目次

Editorials

科学界から、セクシャルハラスメントをなくさなくてはならない。

End harassment p.409

Sexual harassment is a stain on science — and we must all take a stand against it.

doi: 10.1038/502409b

欧州研究会議(ERC)は、優れた科学を推進してきた実績を維持すると同時に、助成の不均衡の問題にも取り組んでいくべきだ。

High maintenance p.409

The next president of the European Research Council will face the dual challenge of preserving the agency’s reputation for excellence while trying to address funding inequalities.

doi: 10.1038/502409a

NMRが、工業化学の難問であった反応炉中の温度変化を知る手がかりになりそうだ。

Magnetic map p.410

Chemists present a way to infer the enigmatic temperature variations inside a reactor.

doi: 10.1038/502410a

News

麻酔薬の死刑執行への利用が、米国の医療用麻酔薬の供給を滞らせる恐れが。

Death row incurs drug penalty p.417

Bid to use common anaesthetic for executions threatens to cut off supply to US hospitals.

doi: 10.1038/502417a

南米の学術誌オープンアクセスサイトSciELOが、開設から15年に。

Brazil fêtes open-access site p.418

South American SciELO project weighs up future after 15 years of free publishing.

doi: 10.1038/502418a

米国の政府機関閉鎖が、科学界に後遺症を。

Pain of US shutdown lingers p.419

Researchers fear that continuing budget fights will further harm government-funded science.

doi: 10.1038/502419a

ヨーロッパで、漁業補助金をめぐって論争が。

Europe debates fisheries funding p.420

Campaigners want subsidies to be focused on conservation.

doi: 10.1038/502420a

米国のLUX暗黒物質探索実験が、間もなく初の実験結果を発表へ。

Final word is near on dark-matter signal p.421

An influential US experiment prepares to release its first results.

doi: 10.1038/502421a

実際の火山灰で作った人工雲を使って、航空機を噴火から守る安全装置の野外試験が。

Volcanic-ash sensor to take flight p.422

Researchers will fly jet towards giant artificial particle cloud to test safety device.

doi: 10.1038/502422a

Features

古生物学:T. rex の真実

Palaeontology: The truth about T. rex p.424

Even one of the best known dinosaurs has kept some secrets. Here is what palaeontologists most want to know about the Famous tyrant.

doi: 10.1038/502424a

脳の解読:心を読み取る

Brain decoding: Reading minds p.428

By scanning blobs of brain activity, scientists may be able to decode people's thoughts, their dreams and even their intentions.

doi: 10.1038/502428a

News & Views

古人類学:小さい脳と大きな口

Palaeoanthropology: Small-brained and big-mouthed p.452

グルジアのドマニシの遺跡から出土したヒト族のほぼ完全な頭蓋骨は、著しく原始的な形態を示しており、初期のヒト属の動物群は幅広い多様性を示す単一系統として進化したと、発見者が考えたくなるようなものである。

doi: 10.1038/502452a

天体物理学:均一性のためのレシピ

Astrophysics: Recipe for regularity p.453

詳細な天体物理学的モデルが示され、星形成が活発に起きている銀河に関して遠赤外線と電波の相関が再現されただけでなく、こうした関係が高赤方偏移領域でどのように修正されるかも予測されている。

doi: 10.1038/502453a

生理学:代謝でのメヌエット

Physiology: A metabolic minuet p.454

2つの近縁の核内受容体が、2つの別の組織での概日性の脂肪代謝に脂質メッセンジャーを仲介として関わっていることが分かった。このシグナル伝達経路は代謝性疾患の解明に関係している可能性がある。

doi: 10.1038/502454a

応用物理学:支配権を握るのは材料科学

Applied physics: Materials scientists take control p.455

Ruddlesden–Popper型構造と呼ばれる、一連の複合酸化物材料を制御する新しい方法が見つかった。このことは、電気的に調節可能なマイクロ波デバイスの作製につながる可能性がある。

doi: 10.1038/nature12696

古生物学:「内から外へ」モデルをひっくり返す

Palaeontology: Inside-out turned upside-down p.457

コノドントエレメントの顕微鏡による巧妙な解析から、この不可解な化石構造は、以前に推定されていたような、脊椎動物の歯の進化的前段階に当たるものではないことが示された。

