Editorials
環境を悪化させる石油生産現場での遊離天然ガス焼却は不当な資源の浪費でもあり、米国はこれに代わる方法を探すべきだ。
Wasted energy p.281
The burning off of gas during oil extraction is environmentally unsound and unjustifiable. The United States should instead be seeking to make use of this natural resource.
doi: 10.1038/495281a
ワシントン条約（CITES）締約国会議の成功は、絶滅危惧種の保護を前進させる大きな一歩だ。
CITES for sore eyes p.281
Successes at last week’s wildlife-trade treaty meeting must be backed up with action.
doi: 10.1038/495281b
社会との関わりを重視する新しいローマ法王は、科学との対話、友好関係をさらに深めると期待される。
A pope for today p.282
Latest pontiff looks to enhance social relevance of Catholic Church.
doi: 10.1038/495282a
News
米国が、チンパンジーを使った公的資金による研究を終了へ。
Time called on chimp work p.289
NIH likely to retire hundreds of government-owned chimpanzees.
doi: 10.1038/495289a
シェールガスの急成長で、ガスフレアとメタンガス漏出が問題に。
Oil boom raises burning issues p.290
Unburned methane could be adding to the environmental impact of gas flares in North Dakota.
doi: 10.1038/495290a
NASAの火星探査機キュリオシティに不具合が発生し、探査活動を急ぐ必要も。
Mars rover under pressure to reach mountain goal p.292
Curiosity’s memory glitch prompts mission scientists to pick up the pace.
doi: 10.1038/495292a
バイオインフォマティクス企業が、クラウドによる遺伝子解析サービスに続々と。
Gene-analysis firms reach for the cloud p.293
Online bioinformatics companies rush to provide genomics platforms and software for hospitals.
doi: 10.1038/495293a
英企業が、深海底から有用資源を豊富に含む鉱物塊を採掘する計画を。
UK company pursues deep-sea bonanza p.294
After decades of preparation, firm moves forward with plans to harvest mineral-rich nuggets from sea floor.
doi: 10.1038/495294a
テキストマイニングをめぐって、科学者と出版社の意見に対立が。
Text-mining spat heats up p.295
Scientists and publishers clash over licences that would let machines read research papers.
doi: 10.1038/495295a
News Features
天文学：星の追跡者
Astronomy: Star tracker p.296
Andrea Ghezは、新しい技術を進んで取り入れ、銀河系の中央にある巨大なブラックホールの解明に取り組んでいる。
doi: 10.1038/495296a
長期的研究：悠々たる科学
Long-term research: Slow science p.300
世界で最も長期にわたって行われている実験が、科学とは短距離走ではなく、マラソンであることを思い出させてくれる。
doi: 10.1038/495300a
News & Views
光学デバイス：眼鏡の要らない3D画像
Optical devices: 3D without the glasses p.316
特別な眼鏡を必要としない三次元ディスプレイ技術が発明された。これは、モバイル機器で現在使われている技術に対するまた別の選択肢として関心を集めそうだ。この技術は学校で物理を習った程度の学生でも知っているような光学的効果を利用している。
doi: 10.1038/495316a
幹細胞：血液細胞の輸送に関わっている鎮痛剤
Stem cells: Painkillers caught in blood-cell trafficking p.317
造血幹細胞と前駆細胞は骨髄から循環系へ移動して血液細胞を補充し、細胞数を正常なレベルに維持している。プロスタグランジンが仲介するシグナル伝達経路が阻害されると、この過程が促進されるらしい。
doi: 10.1038/nature12085
地球科学：主に平野で
Earth science: Mainly in the plain p.318
景観からの全球的質量損失の主な原因は、山地ではなく、平坦な地形で起こる物理的浸食と化学的な風化作用であるという知見は、地球の表面がどのように進化してきたかについての我々の考え方に疑問を投げかけるものだ。
doi: 10.1038/495318a
がん：上流のトラブル
Cancer: Trouble upstream p.320
テロメラーゼという酵素の成分の1つをコードする遺伝子のプロモーター配列に生じた変異が、黒色腫患者で見つかった。このことは、この調節領域に生じた変異が腫瘍発生を促進しうることを示唆している。
doi: 10.1038/495320a
物性物理学：フラストレートしたトリオ
Condensed-matter physics: A frustrated trio p.321
幾何学的フラストレーションは、系の成分の空間配置とそれらの相互作用が適合していないことから生じる。こうした影響が三角形に配置された3つの量子ドットで観察された。
doi: 10.1038/495321a
分子生物学：RNAワールドを作り変える環状RNA
