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Editorials

インフルエンザウイルスなどの機能獲得研究をめぐって激しい議論が続いてきたが、どう対処するのが最善か、そろそろ合意を目指すべきだ。

A ripe time for gaining ground p.403

After three years of heated debate, the advocates and critics of gain-of-function research must work to agree on how best to regulate the work.

doi: 10.1038/514403a

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ソーシャルメディアを介した難病治療研究の支援募金運動が成功を収めたが、医学研究の支援には、動物実験の問題などについて科学機関が声明を出すという別の方法もある。

The ice bucket p.403

Social-media fun for medical research bypasses animal sensitivities.

doi: 10.1038/514403b

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ヨーロッパでは家畜用医薬品がハゲワシ類への脅威となっており、対策が必要だ。

Toxic influence p.404

Europe must act to stop livestock drugs from wiping out its vulture populations.

doi: 10.1038/514404a

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News

米政府が、危険なウイルスの機能獲得研究への助成を、一時停止へ。

US suspends risky disease research p.411

Government to cease funding gain-of-function studies that make viruses more dangerous, pending a safety assessment.

doi: 10.1038/514411a

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米国の中間選挙が間近だが、科学予算緊縮の見直しは望み薄に。

US midterm elections offer little hope for science p.412

November vote is unlikely to break a political stalemate that has squeezed research funding.

doi: 10.1038/514412a

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最古の現生人類ゲノムが解読され、出アフリカの経緯に興味深い手掛かりが。

Oldest-known human genome sequenced p.413

DNA shows a group of modern humans roamed across Asia.

doi: 10.1038/514413a

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太陽光の活用で絶望的な故障を克服し、第二のミッションを開始したNASAのケプラー宇宙望遠鏡から、早くも有望なデータが。

Sun’s stroke keeps Kepler online p.414

Space telescope beats mechanical failures to begin a second mission that will trace new celestial targets.

doi: 10.1038/514414a

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タンパク質の動的構造解析データが増えており、そうしたデータの保管がタンパク質データバンク(PDB)の大きな課題に。

Data bank struggles as protein imaging ups its game p.416

Hybrid methods to solve structures of molecular machines create a storage headache.

doi: 10.1038/514416a

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News Features

研究:倫理チーム

Human-subjects research: The ethics squad p.418

生命倫理学者たちが、科学研究で直面する幅広い倫理問題についての助言サービスを始めている。

doi: 10.1038/514418a

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古生物学:「ホビット物語」

The discovery of Homo floresiensis: Tales of the hobbit p.422

1万8000年前に生きていた現生人類の重要な親戚、ホモ・フローレシエンシスの発見に関わった科学者たちに話を聞く。

doi: 10.1038/514422a

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News & Views

気候変動:天然ガス使用構想に見つかったひび

Climate change: A crack in the natural-gas bridge p.436

統合評価モデルを使って、新たな気候政策の制定がなければ、天然ガスを潤沢に供給しても温室効果ガス排出量と気候変動にはわずかな影響しかないだろうという予測が示された。

doi: 10.1038/nature13927

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HIV:エンベロープタンパク質の目印

HIV: A stamp on the envelope p.437

HIV-1エンベロープ三量体タンパク質が標的細胞と融合する前の状態を捕捉した高分解能結晶構造は、このタンパク質複合体に対する防御免疫応答を引き出すようなワクチンの設計に役立ちそうだ。

doi: 10.1038/nature13926

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肺疾患:細胞移植による治療

Lung disease: Treatment by cell transplant p.438

遺伝子を修正したマクロファージ細胞のマウス肺への直接移植は、遺伝性の肺疾患でヒトでも見られる肺胞蛋白症の治療に効果があることが明らかになった。

doi: 10.1038/nature13758

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天文学:生まれたての惑星系をめぐる彗星群

Astronomy: Hurling comets around a planetary nursery p.440

若い惑星系中の恒星の近傍を通る多数の彗星の分析から、こうした彗星は大きく2つに分けられることが分かった。その1つは古くてガスの抜けた彗星群、もう1つはより若い彗星群で、おそらくもっと大型の惑星天体の分裂に関係していると思われる。

