目次

Editorials

責任ある研究を行うためには、冗長だと思われるような審査が必要な場合もある。

Moral authority p.5

Research must be seen to be accountable, even if that means hanging on to redundant reviews.

doi: 10.1038/498005b

科学者は、オープンアクセスを推進し、研究成果を確認しようとする助成機関の活動を、快く受け入れるべきだ。

The paper trail p.5

Scientists must embrace funding-agency efforts to track research outputs and encourage open access to the literature.

doi: 10.1038/498005a

Natureでは論文の添付データを拡充するため、新たにオンラインでアクセスできるExtended Data欄を導入する。

Nature papers enhanced p.6

doi: 10.1038/498006a

News

木材から作った成形材は本当に環境に優しいか、疑問が。

‘Plastic wood’ is no green guarantee p.13

Researchers question benefits of tropical-wood substitute.

doi: 10.1038/498013a

データマイニングをめぐり、科学界と出版界との意見の食い違いが鮮明に。

Tensions grow as data-mining discussions fall apart p.14

Scientists want to exempt computer-based text crawling from Europe’s copyright law.

doi: 10.1038/498014a

合成生物学手法で発光シロイヌナズナを作る計画に、批判が。

Glowing plants spark debate p.15

Critics irked over planned release of engineered organism.

doi: 10.1038/498015a

DNAの情報と臨床情報とをつなごうと、データ共有促進のための国際コンソーシアムが。

Geneticists push for global data-sharing p.16

International organization aims to promote exchange and linking of DNA sequences and clinical information.

doi: 10.1038/498017a

EUの漁業資源の乱獲防止交渉が、合意に。

Europe reforms its fisheries p.17

Agreement would set catch limits that are in line with scientific advice.

doi: 10.1038/498016a

WHOが、改革によって予算の健全化を図り、柔軟な活動が可能に。

Agency gets a grip on budget p.18

Reforms increase flexibility and shift spending towards non-communicable disorders.

doi: 10.1038/498018a

News Features

量子原子

Quantum physics: The quantum atom p.21

ニールス・ボーアの原子模型の発表から100年を記念して、彼が遺したものと原子構造をめぐる今後の課題を特集する。

doi: 10.1038/498021a

極端な原子

Bohr's model: Extreme atoms p.22

物理学者たちは、原子を引き延ばし、引き裂き、ゆがめて、量子の世界の限界を探っている。

doi: 10.1038/498022a

News & Views

フォーラム:理論物理学:原子のサイズを品定め

Theoretical physics: Sizing up atoms p.40

ニールス・ボーアの原子構造モデルは、原子の最大の大きさはどのくらいになるかという問題を提起した。それから100年経った今、この問題はまだ解答が得られていない。このフォーラムでは、2人の物理学者が原子と核のサイズの限界について論じている。

doi: 10.1038/498040a

高温超伝導:隠れた秩序の響き

High-temperature superconductivity: The sound of a hidden order p.41

銅酸化物超伝導体での超音波測定によって、エキゾチックな物質相が明らかになった。この相は自発的な量子流のループからなり、これまで観測の難しさの点で抜きんでていたのである。

doi: 10.1038/498041a

免疫学:自然免疫の調節細胞

Immunology: An innate regulatory cell p.42

自然リンパ球がCD4+ T細胞を制御できることがわかり、免疫系調節のまた別の形態と思われるものが明らかになった。これによって、体が常在菌と病原性細菌を区別する仕組みを説明できるかもしれない。

doi: 10.1038/498042a

技術:分子内部に及んだ光分光学

Techniques: Optical spectroscopy goes intramolecular p.44

光分光画像化が、サブナノメートルの空間分解能を達成する手法によって、一気に分子内部の領域にまで及んだ。この技術は光化学やナノテクノロジーの分野での応用が考えられる。

doi: 10.1038/498044a

生化学:イリドは舞い降りた

Biochemistry: The ylide has landed p.45

酵素の共基質であるSAMはずっと以前から、化学的に異なる2つの役割を持つことが知られていた。CmoA酵素の研究から、SAMには第三番目の働きが隠されていたことが示唆された。それはイリドと呼ばれる化学種を作り出すことである。