Molecular biology: Circles reshape the RNA world p.322
RNAの多芸多才ぶりには限界がないようだ。意外な新発見は環状RNAについてのもので、環状RNAが別種の調節性RNAであるマイクロRNAの機能を無効にするように働くことがわかったのである。
doi: 10.1038/nature11956
天文学：真価を発揮するALMA望遠鏡
Astronomy: The ALMA telescope shows its true colours p.324
重力レンズで増光された明るい銀河が、宇宙時間の広がりを越えて見つかった。これはまだ建設途上にあるALMA望遠鏡から得られた初めての成果で、こうした銀河の赤方偏移と内部構造を明らかにする、この望遠鏡の能力を示したものと言える。
doi: 10.1038/nature12084
進化ゲノミクス：選択を見抜く
Evolutionary genomics: Detecting selection p.325
集団遺伝学とゲノム塩基配列解読技術の進歩によって、選択を経てきたDNAの遺伝子特徴が不明の断片を見分けることが可能になっている。これによって、進化に関するいくつかの問題の答えが得られたが、一連の謎も生じることになった。
doi: 10.1038/495325a
Articles
神経科学：発話の調音に関わるヒト感覚運動皮質の機能的構成
Functional organization of human sensorimotor cortex for speech articulation p.327
Multi-electrode cortical recordings during the production of different consonant-vowel syllables reveal distinct speech-articulator representations that are arranged somatotopically, with temporal and spatial patterns of activity across the neural population corresponding to phonetic features and dynamics.
doi: 10.1038/nature11911
分子生物学：環状RNAは調節能を持つ動物RNAの大きなグループである
Circular RNAs are a large class of animal RNAs with regulatory potency p.333
Biochemical, functional and computational analyses are combined to show that circular RNAs are a large class of animal RNAs with regulatory potency.
doi: 10.1038/nature11928
分子生物学：DNA複製起点ライセンシングのATPアーゼに依存した品質管理
ATPase-dependent quality control of DNA replication origin licensing p.339
The authors describe how the eukaryotic replicative helicase is recruited to origins and reveal a novel ATPase-dependent quality control mechanism.
doi: 10.1038/nature11920
Letters
宇宙：重力レンズ効果によって明らかにされた初期宇宙における塵に富んだスターバースト銀河
Dusty starburst galaxies in the early Universe as revealed by gravitational lensing p.344
In the past decade, our understanding of galaxy evolution has been revolutionized by the discovery that luminous, dusty starburst galaxies were 1,000 times more abundant in the early Universe than at present. It has, however, been difficult to measure the complete redshift distribution of these objects, especially at the highest redshifts (z > 4). Here we report a redshift survey at a wavelength of three millimetres, targeting carbon monoxide line emission from the star-forming molecular gas in the direction of extraordinarily bright millimetre-wave-selected sources. High-resolution imaging demonstrates that these sources are strongly gravitationally lensed by foreground galaxies. We detect spectral lines in 23 out of 26 sources and multiple lines in 12 of those 23 sources, from which we obtain robust, unambiguous redshifts. At least 10 of the sources are found to lie at z > 4, indicating that the fraction of dusty starburst galaxies at high redshifts is greater than previously thought. Models of lens geometries in the sample indicate that the background objects are ultra-luminous infrared galaxies, powered by extreme bursts of star formation.