doi: 10.1038/514440a

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生理学:広くしてあるから入っておいで

Physiology: Relax and come in p.441

炎症の際には、免疫細胞が流れ込むためにリンパ節が腫れる。新たな研究によって、リンパ節を形作っている収縮性細胞の弛緩を引き起こすシグナル伝達経路が突き止められた。

doi: 10.1038/514441a

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HIV:効能には定常性が必要

HIV: Potency needs constancy p.442

抗体療法やワクチンの有効性を最適化する方法を明らかにした研究で、強力なHIV-1中和抗体の活性は抗体のFc領域への細胞の結合に依存することが確証された。

doi: 10.1038/514442a

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Articles

遺伝学:シベリア西部で発掘された4万5000年前の現生人類のゲノム塩基配列

Genome sequence of a 45,000-year-old modern human from western Siberia p.445

The high-quality genome sequence of a 45,000-year-old modern human from Siberia reveals that gene flow from Neanderthals into the ancestors of this individual had already occurred about 7,000 to 13,000 years earlier; genomic comparisons show that he belonged to a population that lived close in time to the separation of populations in east and west Eurasia and that may represent an early modern human radiation out of Africa that has no direct descendants today.

doi: 10.1038/nature13810

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医学:肺内マクロファージ移植治療

Pulmonary macrophage transplantation therapy p.450

This study reports the correction of pulmonary alveolar proteinosis (PAP) in Csf2rb–/– mice by a single transfer of either wild-type or gene-corrected macrophages directly to the lungs — the transplanted macrophages persisted for at least 1 year; this transplantation strategy obviated the need for myeloablation and immunosuppression and should be a feasible therapy for humans with hereditary PAP.

doi: 10.1038/nature13807

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構造生物学:融合前のHIV-1 Env三量体の構造と免疫認識

Structure and immune recognition of trimeric pre-fusion HIV-1 Env p.455

A crystal structure of the human immunodeficiency virus Env trimer, used by the virus to infect cells, is determined here; the new structure, which shows the pre-fusion form of Env, increases our understanding of the fusion mechanism and of how the conformation of Env allows the virus to evade the immune response.

doi: 10.1038/nature13808

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Letters

宇宙:がか座β星系における太陽系外彗星の2つの種族

Two families of exocomets in the β Pictoris system p.462

The young planetary system surrounding the star β Pictoris harbours active minor bodies. These asteroids and comets produce a large amount of dust and gas through collisions and evaporation, as happened early in the history of our Solar System. Spectroscopic observations of β Pictoris reveal a high rate of transits of small evaporating bodies, that is, exocomets. Here we report an analysis of more than 1,000 archival spectra gathered between 2003 and 2011, which provides a sample of about 6,000 variable absorption signatures arising from exocomets transiting the disk of the parent star. Statistical analysis of the observed properties of these exocomets allows us to identify two populations with different physical properties. One family consists of exocomets producing shallow absorption lines, which can be attributed to old exhausted (that is, strongly depleted in volatiles) comets trapped in a mean motion resonance with a massive planet. Another family consists of exocomets producing deep absorption lines, which may be related to the recent fragmentation of one or a few parent bodies. Our results show that the evaporating bodies observed for decades in the β Pictoris system are analogous to the comets in our own Solar System.

doi: 10.1038/nature13849

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宇宙:太陽面爆発の誘因となる磁場環境の特徴と予測

Characterizing and predicting the magnetic environment leading to solar eruptions p.465

Modelling the solar magnetic field using observations of the photospheric field in the four-day period preceding a coronal mass ejection shows that the formation and later ejection of a twisted rope of magnetic flux provides the physical mechanism responsible for the ejection.

