目次

Editorials

地表の水の変化の大半は、人為的原因によるものであり、水の管理は最優先課題だ。

Get water governance on the global agenda p.169

Human activity causes most changes in Earth’s surface water, so policies for its governance must become a priority.

doi: 10.1038/540169b

ペットの動物を対象とした臨床試験は、ペット用医薬品はもとよりヒトの医薬品開発にも有用であり、こうした試験を妨げる過剰な規制は見直すべきだ。

Reform regulations to make pet clinical trials easier p.169

Trials in animals can aid both veterinary and human medicine, but complicated rules can stifle them.

doi: 10.1038/540169a

子どもの心に響き、科学への憧れを生む本がある。

Turn children on to science through reading p.170

Books have the power to trigger a lifelong urge to know more about the world and its environs.

doi: 10.1038/540170a

News

欧州宇宙機関(ESA)の火星探査計画「エクソマーズ」の第一弾の着陸機は失敗したが、第二弾の探査機には予定通り予算が。

Europe’s first Mars rover gets funding — despite crash of test craft p.177

But the European Space Agency's participation in a mission to deflect an asteroid moon is now cancelled.

doi: 10.1038/nature.2016.21091

ゲノム解読により、アメリカ先住民の起源をめぐる論争に決着が。

North America’s oldest mummy returned to US tribe after genome sequencing p.178

DNA proves Native American roots of 10,600-year-old skeleton.

doi: 10.1038/540178a

メキシコでのヒト胚研究が、当局による生殖医療の規制強化によって禁止される恐れが。

Mexico proposal to ban human-embryo research would stifle science p.180

Researchers in the country have only just started using homegrown human embryonic stem cells

doi: 10.1038/540180a

米国のポスドク研究者の賃上げは、残業手当に関する法的争いのせいで棚上げに。

Battle over US overtime pay rules leaves many postdocs in limbo p.181

Institutions struggle to respond after court blocks regulations that would have increased wages for junior researchers.

doi: 10.1038/nature.2016.21084

英国のEU離脱や米国大統領選などに見られるナショナリズムの再燃の要因について、研究者たちが当惑を。

Researchers baffled by nationalist surge p.182

Economic woes wrought by globalization are only part of the cause.

doi: 10.1038/540182a

ブラジルのアマゾンの森林破壊が、過去8年で最悪に。

Deforestation spikes in Brazilian Amazon p.182

Illegal land clearing hits highest levels since 2008 as environmental policies come under attack.

doi: 10.1038/nature.2016.21083

News Features

ゲノミクス:囚われの果ての「自由」

What DNA reveals about St Helena’s freed slaves p.184

英国領セントヘレナ島には、アフリカから運ばれる途中で解放され死んでいった多くの奴隷たちの墓があり、そうした死者のDNA解析から、出身地域や死因などが明らかになりつつある。

doi: 10.1038/540184a

News & Views

フォーラム:気候科学:グリーンランドの氷の歴史

Climate science: The history of Greenland's ice p.202

グリーンランドの氷床が完全に溶けてしまえば、全球の海水準は数メートル上昇するだろう。2つの研究で、氷床の過去の挙動に基づいて、温暖化した地球でのこの氷床の脆弱性の評価が行われたが、その結論は一見したところ矛盾するものだった。2人の地球化学者と1人の氷河学研究者がこの問題について論じている。

doi: 10.1038/540202a

ウイルス学:寄生体に寄生するものが宿主の隣人を助ける

Virology: A parasite's parasite saves host's neighbours p.204

ウイルスは、寄生性ウイルス(ウイルスに寄生し細胞資源に関して競合する)に攻撃されることがある。そのような寄生性ウイルスの1つが、宿主細胞集団をウイルスの攻撃から守ることがあるのが今回明らかになった。

doi: 10.1038/540204a

天体物理学:宇宙時間にわたる元素存在量

Astrophysics: Elemental abundances across cosmic time p.205

初期宇宙に存在した大質量銀河の1つの化学組成によって、非常に短い星形成期間が明らかになった。この結果は銀河と宇宙自体の進化についての我々の考え方に疑問を投げ掛けるものだ。