doi: 10.1038/nature12001
工学：眼鏡の不要な広角三次元ディスプレイに向けた多方向バックライト
A multi-directional backlight for a wide-angle, glasses-free three-dimensional display p.348
Multiview three-dimensional (3D) displays can project the correct perspectives of a 3D image in many spatial directions simultaneously. They provide a 3D stereoscopic experience to many viewers at the same time with full motion parallax and do not require special glasses or eye tracking. None of the leading multiview 3D solutions is particularly well suited to mobile devices (watches, mobile phones or tablets), which require the combination of a thin, portable form factor, a high spatial resolution and a wide full-parallax view zone (for short viewing distance from potentially steep angles). Here we introduce a multi-directional diffractive backlight technology that permits the rendering of high-resolution, full-parallax 3D images in a very wide view zone (up to 180 degrees in principle) at an observation distance of up to a metre. The key to our design is a guided-wave illumination technique based on light-emitting diodes that produces wide-angle multiview images in colour from a thin planar transparent lightguide. Pixels associated with different views or colours are spatially multiplexed and can be independently addressed and modulated at video rate using an external shutter plane. To illustrate the capabilities of this technology, we use simple ink masks or a high-resolution commercial liquid-crystal display unit to demonstrate passive and active (30 frames per second) modulation of a 64-view backlight, producing 3D images with a spatial resolution of 88 pixels per inch and full-motion parallax in an unprecedented view zone of 90 degrees. We also present several transparent hand-held prototypes showing animated sequences of up to six different 200-view images at a resolution of 127 pixels per inch.
doi: 10.1038/nature11972
地球：完新世における全球の窒素循環の変化
Changes in global nitrogen cycling during the Holocene epoch p.352
Human activities have doubled the pre-industrial supply of reactive nitrogen on Earth, and future rates of increase are expected to accelerate. Yet little is known about the capacity of the biosphere to buffer increased nitrogen influx. Past changes in global ecosystems following deglaciation at the end of the Pleistocene epoch provide an opportunity to understand better how nitrogen cycling in the terrestrial biosphere responded to changes in carbon cycling. We analysed published records of stable nitrogen isotopic values (δ15N) in sediments from 86 lakes on six continents. Here we show that the value of sedimentary δ15N declined from 15,000 years before present to 7,056 ± 597 years before present, a period of increasing atmospheric carbon dioxide concentrations and terrestrial carbon accumulation. Comparison of the nitrogen isotope record with concomitant carbon accumulation on land and nitrous oxide in the atmosphere suggests millennia of declining nitrogen availability in terrestrial ecosystems during the Pleistocene–Holocene transition around 11,000 years before present. In contrast, we do not observe a consistent change in global sedimentary δ15N values during the past 500 years, despite the potential effects of changing temperature and nitrogen influx from anthropogenic sources. We propose that the lack of a single response may indicate that modern increases in atmospheric carbon dioxide and net carbon sequestration in the biosphere have the potential to offset recent increased supplies of reactive nitrogen in some ecosystems.
doi: 10.1038/nature11916
地球：リソスフェア–アセノスフェア境界に見られるメルトに富んだ流路
Melt-rich channel observed at the lithosphere–asthenosphere boundary p.356
The lithosphere–asthenosphere boundary (LAB) separates rigid oceanic plates from the underlying warm ductile asthenosphere. Although a viscosity decrease beneath this boundary is essential for plate tectonics, a consensus on its origin remains elusive. Seismic studies identify a prominent velocity discontinuity at depths thought to coincide with the LAB but disagree on its cause, generally invoking either partial melting or a mantle dehydration boundary as explanations. Here we use sea-floor magnetotelluric data to image the electrical conductivity of the LAB beneath the edge of the Cocos plate at the Middle America trench offshore of Nicaragua. Underneath the resistive oceanic lithosphere, the magnetotelluric data reveal a high-conductivity layer confined to depths of 45 to 70 kilometres. Because partial melts are stable at these depths in a warm damp mantle, we interpret the conductor to be a partially molten layer capped by an impermeable frozen lid that is the base of the lithosphere. A conductivity anisotropy parallel to plate motion indicates that this melt has been sheared into flow-aligned tube-like structures. We infer that the LAB beneath young plates consists of a thin, partially molten, channel of low viscosity that acts to decouple the overlying brittle lithosphere from the deeper convecting mantle. Because this boundary layer has the potential to behave as a lubricant to plate motion, its proximity to the trench may have implications for subduction dynamics.