doi: 10.1038/nature12695

無機化学:ホウ素の還元的役割

Inorganic chemistry: A reducing role for boron p.458

一酸化炭素分子は通常、金属触媒を使えば相互に連結させることが可能である。非金属元素であるホウ素が、このような反応を仲介することが分かったのは意外な発見であり、炭素−炭素結合を生成する過程に役立つのではないかと期待されている。

doi: 10.1038/502458a

天文学:遠方銀河までの距離の新記録

Astronomy: New distance record for galaxies p.459

遠方銀河の43の候補について分光学的測定が行われ、そのうちの1つが、現在までに厳密な測定が行われた中で最も遠い所にあることが確認された。さらに、この銀河では天の川銀河の100倍以上の速さで星形成が起こっていることも分かった。

doi: 10.1038/502459a

Articles

神経科学:DEETを感知するにおい分子受容体およびニューロンと、新しい昆虫忌避剤

Odour receptors and neurons for DEET and new insect repellents p.507

doi: 10.1038/nature12594

細胞:ニッチ内の空間構成は幹細胞運命決定因子の1つである

Spatial organization within a niche as a determinant of stem-cell fate p.513

doi: 10.1038/nature12602

分子生物学:box C/D酵素の構造から明らかになったRNAメチル化の調節機構

The structure of the box C/D enzyme reveals regulation of RNA methylation p.519

doi: 10.1038/nature12581

Letters

宇宙:ビッグバン後7億年の赤方偏移7.51にある、急激に星を形成する銀河

A galaxy rapidly forming stars 700 million years after the Big Bang at redshift 7.51 p.524

Of several dozen galaxies observed spectroscopically that are candidates for having a redshift (z) in excess of seven, only five have had their redshifts confirmed via Lyman α emission, at z = 7.008, 7.045, 7.109, 7.213 and 7.215 (refs 1, 2, 3, 4). The small fraction of confirmed galaxies may indicate that the neutral fraction in the intergalactic medium rises quickly at z > 6.5, given that Lyman α is resonantly scattered by neutral gas. The small samples and limited depth of previous observations, however, makes these conclusions tentative. Here we report a deep near-infrared spectroscopic survey of 43 photometrically-selected galaxies with z > 6.5. We detect a near-infrared emission line from only a single galaxy, confirming that some process is making Lyman α difficult to detect. The detected emission line at a wavelength of 1.0343 micrometres is likely to be Lyman α emission, placing this galaxy at a redshift z = 7.51, an epoch 700 million years after the Big Bang. This galaxy’s colours are consistent with significant metal content, implying that galaxies become enriched rapidly. We calculate a surprisingly high star-formation rate of about 330 solar masses per year, which is more than a factor of 100 greater than that seen in the Milky Way. Such a galaxy is unexpected in a survey of our size, suggesting that the early Universe may harbour a larger number of intense sites of star formation than expected.

doi: 10.1038/nature12657

物性物理学:高温超伝導体に似たギャップ挙動を示す界面超伝導体

Interface superconductor with gap behaviour like a high-temperature superconductor p.528

The physics of the superconducting state in two-dimensional (2D) electron systems is relevant to understanding the high-transition-temperature copper oxide superconductors and for the development of future superconductors based on interface electron systems. But it is not yet understood how fundamental superconducting parameters, such as the spectral density of states, change when these superconducting electron systems are depleted of charge carriers. Here we use tunnel spectroscopy with planar junctions to measure the behaviour of the electronic spectral density of states as a function of carrier density, clarifying this issue experimentally. We chose the conducting LaAlO3–SrTiO3 interface as the 2D superconductor, because this electron system can be tuned continuously with an electric gate field. We observed an energy gap of the order of 40 microelectronvolts in the density of states, whose shape is well described by the Bardeen–Cooper–Schrieffer superconducting gap function. In contrast to the dome-shaped dependence of the critical temperature, the gap increases with charge carrier depletion in both the underdoped region and the overdoped region. These results are analogous to the pseudogap behaviour of the high-transition-temperature copper oxide superconductors and imply that the smooth continuation of the superconducting gap into pseudogap-like behaviour could be a general property of 2D superconductivity.

