目次

Editorials

エボラ出血熱の流行で疲弊した西アフリカ地域では、妊娠した女性への支援が必要だ。

Fatal fallout p.5

The Ebola epidemic has had a dire effect on the health prospects of pregnant women.

doi: 10.1038/519005b

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気候変動懐疑論者であるWillie Soonの資金的背景の調査は、政治的動機によるものであり、学問の自由を脅かす恐れがある。

Gone fishing p.5

An investigation into the funding sources of climate scientists who have testified to the US Congress makes demands that have the potential to infringe on academic freedom.

doi: 10.1038/519005a

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ドレスの色が「青かどうか」をめぐるネット上での論争で、視覚認識の科学が注目を浴びている。

Hues and cry p.6

A blue dress divided the Internet — and put the science of visual perception in the spotlight.

doi: 10.1038/519006a

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News

アフリカで、エボラ出血熱流行が人々の心の健康に大きな傷を。

Ebola’s mental-health wounds linger in Africa p.13

Health-care workers struggle to help people who have been traumatized by the epidemic.

doi: 10.1038/519013a

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米国防高等研究計画局(DARPA)の緊急救援作業ロボットコンペで、25台が決勝に。

Robo-rescuers battle it out in disaster challenge p.14

Nimble bots to go head-to-head for $2-million DARPA prize.

doi: 10.1038/519014a

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IPCC(気候変動に関する政府間パネル)が、新議長選出を前に、その評価プロセスなどについて細部の変更を。

UN climate panel charts next steps p.15

IPCC prepares for new leadership and plans another assessment of climate science.

doi: 10.1038/519015a

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国連が、噴火記録や周辺人口などから世界の火山の災害リスクを評価し、公表を。

World's deadliest volcanoes identified p.16

Indonesia's population most at risk from eruptions.

doi: 10.1038/519016a

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がん治療ワクチンとして米国で初めて認可されたProvengeが、開発会社の破綻を乗り切り、存続へ。

Therapeutic cancer vaccine survives biotech bust p.17

Pharmaceutical company rescues landmark prostate-cancer treatment, Provenge.

doi: 10.1038/519017a

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干ばつに悩まされる米南西部に、貯水池からの蒸発を薄層で防ぐアイデアが。

Slick idea proposed to stretch water supplies p.18

In drought-ridden US, water managers consider using a coating one molecule thick to reduce evaporation from reservoirs.

doi: 10.1038/519018a

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News Features

発展途上国:少数派の少数派

Developing world: The minority minority p.20

女性研究者自体が少数派である途上国の科学界で、世界的に見ても女性の少ない物理科学分野で活躍している3人の研究者を紹介する。

doi: 10.1038/519020a

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公衆衛生:エボラの消えない傷痕

Maternal health: Ebola’s lasting legacy p.24

エボラ出血熱の大流行がもたらした最も深刻な被害の1つは、母体の健康への悪影響かもしれない。

doi: 10.1038/519024a

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News & Views

HIV:自身の受容体にくぎ付けにされる

HIV: Tied down by its own receptor p.36

HIVウイルスのエンベロープに結合する人工タンパク質が、サルやヒトでエイズを引き起こすウイルスへの感染からサルを守ることが分かった。遺伝子治療のこのような手法は、作製が困難なHIVワクチンの代わりとなるかもしれない。

doi: 10.1038/nature14205

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材料科学:燃料の要らないナノスケール運動

Materials science: Nanoscale locomotion without fuel p.37

グラフェンからなるナノ構造体をその下にある基板の固さを調節して一方向に動かすことができる仕組みが、コンピューターシミュレーションにより明らかにされた。

doi: 10.1038/519037a

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神経科学:「腹ぺこ!」の細胞基盤

Neuroscience: A cellular basis for the munchies p.38

マリファナが、「munchies」と言われる、我慢しにくい空腹感を引き起こす仕組みはどのようなものなのだろうか。逆説的な答えだが、これには、食欲を抑制することでよく知られている脳回路の異例な形の活性化が関わっているらしい。