doi: 10.1038/nature11939
進化：イヌの家畜化に関連するゲノムの特徴は、デンプンの多い食餌への適応を示している
The genomic signature of dog domestication reveals adaptation to a starch-rich diet p.360
The domestication of dogs was an important episode in the development of human civilization. The precise timing and location of this event is debated and little is known about the genetic changes that accompanied the transformation of ancient wolves into domestic dogs. Here we conduct whole-genome resequencing of dogs and wolves to identify 3.8 million genetic variants used to identify 36 genomic regions that probably represent targets for selection during dog domestication. Nineteen of these regions contain genes important in brain function, eight of which belong to nervous system development pathways and potentially underlie behavioural changes central to dog domestication. Ten genes with key roles in starch digestion and fat metabolism also show signals of selection. We identify candidate mutations in key genes and provide functional support for an increased starch digestion in dogs relative to wolves. Our results indicate that novel adaptations allowing the early ancestors of modern dogs to thrive on a diet rich in starch, relative to the carnivorous diet of wolves, constituted a crucial step in the early domestication of dogs.
doi: 10.1038/nature11837
細胞：プロスタグランジンE2による、幹細胞と前駆細胞でそれぞれ異なる輸送
Differential stem- and progenitor-cell trafficking by prostaglandin E2 p.365
To maintain lifelong production of blood cells, haematopoietic stem cells (HSCs) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSCs reside in several, perhaps overlapping, niches that produce regulatory molecules and signals necessary for homeostasis and for increased output after stress or injury. Despite considerable advances in the specific cellular or molecular mechanisms governing HSC–niche interactions, little is known about the regulatory function in the intact mammalian haematopoietic niche. Recently, we and others described a positive regulatory role for prostaglandin E2 (PGE2) on HSC function ex vivo. Here we show that inhibition of endogenous PGE2 by non-steroidal anti-inflammatory drug (NSAID) treatment in mice results in modest HSC egress from the bone marrow. Surprisingly, this was independent of the SDF-1–CXCR4 axis implicated in stem-cell migration. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin. Haematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in other species. PGE2 receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced E-prostanoid 4 (EP4) receptor signalling. These results not only uncover unique regulatory roles for EP4 signalling in HSC retention in the niche, but also define a rapidly translatable strategy to enhance transplantation therapeutically.
doi: 10.1038/nature11929
細胞：多能性の確立におけるTET1およびTET2のNANOG依存的機能
NANOG-dependent function of TET1 and TET2 in establishment of pluripotency p.370
Molecular control of the pluripotent state is thought to reside in a core circuitry of master transcription factors including the homeodomain-containing protein NANOG, which has an essential role in establishing ground state pluripotency during somatic cell reprogramming. Whereas the genomic occupancy of NANOG has been extensively investigated, comparatively little is known about NANOG-associated proteins and their contribution to the NANOG-mediated reprogramming process. Using enhanced purification techniques and a stringent computational algorithm, we identify 27 high-confidence protein interaction partners of NANOG in mouse embryonic stem cells. These consist of 19 previously unknown partners of NANOG that have not been reported before, including the ten-eleven translocation (TET) family methylcytosine hydroxylase TET1. We confirm physical association of NANOG with TET1, and demonstrate that TET1, in synergy with NANOG, enhances the efficiency of reprogramming. We also find physical association and reprogramming synergy of TET2 with NANOG, and demonstrate that knockdown of TET2 abolishes the reprogramming synergy of NANOG with a catalytically deficient mutant of TET1. These results indicate that the physical interaction between NANOG and TET1/TET2 proteins facilitates reprogramming in a manner that is dependent on the catalytic activity of TET1/TET2. TET1 and NANOG co-occupy genomic loci of genes associated with both maintenance of pluripotency and lineage commitment in embryonic stem cells, and TET1 binding is reduced upon NANOG depletion. Co-expression of NANOG and TET1 increases 5-hydroxymethylcytosine levels at the top-ranked common target loci Esrrb and Oct4 (also called Pou5f1), resulting in priming of their expression before reprogramming to naive pluripotency. We propose that TET1 is recruited by NANOG to enhance the expression of a subset of key reprogramming target genes. These results provide an insight into the reprogramming mechanism of NANOG and uncover a new role for 5-methylcytosine hydroxylases in the establishment of naive pluripotency.