doi: 10.1038/540205a

神経変性疾患:アルツハイマー病での神経の同期

Neurodegenerative Disorders: Neural synchronization in Alzheimer's disease p.207

アルツハイマー病では、神経回路によって発生する電気的振動が破壊される。この病気のマウスモデルで、この振動を回復させると免疫細胞が活性化され、病気と関連するとされているアミロイドβタンパク質が脳から除去されることが今回明らかになった。

doi: 10.1038/540207a

回顧:地球の公転軌道と氷河期が結び付けられてからの40年

In Retrospect: Forty years of linking orbits to ice ages p.208

1976年、地球の公転軌道のわずかなゆらぎが、過去数百万年の大氷河時代の氷期サイクルにつながったことが実証された。この発見は気候科学に広く関係するもので、その詳細については現在も議論が盛んに行われている。

doi: 10.1038/540208a

生物医学:細胞のエネルギー工場を置き換える

Biomedicine: Replacing the cell's power plants p.210

ミトコンドリアDNAに変異が生じているヒト卵子の核DNAを、ドナーの卵子に移植する実験が成功した。これはミトコンドリア病の治療法実現の期待に一歩近づく成果である。

doi: 10.1038/nature20483

幹細胞:ナイーブ幹細胞を目指す努力

Stem cells: Aspiring to naivety p.211

ヒト体内のあらゆる種類の細胞を生じることができる幹細胞は、生物医学研究の主役の1つである。ヒト胚の分子レベルでの解析は、培養幹細胞をin vivoの幹細胞の信頼のおける模造品とするのに役立ちそうだ。

doi: 10.1038/nature20484

Reviews

量子情報:量子物理学における認証されたランダム性

Certified randomness in quantum physics p.213

Quantum technology enables new methods for generating of randomness with minimal assumptions, certified by the violation of a Bell inequality, which opens up new theoretical and experimental research directions and leads to new challenges.

doi: 10.1038/nature20119

生態学:花粉媒介者の保護および人類の幸福に対するその価値

Safeguarding pollinators and their values to human well-being p.220

Wild and managed pollinators are threatened by pressures such as environmental changes and pesticides, leading to risks for pollinator-dependent crop production, meaning more research and better policies are needed to safeguard pollinators and their services.

doi: 10.1038/nature20588

Articles

神経科学:ガンマ周波数の同調はアミロイドの蓄積を軽減してミクログリアを変化させる

Gamma frequency entrainment attenuates amyloid load and modifies microglia p.230

Mouse models of Alzheimer’s disease show reduced, behaviourally driven gamma oscillations before the onset of plaque formation or cognitive decline; driving neurons to oscillate at gamma frequency (40 Hz) reduces levels of amyloid-β peptides.

doi: 10.1038/nature20587

免疫学:S-2-ヒドロキシグルタル酸はCD8+ Tリンパ球の運命を調節する

S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate p.236

S-2-hydroxyglutarate produced by CD8+ T cells under hypoxic conditions affects locus-specific histone and DNA methylation patterns, which enhances T-cell proliferation, survival and recall responses.

doi: 10.1038/nature20165

分子生物学:ショウジョウバエでm6Aはニューロン機能と性決定を調節する

m6A modulates neuronal functions and sex determination in Drosophila p.242

One of the most abundant modifications found in messenger RNAs is N6-methyladenosine (m6A); here, this modification is shown to alter gene expression during sex determination and affect neuronal functions and behaviour in Drosophila via the m6A reader protein YT521-B.

doi: 10.1038/nature20568

Letters

宇宙論:赤方偏移2.1に位置する静穏な種族IIの大質量銀河

A massive, quiescent, population II galaxy at a redshift of 2.1 p.248

The ratio of magnesium to iron abundance is measured for a massive quiescent galaxy at a redshift of 2.1, corresponding to when the Universe was three billion years old.

doi: 10.1038/nature20570

気候科学:更新世においてグリーンランドには長期間ほとんど氷がなかった

Greenland was nearly ice-free for extended periods during the Pleistocene p.252

Measurements of cosmic-ray-produced 10Be and 26Al in a bedrock core from beneath the summit of the Greenland Ice Sheet show that Greenland was nearly ice-free for extended periods under Pleistocene climate forcing.

