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Editorials

研究が社会に与えるインパクトを重視している英国の評価基準は、科学の持つ力の再認識につながる優れた着眼だ。

Telling stories p.137

The UK Research Excellence Framework’s focus on impact is a useful reminder of all the ways that science can help society — both economically and by other means.

doi: 10.1038/518137a

米国は、国内で相次ぐ麻疹(はしか)の流行を、ワクチン接種推進への契機とすべきだ。

Spot the difference p.137

The US measles outbreak highlights why most states should reconsider their vaccination rules.

doi: 10.1038/518137b

2015年は国連の宣言する国際光年であり、今週号では、光と光技術について特集する。

A single light p.138

A year of illumination switches on with a Nature special issue.

doi: 10.1038/518138a

News

英国では先駆的不妊治療であるミトコンドリア置換法による体外受精が認可される見通しで、この動きが他の国々へと波及を。

World hails UK vote on three-person embryos p.145

British approval for pioneering fertility technique leads other nations to consider rule changes.

doi: 10.1038/518145a

NIHは若手研究者への助成を増やすための新システムを検討しているが、その効果を疑う声も。

NIH plan to give ageing scientists cash draws scepticism p.146

Agency wants to pay senior biomedical researchers to wind down their labs.

doi: 10.1038/518146a

ダーウィンフィンチのゲノムが解読され、くちばしの特徴の違いをもたらす遺伝子が明らかに。

Darwin’s iconic finches join genome club p.147

Scientists pinpoint genes behind famous beak variations.

doi: 10.1038/518147a

世界のはしか根絶の努力は停滞しており、小規模ではあるが先進国でも流行が。

Measles by the numbers: A race to eradication p.148

The US media are abuzz after an outbreak of measles in Disneyland but the disease will keep on popping up until it is wiped out worldwide.

doi: 10.1038/518148a

インパクトのある事例研究でより多く使われている言葉が、言語解析で明らかに。

Impact of UK research revealed in 7,000 case studies p.150

Language analysis reflects how projects succeeded in unique assessment.

doi: 10.1038/518150a

News Features

特集:光:夢のような光

Light fantastic p.153

光の特性を極限にまで広げる光科学の最前線を探る。

doi: 10.1038/518153a

特集:光:導きの光

Optics: Leading lights p.154

光を成形したり、スクイーズしたり、また活性化したり、結んだりするなど、驚くべき課題に挑んでいる光の科学者3人を紹介する。

doi: 10.1038/518154a

特集:光:ずば抜けた視力

Optics: Super vision p.158

天文学技術を利用して、生体組織のような不透明な物体を透視する方法の研究が進んでいる。

doi: 10.1038/518158a

News & Views

フォーラム:宇宙論:宇宙で最古の光

Cosmology: The oldest cosmic light p.170

宇宙マイクロ波背景放射は、ビッグバンが遺したかすかな光である。これは全天に広がり、宇宙の初期の歴史を記録している。2人の専門家が別々に、この太古の光について知られていることの要点を、理論と宇宙観測の観点の両方から述べている。

doi: 10.1038/518170a

細胞生物学:周りを引きずり落とす細胞死

Cell biology: Death drags down the neighbourhood p.171

死にかけている細胞についての分析から、こうした細胞は近隣の細胞を引っ張っていて、組織形態の変化に能動的な役割を果たしていることが分かった。これによって近くの細胞の頂端部が収縮し、それが組織の折りたたみにつながるのである。

doi: 10.1038/nature14198

星形成:きょうだい間の競争は生まれた時から始まる

Star formation: Sibling rivalry begins at birth p.173

近傍にある分子ガス雲の高分解能での天文学的観測によって形成途上にある4個一組の星が見つかった。この系が、これまでに観測された中で最も若い多重星系であることはおそらく間違いない。

doi: 10.1038/518173a

DNA修復:お決まりの末端を処理して異なる結果を得る

DNA repair: Familiar ends with alternative endings p.174

生物種を忠実に増殖させていくには、複数あるDNA修復経路の複雑なバランスをうまく保ってゲノムの完全性を維持していく必要がある。新たな研究で、こうした経路のうちでほとんど解明されていなかった1つが調べられ、一部のがんでのその役割が明らかになった。

doi: 10.1038/nature14200

地球化学:大洋から炭素が放出されたら

Geochemistry: When carbon escaped from the sea p.176

ごく小型のプランクトンの化石中のホウ素同位体記録から、最終氷期の末期に地球が温暖化した際に大洋の一部海域が二酸化炭素の大気への供給源となっていたことの新しい証拠が得られた。

doi: 10.1038/518176a

神経変性:低温ショックが脳を守る

Neurodegeneration: Cold shock protects the brain p.177

低体温症の際に放出されるタンパク質が、マウスで神経細胞死を防止し、神経相互間の接続を保存するように働いて、神経変性疾患の進行に影響を与えることが分かった。

doi: 10.1038/nature14195

Review

超伝導:銅酸化物系における量子物質から高温超伝導まで

From quantum matter to high-temperature superconductivity in copper oxides p.179

A review of the phases of copper oxides (especially the ‘strange metal’), discussing their high-temperature superconductivity and their various forms of quantum matter, and the implications for fundamental theory.

