目次

Editorials

地球温暖化に対して言葉だけの対応や小手先の対策を続ける、政治的惰性を打破すべきだ。

Words are not enough p.153

The political inertia that characterizes the world’s response to global warming cannot continue. Politicians and policy-makers must follow the climate’s lead — and change.

doi: 10.1038/492153a

水中から陸上へと生命がたどった道筋について、化石から、また予想外の見方が登場した。

Life on land p.153

Evidence for the first land life is controversial, but the fossil record has a tendency to surprise.

doi: 10.1038/492153b

ネイチャー・パブリッシング・グループ(NPG)が、Nature を含む9つのジャーナルを閲覧可能な、iPadアプリの新バージョンの提供を開始。

Announcement: A new iPad app for Nature readers p.154

doi: 10.1038/492154a

News

米国の小惑星有人探査計画の行く手に暗雲が。

Duelling visions stall NASA p.161

A US plan to send humans to explore an asteroid is losing momentum.

doi: 10.1038/492161a

深海底から真菌が見つかり、新たな抗生物質の発見に期待が。

Ancient fungi found in deep-sea mud p.163

Discovery raises hopes that sea floor could yield previously unknown antibiotics.

doi: 10.1038/492163a

六ホウ化サマリウム(SmB6)が、「トポロジカル絶縁体」の解明の手がかりに。

Hopes surface for exotic insulator p.165

Findings by three teams may solve a 40-year-old mystery.

doi: 10.1038/492165a

中東でコロナウイルスに似た新ウイルス感染が相次いで見つかり、監視を強化へ。

Clusters of coronavirus cases put scientists on alert p.166

Surveillance ramped up after novel virus is identified in three Middle Eastern countries.

doi: 10.1038/492166a

NIHが、若手研究者の養成プログラムを拡充し、多様性を高める取り組みを。

NIH tackles major workforce issues p.167

US agency aims to expand training options for graduate students and to increase demographic diversity.

doi: 10.1038/492167a

閉鎖予定だったメルクセローノ社の研究拠点が、巨額の寄付を得て、復活へ。

Cash injection set to revive Swiss drug site p.168

Merck Serono facility could become biotech research hub.

doi: 10.1038/492168a

News Features

極地研究:はさみ付きのトラブル

Polar research: Trouble bares its claws p.170

海水温の上昇によって南極の大陸棚にカニが侵入し、貴重な生態系が脅かされている。

doi: 10.1038/492170a

コンピューター工学:熱を感じる

Computer engineering: Feeling the heat p.174

集積回路の小型化が進むにつれ、その冷却方法が重要な課題となっている。

doi: 10.1038/492174a

News & Views

フォーラム:合成:建設的な議論

Synthesis: A constructive debate p.188

合成化学は有用な化合物、特に自然から得ることが難しい化合物を作り出すのにずっと使われてきた。だが、合成生物学はまた別の戦略として発達しつつある。1人の生物学研究者と2人の化学研究者が、それぞれの専門分野における優れた合成能力の価値について論じている。

doi: 10.1038/492188a

細胞生物学:リボソームの荷揚げを許可する

Cell biology: All clear for ribosome landing p.189

RNAの足場によって安定化される顕著な構造再編成が見つかったことは、新生タンパク質が細胞質からどのようにして搬出されるかを説明するのに役立つ。

doi: 10.1038/492189a

宇宙物理学:離れた連星系は当初は3つの星として生まれた

Astrophysics: A pas de trois birth for wide binary stars p.191

理論では、真の双子星は遠く離れていることはないだろうと考えられているが、非常に遠く離れた連星系がこの説に疑問を投げかけている。シミュレーションでは、このような双子星は実際には三つ子であり、そのうちの2つが1つの星のように装って、3つ目の星を遠くに追いやっていることが示唆されている。

doi: 10.1038/nature11762

天文学:塵の問題をクリアする

Astronomy: Clearing up the dust p.192

宇宙が発達していく際の星形成の歴史の構築には、星の光が銀河内の塵によってどのようにして吸収されていくのかを解明しなくてはならない。銀河全体にわたるこのような吸収は以前に考えられていたほど普遍性はないらしいことがわかってきた。