doi: 10.1038/nature12494

材料科学:次元数と欠陥低減を利用して、調節可能なマイクロ波誘電体を創出する

Exploiting dimensionality and defect mitigation to create tunable microwave dielectrics p.532

The miniaturization and integration of frequency-agile microwave circuits—relevant to electronically tunable filters, antennas, resonators and phase shifters—with microelectronics offers tantalizing device possibilities, yet requires thin films whose dielectric constant at gigahertz frequencies can be tuned by applying a quasi-static electric field. Appropriate systems such as BaxSr1−xTiO3 have a paraelectric–ferroelectric transition just below ambient temperature, providing high tunability. Unfortunately, such films suffer significant losses arising from defects. Recognizing that progress is stymied by dielectric loss, we start with a system with exceptionally low loss—Srn+1TinO3n+1 phases—in which (SrO)2 crystallographic shear planes provide an alternative to the formation of point defects for accommodating non-stoichiometry. Here we report the experimental realization of a highly tunable ground state arising from the emergence of a local ferroelectric instability in biaxially strained Srn+1TinO3n+1 phases with n ≥ 3 at frequencies up to 125 GHz. In contrast to traditional methods of modifying ferroelectrics—doping or strain—in this unique system an increase in the separation between the (SrO)2 planes, which can be achieved by changing n, bolsters the local ferroelectric instability. This new control parameter, n, can be exploited to achieve a figure of merit at room temperature that rivals all known tunable microwave dielectrics.

doi: 10.1038/nature12582

化学:不均一反応における気体の温度マップ

Thermal maps of gases in heterogeneous reactions p.537

More than 85 per cent of all chemical industry products are made using catalysts, the overwhelming majority of which are heterogeneous catalysts that function at the gas–solid interface. Consequently, much effort is invested in optimizing the design of catalytic reactors, usually by modelling the coupling between heat transfer, fluid dynamics and surface reaction kinetics. The complexity involved requires a calibration of model approximations against experimental observations, with temperature maps being particularly valuable because temperature control is often essential for optimal operation and because temperature gradients contain information about the energetics of a reaction. However, it is challenging to probe the behaviour of a gas inside a reactor without disturbing its flow, particularly when trying also to map the physical parameters and gradients that dictate heat and mass flow and catalytic efficiency. Although optical techniques and sensors have been used for that purpose, the former perform poorly in opaque media and the latter perturb the flow. NMR thermometry can measure temperature non-invasively, but traditional approaches applied to gases produce signals that depend only weakly on temperature are rapidly attenuated by diffusion or require contrast agents that may interfere with reactions. Here we present a new NMR thermometry technique that circumvents these problems by exploiting the inverse relationship between NMR linewidths and temperature caused by motional averaging in a weak magnetic field gradient. We demonstrate the concept by non-invasively mapping gas temperatures during the hydrogenation of propylene in reactors packed with metal nanoparticles and metal–organic framework catalysts, with measurement errors of less than four per cent of the absolute temperature. These results establish our technique as a non-invasive tool for locating hot and cold spots in catalyst-packed gas–solid reactors, with unprecedented capabilities for testing the approximations used in reactor modelling.

doi: 10.1038/nature12568

気候:21世紀のエルニーニョと関連する降水変動の確かな予測

Robust twenty-first-century projections of El Niño and related precipitation variability p.541