doi: 10.1038/nature12247

気候科学:木を植えよ、だがよく手入れをしなくてはいけない

Climate science: Plant a tree, but tend it well p.47

人類による擾乱から立ち直った森林は、かなりな規模のシンクとして働き、人間活動によって放出された二酸化炭素の吸収に役立つ。シミュレーションでは、栄養が限られるとこうした効果が低減することが示唆された。

doi: 10.1038/498047a

ゲノミクス:腸内細菌叢に基づく予想

Genomics: A gut prediction p.48

2型糖尿病患者の腸内細菌叢が示す特徴的なプロファイルは、診断と治療の役に立つ可能性があるが、民族や性別によって異なる特徴が生じることは、さらなる研究の必要性をはっきり示している。

doi: 10.1038/nature12251

Review

気候:氷床の質量収支と気候変動

Ice-sheet mass balance and climate change p.51

Since the 2007 Intergovernmental Panel on Climate Change Fourth Assessment Report, new observations of ice-sheet mass balance and improved computer simulations of ice-sheet response to continuing climate change have been published. Whereas Greenland is losing ice mass at an increasing pace, current Antarctic ice loss is likely to be less than some recently published estimates. It remains unclear whether East Antarctica has been gaining or losing ice mass over the past 20 years, and uncertainties in ice-mass change for West Antarctica and the Antarctic Peninsula remain large. We discuss the past six years of progress and examine the key problems that remain.

doi: 10.1038/nature12238

Articles

古生物学:既知のもので最古の霊長類骨格と直鼻猿類の初期進化

The oldest known primate skeleton and early haplorhine evolution p.60

Understanding the earliest phases of primate evolution is obscured by gaps in the fossil record, but some light is shed by the discovery of a nearly complete and substantially articulated skeleton of a tiny primate from the early Eocene; the new primate lies near the pivotal evolutionary dichotomy separating the tarsier and anthropoid lineages and it possesses features that are characteristic of subsequent members of both lineages.

doi: 10.1038/nature12200

神経科学:ラットは両眼視野の持続的融合を犠牲にして頭上の視野を維持する

Rats maintain an overhead binocular field at the expense of constant fusion p.65

In freely moving rodents, eye movements serve to keep the visual fields of the two eyes continuously overlapping overhead at the expense of continuous alignment, a strategy that may have evolved to maintain constant overhead surveillance of predators.

doi: 10.1038/nature12153

細胞:KAT5のチロシンリン酸化がクロマチン変化の感知とATMシグナル伝達を共役させる

KAT5 tyrosine phosphorylation couples chromatin sensing to ATM signalling p.70

KAT5 tyrosine phosphorylation, mediated by the tyrosine kinase c-Abl, increases after DNA damage, promoting KAT5 binding to histone H3K9me3, which triggers KAT5-mediated acetylation of the ATM kinase; this promotes the activation of the DNA damage checkpoint and cell survival.

doi: 10.1038/nature12201

Letters

物性物理学:YBa2Cu3O6+δでは相転移線が擬ギャップの境目になる

Bounding the pseudogap with a line of phase transitions in YBa2Cu3O6+δ p.75

Close to optimal doping, the copper oxide superconductors show ‘strange metal’ behaviour, suggestive of strong fluctuations associated with a quantum critical point. Such a critical point requires a line of classical phase transitions terminating at zero temperature near optimal doping inside the superconducting ‘dome’. The underdoped region of the temperature–doping phase diagram from which superconductivity emerges is referred to as the ‘pseudogap’ because evidence exists for partial gapping of the conduction electrons, but so far there is no compelling thermodynamic evidence as to whether the pseudogap is a distinct phase or a continuous evolution of physical properties on cooling. Here we report that the pseudogap in YBa2Cu3O6+δ is a distinct phase, bounded by a line of phase transitions. The doping dependence of this line is such that it terminates at zero temperature inside the superconducting dome. From this we conclude that quantum criticality drives the strange metallic behaviour and therefore superconductivity in the copper oxide superconductors.

doi: 10.1038/nature12165

物理学:共鳴相互作用するフェルミガスの第二音波と超流動分率

Second sound and the superfluid fraction in a Fermi gas with resonant interactions p.78