doi: 10.1038/492192a

経済学:赤字の多様性保全

Economics: Conservation in the red p.193

生物多様性条約は、種の絶滅という脅威を2020年までに地球全体で低減することを約束している。解析によれば、この目標は達成可能だが、それには投資が現在よりもかなり増やすことが必要だと考えられる。

doi: 10.1038/492193a

細胞生物学:脱アセチル化による細胞死

Cell biology: Death by deacetylation p.194

壊死はさまざまな疾患に関連して見られるが、プログラムされた細胞死の中でおそらくは最も解明が進んでいないものである。今回、タンパク質のサーチュインが、脱アセチル化反応を介して壊死の一部を調節していることが明らかになった。

doi: 10.1038/nature11761

生化学:たやすく越された分子ハードル

Biochemistry: Molecular hurdles cleared with ease p.195

1分子観察研究によって、二本鎖DNAの片方の鎖に巻きついてから鎖に沿ってすべっていき、その鎖をもう一方の鎖から分ける働きをする輪状の酵素が明らかになった、この酵素は、経路上に分子障壁があれば自身の輪を一時的に開くことでそれを回避している。

doi: 10.1038/nature11758

応用物理学:熱を光に変換する分子群

Applied physics: Molecules that convert heat into light p.197

ある蛍光性有機分子群が設計され、効率が非常に高い発光ダイオードの作製が可能になった。このデバイスは、従来からある類似品に対する競争相手となるかもしれない。

doi: 10.1038/492197a

Articles

細胞:NAD依存性デアセチラーゼSIRT2はプログラムされた壊死に必要である

The NAD-dependent deacetylase SIRT2 is required for programmed necrosis p.199

Although initially viewed as unregulated, increasing evidence suggests that cellular necrosis often proceeds through a specific molecular program. In particular, death ligands such as tumour necrosis factor (TNF)-α activate necrosis by stimulating the formation of a complex containing receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3). Relatively little is known regarding how this complex formation is regulated. Here, we show that the NAD-dependent deacetylase SIRT2 binds constitutively to RIP3 and that deletion or knockdown of SIRT2 prevents formation of the RIP1–RIP3 complex in mice. Furthermore, genetic or pharmacological inhibition of SIRT2 blocks cellular necrosis induced by TNF-α. We further demonstrate that RIP1 is a critical target of SIRT2-dependent deacetylation. Using gain- and loss-of-function mutants, we demonstrate that acetylation of RIP1 lysine 530 modulates RIP1–RIP3 complex formation and TNF-α-stimulated necrosis. In the setting of ischaemia-reperfusion injury, RIP1 is deacetylated in a SIRT2-dependent fashion. Furthermore, the hearts of Sirt2−/− mice, or wild-type mice treated with a specific pharmacological inhibitor of SIRT2, show marked protection from ischaemic injury. Taken together, these results implicate SIRT2 as an important regulator of programmed necrosis and indicate that inhibitors of this deacetylase may constitute a novel approach to protect against necrotic injuries, including ischaemic stroke and myocardial infarction.

doi: 10.1038/nature11700

細胞:DNA複製ヘリカーゼによるタンパク質障害物の回避

Bypass of a protein barrier by a replicative DNA helicase p.205

Replicative DNA helicases generally unwind DNA as a single hexamer that encircles and translocates along one strand of the duplex while excluding the complementary strand (known as steric exclusion). By contrast, large T antigen, the replicative DNA helicase of the simian virus 40 (SV40), is reported to function as a pair of stacked hexamers that pumps double-stranded DNA through its central channel while laterally extruding single-stranded DNA. Here we use single-molecule and ensemble assays to show that large T antigen assembled on the SV40 origin unwinds DNA efficiently as a single hexamer that translocates on single-stranded DNA in the 3′-to-5′ direction. Unexpectedly, large T antigen unwinds DNA past a DNA–protein crosslink on the translocation strand, suggesting that the large T antigen ring can open to bypass bulky adducts. Together, our data underscore the profound conservation among replicative helicase mechanisms, and reveal a new level of plasticity in the interactions of replicative helicases with DNA damage.