doi: 10.1038/nature14206

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分子生物学:生物のドメインを超えて存在するシグナル

Molecular biology: Signals across domains of life p.40

メッセンジャーRNAに含まれ、タンパク質合成を開始させるシグナル配列は生物のドメイン間で互換性があるとは考えられていなかった。節足動物に感染するウイルスから送られるシグナルが細菌で機能することが分かり、こうした考え方に疑問が投げ掛けられた。

doi: 10.1038/nature14202

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材料科学:圧力を使うゲーティング機構

Materials science: Gating mechanism under pressure p.41

膜にあって液体で満たされている小孔を可逆的に開閉できるように設計しておくと、決まった圧力をかければ特定の液体だけが通過できるようになる。これを使うと、混ざり合わない液体の混合物を、ゲート開閉によって調節しながら分離できるようになる。

doi: 10.1038/519041a

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触媒:スイッチ1つで2通りの機能が切り替えられる触媒

Catalysis: Dual catalysis at the flick of a switch p.42

光活性化触媒ともう1種類の触媒の2つを組み合わせて使うことで、新しい化学反応が容易に行えるようになり、複雑な構造を持つ有機分子の合成に新しい道が開けた。

doi: 10.1038/519042a

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Articles

神経科学:視床下部POMCニューロンがカンナビノイド誘導性摂食を促進する

Hypothalamic POMC neurons promote cannabinoid-induced feeding p.45

Cannabinoid-induced feeding signals are shown to enhance pro-opiomelanocortin (POMC) neuronal activity in mice, causing an enhancement of β-endorphin release, which is crucial in causing this cannabinoid-induced response; these results uncover an overlooked role of hypothalamic POMC neurons in the promotion of feeding by cannabinoids.

doi: 10.1038/nature14260

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神経科学:運動の計画と運動に関わる運動皮質回路

A motor cortex circuit for motor planning and movement p.51

During movement preparation, motor cortical neuronal subpopulations that project to downstream motor areas are more selective for the direction of upcoming movement than those that project to other cortical targets, especially immediately before movement, emphasizing the need to interpret complex neuronal responses measured during behaviour in the context of hierarchically organized cortical circuits.

doi: 10.1038/nature14178

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医学:gp130–Src–YAPモジュールは炎症と上皮再生を結び付ける

A gp130–Src–YAP module links inflammation to epithelial regeneration p.57

This study demonstrates the activation of a STAT3-independent healing pathway in response to mucosal injury which involves the co-receptor for IL-6 cytokines gp130 and downstream effectors Src, Yes, YAP and Notch.

doi: 10.1038/nature14228

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Letters

宇宙物理学:惑星状星雲Henize 2-428の、双縮退しスーパー・チャンドラセカール状態を示すコア

The double-degenerate, super-Chandrasekhar nucleus of the planetary nebula Henize 2-428 p.63

The probable evolution of the planetary nebula Henize 2-428 is examined, from a close binary system in which both stars ejected their envelopes to the white dwarf stage with a short orbital period and combined mass above the Chandrasekhar limit, suggesting that the system should merge in about 700 million years and trigger a type Ia supernova.

doi: 10.1038/nature14124

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量子物理学:超伝導量子回路における繰り返しエラー検出による状態保存

State preservation by repetitive error detection in a superconducting quantum circuit p.66

A quantum error correction scheme is demonstrated in a system of superconducting qubits, and repeated quantum non-demolition measurements are used to track errors and reduce the failure rate; increasing the system size from five to nine qubits improves the failure rate further.

doi: 10.1038/nature14270

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材料科学:調節可能な多相選択性と防汚挙動を示す液体ベースのゲーティング機構

Liquid-based gating mechanism with tunable multiphase selectivity and antifouling behaviour p.70

A rapid, reversible, non-fouling gating mechanism is created by infusing a porous membrane with a capillary-stabilized liquid that reconfigures under pressure to form a liquid-lined pathway, enabling selective multiphase transport with rationally tunable differential response profiles for a variety of liquids and gases.

doi: 10.1038/nature14253

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有機化学:有機触媒反応および光酸化還元触媒反応によるアリルsp3 C–H結合の直接アリール化

The direct arylation of allylic sp3 C–H bonds via organic and photoredox catalysis p.74