doi: 10.1038/nature11925
発生生物学：軟骨細胞の多段階からなる拡大が骨格各部分の比率の違いの原因である
Multiple phases of chondrocyte enlargement underlie differences in skeletal proportions p.375
The wide diversity of skeletal proportions in mammals is evident upon a survey of any natural history museum's collections and allows us to distinguish between species even when reduced to their calcified components. Similarly, each individual is comprised of a variety of bones of differing lengths. The largest contribution to the lengthening of a skeletal element, and to the differential elongation of elements, comes from a dramatic increase in the volume of hypertrophic chondrocytes in the growth plate as they undergo terminal differentiation. However, the mechanisms of chondrocyte volume enlargement have remained a mystery. Here we use quantitative phase microscopy to show that mammalian chondrocytes undergo three distinct phases of volume increase, including a phase of massive cell swelling in which the cellular dry mass is significantly diluted. In light of the tight fluid regulatory mechanisms known to control volume in many cell types, this is a remarkable mechanism for increasing cell size and regulating growth rate. It is, however, the duration of the final phase of volume enlargement by proportional dry mass increase at low density that varies most between rapidly and slowly elongating growth plates. Moreover, we find that this third phase is locally regulated through a mechanism dependent on insulin-like growth factor. This study provides a framework for understanding how skeletal size is regulated and for exploring how cells sense, modify and establish a volume set point.
doi: 10.1038/nature11940
生理：BMPシグナル伝達障害による褐色脂肪の不足は白色脂肪の補償的な褐色化を引き起こす
Brown-fat paucity due to impaired BMP signalling induces compensatory browning of white fat p.379
Maintenance of body temperature is essential for the survival of homeotherms. Brown adipose tissue (BAT) is a specialized fat tissue that is dedicated to thermoregulation. Owing to its remarkable capacity to dissipate stored energy and its demonstrated presence in adult humans, BAT holds great promise for the treatment of obesity and metabolic syndrome. Rodent data suggest the existence of two types of brown fat cells: constitutive BAT (cBAT), which is of embryonic origin and anatomically located in the interscapular region of mice; and recruitable BAT (rBAT), which resides within white adipose tissue (WAT) and skeletal muscle, and has alternatively been called beige, brite or inducible BAT. Bone morphogenetic proteins (BMPs) regulate the formation and thermogenic activity of BAT. Here we use mouse models to provide evidence for a systemically active regulatory mechanism that controls whole-body BAT activity for thermoregulation and energy homeostasis. Genetic ablation of the type 1A BMP receptor (Bmpr1a) in brown adipogenic progenitor cells leads to a severe paucity of cBAT. This in turn increases sympathetic input to WAT, thereby promoting the formation of rBAT within white fat depots. This previously unknown compensatory mechanism, aimed at restoring total brown-fat-mediated thermogenic capacity in the body, is sufficient to maintain normal temperature homeostasis and resistance to diet-induced obesity. These data suggest an important physiological cross-talk between constitutive and recruitable brown fat cells. This sophisticated regulatory mechanism of body temperature may participate in the control of energy balance and metabolic disease.