doi: 10.1038/nature20146

気候科学:過去750万年にわたって持続的で動的であった東グリーンランド氷床

A persistent and dynamic East Greenland Ice Sheet over the past 7.5 million years p.256

10Be and 26Al isotopic evidence in quartz sand from the seafloor shows that a dynamic East Greenland Ice Sheet has existed for the past 7.5 million years.

doi: 10.1038/nature20147

テクトニクス:東太平洋海膨における海底拡大事象のダイナミクス

Dynamics of a seafloor-spreading episode at the East Pacific Rise p.261

Seismic observations clarify the roles of magma pressure and tectonic stress in the development of seafloor spreading during the most recent eruption at the East Pacific Rise.

doi: 10.1038/nature20116

生物多様性:土地利用の強化は草原群集で多栄養段階の均質化を引き起こす

Land-use intensification causes multitrophic homogenization of grassland communities p.266

Analysis of a large grassland biodiversity dataset shows that increases in local land-use intensity cause biotic homogenization at landscape scale across microbial, plant and animal groups, both above- and belowground, that is largely independent of changes in local diversity.

doi: 10.1038/nature20575

生物医学:ミトコンドリアDNAに病原性変異を持つヒト卵母細胞でのミトコンドリア置換

Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations p.270

Analysis of mitochondrial replacement therapy shows, even with efficient mutant mitochondrial DNA replacement and maintenance in embryonic stem cells, a gradual loss of donor mitochondrial DNA in some lines owing to a polymorphism in the D-loop, potentially causing preferential replication of specific mitochondrial DNA haplotypes.

doi: 10.1038/nature20592

幹細胞:常在幹細胞におけるPDGFRαイントロンのポリアデニル化は筋繊維症を軽減させる

Intronic polyadenylation of PDGFRα in resident stem cells attenuates muscle fibrosis p.276

Platelet-derived growth factor receptor α (PDGFRα) exhibits divergent effects in skeletal muscle. At physiological levels, signalling through this receptor promotes muscle development in growing embryos and angiogenesis in regenerating adult muscle. However, both increased PDGF ligand abundance and enhanced PDGFRα pathway activity cause pathological fibrosis. This excessive collagen deposition, which is seen in aged and diseased muscle, interferes with muscle function and limits the effectiveness of gene- and cell-based therapies for muscle disorders. Although compelling evidence exists for the role of PDGFRα in fibrosis, little is known about the cells through which this pathway acts. Here we show in mice that PDGFRα signalling regulates a population of muscle-resident fibro/adipogenic progenitors (FAPs) that play a supportive role in muscle regeneration but may also cause fibrosis when aberrantly regulated. We found that FAPs produce multiple transcriptional variants of Pdgfra with different polyadenylation sites, including an intronic variant that codes for a protein isoform containing a truncated kinase domain. This variant, upregulated during regeneration, acts as a decoy to inhibit PDGF signalling and to prevent FAP over-activation. Moreover, increasing the expression of this isoform limits fibrosis in vivo in mice, suggesting both biological relevance and therapeutic potential of modulating polyadenylation patterns in stem-cell populations.

doi: 10.1038/nature20160

微生物学:ミクロシンは炎症の起こっている腸管で腸内細菌科の細菌間に競争を引き起こす

Microcins mediate competition among Enterobacteriaceae in the inflamed gut p.280

Certain commensal enterobacteria secrete small proteins called microcins that suppress the growth of other bacteria in the inflamed gut, conferring an intra- and interspecies competitive advantage.