Superfluidity is a macroscopic quantum phenomenon occurring in systems as diverse as liquid helium and neutron stars. It occurs below a critical temperature and leads to peculiar behaviour such as frictionless flow, the formation of quantized vortices and quenching of the moment of inertia. Ultracold atomic gases offer control of interactions and external confinement, providing unique opportunities to explore superfluid phenomena. Many such (finite-temperature) phenomena can be explained in terms of a two-fluid mixture comprising a normal component, which behaves like an ordinary fluid, and a superfluid component with zero viscosity and zero entropy. The two-component nature of a superfluid is manifest in ‘second sound’, an entropy wave in which the superfluid and the non-superfluid components oscillate with opposite phases (as opposed to ordinary ‘first sound’, where they oscillate in phase). Here we report the observation of second sound in an ultracold Fermi gas with resonant interactions. The speed of second sound depends explicitly on the value of the superfluid fraction, a quantity that is sensitive to the spectrum of elementary excitations. Our measurements allow us to extract the temperature dependence of the superfluid fraction, a previously inaccessible quantity that will provide a benchmark for theories of strongly interacting quantum gases.

doi: 10.1038/nature12136

応用物理学:プラズモン増強ラマン散乱による単一分子の化学マッピング

Chemical mapping of a single molecule by plasmon-enhanced Raman scattering p.82

Visualizing individual molecules with chemical recognition is a longstanding target in catalysis, molecular nanotechnology and biotechnology. Molecular vibrations provide a valuable ‘fingerprint’ for such identification. Vibrational spectroscopy based on tip-enhanced Raman scattering allows us to access the spectral signals of molecular species very efficiently via the strong localized plasmonic fields produced at the tip apex. However, the best spatial resolution of the tip-enhanced Raman scattering imaging is still limited to 3−15 nanometres, which is not adequate for resolving a single molecule chemically. Here we demonstrate Raman spectral imaging with spatial resolution below one nanometre, resolving the inner structure and surface configuration of a single molecule. This is achieved by spectrally matching the resonance of the nanocavity plasmon to the molecular vibronic transitions, particularly the downward transition responsible for the emission of Raman photons. This matching is made possible by the extremely precise tuning capability provided by scanning tunnelling microscopy. Experimental evidence suggests that the highly confined and broadband nature of the nanocavity plasmon field in the tunnelling gap is essential for ultrahigh-resolution imaging through the generation of an efficient double-resonance enhancement for both Raman excitation and Raman emission. Our technique not only allows for chemical imaging at the single-molecule level, but also offers a new way to study the optical processes and photochemistry of a single molecule.

doi: 10.1038/nature12151

地球:始生代の大気中のアルゴン同位体組成から初期地球のダイナミクスを探る

Argon isotopic composition of Archaean atmosphere probes early Earth geodynamics p.87

Understanding the growth rate of the continental crust through time is a fundamental issue in Earth sciences. The isotopic signatures of noble gases in the silicate Earth (mantle, crust) and in the atmosphere afford exceptional insight into the evolution through time of these geochemical reservoirs. However, no data for the compositions of these reservoirs exists for the distant past, and temporal exchange rates between Earth’s interior and its surface are severely under-constrained owing to a lack of samples preserving the original signature of the atmosphere at the time of their formation. Here, we report the analysis of argon in Archaean (3.5-billion-year-old) hydrothermal quartz. Noble gases are hosted in primary fluid inclusions containing a mixture of Archaean freshwater and hydrothermal fluid. Our analysis reveals Archaean atmospheric argon with a 40Ar/36Ar value of 143 ± 24, lower than the present-day value of 298.6 (for which 40Ar has been produced by the radioactive decay of the potassium isotope 40K, with a half-life of 1.25 billion years; 36Ar is primordial in origin). This ratio is consistent with an early development of the felsic crust, which might have had an important role in climate variability during the first half of Earth’s history.

doi: 10.1038/nature12152

行動生態学:収穫アリコロニーで見られる集団制御による採餌活動の抑制がもたらす報酬

The rewards of restraint in the collective regulation of foraging by harvester ant colonies p.91

