米国カリフォルニア州の低炭素燃料基準は、国レベルでの基準を考える際にも、多くを学べる手本となる。
The cleaner state p.157
Federal regulators could learn much from California’s low-carbon fuel programme.
doi: 10.1038/497157b
Volume 497 Number 7448
今週のハイライト
Cover Story: 洋ナシ形になる：CERNで観測されたエキゾチックなラジウム224原子核
神経科学: 口と顔の動きを制御する親時計
老化: 視床下部による老化過程の制御
構造生物学: mTORキナーゼの構造
量子物理学: 光子の量子もつれの実在性
物理: スカーミオンがフェルミ液体挙動の破綻を引き起こす
気候: 海水準上昇におけるグリーンランドの役割を見直す
細胞: サイトカインが指示する幹細胞分化
細菌学: 身元を隠す病原性細菌
細胞: 死んだ細胞のシグナル伝達機能
構造生物学: 細菌の微量栄養素輸送体
目次
Editorials
米最高裁は、公的助成を受ける研究者の「政府方針に賛同せずに沈黙を守る」権利を擁護すべきだ。
Right to remain silent p.157
The US Supreme Court should overturn the 2003 law that requires federally funded HIV/AIDS programmes abroad to denounce prostitution.
doi: 10.1038/497157a
動物実験を擁護するPro-Test運動は、過激な動物実験反対運動に脅かされる科学者たちに勇気を与えるだろう。
Voice of Pro-Test p.158
Confidence is rising among scientists defending animal research. It should be encouraged.
doi: 10.1038/497158a
News
米オバマ政権が、備蓄核兵器管理の予算を大幅増額へ。
US warheads to get a facelift p.165
Obama boosts ‘stockpile stewardship’ funds at energy labs.
doi: 10.1038/497165a
大西洋の海流の変化を調査する、3つの大規模な計画が。
Oceans under surveillance p.167
Three projects seek to track changes in Atlantic overturning circulation currents.
doi: 10.1038/497167a
米国のヘリウム価格上昇を受け、ロシアやカタールのヘリウムガス田開発が盛んに。
US bill would keep helium store afloat p.168
Russia and Qatar prepare to dominate market as gas price inflation puts researchers under pressure.
doi: 10.1038/497168a
ジャマイカダンスと性選択に関する論文をめぐり、データねつ造を認める調査結果が。
Symmetry study deemed a fraud p.170
University finds evidence of fakery in Jamaican dance data.
doi: 10.1038/497170a
News Features
倫理：ゲノムのハッカー
Privacy protections: The genome hacker p.172
DNAデータベースに登録された「匿名」のDNAデータから、被験者が特定できることが明らかになった。
doi: 10.1038/497172a
補綴学：感覚をもう一度
Neuroprosthetics: Once more, with feeling p.176
義手の機能は非常に向上してきており、これからの課題は、触覚を持った義手の開発である。
doi: 10.1038/497176a
News & Views
フォーラム：核物理学：エキゾチックな洋ナシ形の原子核
Exotic pear-shaped nuclei p.190
ある種の核が作る洋ナシ形の形状は捉えにくく、理論的予測も難しいが、この形状がついに正確に測定された。この結果が核物理学および素粒子物理学に意味するものについて、2人の専門家が見解を語っている。
doi: 10.1038/497190a
銀河形成：注目を集める宇宙のクモの巣状構造
The cosmic web in focus p.191
互いに近傍にあるアンドロメダ銀河とさんかく座銀河の間にのびているわずかな中性水素ガス成分が観測されたことから、この捉えにくい銀河間媒質の分光画像が高解像度で得られるようになった。
doi: 10.1038/497191a
構造生物学：マスター調節因子のセキュリティ対策
Security measures of a master regulator p.193
mTORキナーゼの、触媒活性を持った状態の結晶構造がついに明らかにされた。この酵素は、細胞増殖のマスター調節因子である。この構造から、活性部位への基質の接近を制御する「門番」機構の存在が示された。
doi: 10.1038/nature12101
免疫学：警報を鳴らす記憶細胞
Memory cells sound the alarm p.194
粘膜表面にある記憶免疫細胞が病原体と遭遇するとシグナルを発し、他の記憶細胞をその場所に動員することがわかった。この知見は、ワクチンの設計に関わってくる可能性がある。
doi: 10.1038/497194b
細胞生物学：筋肉に新しい生をもたらす細胞死
Death brings new life to muscle p.196
筋芽細胞と呼ばれる筋細胞の融合は、動物の一生を通じて骨格筋の形成と維持の基盤となっている。哺乳類では、細胞死がシグナルとして働いてこの過程を増強していることがだんだんに明らかになってきた。
doi: 10.1038/nature12097
生理学：炎症と老化をリンクする脳
Inflammation links ageing to the brain p.197
脳の視床下部では、炎症により活性化したシグナル伝達経路が老化関連ホルモンの産生を制御している。この知見は、炎症、ストレス応答と全身の老化とを結び付けるものだ。
doi: 10.1038/nature12100
Articles
物理：放射性加速ビームを用いた洋ナシ形原子核の研究
Studies of pear-shaped nuclei using accelerated radioactive beams p.199
