目次

Editorials

欧州連合(EU)および欧州宇宙機関(ESA)が、地球観測プログラム「コペルニクス計画」で衛星から得られるデータを公開することは、称賛に値する。

Look back in wonder p.149

The launch of the first Sentinel satellite heralds an era in which detailed data on everything from earthquakes to urbanization will be freely available to anyone interested in Earth’s future.

doi: 10.1038/508149a

ウクライナ問題をめぐるロシアへの制裁はやむを得ないが、科学分野での協力関係を断ち切るのは良くない。

Political science p.149

Russia deserves to be sanctioned, but halting scientific collaboration is not the way to do it.

doi: 10.1038/508149b

銅は古くから利用されている金属であるが、新たに触媒やがん治療にも役立つ可能性が示された。

Copper rewired p.150

Two Nature papers signal new roles for this ancient metal in catalysis and cancer therapy.

doi: 10.1038/508150a

News

NIHの再生医療センター(CRM)長が突然辞任し、センター閉鎖の可能性も。

NIH stem-cell programme closes p.157

Director resigns as just one clinical-trial award is made.

doi: 10.1038/508157a

代謝経路を標的としたがん治療の早期臨床試験で、期待の持てる結果が。

Metabolic quirks yield tumour hope p.158

Early clinical-trial results show promise for targeting cancer-related biochemical pathways.

doi: 10.1038/508158a

タバコと同様に電子タバコも、細胞に悪影響を及ぼす恐れが。

E-cigarettes affect cells p.159

Questions raised over health effects of devices.

doi: 10.1038/508159a

コペルニクス計画の最初の衛星「センチネル1A」の打ち上げが成功し、地球観測が新たな時代に。

Earth observation enters next phase p.160

Expectations high as first European Sentinel satellite launches.

doi: 10.1038/508160a

NIHとウェルカムトラストがオープンアクセス誌での発表の推奨を強化し、従わない場合には助成の打ち切りも。

Funders punish open-access dodgers p.161

Agencies withhold grant money from researchers who do not make publications openly available.

doi: 10.1038/508161a

西側諸国に、ロシアとの科学協力を解消する動きが。

Western science severs ties with Russia p.162

Country’s science renaissance threatened as NATO and NASA suspend links.

doi: 10.1038/508162a

絶滅の危機に瀕する海南テナガザルを救おうと、研究者たちが緊急行動へ。

Time running out for rarest primate p.163

Rescue bid launched to save Hainan gibbon from becoming first ape driven to extinction by humans.

doi: 10.1038/508163a

News Features

洪水:流れを阻む

Floods: Holding back the tide p.164

ガンジス・ブラマプトラ川のデルタに住む何百万も人々を、海面上昇と洪水から救うため、対策が急がれている。

doi: 10.1038/508164a

エピジェネティクス:老化時計の監視人

Biomarkers and ageing: The clock-watcher p.168

生物数学者Steve Horvathは、エピジェネティック標識を手がかりに、ヒトの老化を驚くほど正確に測定する方法を発見した。

doi: 10.1038/508168a

News & Views

太陽系:小惑星表面を砕く

Solar system: Cracking up on asteroids p.190

小型の小惑星の表面で岩石が割れ、さらに粉末状の岩石破片が生じる主な原因は、昼夜の気温変化であることが、実験とモデリングを組み合わせて明らかになった。

doi: 10.1038/nature13222

がん:損傷防止機構を標的とする

Cancer: Damage prevention targeted p.191

MTH1タンパク質は酸化されたヌクレオチドが誤ってDNAに取り込まれるのを防止している。小型分子を使ってMTH1を選択的に阻害すると腫瘍増殖が抑制されることが、2つの研究によって明らかにされた。

doi: 10.1038/nature13221

生物地球科学:アフリカの温室効果ガス収支は赤字状態

Biogeoscience: Africa's greenhouse-gas budget is in the red p.192

アフリカは大きな炭素シンクなのではないかと考えられてきた。このようなシンクは、二酸化炭素放出を低減する試みにとって大きな価値がある。だが、今回行われた解析によって、アフリカが、正味の温室効果ガス供給源となって地球温暖化を促進する可能性が示された。