Collective behaviour, arising from local interactions, allows groups to respond to changing conditions. Long-term studies have shown that the traits of individual mammals and birds are associated with their reproductive success, but little is known about the evolutionary ecology of collective behaviour in natural populations. An ant colony operates without central control, regulating its activity through a network of local interactions. This work shows that variation among harvester ant (Pogonomyrmex barbatus) colonies in collective response to changing conditions is related to variation in colony lifetime reproductive success in the production of offspring colonies. Desiccation costs are high for harvester ants foraging in the desert. More successful colonies tend to forage less when conditions are dry, and show relatively stable foraging activity when conditions are more humid. Restraint from foraging does not compromise a colony’s long-term survival; colonies that fail to forage at all on many days survive as long, over the colony’s 20–30-year lifespan, as those that forage more regularly. Sensitivity to conditions in which to reduce foraging activity may be transmissible from parent to offspring colony. These results indicate that natural selection is shaping the collective behaviour that regulates foraging activity, and that the selection pressure, related to climate, may grow stronger if the current drought in their habitat persists.

doi: 10.1038/nature12137

ゲノミクス:微小な植物ゲノムの構造と進化

Architecture and evolution of a minute plant genome OPEN p.94

It has been argued that the evolution of plant genome size is principally unidirectional and increasing owing to the varied action of whole-genome duplications (WGDs) and mobile element proliferation. However, extreme genome size reductions have been reported in the angiosperm family tree. Here we report the sequence of the 82-megabase genome of the carnivorous bladderwort plant Utricularia gibba. Despite its tiny size, the U. gibba genome accommodates a typical number of genes for a plant, with the main difference from other plant genomes arising from a drastic reduction in non-genic DNA. Unexpectedly, we identified at least three rounds of WGD in U. gibba since common ancestry with tomato (Solanum) and grape (Vitis). The compressed architecture of the U. gibba genome indicates that a small fraction of intergenic DNA, with few or no active retrotransposons, is sufficient to regulate and integrate all the processes required for the development and reproduction of a complex organism.

doi: 10.1038/nature12132

微生物学:グルコース制御が正常、異常および糖尿病型であるヨーロッパ系女性の腸内メタゲノム

Gut metagenome in European women with normal, impaired and diabetic glucose control p.99

Type 2 diabetes (T2D) is a result of complex gene–environment interactions, and several risk factors have been identified, including age, family history, diet, sedentary lifestyle and obesity. Statistical models that combine known risk factors for T2D can partly identify individuals at high risk of developing the disease. However, these studies have so far indicated that human genetics contributes little to the models, whereas socio-demographic and environmental factors have greater influence. Recent evidence suggests the importance of the gut microbiota as an environmental factor, and an altered gut microbiota has been linked to metabolic diseases including obesity, diabetes and cardiovascular disease. Here we use shotgun sequencing to characterize the faecal metagenome of 145 European women with normal, impaired or diabetic glucose control. We observe compositional and functional alterations in the metagenomes of women with T2D, and develop a mathematical model based on metagenomic profiles that identified T2D with high accuracy. We applied this model to women with impaired glucose tolerance, and show that it can identify women who have a diabetes-like metabolism. Furthermore, glucose control and medication were unlikely to have major confounding effects. We also applied our model to a recently described Chinese cohort and show that the discriminant metagenomic markers for T2D differ between the European and Chinese cohorts. Therefore, metagenomic predictive tools for T2D should be specific for the age and geographical location of the populations studied.

doi: 10.1038/nature12198

神経科学:鳴禽類とヒト乳幼児における音節組み合わせ能力の段階的獲得

Stepwise acquisition of vocal combinatorial capacity in songbirds and human infants p.104