There is strong circumstantial evidence that certain heavy, unstable atomic nuclei are ‘octupole deformed’, that is, distorted into a pear shape. This contrasts with the more prevalent rugby-ball shape of nuclei with reflection-symmetric, quadrupole deformations. The elusive octupole deformed nuclei are of importance for nuclear structure theory, and also in searches for physics beyond the standard model; any measurable electric-dipole moment (a signature of the latter) is expected to be amplified in such nuclei. Here we determine electric octupole transition strengths (a direct measure of octupole correlations) for short-lived isotopes of radon and radium. Coulomb excitation experiments were performed using accelerated beams of heavy, radioactive ions. Our data on
doi: 10.1038/nature12073
神経科学：洞毛運動と呼吸から明らかになった口腔顔面リズムの階層性
Hierarchy of orofacial rhythms revealed through whisking and breathing p.205
Whisking and sniffing are predominant aspects of exploratory behaviour in rodents. Yet the neural mechanisms that generate and coordinate these and other orofacial motor patterns remain largely uncharacterized. Here we use anatomical, behavioural, electrophysiological and pharmacological tools to show that whisking and sniffing are coordinated by respiratory centres in the ventral medulla. We delineate a distinct region in the ventral medulla that provides rhythmic input to the facial motor neurons that drive protraction of the vibrissae. Neuronal output from this region is reset at each inspiration by direct input from the pre-Bötzinger complex, such that high-frequency sniffing has a one-to-one relationship with whisking, whereas basal respiration is accompanied by intervening whisks that occur between breaths. We conjecture that the respiratory nuclei, which project to other premotor regions for oral and facial control, function as a master clock for behaviours that coordinate with breathing.
doi: 10.1038/nature12076
老化：IKK-β、NF-κBおよびGnRHが関与する、視床下部における全身老化のプログラム化
Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH p.211
Ageing is a result of gradual and overall functional deteriorations across the body; however, it is unknown whether an individual tissue primarily works to mediate the ageing progress and control lifespan. Here we show that the hypothalamus is important for the development of whole-body ageing in mice, and that the underlying basis involves hypothalamic immunity mediated by IκB kinase-β (IKK-β), nuclear factor κB (NF-κB) and related microglia–neuron immune crosstalk. Several interventional models were developed showing that ageing retardation and lifespan extension are achieved in mice by preventing ageing-related hypothalamic or brain IKK-β and NF-κB activation. Mechanistic studies further revealed that IKK-β and NF-κB inhibit gonadotropin-releasing hormone (GnRH) to mediate ageing-related hypothalamic GnRH decline, and GnRH treatment amends ageing-impaired neurogenesis and decelerates ageing. In conclusion, the hypothalamus has a programmatic role in ageing development via immune–neuroendocrine integration, and immune inhibition or GnRH restoration in the hypothalamus/brain represent two potential strategies for optimizing lifespan and combating ageing-related health problems.