doi: 10.1038/508192a

代謝:脂肪をため込む遺伝子を標的とする

Metabolism: Targeting a fat-accumulation gene p.194

太り過ぎのマウスの脂肪細胞では、代謝経路の2つの交差点を結び付ける酵素が増加していることが分かった。この酵素をコードしている遺伝子を阻害すると、マウスは食餌誘導性の肥満を起こしにくくなる。

doi: 10.1038/508194a

量子物理学:強力なハイブリッドカップル

Quantum physics: A strong hybrid couple p.195

光共振器中にある単一原子が、入射光子と強く相互作用して光子の状態を切り替えることが分かった。この知見は、光量子計算や光量子ネットワークへの道を開くものだ。

doi: 10.1038/508195a

構造生物学:好熱性紅色イオウ光合成細菌の反応中心

Structural biology: The purple heart of photosynthesis p.196

紅色細菌の一種に由来する、光合成反応中心と集光アンテナタンパク質との複合体の構造から、新種の集光タンパク質が明らかになり、また電子伝達分子を、他に出口のないこの閉鎖系から脱出させるためのチャネルの存在が明らかになった。

doi: 10.1038/nature13219

Articles

神経科学:出生前ヒト脳の転写の全体像

Transcriptional landscape of the prenatal human brain p.199

A spatially resolved transcriptional atlas of the mid-gestational developing human brain has been created using laser-capture microdissection and microarray technology, providing a comprehensive reference resource which also enables new hypotheses about the nature of human brain evolution and the origins of neurodevelopmental disorders.

doi: 10.1038/nature13185

神経科学:マウス脳における中規模のコネクトーム

A mesoscale connectome of the mouse brain p.207

In mouse, an axonal connectivity map showing the wiring patterns across the entire brain has been created using an EGFP-expressing adeno-associated virus tracing technique, providing the first such whole-brain map for a vertebrate species.

doi: 10.1038/nature13186

がん:MTH1阻害はdNTPプールからの損傷ヌクレオチド排除を妨げることでがんを根絶する

MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool p.215

In order to find a general treatment for cancer, this study found that MTH1 activity is essential for the survival of transformed cells, and isolated two small-molecule inhibitors of MTH1, TH287 and TH588 — in the presence of these inhibitors, damaged nucleotides are incorporated into DNA only in cancer cells, causing cytotoxicity and eliciting a beneficial response in patient-derived mouse xenograft models.

doi: 10.1038/nature13181

がん:MTH1を(S)-クリゾチニブの立体構造特異的標的とする抗がん治療戦略

Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy p.222

A chemoproteomic screen is used here to identify MTH1 as the target of SCH51344, an experimental RAS-dependent cancer drug; a further search for inhibitors revealed (S)-crizotinib as a potent MTH1 antagonist, which suppresses tumour growth in animal models of colon cancer, and could be part of a new class of anticancer drugs.

doi: 10.1038/nature13194

構造生物学:Thermochromatium tepidum由来のLH1–RC複合体の3.0 Å分解能での構造

Structure of the LH1–RC complex from Thermochromatium tepidum at 3.0 Å p.228

The near-atomic-level structure of a complete bacterial light-harvesting antenna–reaction centre (LH1–RC) complex is described here; the structure reveals how energy is transferred from the LH1 to the RC in a highly efficient way and suggests how ubiquinone might cross a closed LH1 barrier.

