度額を設ける方針を。

NIH grant limits rile biomedical research community p.142

Scientists are split over whether limiting grant support to individuals will help young researchers or hurt collaboration.

doi: 10.1038/nature.2017.21949

免疫細胞の地図が、がん治療に役立つ可能性が。

Cell maps reveal fresh details on how the immune system fights cancer p.143

Immune cells that encompass and invade tumours could dictate the success or failure of therapy.

doi: 10.1038/nature.2017.21931

ガーナで、南アフリカを除くアフリカ大陸初の電波望遠鏡が、まもなく運用開始へ。

Ghana telescope heralds first pan-African array p.144

By converting a defunct communications dish, astronomers are breaking ground on Earth and beyond.

doi: 10.1038/545144a

科学出版界が、有料コンテンツを「適正に共有する」方法について議論を。

Science publishers try new tack to combat unauthorized paper sharing p.145

Rise in copyright breaches prompts industry to discuss ways to allow ‘fair sharing’ of articles.

doi: 10.1038/545145a

News Features

生物工学:偽造とのひそかな闘い

The secret war against counterfeit science p.148

中国では偽の研究試薬が横行しており、こうした事態に一部の科学者たちは反撃を試みている。

doi: 10.1038/545148a

News & Views

幹細胞:サブクローン戦争

Stem cells: Subclone wars p.160

多能性幹細胞は、あらゆる種類の細胞を生み出すが、in vitroで増殖させるとがんを生じる遺伝子変異を獲得する場合があることが今回分かった。この知見は、基礎研究や臨床における多能性細胞の使用に影響を及ぼす。

doi: 10.1038/nature22490

水文学:アジアの氷河は頼りになる水源である

Hydrology: Asian glaciers are a reliable water source p.161

南アジアの一部と中央アジアの人々、経済、農業は山々から流れる水に依存している。こうした地域の一部では、特に氷河の融解が干ばつの重要な水源であることが、今回モデリングによって示唆された。

doi: 10.1038/545161a

構造生物学:揺れ動くイオン輸送酵素

Structural Biology: An ion-transport enzyme that rocks p.162

膜全体にまたがるATPアーゼと呼ばれる酵素の結晶構造から、この酵素は複雑な運動をすることが以前明らかにされている。今回、この運動には、膜の決まった位置での揺動が含まれることが明らかになった。

doi: 10.1038/nature22492

量子物理学:分子の制御を可能にする原子の使者

Quantum Physics: Atomic envoy enables molecular control p.164

仲介原子を使って近傍分子のエネルギー状態を調べ、極めて高い精度の分光法に不可欠な「量子重ね合わせ」を生成する、新たな分子操作法が開発された。

doi: 10.1038/545164a

分子生物学:DNA損傷応答の一長一短

Molecular biology: The long and short of a DNA-damage response p.165

紫外光はDNAを損傷することがあり、遺伝子転写の全般的な停止の引き金となるが、一部の遺伝子は紫外光によって活性化される。この直感に反したふるまいを調べたところ、意外な遺伝子調節機構が明らかになった。

doi: 10.1038/nature22488

人工知能:言語分析の社会への影響

Artificial Intelligence: A social spin on language analysis p.166

オンラインディスカッションにおける個人攻撃の横行と影響の解明は、困難である。クラウドソーシングと機械学習を組み合わせた手法によって解明が進む可能性があるが、限界も考慮しなければならない。

doi: 10.1038/545166a

Articles

水文学:アジアの氷河は干ばつを和らげる地域的に重要な緩衝装置である

Asia’s glaciers are a regionally important buffer against drought p.169

Glaciers in the high mountains of Asia provide a uniquely drought-resilient source of water, supplying summer meltwater sufficient for the basic needs of 136 million people.

doi: 10.1038/nature22062

がん:黒色腫の主要サブタイプのゲノム全体像

Whole-genome landscapes of major melanoma subtypes p.175

The first large, high-coverage whole-genome sequencing study of melanomas from cutaneous, acral and mucosal sites.

doi: 10.1038/nature22071

神経科学:前頭部の視床皮質ループにおける持続的活動の維持

Maintenance of persistent activity in a frontal thalamocortical loop p.181

Thalamic neurons show selective persistent activity that predicts movement direction, and their photoinhibition decreases activity in the anterior lateral motor cortex, and vice versa, suggesting that persistent activity requires reciprocal excitation in a thalamocortical loop.