The El Niño–Southern Oscillation (ENSO) drives substantial variability in rainfall, severe weather, agricultural production, ecosystems and disease in many parts of the world. Given that further human-forced changes in the Earth’s climate system seem inevitable, the possibility exists that the character of ENSO and its impacts might change over the coming century. Although this issue has been investigated many times during the past 20 years, there is very little consensus on future changes in ENSO, apart from an expectation that ENSO will continue to be a dominant source of year-to-year variability. Here we show that there are in fact robust projected changes in the spatial patterns of year-to-year ENSO-driven variability in both surface temperature and precipitation. These changes are evident in the two most recent generations of climate models, using four different scenarios for CO2 and other radiatively active gases. By the mid- to late twenty-first century, the projections include an intensification of both El-Niño-driven drying in the western Pacific Ocean and rainfall increases in the central and eastern equatorial Pacific. Experiments with an Atmospheric General Circulation Model reveal that robust projected changes in precipitation anomalies during El Niño years are primarily determined by a nonlinear response to surface global warming. Uncertain projected changes in the amplitude of ENSO-driven surface temperature variability have only a secondary role. Projected changes in key characteristics of ENSO are consequently much clearer than previously realized.

doi: 10.1038/nature12580

古生物学:コノドントの起源と脊椎動物の石灰化した骨格の由来

The origin of conodonts and of vertebrate mineralized skeletons p.546

Conodonts are an extinct group of jawless vertebrates whose tooth-like elements are the earliest instance of a mineralized skeleton in the vertebrate lineage, inspiring the ‘inside-out’ hypothesis that teeth evolved independently of the vertebrate dermal skeleton and before the origin of jaws. However, these propositions have been based on evidence from derived euconodonts. Here we test hypotheses of a paraconodont ancestry of euconodonts using synchrotron radiation X-ray tomographic microscopy to characterize and compare the microstructure of morphologically similar euconodont and paraconodont elements. Paraconodonts exhibit a range of grades of structural differentiation, including tissues and a pattern of growth common to euconodont basal bodies. The different grades of structural differentiation exhibited by paraconodonts demonstrate the stepwise acquisition of euconodont characters, resolving debate over the relationship between these two groups. By implication, the putative homology of euconodont crown tissue and vertebrate enamel must be rejected as these tissues have evolved independently and convergently. Thus, the precise ontogenetic, structural and topological similarities between conodont elements and vertebrate odontodes appear to be a remarkable instance of convergence. The last common ancestor of conodonts and jawed vertebrates probably lacked mineralized skeletal tissues. The hypothesis that teeth evolved before jaws and the inside-out hypothesis of dental evolution must be rejected; teeth seem to have evolved through the extension of odontogenic competence from the external dermis to internal epithelium soon after the origin of jaws.

doi: 10.1038/nature12645

生理:日周性の血清脂質が肝臓の脂質生成と末梢の脂肪酸利用を統合する

A diurnal serum lipid integrates hepatic lipogenesis and peripheral fatty acid use p.550

Food intake increases the activity of hepatic de novo lipogenesis, which mediates the conversion of glucose to fats for storage or use. In mice, this program follows a circadian rhythm that peaks with nocturnal feeding and is repressed by Rev-erbα/β and an HDAC3-containing complex during the day. The transcriptional activators controlling rhythmic lipid synthesis in the dark cycle remain poorly defined. Disturbances in hepatic lipogenesis are also associated with systemic metabolic phenotypes, suggesting that lipogenesis in the liver communicates with peripheral tissues to control energy substrate homeostasis. Here we identify a PPARδ-dependent de novo lipogenic pathway in the liver that modulates fat use by muscle via a circulating lipid. The nuclear receptor PPARδ controls diurnal expression of lipogenic genes in the dark/feeding cycle. Liver-specific PPARδ activation increases, whereas hepatocyte-Ppard deletion reduces, muscle fatty acid uptake. Unbiased metabolite profiling identifies phosphatidylcholine 18:0/18:1 (PC(18:0/18:1) as a serum lipid regulated by diurnal hepatic PPARδ activity. PC(18:0/18:1) reduces postprandial lipid levels and increases fatty acid use through muscle PPARα. High-fat feeding diminishes rhythmic production of PC(18:0/18:1), whereas PC(18:0/18:1) administration in db/db mice (also known as Lepr−/−) improves metabolic homeostasis. These findings reveal an integrated regulatory circuit coupling lipid synthesis in the liver to energy use in muscle by coordinating the activity of two closely related nuclear receptors. These data implicate alterations in diurnal hepatic PPARδ–PC(18:0/18:1) signalling in metabolic disorders, including obesity.