doi: 10.1038/nature13815

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ナノテクノロジー:エネルギー変換とピエゾトロニクスに使う単原子層MoS2の圧電性

Piezoelectricity of single-atomic-layer MoS2 for energy conversion and piezotronics p.470

The two-dimensional semiconducting material molybdenum disulphide shows strong piezoelectricity in its single-layered form, suggesting possible applications in nanoscale electromechanical devices for sensing and energy harvesting.

doi: 10.1038/nature13792

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無機化学:9価の形式酸化状態をとるイリジウム含有化合物の同定

Identification of an iridium-containing compound with a formal oxidation state of IX p.475

The tetrahedral iridium tetroxide cation [IrO4]+, which has an iridium 5d0 valence electron configuration and a formal oxidation state of IX, is generated in the gas phase, identified by infrared photodissociation spectroscopy, and predicted, by quantum chemical calculations, to be the most stable of all possible [IrO4]+ isomers.

doi: 10.1038/nature13795

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気候科学:永久凍土の融解に対する微生物群集の反応が調節するメタンの動態

Methane dynamics regulated by microbial community response to permafrost thaw p.478

The abundance of key microbial lineages can be used to predict atmospherically relevant patterns in methane isotopes and the proportion of carbon metabolized to methane during permafrost thaw, suggesting that microbial ecology may be important in ecosystem-scale responses to global change.

doi: 10.1038/nature13798

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気候科学:10年スケールの気候変動に対する天然ガス使用量の増加の限定的な影響

Limited impact on decadal-scale climate change from increased use of natural gas p.482

It has been hoped that making abundant natural gas available by hydraulic fracturing (fracking) would reduce greenhouse gas emissions but now modelling shows that increased consumption will have limited effect on climate change.

doi: 10.1038/nature13837

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農業:低い環境コストで多くの穀物を生産する

Producing more grain with lower environmental costs p.486

In an experiment across China to test integrated soil–crop system management for rice, wheat and maize against current practice, improvements in grain yield are equivalent to high-input techniques, but nutrient use, nutrient loss and greenhouse gas emissions are lower than current practice.

doi: 10.1038/nature13609

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発生生物学:後脳分節化のHox調節ネットワークは脊椎動物系統樹の基部に保存されている

A Hox regulatory network of hindbrain segmentation is conserved to the base of vertebrates p.490

Nested Hox expression domains are found in jawed vertebrates and in non-vertebrate chordates, but it is unclear whether there is a link between brain regionalization and Hox expression in jawless vertebrates; here, Hox expression is shown to be integrated with hindbrain segmentation in lampreys.

doi: 10.1038/nature13723

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進化遺伝学:コロンブス以前のマイコバクテリウム属細菌のゲノムから、新世界のヒト結核の起源の1つがアシカ・アザラシ類であることが判明

Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis p.494

Three 1,000-year-old mycobacterial genomes from Peruvian human skeletons reveal that a member of the Mycobacterium tuberculosis complex derived from seals caused human disease before contact in the Americas.

doi: 10.1038/nature13591

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免疫学:樹状細胞は細網繊維芽細胞ネットワークの張力とリンパ節の膨張を制御する

Dendritic cells control fibroblastic reticular network tension and lymph node expansion p.498

During inflammation, the lymph node stromal compartment is shown to accommodate high numbers of infiltrating lymphocytes by relaxing the cytoskeleton of fibroblastic reticular cells, allowing the latter to stretch and the lymph node to expand.

doi: 10.1038/nature13814

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細胞:膵δ細胞の齢依存的なインスリン産生細胞への変換による糖尿病からの回復

Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers p.503

Total or near-total loss of insulin-producing β-cells occurs in type 1 diabetes. Restoration of insulin production in type 1 diabetes is thus a major medical challenge. We previously observed in mice in which β-cells are completely ablated that the pancreas reconstitutes new insulin-producing cells in the absence of autoimmunity. The process involves the contribution of islet non-β-cells; specifically, glucagon-producing α-cells begin producing insulin by a process of reprogramming (transdifferentiation) without proliferation. Here we show the influence of age on β-cell reconstitution from heterologous islet cells after near-total β-cell loss in mice. We found that senescence does not alter α-cell plasticity: α-cells can reprogram to produce insulin from puberty through to adulthood, and also in aged individuals, even a long time after β-cell loss. In contrast, before puberty there is no detectable α-cell conversion, although β-cell reconstitution after injury is more efficient, always leading to diabetes recovery. This process occurs through a newly discovered mechanism: the spontaneous en masse reprogramming of somatostatin-producing δ-cells. The juveniles display ‘somatostatin-to-insulin’ δ-cell conversion, involving dedifferentiation, proliferation and re-expression of islet developmental regulators. This juvenile adaptability relies, at least in part, upon the combined action of FoxO1 and downstream effectors. Restoration of insulin producing-cells from non-β-cell origins is thus enabled throughout life via δ- or α-cell spontaneous reprogramming. A landscape with multiple intra-islet cell interconversion events is emerging, offering new perspectives for therapy.

doi: 10.1038/nature13633

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がん:高脂肪食を介するディスバイオーシスが、肥満とは独立に腸のがんの発生を促進する

High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity p.508

A high-fat diet promotes intestinal tumorigenesis independently of obesity in a mouse model with oncogene activation, by changing the composition of the gut microbiota and altering immune regulation.

doi: 10.1038/nature13398

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がん:急性リンパ芽球性白血病で2つのヒストン3リシン27デメチラーゼが果たす対照的な役割

Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia p.513

T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with a poor prognosis and no available targeted therapies; now two histone H3 lysine 27 demethylases, JMJD3 and UTX, are shown to have contrasting roles in human T-ALL cells and a mouse model of the disease, and a small molecule demethylase inhibitor is found to inhibit the growth of T-ALL cell lines, introducing a potential therapeutic avenue for acute leukaemia.

doi: 10.1038/nature13605

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構造生物学:Zn2+輸送性P型ATPアーゼの構造と機構

Structure and mechanism of Zn2+-transporting P-type ATPases p.518

Zinc is an essential micronutrient for all living organisms. It is required for signalling and proper functioning of a range of proteins involved in, for example, DNA binding and enzymatic catalysis. In prokaryotes and photosynthetic eukaryotes, Zn2+-transporting P-type ATPases of class IB (ZntA) are crucial for cellular redistribution and detoxification of Zn2+ and related elements. Here we present crystal structures representing the phosphoenzyme ground state (E2P) and a dephosphorylation intermediate (E2·Pi) of ZntA from Shigella sonnei, determined at 3.2 Å and 2.7 Å resolution, respectively. The structures reveal a similar fold to Cu+-ATPases, with an amphipathic helix at the membrane interface. A conserved electronegative funnel connects this region to the intramembranous high-affinity ion-binding site and may promote specific uptake of cellular Zn2+ ions by the transporter. The E2P structure displays a wide extracellular release pathway reaching the invariant residues at the high-affinity site, including C392, C394 and D714. The pathway closes in the E2·Pi state, in which D714 interacts with the conserved residue K693, which possibly stimulates Zn2+ release as a built-in counter ion, as has been proposed for H+-ATPases. Indeed, transport studies in liposomes provide experimental support for ZntA activity without counter transport. These findings suggest a mechanistic link between PIB-type Zn2+-ATPases and PIII-type H+-ATPases and at the same time show structural features of the extracellular release pathway that resemble PII-type ATPases such as the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) and Na+, K+-ATPase. These findings considerably increase our understanding of zinc transport in cells and represent new possibilities for biotechnology and biomedicine.

doi: 10.1038/nature13618

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