doi: 10.1038/nature22324

がん幹細胞:LGR5+ヒト大腸がん幹細胞の可視化と標的治療

Visualization and targeting of LGR5+ human colon cancer stem cells p.187

LGR5+ cells in human colorectal cancer tissue xenografted into mice act as cancer stem cells, and differentiated cancer cells can revert to cancer stem cells and express LGR5 after ablation of existing LGR5+ cells.

doi: 10.1038/nature22081

構造生物学:カルシウムポンプ結晶を用いて明らかになったタンパク質–リン脂質相互作用

Protein–phospholipid interplay revealed with crystals of a calcium pump p.193

Solvent contrast modulation reveals how the lipid bilayer actively participates in the conformational switches of Ca2+-ATPase through the actions of tryptophan, arginine and lysine residues, which function as membrane floats and anchors.

doi: 10.1038/nature22357

Letters

惑星科学:イオのロキ・パテラにおける多相の火山性地表更新作用

Multi-phase volcanic resurfacing at Loki Patera on Io p.199

Interferometric telescope observations of the Jovian moon Io reveal that the floor of the Loki Patera volcano has been resurfaced in two waves, with different starting times and velocities.

doi: 10.1038/nature22339

量子物理学:単一分子イオンの純粋量子状態の生成とコヒーレント操作

Preparation and coherent manipulation of pure quantum states of a single molecular ion p.203

By exploiting a co-trapped Ca+ ion, a single CaH+ ion is prepared in pure quantum states, which are coherently manipulated, using a protocol that could easily be extended to other molecular ion species.

doi: 10.1038/nature22338

エネルギー科学:光照射がハロゲン化金属ペロブスカイト膜の形成に与える影響

The effect of illumination on the formation of metal halide perovskite films p.208

Films of metal halide perovskite are used as the absorber material in solar cells, and light irradiation during their formation is shown to affect their crystallization, morphology and photovoltaic performance.

doi: 10.1038/nature22072

化学:脱炭酸的アルケニル化

Decarboxylative alkenylation p.213

Starting with alkyl carboxylic acids, a simple olefin synthesis using any substitution pattern or geometry, based on amide-bond synthesis with nickel- or iron-based catalysis, is described.

doi: 10.1038/nature22307

神経科学:視床による皮質間結合の増幅が注意制御を維持する

Thalamic amplification of cortical connectivity sustains attentional control p.219

The mediodorsal nucleus of the thalamus amplifies the functional connectivity of the prefrontal cortex, thereby sustaining cortical representations of rule sets without relaying categorical information.

doi: 10.1038/nature22073

発生生物学:脈管発生のFGF依存性代謝制御

FGF-dependent metabolic control of vascular development p.224

Fibroblast growth factor receptor (FGFR) signalling is a crucial regulator of endothelial metabolism and vascular development.

doi: 10.1038/nature22322

幹細胞:ヒト多能性幹細胞は頻繁にP53のドミナントネガティブ変異を獲得し、それを増幅する

Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations p.229

The authors surveyed whole-exome and RNA-sequencing data from 252 unique pluripotent stem cell lines, some of which are in the pipeline for clinical use, and found that approximately 5% of cell lines had acquired mutations in the TP53 gene that allow mutant cells to rapidly outcompete non-mutant cells, but do not prevent differentiation.

doi: 10.1038/nature22312

細胞シグナル伝達:カノニカルなWntおよびβカテニンシグナル伝達の表現型を模写する代替Wntアゴニスト

Surrogate Wnt agonists that phenocopy canonical Wnt and β-catenin signalling p.234