doi: 10.1038/nature12710

発生生物学:トウモロコシのGα遺伝子COMPACT PLANT2はCLAVATAシグナル伝達系で機能し、シュート分裂組織のサイズを制御する

The maize Gα gene COMPACT PLANT2 functions in CLAVATA signalling to control shoot meristem size p.555

Shoot growth depends on meristems, pools of stem cells that are maintained by a negative feedback loop between the CLAVATA pathway and the WUSCHEL homeobox gene. CLAVATA signalling involves a secreted peptide, CLAVATA3 (CLV3), and its perception by cell surface leucine-rich repeat (LRR) receptors, including the CLV1 receptor kinase and a LRR receptor-like protein, CLV2 (ref. 4). However, the signalling mechanisms downstream of these receptors are poorly understood, especially for LRR receptor-like proteins, which lack a signalling domain. Here we show that maize COMPACT PLANT2 (CT2) encodes the predicted α-subunit (Gα) of a heterotrimeric GTP binding protein. Maize ct2 phenotypes resemble Arabidopsis thaliana clavata mutants, and genetic, biochemical and functional assays indicate that CT2/Gα transmits a stem-cell-restrictive signal from a CLAVATA LRR receptor, suggesting a new function for Gα signalling in plants. Heterotrimeric GTP-binding proteins are membrane-associated molecular switches that are commonly activated by ligand binding to an associated seven-pass transmembrane (7TM) G-protein-coupled receptor (GPCR). Recent studies have questioned the idea that plant heterotrimeric G proteins interact with canonical GPCRs, and our findings suggest that single pass transmembrane receptors act as GPCRs in plants, challenging the dogma that GPCRs are exclusively 7TM proteins.

doi: 10.1038/nature12583

医学:ヒトMX2はHIV-1感染に対するインターフェロン誘導性侵入後阻害因子である

Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection p.559

Animal cells harbour multiple innate effector mechanisms that inhibit virus replication. For the pathogenic retrovirus human immunodeficiency virus type 1 (HIV-1), these include widely expressed restriction factors, such as APOBEC3 proteins, TRIM5-α, BST2 (refs 4, 5) and SAMHD1 (refs 6, 7), as well as additional factors that are stimulated by type 1 interferon (IFN). Here we use both ectopic expression and gene-silencing experiments to define the human dynamin-like, IFN-induced myxovirus resistance 2 (MX2, also known as MXB) protein as a potent inhibitor of HIV-1 infection and as a key effector of IFN-α-mediated resistance to HIV-1 infection. MX2 suppresses infection by all HIV-1 strains tested, has equivalent or reduced effects on divergent simian immunodeficiency viruses, and does not inhibit other retroviruses such as murine leukaemia virus. The Capsid region of the viral Gag protein dictates susceptibility to MX2, and the block to infection occurs at a late post-entry step, with both the nuclear accumulation and chromosomal integration of nascent viral complementary DNA suppressed. Finally, human MX1 (also known as MXA), a closely related protein that has long been recognized as a broadly acting inhibitor of RNA and DNA viruses, including the orthomyxovirus influenza A virus, does not affect HIV-1, whereas MX2 is ineffective against influenza virus. MX2 is therefore a cell-autonomous, anti-HIV-1 resistance factor whose purposeful mobilization may represent a new therapeutic approach for the treatment of HIV/AIDS.

