目次

Editorial

社会が自然科学から受ける恩恵をさらに拡大したいと望むなら、政府は社会科学や人文科学へも力を注ぐ必要がある。

Time for the social sciences p.5

Governments that want the natural sciences to deliver more for society need to show greater commitment towards the social sciences and humanities.

doi: 10.1038/517005a

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News

ニカラグア運河計画に関する環境アセスメントの結果について、科学者から、第三者評価を求める声が。

Nicaragua defies canal protests p.7

Scientists call for independent environmental assessment.

doi: 10.1038/517007a

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太陽系外惑星研究を行う科学者たちが、今後の地球外生命体探査の構想を統一するための話し合いを。

Planet hunters plot a course p.8

Researchers aim to set aside differences in search for life on distant spheres.

doi: 10.1038/517008a

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エボラ出血熱の回復期患者の血漿を用いる治療法が注目されているが、この治療法は他の新興感染症にも役立つ可能性が。

Ebola raises profile of blood-based therapy p.9

Convalescent plasma therapy is trialled to fight Ebola, but could also be used for new and emerging pathogens.

doi: 10.1038/517009a

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Natureが予想する、今年の科学界で話題になるものは?

What to expect in 2015 p.10

Nature looks at what the New Year holds for science.

doi: 10.1038/517010a

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News Features

2015年の科学

Science in 2015 p.12

研究費、特許、論文など、ますます拡大し続ける世界の研究活動を、数字で予測する。

doi: 10.1038/517012a

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News & Views

分子生物学:mRNA翻訳許可シグナルは発生を制御している

Molecular biology: Entry signals control development p.24

一部の構造エレメントは、通常はタンパク質合成装置によって処理されることがないメッセンジャーRNAが翻訳されるように仕向けている。こうしたエレメント類はまた、胚の発生に関わる遺伝子の発現も制御しているらしいことが今回明らかになった。

doi: 10.1038/nature14069

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材料科学:軟骨そっくりだけど、構造はもっと単純

Materials science: Like cartilage, but simpler p.25

関節中にあって骨を覆っている関節軟骨の性質の一部は、その構成成分の間の反発力に依存している。この性質を模倣した新種の人工ゲルは、方向依存性という珍しい特性を備えている。

doi: 10.1038/517025a

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構造生物学:クローズアップで見る光合成複合体

Structural biology: Photosynthetic complex in close-up p.26

光合成に関わるタンパク質複合体である光化学系IIは、結晶学実験の際にX線による損傷を受けやすい。損傷のない複合体の高分解能構造が今回得られ、その触媒中心の詳細が明らかになった。

doi: 10.1038/nature14072

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微生物学:免疫応答の標的

Microbiology: Diverted on the way to memory p.28

黄色ブドウ球菌(Staphylococcus aureus)のプロテインAは、免疫応答の標的を変更させ、その結果、細菌由来の他の構造に対する免疫応答の有効性が低下することが分かった。この知見は、黄色ブドウ球菌に対して有効なワクチンを開発しようという現在進行中の計画の失敗の説明となる。

doi: 10.1038/nature14083

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細胞周期:出口を見つけるには3つが必要

Cell cycle: It takes three to find the exit p.29

細胞の有糸分裂の際には、染色体対が分割されて、2つの遺伝的に等価な娘細胞に分けられる。分裂酵母を使った研究で、この分割が3種のホスファターゼの連続した活性化によって誘導されることが明らかになった。

doi: 10.1038/nature14080

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地球科学:海洋循環と急速な気候変動

Earth science: Ocean circulation and rapid climate change p.30

最終氷期サイクルの間の海洋循環に関する高分解能データは、北大西洋深層水の形成とそれに伴う熱輸送が以前に考えられていたよりも安定している可能性を示唆している。

doi: 10.1038/nature14084

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Articles

分子生物学:Hoxの5′ UTR内のRNAレギュロンはリボソームに遺伝子調節の特異性をもたらす

RNA regulons in Hox 5′ UTRs confer ribosome specificity to gene regulation p.33

Specialized ribosomes (with a particular protein composition) carry out translation of specific transcripts; analysis of Hox mRNA translation in mice reveals that unique RNA structural elements within their 5′ UTRs, including internal ribosome entry sites and translation inhibitory elements, are responsible for this specialized mode of translation.

doi: 10.1038/nature14010

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構造生物学:リアノジン受容体の構造とコンホメーション切り替え機構

Architecture and conformational switch mechanism of the ryanodine receptor p.39

Using electron cryomicroscopy, the structure of the rabbit RyR1 calcium channel is determined at 6.1 Å resolution in the closed state and 8.5 Å in the open state, revealing how calcium binding to the EF-hand of RyR1 regulates channel opening and facilitates calcium-induced calcium release.