The direct functionalization of unactivated sp3 C–H bonds is still one of the most challenging problems facing synthetic organic chemists. The appeal of such transformations derives from their capacity to facilitate the construction of complex organic molecules via the coupling of simple and otherwise inert building blocks, without introducing extraneous functional groups. Despite notable recent efforts, the establishment of general and mild strategies for the engagement of sp3 C–H bonds in C–C bond forming reactions has proved difficult. Within this context, the discovery of chemical transformations that are able to directly functionalize allylic methyl, methylene and methine carbons in a catalytic manner is a priority. Although protocols for direct oxidation and amination of allylic C–H bonds (that is, C–H bonds where an adjacent carbon is involved in a C = C bond) have become widely established, the engagement of allylic substrates in C–C bond forming reactions has thus far required the use of pre-functionalized coupling partners. In particular, the direct arylation of non-functionalized allylic systems would enable access to a series of known pharmacophores (molecular features responsible for a drug’s action), though a general solution to this long-standing challenge remains elusive. Here we report the use of both photoredox and organic catalysis to accomplish a mild, broadly effective direct allylic C–H arylation. This C–C bond forming reaction readily accommodates a broad range of alkene and electron-deficient arene reactants, and has been used in the direct arylation of benzylic C–H bonds.

doi: 10.1038/nature14255

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生態学:干ばつがアマゾン川流域の森林の炭素動態と炭素フラックスに与える影響

Drought impact on forest carbon dynamics and fluxes in Amazonia p.78

Severe drought in a tropical forest ecosystem suppresses photosynthetic carbon uptake and plant maintenance respiration, but growth is maintained, suggesting that, overall, less carbon is available for tree tissue maintenance and defence, which may cause the subsequent observed increase in tree mortality.

doi: 10.1038/nature14213

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古生物学:復元されたホモ・ハビリスのタイプ標本OH 7は初期ヒト属でかなり早い段階に種多様性が生じたことを示唆する

Reconstructed Homo habilis type OH 7 suggests deep-rooted species diversity in early Homo p.83

Virtually reconstructing the jaw of OH 7 reveals a remarkably primitive shape, suggesting that the Homo habilis lineage originated before 2.3 million years ago; marking deep-rooted species diversity in the genus Homo.

doi: 10.1038/nature14224

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免疫学:AAVを使って発現させたeCD4-Igは複数回のSHIV攻撃投与に対して持続性のある防御を示す

AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges p.87

The new entry inhibitor eCD4-Ig, consisting of the immunoadhesin form of CD4 (CD4-Ig) fused to a small CCR5-mimetic sulfopeptide, avidly binds two highly conserved sites of the HIV-1 Env protein; the inhibitor has high potency and breadth and can neutralize 100% of a diverse panel of neutralization-resistant HIV-1 viruses, and when delivered to macaques using an adeno-associated virus vector, it can provide effective long-term protection from multiple challenges with simian/human immunodeficiency virus.

doi: 10.1038/nature14264

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炎症:食物中の乳化剤がマウスの腸内微生物相に影響を与え、大腸炎とメタボリックシンドロームを助長する

Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome p.92

Emulsifying agents, which are common food additives in the human diet, induce low-grade inflammation and obesity/metabolic syndrome in mice, suggesting that further investigation into the potential impact of dietary emulsifiers on the gut microbiota and human heath are warranted.

doi: 10.1038/nature14232

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老化:耐性幼虫形成とは独立のインスリン/IGF-1シグナル伝達がコラーゲンリモデリングを長寿に関連付ける

Dauer-independent insulin/IGF-1-signalling implicates collagen remodelling in longevity p.97

In Caenorhabditis elegant, reduced insulin/IGF-1 signalling can promote longevity through a program that is genetically distinct from the dauer developmental pathway, and requires SKN-1-dependent collagen remodelling that is a broadly essential feature of longevity assurance pathways.

doi: 10.1038/nature14021

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がん:アキシチニブは固有の結合コンホメーションによりBCR–ABL1(T315I)を効果的に抑制する

Axitinib effectively inhibits BCR-ABL1(T315I) with a distinct binding conformation p.102