doi: 10.1038/nature12542

医学:MX2はHIV-1感染に対するインターフェロン誘導性阻害因子である

MX2 is an interferon-induced inhibitor of HIV-1 infection p.563

HIV-1 replication can be inhibited by type I interferon (IFN), and the expression of a number of gene products with anti-HIV-1 activity is induced by type I IFN. However, none of the known antiretroviral proteins can account for the ability of type I IFN to inhibit early, preintegration phases of the HIV-1 replication cycle in human cells. Here, by comparing gene expression profiles in cell lines that differ in their ability to support the inhibitory action of IFN-α at early steps of the HIV-1 replication cycle, we identify myxovirus resistance 2 (MX2) as an interferon-induced inhibitor of HIV-1 infection. Expression of MX2 reduces permissiveness to a variety of lentiviruses, whereas depletion of MX2 using RNA interference reduces the anti-HIV-1 potency of IFN-α. HIV-1 reverse transcription proceeds normally in MX2-expressing cells, but 2-long terminal repeat circular forms of HIV-1 DNA are less abundant, suggesting that MX2 inhibits HIV-1 nuclear import, or destabilizes nuclear HIV-1 DNA. Consistent with this notion, mutations in the HIV-1 capsid protein that are known, or suspected, to alter the nuclear import pathways used by HIV-1 confer resistance to MX2, whereas preventing cell division increases MX2 potency. Overall, these findings indicate that MX2 is an effector of the anti-HIV-1 activity of type-I IFN, and suggest that MX2 inhibits HIV-1 infection by inhibiting capsid-dependent nuclear import of subviral complexes.

doi: 10.1038/nature12653

細胞生物学:αTAT1はクラスリン被覆ピットでの微小管アセチル化を触媒する

αTAT1 catalyses microtubule acetylation at clathrin-coated pits p.567

In most eukaryotic cells microtubules undergo post-translational modifications such as acetylation of α-tubulin on lysine 40, a widespread modification restricted to a subset of microtubules that turns over slowly. This subset of stable microtubules accumulates in cell protrusions and regulates cell polarization, migration and invasion. However, mechanisms restricting acetylation to these microtubules are unknown. Here we report that clathrin-coated pits (CCPs) control microtubule acetylation through a direct interaction of the α-tubulin acetyltransferase αTAT1 (refs 8, 9) with the clathrin adaptor AP2. We observe that about one-third of growing microtubule ends contact and pause at CCPs and that loss of CCPs decreases lysine 40 acetylation levels. We show that αTAT1 localizes to CCPs through a direct interaction with AP2 that is required for microtubule acetylation. In migrating cells, the polarized orientation of acetylated microtubules correlates with CCP accumulation at the leading edge, and interaction of αTAT1 with AP2 is required for directional migration. We conclude that microtubules contacting CCPs become acetylated by αTAT1. In migrating cells, this mechanism ensures the acetylation of microtubules oriented towards the leading edge, thus promoting directional cell locomotion and chemotaxis.

doi: 10.1038/nature12571

生物工学:微生物による短鎖アルカン類の生産

Microbial production of short-chain alkanes p.571

doi: 10.1038/nature12536

構造生物学:アドレナリンで活性化されたβ2アドレナリン受容体の改造ナノボディにより安定化された構造

Adrenaline-activated structure of β2-adrenoceptor stabilized by an engineered nanobody p.575

G-protein-coupled receptors (GPCRs) are integral membrane proteins that have an essential role in human physiology, yet the molecular processes through which they bind to their endogenous agonists and activate effector proteins remain poorly understood. So far, it has not been possible to capture an active-state GPCR bound to its native neurotransmitter. Crystal structures of agonist-bound GPCRs have relied on the use of either exceptionally high-affinity agonists or receptor stabilization by mutagenesis. Many natural agonists such as adrenaline, which activates the β2-adrenoceptor (β2AR), bind with relatively low affinity, and they are often chemically unstable. Using directed evolution, we engineered a high-affinity camelid antibody fragment that stabilizes the active state of the β2AR, and used this to obtain crystal structures of the activated receptor bound to multiple ligands. Here we present structures of the active-state human β2AR bound to three chemically distinct agonists: the ultrahigh-affinity agonist BI167107, the high-affinity catecholamine agonist hydroxybenzyl isoproterenol, and the low-affinity endogenous agonist adrenaline. The crystal structures reveal a highly conserved overall ligand recognition and activation mode despite diverse ligand chemical structures and affinities that range from 100 nM to ∼80 pM. Overall, the adrenaline-bound receptor structure is similar to the others, but it has substantial rearrangements in extracellular loop three and the extracellular tip of transmembrane helix 6. These structures also reveal a water-mediated hydrogen bond between two conserved tyrosines, which appears to stabilize the active state of the β2AR and related GPCRs.

doi: 10.1038/nature12572

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