doi: 10.1038/nature13197

Letters

宇宙:小さな小惑星表面のレゴリス形成原因としての熱疲労

Thermal fatigue as the origin of regolith on small asteroids p.233

Space missions and thermal infrared observations have shown that small asteroids (kilometre-sized or smaller) are covered by a layer of centimetre-sized or smaller particles, which constitute the regolith. Regolith generation has traditionally been attributed to the fall back of impact ejecta and by the break-up of boulders by micrometeoroid impact. Laboratory experiments and impact models, however, show that crater ejecta velocities are typically greater than several tens of centimetres per second, which corresponds to the gravitational escape velocity of kilometre-sized asteroids. Therefore, impact debris cannot be the main source of regolith on small asteroids. Here we report that thermal fatigue, a mechanism of rock weathering and fragmentation with no subsequent ejection, is the dominant process governing regolith generation on small asteroids. We find that thermal fragmentation induced by the diurnal temperature variations breaks up rocks larger than a few centimetres more quickly than do micrometeoroid impacts. Because thermal fragmentation is independent of asteroid size, this process can also contribute to regolith production on larger asteroids. Production of fresh regolith originating in thermal fatigue fragmentation may be an important process for the rejuvenation of the surfaces of near-Earth asteroids, and may explain the observed lack of low-perihelion, carbonaceous, near-Earth asteroids.

doi: 10.1038/nature13153

量子物理学:飛行する光子と単一トラップ原子間の量子ゲート

A quantum gate between a flying optical photon and a single trapped atom p.237

The steady increase in control over individual quantum systems supports the promotion of a quantum technology that could provide functionalities beyond those of any classical device. Two particularly promising applications have been explored during the past decade: photon-based quantum communication, which guarantees unbreakable encryption but which still has to be scaled to high rates over large distances, and quantum computation, which will fundamentally enhance computability if it can be scaled to a large number of quantum bits (qubits). It was realized early on that a hybrid system of light qubits and matter qubits could solve the scalability problem of each field—that of communication by use of quantum repeaters, and that of computation by use of an optical interconnect between smaller quantum processors. To this end, the development of a robust two-qubit gate that allows the linking of distant computational nodes is “a pressing challenge”. Here we demonstrate such a quantum gate between the spin state of a single trapped atom and the polarization state of an optical photon contained in a faint laser pulse. The gate mechanism presented is deterministic and robust, and is expected to be applicable to almost any matter qubit. It is based on reflection of the photonic qubit from a cavity that provides strong light–matter coupling. To demonstrate its versatility, we use the quantum gate to create atom–photon, atom–photon–photon and photon–photon entangled states from separable input states. We expect our experiment to enable various applications, including the generation of atomic and photonic cluster states and Schrödinger-cat states, deterministic photonic Bell-state measurements, scalable quantum computation and quantum communication using a redundant quantum parity code.

doi: 10.1038/nature13177

量子物理学:単一原子によるナノフォトニック量子位相スイッチ

Nanophotonic quantum phase switch with a single atom p.241

By analogy to transistors in classical electronic circuits, quantum optical switches are important elements of quantum circuits and quantum networks. Operated at the fundamental limit where a single quantum of light or matter controls another field or material system, such a switch may enable applications such as long-distance quantum communication, distributed quantum information processing and metrology, and the exploration of novel quantum states of matter. Here, by strongly coupling a photon to a single atom trapped in the near field of a nanoscale photonic crystal cavity, we realize a system in which a single atom switches the phase of a photon and a single photon modifies the atom’s phase. We experimentally demonstrate an atom-induced optical phase shift that is nonlinear at the two-photon level, a photon number router that separates individual photons and photon pairs into different output modes, and a single-photon switch in which a single ‘gate’ photon controls the propagation of a subsequent probe field. These techniques pave the way to integrated quantum nanophotonic networks involving multiple atomic nodes connected by guided light.