doi: 10.1038/nature20557

免疫学:SIV感染アカゲザルでのTLR7刺激を併用するAd26/MVA治療用ワクチン接種

Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys p.284

The development of immunologic interventions that can target the viral reservoir in HIV-1-infected individuals is a major goal of HIV-1 research. However, little evidence exists that the viral reservoir can be sufficiently targeted to improve virologic control following discontinuation of antiretroviral therapy. Here we show that therapeutic vaccination with Ad26/MVA (recombinant adenovirus serotype 26 (Ad26) prime, modified vaccinia Ankara (MVA) boost) and stimulation of TLR7 (Toll-like receptor 7) improves virologic control and delays viral rebound following discontinuation of antiretroviral therapy in SIV-infected rhesus monkeys that began antiretroviral therapy during acute infection. Therapeutic vaccination with Ad26/MVA resulted in a marked increase in the magnitude and breadth of SIV-specific cellular immune responses in virologically suppressed, SIV-infected monkeys. TLR7 agonist administration led to innate immune stimulation and cellular immune activation. The combination of Ad26/MVA vaccination and TLR7 stimulation resulted in decreased levels of viral DNA in lymph nodes and peripheral blood, and improved virologic control and delayed viral rebound following discontinuation of antiretroviral therapy. The breadth of cellular immune responses correlated inversely with set point viral loads and correlated directly with time to viral rebound. These data demonstrate the potential of therapeutic vaccination combined with innate immune stimulation as a strategy aimed at a functional cure for HIV-1 infection.

doi: 10.1038/nature20583

微生物学:mavirusヴィロファージの宿主ゲノムへの組み込みと巨大ウイルスによる再活性化

Host genome integration and giant virus-induced reactivation of the virophage mavirus p.288

Endogenous viral elements found in a marine protozoan have a function in defence against infection by giant viruses.

doi: 10.1038/nature20593

タンパク質設計:設計されたタンパク質が誘導するナノケージを持つ細胞外小胞の形成

Designed proteins induce the formation of nanocage-containing extracellular vesicles p.292

Autonomously produced hybrid biological nanomaterials termed ‘enveloped protein nanocages’ incorporate features for membrane binding, self-assembly, and ESCRT recruitment for cellular release.

doi: 10.1038/nature20607

細胞生物学:2点接触型および複数点接触型の染色体コンホメーションの、染色体歩行を用いた捕捉

Capturing pairwise and multi-way chromosomal conformations using chromosomal walks p.296

A conformation capture sequencing method is developed to link multiple genomic loci into three-dimensional proximity chains called chromosomal walks (C-walks), adding to our understanding of how higher-order chromosomal structures participate in genome regulation.

doi: 10.1038/nature20158

分子生物学:m6A はショウジョウバエのロバストな性決定のためにSxl mRNA前駆体の選択的スプライシングを促進する

m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination p.301

N6-methyladenosine (m6A) is the most common internal modification of eukaryotic messenger RNA (mRNA) and is decoded by YTH domain proteins. The mammalian mRNA m6A methylosome is a complex of nuclear proteins that includes METTL3 (methyltransferase-like 3), METTL14, WTAP (Wilms tumour 1-associated protein) and KIAA1429. Drosophila has corresponding homologues named Ime4 and KAR4 (Inducer of meiosis 4 and Karyogamy protein 4), and Female-lethal (2)d (Fl(2)d) and Virilizer (Vir). In Drosophila, fl(2)d and vir are required for sex-dependent regulation of alternative splicing of the sex determination factor Sex lethal (Sxl). However, the functions of m6A in introns in the regulation of alternative splicing remain uncertain. Here we show that m6A is absent in the mRNA of Drosophila lacking Ime4. In contrast to mouse and plant knockout models, Drosophila Ime4-null mutants remain viable, though flightless, and show a sex bias towards maleness. This is because m6A is required for female-specific alternative splicing of Sxl, which determines female physiognomy, but also translationally represses male-specific lethal 2 (msl-2) to prevent dosage compensation in females. We further show that the m6A reader protein YT521-B decodes m6A in the sex-specifically spliced intron of Sxl, as its absence phenocopies Ime4 mutants. Loss of m6A also affects alternative splicing of additional genes, predominantly in the 5′ untranslated region, and has global effects on the expression of metabolic genes. The requirement of m6A and its reader YT521-B for female-specific Sxl alternative splicing reveals that this hitherto enigmatic mRNA modification constitutes an ancient and specific mechanism to adjust levels of gene expression.

doi: 10.1038/nature20577

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