doi: 10.1038/nature14165

Articles

遺伝学:脂肪およびインスリンの生物学を体脂肪分布に関連付ける新たな複数の遺伝子座

New genetic loci link adipose and insulin biology to body fat distribution p.187

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

doi: 10.1038/nature14132

遺伝学:ボディーマス指数の遺伝学的研究から肥満についての新たな生物学的手掛かりが得られる

Genetic studies of body mass index yield new insights for obesity biology p.197

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

doi: 10.1038/nature14177

神経科学:嗅内皮質グリッド細胞の受容野の等積変形が誘発する非対称性

Shearing-induced asymmetry in entorhinal grid cells p.207

Grid cells are cells of the brain’s internal map of space that fire when an animal is in a location corresponding to the vertices of a hexagonal grid pattern tiling the entire environment; how the pattern is mapped onto the external environment has remained a mystery, however, new studies in rat reveal that the axes of the grid are determined by the boundaries of the external environment and provide insight into the rotation of the grid axis in relation to these boundaries.

doi: 10.1038/nature14151

Letters

天文学:大きく離れた四重星系の形成

The formation of a quadruple star system with wide separation p.213

Observations of a wide-separation quadruple system in the Perseus star-forming region reveal a young protostar and three gravitationally bound dense gas condensations; each condensation is expected to form a star and the closest pair will form a bound binary, while the quadruple stellar system itself is bound but unstable on timescales of 500,000 years.

doi: 10.1038/nature14166

惑星科学:過去4年間にわたって蓄積した塵の層を放出する67P/チュリュモフ・ゲラシメンコ彗星

Comet 67P/Churyumov-Gerasimenko sheds dust coat accumulated over the past four years p.216

Grains collected from comet 67P/Churyumov-Gerasimenko by the Rosetta mission come from a dusty crust that is predicted to be imminently shed as the comet nears the Sun; the grains are high in sodium and fluffy, not icy, suggesting that they are the precursors of interplanetary dust particles.

doi: 10.1038/nature14159

気候科学:最終退氷期における海洋の二酸化炭素漏出を示すホウ素同位体の証拠

Boron isotope evidence for oceanic carbon dioxide leakage during the last deglaciation p.219

The boron isotope pH proxy in sediment-core planktic foraminifera is used as a tracer of oceanic CO2 outgassing to show that surface waters which derive partly from deep water upwelled in the Southern Ocean became a significant source of carbon to the atmosphere during the last deglaciation.

doi: 10.1038/nature14155

気候科学:グリーンランド北東部の表面の融解水による氷底湖の涵養

Recharge of a subglacial lake by surface meltwater in northeast Greenland p.223

Observations of rapid, persistent elevation gains that occur on the ice surface above a subglacial lake as the lake is refilled with surface meltwater during the summer melt period in Greenland show that surface meltwater may be trapped and stored at the bed of an ice sheet, affecting ice dynamics downstream.

doi: 10.1038/nature14116

考古学:ジャワ島トリニールのホモ・エレクトスは道具の制作や彫刻に貝殻を使っていた

Homo erectus at Trinil on Java used shells for tool production and engraving p.228

Argon and luminescence dating of fossil shell infills from Trinil in Java, where Homo erectus lived, reveals that the hominin-bearing deposits are younger than previously thought; perforated shells, a shell tool and an engraved shell indicate that Homo erectus ate freshwater mussels, used their shells as tools and was able to create abstract engravings.

doi: 10.1038/nature13962

神経科学:グリッド細胞の対称性は環境の形状によって変えられる

Grid cell symmetry is shaped by environmental geometry p.232

Neuronal grid cells fire in a spatial grid pattern laid out across the surface of a familiar environment, however the role of environmental boundaries in the construction of this pattern is not well understood; this study shows that the grid pattern orients to the walls of polarized environments such as squares but not circles and that the hexagonal grid symmetry is permanently broken in highly polarized environments such as trapezoids.

doi: 10.1038/nature14153

神経科学:RBM3はシナプスの構造的可塑性と神経変性に対する冷却の保護効果に関わっている

RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration p.236

Structural synaptic plasticity and remodelling are features of the healthy adult brain and are seen during hibernation; a hibernation-inspired model of mouse cooling used to study synaptic regeneration has identified the ‘cold-shock’ RNA-binding protein, RBM3, as a regulator of synaptic assembly, deficiency of which contributes to synapse loss in neurodegenerative disease.

doi: 10.1038/nature14142

がん:収斂によるPTEN欠失がPI(3)Kα阻害剤に対する臨床耐性を引き起こす

Convergent loss of PTEN leads to clinical resistance to a PI(3)Kα inhibitor p.240