doi: 10.1038/nature13188

地球:大陸成長の力学

Dynamics of continental accretion p.245

Subduction zones become congested when they try to consume buoyant, exotic crust. The accretionary mountain belts (orogens) that form at these convergent plate margins have been the principal sites of lateral continental growth through Earth’s history. Modern examples of accretionary margins are the North American Cordilleras and southwest Pacific subduction zones. The geologic record contains abundant accretionary orogens, such as the Tasmanides, along the eastern margin of the supercontinent Gondwana, and the Altaïdes, which formed on the southern margin of Laurasia. In modern and ancient examples of long-lived accretionary orogens, the overriding plate is subjected to episodes of crustal extension and back-arc basin development, often related to subduction rollback and transient episodes of orogenesis and crustal shortening, coincident with accretion of exotic crust. Here we present three-dimensional dynamic models that show how accretionary margins evolve from the initial collision, through a period of plate margin instability, to re-establishment of a stable convergent margin. The models illustrate how significant curvature of the orogenic system develops, as well as the mechanism for tectonic escape of the back-arc region. The complexity of the morphology and the evolution of the system are caused by lateral rollback of a tightly arcuate trench migrating parallel to the plate boundary and orthogonally to the convergence direction. We find geological and geophysical evidence for this process in the Tasmanides of eastern Australia, and infer that this is a recurrent and global phenomenon.

doi: 10.1038/nature13033

遺伝:転写に影響するヒトのエピスタシスの検出と再現

Detection and replication of epistasis influencing transcription in humans p.249

Epistasis is the phenomenon whereby one polymorphism’s effect on a trait depends on other polymorphisms present in the genome. The extent to which epistasis influences complex traits and contributes to their variation is a fundamental question in evolution and human genetics. Although often demonstrated in artificial gene manipulation studies in model organisms, and some examples have been reported in other species, few examples exist for epistasis among natural polymorphisms in human traits. Its absence from empirical findings may simply be due to low incidence in the genetic control of complex traits, but an alternative view is that it has previously been too technically challenging to detect owing to statistical and computational issues. Here we show, using advanced computation and a gene expression study design, that many instances of epistasis are found between common single nucleotide polymorphisms (SNPs). In a cohort of 846 individuals with 7,339 gene expression levels measured in peripheral blood, we found 501 significant pairwise interactions between common SNPs influencing the expression of 238 genes (P < 2.91 × 10−16). Replication of these interactions in two independent data sets showed both concordance of direction of epistatic effects (P = 5.56 × 10−31) and enrichment of interaction P values, with 30 being significant at a conservative threshold of P < 9.98 × 10−5. Forty-four of the genetic interactions are located within 5 megabases of regions of known physical chromosome interactions (P = 1.8 × 10−10). Epistatic networks of three SNPs or more influence the expression levels of 129 genes, whereby one cis-acting SNP is modulated by several trans-acting SNPs. For example, MBNL1 is influenced by an additive effect at rs13069559, which itself is masked by trans-SNPs on 14 different chromosomes, with nearly identical genotype–phenotype maps for each cistrans interaction. This study presents the first evidence, to our knowledge, for many instances of segregating common polymorphisms interacting to influence human traits.

doi: 10.1038/nature13005

医学:現代の鳥インフルエンザウイルスの内在遺伝子に対する同期した全球規模の選択的一掃

A synchronized global sweep of the internal genes of modern avian influenza virus p.254

Zoonotic infectious diseases such as influenza continue to pose a grave threat to human health. However, the factors that mediate the emergence of RNA viruses such as influenza A virus (IAV) are still incompletely understood. Phylogenetic inference is crucial to reconstructing the origins and tracing the flow of IAV within and between hosts. Here we show that explicitly allowing IAV host lineages to have independent rates of molecular evolution is necessary for reliable phylogenetic inference of IAV and that methods that do not do so, including ‘relaxed’ molecular clock models, can be positively misleading. A phylogenomic analysis using a host-specific local clock model recovers extremely consistent evolutionary histories across all genomic segments and demonstrates that the equine H7N7 lineage is a sister clade to strains from birds—as well as those from humans, swine and the equine H3N8 lineage—sharing an ancestor with them in the mid to late 1800s. Moreover, major western and eastern hemisphere avian influenza lineages inferred for each gene coalesce in the late 1800s. On the basis of these phylogenies and the synchrony of these key nodes, we infer that the internal genes of avian influenza virus (AIV) underwent a global selective sweep beginning in the late 1800s, a process that continued throughout the twentieth century and up to the present. The resulting western hemispheric AIV lineage subsequently contributed most of the genomic segments to the 1918 pandemic virus and, independently, the 1963 equine H3N8 panzootic lineage. This approach provides a clear resolution of evolutionary patterns and processes in IAV, including the flow of viral genes and genomes within and between host lineages.