doi: 10.1038/nature11943
分子生物学：マイクロRNAスポンジとして効率よく機能する天然の環状RNA
Natural RNA circles function as efficient microRNA sponges p.384
MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.
doi: 10.1038/nature11993
細胞生物学：オートファゴソームは小胞体とミトコンドリアの接触部位で形成される
Autophagosomes form at ER–mitochondria contact sites p.389
Autophagy is a tightly regulated intracellular bulk degradation/recycling system that has fundamental roles in cellular homeostasis. Autophagy is initiated by isolation membranes, which form and elongate as they engulf portions of the cytoplasm and organelles. Eventually isolation membranes close to form double membrane-bound autophagosomes and fuse with lysosomes to degrade their contents. The physiological role of autophagy has been determined since its discovery, but the origin of autophagosomal membranes has remained unclear. At present, there is much controversy about the organelle from which the membranes originate—the endoplasmic reticulum (ER), mitochondria and plasma membrane. Here we show that autophagosomes form at the ER–mitochondria contact site in mammalian cells. Imaging data reveal that the pre-autophagosome/autophagosome marker ATG14 (also known as ATG14L) relocalizes to the ER–mitochondria contact site after starvation, and the autophagosome-formation marker ATG5 also localizes at the site until formation is complete. Subcellular fractionation showed that ATG14 co-fractionates in the mitochondria-associated ER membrane fraction under starvation conditions. Disruption of the ER–mitochondria contact site prevents the formation of ATG14 puncta. The ER-resident SNARE protein syntaxin 17 (STX17) binds ATG14 and recruits it to the ER–mitochondria contact site. These results provide new insight into organelle biogenesis by demonstrating that the ER–mitochondria contact site is important in autophagosome formation.
doi: 10.1038/nature11910
構造生物学：HNF-4α核内受容体複合体の構造における多ドメインの統合
Multidomain integration in the structure of the HNF-4α nuclear receptor complex p.394
The hepatocyte nuclear factor 4α (HNF-4α; also known as NR2A1) is a member of the nuclear receptor (NR) family of transcription factors, which have conserved DNA-binding domains and ligand-binding domains. HNF-4α is the most abundant DNA-binding protein in the liver, where some 40% of the actively transcribed genes have a HNF-4α response element. These regulated genes are largely involved in the hepatic gluconeogenic program and lipid metabolism. In the pancreas HNF-4α is also a master regulator, controlling an estimated 11% of islet genes. HNF-4α protein mutations are linked to maturity-onset diabetes of the young, type 1 (MODY1) and hyperinsulinaemic hypoglycaemia. Previous structural analyses of NRs, although productive in elucidating the structure of individual domains, have lagged behind in revealing the connectivity patterns of NR domains. Here we describe the 2.9 Å crystal structure of the multidomain human HNF-4α homodimer bound to its DNA response element and coactivator-derived peptides. A convergence zone connects multiple receptor domains in an asymmetric fashion, joining distinct elements from each monomer. An arginine target of PRMT1 methylation protrudes directly into this convergence zone and sustains its integrity. A serine target of protein kinase C is also responsible for maintaining domain–domain interactions. These post-translational modifications lead to changes in DNA binding by communicating through the tightly connected surfaces of the quaternary fold. We find that some MODY1 mutations, positioned on the ligand-binding domain and hinge regions of the receptor, compromise DNA binding at a distance by communicating through the interjunctional surfaces of the complex. The overall domain representation of the HNF-4α homodimer is different from that of the PPAR-γ–RXR-α heterodimer, even when both NR complexes are assembled on the same DNA element. Our findings suggest that unique quaternary folds and interdomain connections in NRs could be exploited by small-molecule allosteric modulators that affect distal functions in these polypeptides.
doi: 10.1038/nature11966