Human language, as well as birdsong, relies on the ability to arrange vocal elements in new sequences. However, little is known about the ontogenetic origin of this capacity. Here we track the development of vocal combinatorial capacity in three species of vocal learners, combining an experimental approach in zebra finches (Taeniopygia guttata) with an analysis of natural development of vocal transitions in Bengalese finches (Lonchura striata domestica) and pre-lingual human infants. We find a common, stepwise pattern of acquiring vocal transitions across species. In our first study, juvenile zebra finches were trained to perform one song and then the training target was altered, prompting the birds to swap syllable order, or insert a new syllable into a string. All birds solved these permutation tasks in a series of steps, gradually approximating the target sequence by acquiring new pairwise syllable transitions, sometimes too slowly to accomplish the task fully. Similarly, in the more complex songs of Bengalese finches, branching points and bidirectional transitions in song syntax were acquired in a stepwise fashion, starting from a more restrictive set of vocal transitions. The babbling of pre-lingual human infants showed a similar pattern: instead of a single developmental shift from reduplicated to variegated babbling (that is, from repetitive to diverse sequences), we observed multiple shifts, where each new syllable type slowly acquired a diversity of pairwise transitions, asynchronously over development. Collectively, these results point to a common generative process that is conserved across species, suggesting that the long-noted gap between perceptual versus motor combinatorial capabilities in human infants may arise partly from the challenges in constructing new pairwise vocal transitions.

doi: 10.1038/nature12173

がん:がん遺伝子誘導性老化におけるミトコンドリアのゲートキーパー、ピルビン酸デヒドロゲナーゼの主要な役割

A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence p.109

In response to tenacious stress signals, such as the unscheduled activation of oncogenes, cells can mobilize tumour suppressor networks to avert the hazard of malignant transformation. A large body of evidence indicates that oncogene-induced senescence (OIS) acts as such a break, withdrawing cells from the proliferative pool almost irreversibly, thus crafting a vital pathophysiological mechanism that protects against cancer. Despite the widespread contribution of OIS to the cessation of tumorigenic expansion in animal models and humans, we have only just begun to define the underlying mechanism and identify key players. Although deregulation of metabolism is intimately linked to the proliferative capacity of cells, and senescent cells are thought to remain metabolically active, little has been investigated in detail about the role of cellular metabolism in OIS. Here we show, by metabolic profiling and functional perturbations, that the mitochondrial gatekeeper pyruvate dehydrogenase (PDH) is a crucial mediator of senescence induced by BRAFV600E, an oncogene commonly mutated in melanoma and other cancers. BRAFV600E-induced senescence was accompanied by simultaneous suppression of the PDH-inhibitory enzyme pyruvate dehydrogenase kinase 1 (PDK1) and induction of the PDH-activating enzyme pyruvate dehydrogenase phosphatase 2 (PDP2). The resulting combined activation of PDH enhanced the use of pyruvate in the tricarboxylic acid cycle, causing increased respiration and redox stress. Abrogation of OIS, a rate-limiting step towards oncogenic transformation, coincided with reversion of these processes. Further supporting a crucial role of PDH in OIS, enforced normalization of either PDK1 or PDP2 expression levels inhibited PDH and abrogated OIS, thereby licensing BRAFV600E-driven melanoma development. Finally, depletion of PDK1 eradicated melanoma subpopulations resistant to targeted BRAF inhibition, and caused regression of established melanomas. These results reveal a mechanistic relationship between OIS and a key metabolic signalling axis, which may be exploited therapeutically.

doi: 10.1038/nature12154

免疫:自然リンパ球は腸内常在共生菌に対するCD4+ T細胞応答を調節する

Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria p.113

Innate lymphoid cells (ILCs) are a recently characterized family of immune cells that have critical roles in cytokine-mediated regulation of intestinal epithelial cell barrier integrity. Alterations in ILC responses are associated with multiple chronic human diseases, including inflammatory bowel disease, implicating a role for ILCs in disease pathogenesis. Owing to an inability to target ILCs selectively, experimental studies assessing ILC function have predominantly used mice lacking adaptive immune cells. However, in lymphocyte-sufficient hosts ILCs are vastly outnumbered by CD4+ T cells, which express similar profiles of effector cytokines. Therefore, the function of ILCs in the presence of adaptive immunity and their potential to influence adaptive immune cell responses remain unknown. To test this, we used genetic or antibody-mediated depletion strategies to target murine ILCs in the presence of an adaptive immune system. We show that loss of retinoic-acid-receptor-related orphan receptor-γt-positive (RORγt+) ILCs was associated with dysregulated adaptive immune cell responses against commensal bacteria and low-grade systemic inflammation. Remarkably, ILC-mediated regulation of adaptive immune cells occurred independently of interleukin (IL)-17A, IL-22 or IL-23. Genome-wide transcriptional profiling and functional analyses revealed that RORγt+ ILCs express major histocompatibility complex class II (MHCII) and can process and present antigen. However, rather than inducing T-cell proliferation, ILCs acted to limit commensal bacteria-specific CD4+ T-cell responses. Consistent with this, selective deletion of MHCII in murine RORγt+ ILCs resulted in dysregulated commensal bacteria-dependent CD4+ T-cell responses that promoted spontaneous intestinal inflammation. These data identify that ILCs maintain intestinal homeostasis through MHCII-dependent interactions with CD4+ T cells that limit pathological adaptive immune cell responses to commensal bacteria.