doi: 10.1038/nature13016

医学:ニコチンアミド N-メチルトランスフェラーゼのノックダウンは食餌性肥満を防ぐ

Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity p.258

In obesity and type 2 diabetes, Glut4 glucose transporter expression is decreased selectively in adipocytes. Adipose-specific knockout or overexpression of Glut4 alters systemic insulin sensitivity. Here we show, using DNA array analyses, that nicotinamide N-methyltransferase (Nnmt) is the most strongly reciprocally regulated gene when comparing gene expression in white adipose tissue (WAT) from adipose-specific Glut4-knockout or adipose-specific Glut4-overexpressing mice with their respective controls. NNMT methylates nicotinamide (vitamin B3) using S-adenosylmethionine (SAM) as a methyl donor. Nicotinamide is a precursor of NAD+, an important cofactor linking cellular redox states with energy metabolism. SAM provides propylamine for polyamine biosynthesis and donates a methyl group for histone methylation. Polyamine flux including synthesis, catabolism and excretion, is controlled by the rate-limiting enzymes ornithine decarboxylase (ODC) and spermidine–spermine N1-acetyltransferase (SSAT; encoded by Sat1) and by polyamine oxidase (PAO), and has a major role in energy metabolism. We report that NNMT expression is increased in WAT and liver of obese and diabetic mice. Nnmt knockdown in WAT and liver protects against diet-induced obesity by augmenting cellular energy expenditure. NNMT inhibition increases adipose SAM and NAD+ levels and upregulates ODC and SSAT activity as well as expression, owing to the effects of NNMT on histone H3 lysine 4 methylation in adipose tissue. Direct evidence for increased polyamine flux resulting from NNMT inhibition includes elevated urinary excretion and adipocyte secretion of diacetylspermine, a product of polyamine metabolism. NNMT inhibition in adipocytes increases oxygen consumption in an ODC-, SSAT- and PAO-dependent manner. Thus, NNMT is a novel regulator of histone methylation, polyamine flux and NAD+-dependent SIRT1 signalling, and is a unique and attractive target for treating obesity and type 2 diabetes.

doi: 10.1038/nature13198

細胞生物学:ZMYND11はヒストンH3.3K36me3を転写伸長および腫瘍抑制に結び付ける

ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression p.263

Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.

doi: 10.1038/nature13045

生化学:生きた動物の骨髄中の局所的酸素濃度の直接測定

Direct measurement of local oxygen concentration in the bone marrow of live animals p.269

Characterization of how the microenvironment, or niche, regulates stem cell activity is central to understanding stem cell biology and to developing strategies for the therapeutic manipulation of stem cells. Low oxygen tension (hypoxia) is commonly thought to be a shared niche characteristic in maintaining quiescence in multiple stem cell types. However, support for the existence of a hypoxic niche has largely come from indirect evidence such as proteomic analysis, expression of hypoxia inducible factor-1α (Hif-1α) and related genes, and staining with surrogate hypoxic markers (for example, pimonidazole). Here we perform direct in vivo measurements of local oxygen tension (pO2) in the bone marrow of live mice. Using two-photon phosphorescence lifetime microscopy, we determined the absolute pO2 of the bone marrow to be quite low (<32 mm Hg) despite very high vascular density. We further uncovered heterogeneities in local pO2, with the lowest pO2 (∼9.9 mm Hg, or 1.3%) found in deeper peri-sinusoidal regions. The endosteal region, by contrast, is less hypoxic as it is perfused with small arteries that are often positive for the marker nestin. These pO2 values change markedly after radiation and chemotherapy, pointing to the role of stress in altering the stem cell metabolic microenvironment.

doi: 10.1038/nature13034

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