doi: 10.1038/nature11730

構造生物学:ツインアルギニンタンパク質輸送系のTatCコアの構造

Structure of the TatC core of the twin-arginine protein transport system p.210

The twin-arginine translocation (Tat) pathway is one of two general protein transport systems found in the prokaryotic cytoplasmic membrane and is conserved in the thylakoid membrane of plant chloroplasts. The defining, and highly unusual, property of the Tat pathway is that it transports folded proteins, a task that must be achieved without allowing appreciable ion leakage across the membrane. The integral membrane TatC protein is the central component of the Tat pathway. TatC captures substrate proteins by binding their signal peptides. TatC then recruits TatA family proteins to form the active translocation complex. Here we report the crystal structure of TatC from the hyperthermophilic bacterium Aquifex aeolicus. This structure provides a molecular description of the core of the Tat translocation system and a framework for understanding the unique Tat transport mechanism.

doi: 10.1038/nature11683

薬学:多重薬理作用プロファイルを持つリガンドの自動設計

Automated design of ligands to polypharmacological profiles p.215

The clinical efficacy and safety of a drug is determined by its activity profile across many proteins in the proteome. However, designing drugs with a specific multi-target profile is both complex and difficult. Therefore methods to design drugs rationally a priori against profiles of several proteins would have immense value in drug discovery. Here we describe a new approach for the automated design of ligands against profiles of multiple drug targets. The method is demonstrated by the evolution of an approved acetylcholinesterase inhibitor drug into brain-penetrable ligands with either specific polypharmacology or exquisite selectivity profiles for G-protein-coupled receptors. Overall, 800 ligand–target predictions of prospectively designed ligands were tested experimentally, of which 75% were confirmed to be correct. We also demonstrate target engagement in vivo. The approach can be a useful source of drug leads when multi-target profiles are required to achieve either selectivity over other drug targets or a desired polypharmacology.

doi: 10.1038/nature11691

Letters

宇宙:三重連星系の力学的な進化による最も離れた連星系の形成

Formation of the widest binary stars from dynamical unfolding of triple systems p.221

An explanation for the formation of binary systems in which the components are extremely far apart is proposed: triple systems can break up and send one component far away by taking energy from the remaining binary, bringing the two stars so close together that from a distance they appear like one star.

doi: 10.1038/nature11662

物理:Fe XVII発光問題の起源としての予想外に低い振動子強度

An unexpectedly low oscillator strength as the origin of the Fe xvii emission problem p.225

Fluorescence of iron ions induced by an X-ray laser allows the relative oscillator strength for Fe xvii emission to be determined; it is found to differ by 3.6σ from the best quantum mechanical calculations, suggesting that the poor agreement between prediction and observations of the brightest Fe xvii line is rooted in the quality of the underlying atomic wavefunctions used in the models.

doi: 10.1038/nature11627

物理:量子カスケードレーザーに基づく中赤外周波数コム

Mid-infrared frequency comb based on a quantum cascade laser p.229

A broadband, compact, all-electrically driven mid-infrared frequency comb based on a quantum cascade laser widens the scope of application of combs in this frequency range beyond that of sources which depend on a chain of optical components.

doi: 10.1038/nature11620

材料科学:遅延蛍光を利用した高効率有機発光ダイオード

Highly efficient organic light-emitting diodes from delayed fluorescence p.234

A class of metal-free organic electroluminescent molecules is designed in which both singlet and triplet excitons contribute to light emission, leading to an intrinsic fluorescence efficiency greater than 90 per cent and an external electroluminescence efficiency comparable to that achieved in high-efficiency phosphorescence-based organic light-emitting diodes.

doi: 10.1038/nature11687

気候:降雪の増加による南極からの将来の氷の流出量の増加

Increased future ice discharge from Antarctica owing to higher snowfall p.239

Climate models predict that precipitation will increase in Antarctica, leading to potential ice mass gain and an offset to sea level rise, but here it is shown that enhanced snowfall on Antarctica is likely to increase ice discharge and thereby negate 30% to 65% of the snowfall-induced ice gain.

doi: 10.1038/nature11616

地球:形態不安定性により生じる深部での溶けた鉄のマントルへの貫入

Deep penetration of molten iron into the mantle caused by a morphological instability p.243