doi: 10.1038/nature12240

心血管生物学:AIBPが介在するコレステロール排出による血管新生の制御

Control of angiogenesis by AIBP-mediated cholesterol efflux p.118

Cholesterol is a structural component of the cell and is indispensable for normal cellular function, although its excess often leads to abnormal proliferation, migration, inflammatory responses and/or cell death. To prevent cholesterol overload, ATP-binding cassette (ABC) transporters mediate cholesterol efflux from the cells to apolipoprotein A-I (apoA-I) and the apoA-I-containing high-density lipoprotein (HDL). Maintaining efficient cholesterol efflux is essential for normal cellular function. However, the role of cholesterol efflux in angiogenesis and the identity of its local regulators are poorly understood. Here we show that apoA-I binding protein (AIBP) accelerates cholesterol efflux from endothelial cells to HDL and thereby regulates angiogenesis. AIBP- and HDL-mediated cholesterol depletion reduces lipid rafts, interferes with VEGFR2 (also known as KDR) dimerization and signalling and inhibits vascular endothelial growth factor-induced angiogenesis in vitro and mouse aortic neovascularization ex vivo. Notably, Aibp, a zebrafish homologue of human AIBP, regulates the membrane lipid order in embryonic zebrafish vasculature and functions as a non-cell-autonomous regulator of angiogenesis. aibp knockdown results in dysregulated sprouting/branching angiogenesis, whereas forced Aibp expression inhibits angiogenesis. Dysregulated angiogenesis is phenocopied in Abca1 (also known as Abca1a) Abcg1-deficient embryos, and cholesterol levels are increased in Aibp-deficient and Abca1 Abcg1-deficient embryos. Our findings demonstrate that secreted AIBP positively regulates cholesterol efflux from endothelial cells and that effective cholesterol efflux is critical for proper angiogenesis.

doi: 10.1038/nature12166

生化学:tRNA機能を調節する代謝産物カルボキシ-SAMの、構造を手がかりにした発見

Structure-guided discovery of the metabolite carboxy-SAM that modulates tRNA function p.123

The identification of novel metabolites and the characterization of their biological functions are major challenges in biology. X-ray crystallography can reveal unanticipated ligands that persist through purification and crystallization. These adventitious protein–ligand complexes provide insights into new activities, pathways and regulatory mechanisms. We describe a new metabolite, carboxy-S-adenosyl-l-methionine (Cx-SAM), its biosynthetic pathway and its role in transfer RNA modification. The structure of CmoA, a member of the SAM-dependent methyltransferase superfamily, revealed a ligand consistent with Cx-SAM in the catalytic site. Mechanistic analyses showed an unprecedented role for prephenate as the carboxyl donor and the involvement of a unique ylide intermediate as the carboxyl acceptor in the CmoA-mediated conversion of SAM to Cx-SAM. A second member of the SAM-dependent methyltransferase superfamily, CmoB, recognizes Cx-SAM and acts as a carboxymethyltransferase to convert 5-hydroxyuridine into 5-oxyacetyl uridine at the wobble position of multiple tRNAs in Gram-negative bacteria, resulting in expanded codon-recognition properties. CmoA and CmoB represent the first documented synthase and transferase for Cx-SAM. These findings reveal new functional diversity in the SAM-dependent methyltransferase superfamily and expand the metabolic and biological contributions of SAM-based biochemistry. These discoveries highlight the value of structural genomics approaches in identifying ligands within the context of their physiologically relevant macromolecular binding partners, and in revealing their functions.

doi: 10.1038/nature12180

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