Broad and deep tumour genome sequencing has shed new light on tumour heterogeneity and provided important insights into the evolution of metastases arising from different clones. There is an additional layer of complexity, in that tumour evolution may be influenced by selective pressure provided by therapy, in a similar fashion to that occurring in infectious diseases. Here we studied tumour genomic evolution in a patient (index patient) with metastatic breast cancer bearing an activating PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha, PI(3)Kα) mutation. The patient was treated with the PI(3)Kα inhibitor BYL719, which achieved a lasting clinical response, but the patient eventually became resistant to this drug (emergence of lung metastases) and died shortly thereafter. A rapid autopsy was performed and material from a total of 14 metastatic sites was collected and sequenced. All metastatic lesions, when compared to the pre-treatment tumour, had a copy loss of PTEN (phosphatase and tensin homolog) and those lesions that became refractory to BYL719 had additional and different PTEN genetic alterations, resulting in the loss of PTEN expression. To put these results in context, we examined six other patients also treated with BYL719. Acquired bi-allelic loss of PTEN was found in one of these patients, whereas in two others PIK3CA mutations present in the primary tumour were no longer detected at the time of progression. To characterize our findings functionally, we examined the effects of PTEN knockdown in several preclinical models (both in cell lines intrinsically sensitive to BYL719 and in PTEN-null xenografts derived from our index patient), which we found resulted in resistance to BYL719, whereas simultaneous PI(3)K p110β blockade reverted this resistance phenotype. We conclude that parallel genetic evolution of separate metastatic sites with different PTEN genomic alterations leads to a convergent PTEN-null phenotype resistant to PI(3)Kα inhibition.

doi: 10.1038/nature13948

発生生物学:アポトーシス細胞により生み出された頂底方向の力が上皮組織の折りたたみを促す

Apico-basal forces exerted by apoptotic cells drive epithelium folding p.245

Apoptotic cell death is required for morphogenesis of the developing leg joint of fruitflies; using this model system, the authors show here that within apoptotic cells a transient pulling force exerted through a highly dynamic apico-basal myosin II cable-like structure acts as a mechanical signal to increase tissue tension and modify tissue shape.

doi: 10.1038/nature14152

分子生物学:RNAヘリカーゼDDX21は転写とリボソームRNAプロセシングを協調させる

RNA helicase DDX21 coordinates transcription and ribosomal RNA processing p.249

DEAD-box RNA helicase DDX21 is involved in both the transcription and RNA processing of ribosomal genes in human cells, sensing the transcriptional status of both RNA polymerase I and RNA polymerase II and associating with non-coding RNAs involved in ribonucleoprotein formation, possibly allowing for coordinated regulation of protein synthesis.

doi: 10.1038/nature13923

分子生物学:哺乳類のポリメラーゼθは代替的なNHEJを促進して組換えを抑制する

Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination p.254

The alternative non-homologous end-joining (NHEJ) machinery facilitates several genomic rearrangements, some of which can lead to cellular transformation. This error-prone repair pathway is triggered upon telomere de-protection to promote the formation of deleterious chromosome end-to-end fusions. Using next-generation sequencing technology, here we show that repair by alternative NHEJ yields non-TTAGGG nucleotide insertions at fusion breakpoints of dysfunctional telomeres. Investigating the enzymatic activity responsible for the random insertions enabled us to identify polymerase theta (Polθ; encoded by Polq in mice) as a crucial alternative NHEJ factor in mammalian cells. Polq inhibition suppresses alternative NHEJ at dysfunctional telomeres, and hinders chromosomal translocations at non-telomeric loci. In addition, we found that loss of Polq in mice results in increased rates of homology-directed repair, evident by recombination of dysfunctional telomeres and accumulation of RAD51 at double-stranded breaks. Lastly, we show that depletion of Polθ has a synergistic effect on cell survival in the absence of BRCA genes, suggesting that the inhibition of this mutagenic polymerase represents a valid therapeutic avenue for tumours carrying mutations in homology-directed repair genes.

doi: 10.1038/nature14157

分子生物学:相同組換えのできない腫瘍は、Polθを介した修復に依存している

Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair p.258

Large-scale genomic studies have shown that half of epithelial ovarian cancers (EOCs) have alterations in genes regulating homologous recombination (HR) repair. Loss of HR accounts for the genomic instability of EOCs and for their cellular hyper-dependence on alternative poly-ADP ribose polymerase (PARP)-mediated DNA repair mechanisms. Previous studies have implicated the DNA polymerase θ (Polθ also known as POLQ, encoded by POLQ) in a pathway required for the repair of DNA double-strand breaks, referred to as the error-prone microhomology-mediated end-joining (MMEJ) pathway. Whether Polθ interacts with canonical DNA repair pathways to prevent genomic instability remains unknown. Here we report an inverse correlation between HR activity and Polθ expression in EOCs. Knockdown of Polθ in HR-proficient cells upregulates HR activity and RAD51 nucleofilament assembly, while knockdown of Polθ in HR-deficient EOCs enhances cell death. Consistent with these results, genetic inactivation of an HR gene (Fancd2) and Polq in mice results in embryonic lethality. Moreover, Polθ contains RAD51 binding motifs and it blocks RAD51-mediated recombination. Our results reveal a synthetic lethal relationship between the HR pathway and Polθ-mediated repair in EOCs, and identify Polθ as a novel druggable target for cancer therapy.

doi: 10.1038/nature14184

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