A morphological instability causing blobs of iron-rich liquid to penetrate iron oxides is described, providing a mechanism for the iron-rich regions in the mantle.

doi: 10.1038/nature11663

脳:能動的知覚課題遂行中の知覚入力と運動入力の樹状突起における非線形的統合

Nonlinear dendritic integration of sensory and motor input during an active sensing task p.247

Recordings from cortical neuron dendrites of head-fixed mice during an object-localization task provide direct evidence that a novel global nonlinearity has a role in integrating sensory and motor information during a behaviour-related computation.

doi: 10.1038/nature11601

炎症:インターロイキン受容体はMYD88–ARNO–ARF6カスケードを活性化して血管の安定性を障害する

Interleukin receptor activates a MYD88–ARNO–ARF6 cascade to disrupt vascular stability p.252

Interleukin-1β-induced disruption to endothelial stability and vascular permeability in a human in vitro model is shown to be independent of downstream nuclear factor-κB activation, relying instead on a MYD88–ARNO–ARF6 signalling cascade; inhibiting proteins involved in this pathway is shown to improve outcomes in animal models of inflammatory disease.

doi: 10.1038/nature11603

植物:ダイズシストセンチュウ抵抗性遺伝子は病原体に対する植物の新たな抵抗性機構を示す

A soybean cyst nematode resistance gene points to a new mechanism of plant resistance to pathogens p.256

This study reports the identification of the first soybean gene that has a role in resistance to soybean cyst nematode; this finding should help to improve crop resistance to nematodes.

doi: 10.1038/nature11651

細胞:酵母では若齢での液胞内のpH上昇がミトコンドリアの機能と寿命を制限する

An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast p.261

Vacuolar acidity in yeast is shown to decline with age, and preventing this decrease suppresses mitochondrial dysfunction and extends the lifespan of yeast.

doi: 10.1038/nature11654

生化学:ユビキチン鎖のコンホメーションは相互作用するタンパク質の認識や活性を調節する

Ubiquitin chain conformation regulates recognition and activity of interacting proteins p.266

Single-molecule FRET assays used to probe the conformational dynamics of ubiquitin chains reveal that conformational selection is an important mechanism of ubiquitin chain recognition.

doi: 10.1038/nature11722

生化学:活性化されたGTPアーゼのRNA足場上での移動は共翻訳されるタンパク質の標的化を促進する

Activated GTPase movement on an RNA scaffold drives co-translational protein targeting p.271

Single-molecule fluorescence microscopy techniques are used to elucidate features of the highly conserved protein-targeting machinery known as the signal recognition particle (SRP); the long SRP RNA is shown to be crucial for correct timing and precision of cargo handover to the protein-translocation machinery, a finding that could help to explain how other ribonucleosome complexes function during complex cellular processes.

doi: 10.1038/nature11726

細胞:細胞質分裂ではセントラルスピンドリンが紡錘体と細胞膜を結びつける

Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis p.276

Structural and functional analysis of the centralspindlin complex shows that it connects the mitotic spindle to the plasma membrane during cytokinesis through interactions of the C1 domain of centralspindlin’s MgcRacGAP subunit with phosphoinositide lipids.

doi: 10.1038/nature11773

細胞:ISWIの調節には、ヌクレオソームエピトープによる拮抗を受ける阻害性モジュールがかかわっている

Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes p.280

Two separate regulatory regions on the Drosophila chromatin remodeller ISWI are defined, AutoN and NegC, which negatively regulate ATP hydrolysis and the coupling of ATP hydrolysis to productive DNA translocation, respectively; epitopes on nucleosomes activate ISWI by inhibiting these negative regulatory domains, ensuring that remodelling occurs only in the appropriate chromatin context.

doi: 10.1038/nature11625

細胞:テロメアタンパク質TPP1のTELはテロメラーゼの動員と処理能力にかかわっている

The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity p.285

Using separation-of-function mutations of TPP1 that inhibit telomerase binding while maintaining telomere capping, a region on the surface of TPP1, the TEL patch, is identified and found to be required for both binding telomerase and enhancing its processivity.

doi: 10.1038/nature11648

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