Wnt proteins modulate cell proliferation and differentiation and the self-renewal of stem cells by inducing β-catenin-dependent signalling through the Wnt receptor frizzled (FZD) and the co-receptors LRP5 and LRP6 to regulate cell fate decisions and the growth and repair of several tissues. The 19 mammalian Wnt proteins are cross-reactive with the 10 FZD receptors, and this has complicated the attribution of distinct biological functions to specific FZD and Wnt subtype interactions. Furthermore, Wnt proteins are modified post-translationally by palmitoylation, which is essential for their secretion, function and interaction with FZD receptors. As a result of their acylation, Wnt proteins are very hydrophobic and require detergents for purification, which presents major obstacles to the preparation and application of recombinant Wnt proteins. This hydrophobicity has hindered the determination of the molecular mechanisms of Wnt signalling activation and the functional importance of FZD subtypes, and the use of Wnt proteins as therapeutic agents. Here we develop surrogate Wnt agonists, water-soluble FZD–LRP5/LRP6 heterodimerizers, with FZD5/FZD8-specific and broadly FZD-reactive binding domains. Similar to WNT3A, these Wnt agonists elicit a characteristic β-catenin signalling response in a FZD-selective fashion, enhance the osteogenic lineage commitment of primary mouse and human mesenchymal stem cells, and support the growth of a broad range of primary human organoid cultures. In addition, the surrogates can be systemically expressed and exhibit Wnt activity in vivo in the mouse liver, regulating metabolic liver zonation and promoting hepatocyte proliferation, resulting in hepatomegaly. These surrogates demonstrate that canonical Wnt signalling can be activated by bi-specific ligands that induce receptor heterodimerization. Furthermore, these easily produced, non-lipidated Wnt surrogate agonists facilitate functional studies of Wnt signalling and the exploration of Wnt agonists for translational applications in regenerative medicine.

doi: 10.1038/nature22306

幹細胞:Lgr5+腸幹細胞の自己複製におけるWntとR-spondinのリガンドの差異

Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal p.238

The canonical Wnt/β-catenin signalling pathway governs diverse developmental, homeostatic and pathological processes. Palmitoylated Wnt ligands engage cell-surface frizzled (FZD) receptors and LRP5 and LRP6 co-receptors, enabling β-catenin nuclear translocation and TCF/LEF-dependent gene transactivation. Mutations in Wnt downstream signalling components have revealed diverse functions thought to be carried out by Wnt ligands themselves. However, redundancy between the 19 mammalian Wnt proteins and 10 FZD receptors and Wnt hydrophobicity have made it difficult to attribute these functions directly to Wnt ligands. For example, individual mutations in Wnt ligands have not revealed homeostatic phenotypes in the intestinal epithelium—an archetypal canonical, Wnt pathway-dependent, rapidly self-renewing tissue, the regeneration of which is fueled by proliferative crypt Lgr5+ intestinal stem cells (ISCs). R-spondin ligands (RSPO1–RSPO4) engage distinct LGR4–LGR6, RNF43 and ZNRF3 receptor classes, markedly potentiate canonical Wnt/β-catenin signalling, and induce intestinal organoid growth in vitro and Lgr5+ ISCs in vivo. However, the interchangeability, functional cooperation and relative contributions of Wnt versus RSPO ligands to in vivo canonical Wnt signalling and ISC biology remain unknown. Here we identify the functional roles of Wnt and RSPO ligands in the intestinal crypt stem-cell niche. We show that the default fate of Lgr5+ ISCs is to differentiate, unless both RSPO and Wnt ligands are present. However, gain-of-function studies using RSPO ligands and a new non-lipidated Wnt analogue reveal that these ligands have qualitatively distinct, non-interchangeable roles in ISCs. Wnt proteins are unable to induce Lgr5+ ISC self-renewal, but instead confer a basal competency by maintaining RSPO receptor expression that enables RSPO ligands to actively drive and specify the extent of stem-cell expansion. This functionally non-equivalent yet cooperative interaction between Wnt and RSPO ligands establishes a molecular precedent for regulation of mammalian stem cells by distinct priming and self-renewal factors, with broad implications for precise control of tissue regeneration.

doi: 10.1038/nature22313

免疫学:抗原特異的制御性T細胞によるHLA関連自己免疫の優性保護

Dominant protection from HLA-linked autoimmunity by antigen-specific regulatory T cells p.243

The molecular mechanism of Goodpasture disease is modelled to mechanistically determine how a human leukocyte antigen (HLA) allele can exert its dominant protective effect in autoimmune disease.

doi: 10.1038/nature22329

構造生物学:コアメディエーターの3.4 Å分解能での構造により拡張された転写開始複合体モデル

Core Mediator structure at 3.4 Å extends model of transcription initiation complex p.248

The 3.4 Å crystal structure of the 15-subunit core Mediator complex in yeast.

doi: 10.1038/nature22328

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