doi: 10.1038/nature13916

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構造生物学:哺乳類リアノジン受容体の構造

Structure of a mammalian ryanodine receptor p.44

Using electron cryomicroscopy, the closed-state structure of rabbit RyR1 is determined at 4.8 Å resolution; analysis confirms that the RyR1 architecture consists of a six-transmembrane ion channel with a cytosolic α-solenoid scaffold, and suggests a mechanism for Ca2+-induced channel opening.

doi: 10.1038/nature13950

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構造生物学:ウサギ由来リアノジン受容体RyR1のニア原子分解能での構造

Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution p.50

Using electron cryomicroscopy, the structure of the closed-state rabbit ryanodine receptor RyR1 in complex with its modulator FKBP12 is solved at 3.8 Å; in addition to determining structural details of the ion-conducting channel domain, three previously uncharacterized domains help to reveal a molecular scaffold that allows long-range allosteric regulation of channel activities.

doi: 10.1038/nature14063

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Letters

天体物理学:太陽の内部温度での予想よりも高かった鉄オパシティーの測定値

A higher-than-predicted measurement of iron opacity at solar interior temperatures p.56

Laboratory measurements of iron opacity made under conditions similar to those inside the Sun reveal much higher opacity than predicted, helping to resolve inconsistencies within stellar models of the internal temperatures of stars.

doi: 10.1038/nature14048

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惑星科学:タイタンの予測より大きな躍動運動のしきい値風速

Higher-than-predicted saltation threshold wind speeds on Titan p.60

Wind tunnel experiments designed to simulate the conditions on Saturn’s moon Titan yield threshold wind speeds for particle saltation higher than those predicted by models derived from simulations of terrestrial-planet conditions; the results can be reconciled by modifying the models to take into account the low ratio of particle density to fluid density on Titan.

doi: 10.1038/nature14088

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量子物理学:中性物質における量子化コンダクタンスの観測

Observation of quantized conductance in neutral matter p.64

Quantized conductance in the transport of neutral atoms is observed in an optically produced channel — either a quantum point contact or a quantum wire — between two atom reservoirs; the lowest non-zero conductance value is the universal conductance quantum, the reciprocal of Planck’s constant.

doi: 10.1038/nature14049

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材料化学:平行配向ナノシート間の静電反発力に起因する異方的力学特性を示すヒドロゲル

An anisotropic hydrogel with electrostatic repulsion between cofacially aligned nanosheets p.68

Usually materials design focuses on attractive interactions, but here a hydrogel is described whose properties are dominated by electrostatic repulsion between negatively charged titanate nanosheets embedded within it; the material, inspired by articular cartilage, deforms easily when sheared parallel to the sheets but resists compressive forces applied orthogonally.

doi: 10.1038/nature14060

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気候科学:最終氷期サイクルにおける大西洋深部の南北方向の強い鉛直循環

Strong and deep Atlantic meridional overturning circulation during the last glacial cycle p.73

Reconstruction of the Atlantic meridional overturning circulation from a highly resolved marine sedimentary record shows that a deep, vigorous overturning circulation mode has persisted for most of the last glacial cycle, dominating ocean circulation in the Atlantic, but that a shallower glacial mode prevailed during glacial maxima.

doi: 10.1038/nature14059

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分子進化学:古細菌の主要分岐群の出現は細菌からの遺伝子獲得に対応している

Origins of major archaeal clades correspond to gene acquisitions from bacteria p.77

A comparison of protein-coding genes from 134 archaeal genomes with their homologues in 1,847 bacterial genomes reveals that, during evolution, genes are transferred more often from bacteria to archaea than vice versa, and that gene influxes from bacteria can bring about the origin of major archaeal groups.

doi: 10.1038/nature13805

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幹細胞:プロテインC受容体の発現によって多能性の乳腺幹細胞を同定

Identification of multipotent mammary stem cells by protein C receptor expression p.81

Using transplantation and lineage-tracing strategies, protein C receptor is identified as a marker of mammary stem cells in mice, with potential implications for understanding the initiation of breast cancer.

doi: 10.1038/nature13851

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ウイルス学:A型肝炎ウイルスとピコルナウイルスの起源

Hepatitis A virus and the origins of picornaviruses p.85

Hepatitis A virus is a picornavirus that causes significant morbidity but remains poorly understood; this paper now provides high-resolution crystal structures of both the mature and the empty hepatitis A virus particle, which show that the three-dimensional structure resembles insect picorna-like viruses.

doi: 10.1038/nature13806

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免疫学:ヒト細胞内ISG15はインターフェロンα/βの過剰増幅と自己炎症を防ぐ

Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation p.89

Intracellular ISG15 is an interferon (IFN)-α/β-inducible ubiquitin-like modifier which can covalently bind other proteins in a process called ISGylation; it is an effector of IFN-α/β-dependent antiviral immunity in mice. We previously published a study describing humans with inherited ISG15 deficiency but without unusually severe viral diseases. We showed that these patients were prone to mycobacterial disease and that human ISG15 was non-redundant as an extracellular IFN-γ-inducing molecule. We show here that ISG15-deficient patients also display unanticipated cellular, immunological and clinical signs of enhanced IFN-α/β immunity, reminiscent of the Mendelian autoinflammatory interferonopathies Aicardi–Goutières syndrome and spondyloenchondrodysplasia. We further show that an absence of intracellular ISG15 in the patients’ cells prevents the accumulation of USP18, a potent negative regulator of IFN-α/β signalling, resulting in the enhancement and amplification of IFN-α/β responses. Human ISG15, therefore, is not only redundant for antiviral immunity, but is a key negative regulator of IFN-α/β immunity. In humans, intracellular ISG15 is IFN-α/β-inducible not to serve as a substrate for ISGylation-dependent antiviral immunity, but to ensure USP18-dependent regulation of IFN-α/β and prevention of IFN-α/β-dependent autoinflammation.

doi: 10.1038/nature13801

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細胞生物学:PP1–PP2Aホスファターゼの連携が有糸分裂の進行を制御する

A PP1–PP2A phosphatase relay controls mitotic progression p.94

The activation and coordination of phosphatase activity is important during mitotic exit; here, a mitotic phosphatase relay is described in fission yeast between the two major phosphatases, PP1 and PP2A, a mode of regulation that may be a feature of signalling networks across eukaryotes.

doi: 10.1038/nature14019

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構造生物学:フェムト秒X線パルスによって1.95 Å分解能で明らかにされた、光化学系IIの本来の構造

Native structure of photosystem II at 1.95 Å resolution viewed by femtosecond X-ray pulses p.99

Photosynthesis converts light energy into biologically useful chemical energy vital to life on Earth. The initial reaction of photosynthesis takes place in photosystem II (PSII), a 700-kilodalton homodimeric membrane protein complex that catalyses photo-oxidation of water into dioxygen through an S-state cycle of the oxygen evolving complex (OEC). The structure of PSII has been solved by X-ray diffraction (XRD) at 1.9 ångström resolution, which revealed that the OEC is a Mn4CaO5-cluster coordinated by a well defined protein environment. However, extended X-ray absorption fine structure (EXAFS) studies showed that the manganese cations in the OEC are easily reduced by X-ray irradiation, and slight differences were found in the Mn–Mn distances determined by XRD, EXAFS and theoretical studies. Here we report a ‘radiation-damage-free’ structure of PSII from Thermosynechococcus vulcanus in the S1 state at a resolution of 1.95 ångströms using femtosecond X-ray pulses of the SPring-8 ångström compact free-electron laser (SACLA) and hundreds of large, highly isomorphous PSII crystals. Compared with the structure from XRD, the OEC in the X-ray free electron laser structure has Mn–Mn distances that are shorter by 0.1–0.2 ångströms. The valences of each manganese atom were tentatively assigned as Mn1D(iii), Mn2C(iv), Mn3B(iv) and Mn4A(iii), based on the average Mn–ligand distances and analysis of the Jahn–Teller axis on Mn(iii). One of the oxo-bridged oxygens, O5, has significantly longer distances to Mn than do the other oxo-oxygen atoms, suggesting that O5 is a hydroxide ion instead of a normal oxygen dianion and therefore may serve as one of the substrate oxygen atoms. These findings provide a structural basis for the mechanism of oxygen evolution, and we expect that this structure will provide a blueprint for the design of artificial catalysts for water oxidation.

doi: 10.1038/nature13991

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構造生物学:Methylomicrobium alcaliphilumの膜内在性ステロール還元酵素の構造

Structure of an integral membrane sterol reductase from Methylomicrobium alcaliphilum p.104

Sterols are essential biological molecules in the majority of life forms. Sterol reductases including Δ14-sterol reductase (C14SR, also known as TM7SF2), 7-dehydrocholesterol reductase (DHCR7) and 24-dehydrocholesterol reductase (DHCR24) reduce specific carbon–carbon double bonds of the sterol moiety using a reducing cofactor during sterol biosynthesis. Lamin B receptor (LBR), an integral inner nuclear membrane protein, also contains a functional C14SR domain. Here we report the crystal structure of a Δ14-sterol reductase (MaSR1) from the methanotrophic bacterium Methylomicrobium alcaliphilum 20Z (a homologue of human C14SR, LBR and DHCR7) with the cofactor NADPH. The enzyme contains ten transmembrane segments (TM1–10). Its catalytic domain comprises the carboxy-terminal half (containing TM6–10) and envelops two interconnected pockets, one of which faces the cytoplasm and houses NADPH, while the other one is accessible from the lipid bilayer. Comparison with a soluble steroid 5β-reductase structure suggests that the reducing end of NADPH meets the sterol substrate at the juncture of the two pockets. A sterol reductase activity assay proves that MaSR1 can reduce the double bond of a cholesterol biosynthetic intermediate, demonstrating functional conservation to human C14SR. Therefore, our structure as a prototype of integral membrane sterol reductases provides molecular insight into mutations in DHCR7 and LBR for inborn human diseases.

doi: 10.1038/nature13797

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