The BCR-ABL1 fusion gene is a driver oncogene in chronic myeloid leukaemia and 30–50% of cases of adult acute lymphoblastic leukaemia. Introduction of ABL1 kinase inhibitors (for example, imatinib) has markedly improved patient survival, but acquired drug resistance remains a challenge. Point mutations in the ABL1 kinase domain weaken inhibitor binding and represent the most common clinical resistance mechanism. The BCR–ABL1 kinase domain gatekeeper mutation Thr315Ile (T315I) confers resistance to all approved ABL1 inhibitors except ponatinib, which has toxicity limitations. Here we combine comprehensive drug sensitivity and resistance profiling of patient cells ex vivo with structural analysis to establish the VEGFR tyrosine kinase inhibitor axitinib as a selective and effective inhibitor for T315I-mutant BCR–ABL1-driven leukaemia. Axitinib potently inhibited BCR–ABL1(T315I), at both biochemical and cellular levels, by binding to the active form of ABL1(T315I) in a mutation-selective binding mode. These findings suggest that the T315I mutation shifts the conformational equilibrium of the kinase in favour of an active (DFG-in) A-loop conformation, which has more optimal binding interactions with axitinib. Treatment of a T315I chronic myeloid leukaemia patient with axitinib resulted in a rapid reduction of T315I-positive cells from bone marrow. Taken together, our findings demonstrate an unexpected opportunity to repurpose axitinib, an anti-angiogenic drug approved for renal cancer, as an inhibitor for ABL1 gatekeeper mutant drug-resistant leukaemia patients. This study shows that wild-type proteins do not always sample the conformations available to disease-relevant mutant proteins and that comprehensive drug testing of patient-derived cells can identify unpredictable, clinically significant drug-repositioning opportunities.

doi: 10.1038/nature14119

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生化学:天然変性タンパク質の1つはリン酸化によって折りたたまれて調節スイッチとなる

Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch p.106

The structural polymorphism of intrinsically disordered protein 4E-BP2 allows it to regulate translation initiation through post-translational modification-mediated folding, exemplifying a new and potentially general mechanism of biological regulation mediated by intrinsically disordered proteins.

doi: 10.1038/nature13999

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分子生物学:構造化された真核生物のIRES RNAによる細菌での翻訳開始

Initiation of translation in bacteria by a structured eukaryotic IRES RNA p.110

A eukaryotic viral internal ribosome entry site (IRES) element is described that binds both bacterial and eukaryotic ribosomes and initiates translation in both, demonstrating that RNA structure-based initiation can occur in both these domains of life, although in bacteria the element uses a mechanism that differs from that in eukaryotes.

doi: 10.1038/nature14219

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構造生物学:Fアクチン–トロポミオシン複合体の構造

Structure of the F-actin––tropomyosin complex p.114

Filamentous actin (F-actin) is the major protein of muscle thin filaments, and actin microfilaments are the main component of the eukaryotic cytoskeleton. Mutations in different actin isoforms lead to early-onset autosomal dominant non-syndromic hearing loss, familial thoracic aortic aneurysms and dissections, and multiple variations of myopathies. In striated muscle fibres, the binding of myosin motors to actin filaments is mainly regulated by tropomyosin and troponin. Tropomyosin also binds to F-actin in smooth muscle and in non-muscle cells and stabilizes and regulates the filaments there in the absence of troponin. Although crystal structures for monomeric actin (G-actin) are available, a high-resolution structure of F-actin is still missing, hampering our understanding of how disease-causing mutations affect the function of thin muscle filaments and microfilaments. Here we report the three-dimensional structure of F-actin at a resolution of 3.7 Å in complex with tropomyosin at a resolution of 6.5 Å, determined by electron cryomicroscopy. The structure reveals that the D-loop is ordered and acts as a central region for hydrophobic and electrostatic interactions that stabilize the F-actin filament. We clearly identify map density corresponding to ADP and Mg2+ and explain the possible effect of prominent disease-causing mutants. A comparison of F-actin with G-actin reveals the conformational changes during filament formation and identifies the D-loop as their key mediator. We also confirm that negatively charged tropomyosin interacts with a positively charged groove on F-actin. Comparison of the position of tropomyosin in F-actin–tropomyosin with its position in our previously determined F-actin–tropomyosin–myosin structure reveals a myosin-induced transition of tropomyosin. Our results allow us to understand the role of individual mutations in the genesis of actin- and tropomyosin-related diseases and will serve as a strong foundation for the targeted development of drugs.

doi: 10.1038/nature14033

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