doi: 10.1038/nature12143
構造生物学：mTORキナーゼの構造、反応機構と調節
mTOR kinase structure, mechanism and regulation p.217
The mammalian target of rapamycin (mTOR), a phosphoinositide 3-kinase-related protein kinase, controls cell growth in response to nutrients and growth factors and is frequently deregulated in cancer. Here we report co-crystal structures of a complex of truncated mTOR and mammalian lethal with SEC13 protein 8 (mLST8) with an ATP transition state mimic and with ATP-site inhibitors. The structures reveal an intrinsically active kinase conformation, with catalytic residues and a catalytic mechanism remarkably similar to canonical protein kinases. The active site is highly recessed owing to the FKBP12–rapamycin-binding (FRB) domain and an inhibitory helix protruding from the catalytic cleft. mTOR-activating mutations map to the structural framework that holds these elements in place, indicating that the kinase is controlled by restricted access. In vitro biochemistry shows that the FRB domain acts as a gatekeeper, with its rapamycin-binding site interacting with substrates to grant them access to the restricted active site. Rapamycin–FKBP12 inhibits the kinase by directly blocking substrate recruitment and by further restricting active-site access. The structures also reveal active-site residues and conformational changes that underlie inhibitor potency and specificity.
doi: 10.1038/nature12122
Letters
宇宙：銀河M31とM33の間にある分離した中性ガスの雲
Discrete clouds of neutral gas between the galaxies M31 and M33 p.224
About half of the gas stretching between the galaxies M31 and M33 is shown to be composed of clouds, with the rest distributed in an extended, diffuse component.
doi: 10.1038/nature12082
量子物理学：もつれた光子を使った公平な標本抽出の仮定によらないベル不等式の破れ
Bell violation using entangled photons without the fair-sampling assumption p.227
The fair-sampling loophole is closed in a Bell inequality violation experiment with entangled photons, making the photon the first physical system for which all the main loopholes have been closed.
doi: 10.1038/nature12012
物理：MnSiにおけるトポロジカル非フェルミ液体の形成
Formation of a topological non-Fermi liquid in MnSi p.231
The non-Fermi-liquid regime that emerges in MnSi under high pressures displays a Hall signal that can be traced to topologically non-trivial spin configurations at low pressures — a well-understood skyrmion lattice — empirically suggesting a route towards a breakdown of Fermi liquid theory in pure metals.
doi: 10.1038/nature12023
気候：グリーンランドの主な溢流氷河に起因する温暖化する気候における将来の海水準上昇
Future sea-level rise from Greenland’s main outlet glaciers in a warming climate p.235
A model of the four main outlet glaciers that drain the Greenland Ice Sheet predicts that they will contribute 19 to 30 millimetres to sea-level rise by 2200 in a mid-range future warming scenario, and 29 to 49 millimetres in a more extreme scenario.
doi: 10.1038/nature12068
細胞：M-CSFは単一の造血幹細胞に骨髄細胞系譜の運命を指示する
M-CSF instructs myeloid lineage fate in single haematopoietic stem cells p.239
M-CSF, a myeloid cytokine released during infection and inflammation, instructs myeloid lineage fate in single haematopoietic stem cells by directly inducing PU.1, a known myeloid lineage master regulator; this shows that specific cytokines can act directly on haematopoietic stem cells to instruct a change of cell identity.
doi: 10.1038/nature12026
分子生物学：Lin28–let-7経路におけるパールマン症候群エキソヌクレアーゼDis3l2の役割
A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28–let-7 pathway p.244
This study shows that Dis3l2 is the 3′–5′ exonuclease that mediates the degradation of uridylated precursor let-7 microRNA; this is the first physiological RNA substrate identified for this new exonuclease, which causes the Perlman syndrome of fetal overgrowth and Wilms’ tumour susceptibility when mutated.
doi: 10.1038/nature12119
発生：Meis1は出生後の心筋細胞の細胞周期停止を調節する
Meis1 regulates postnatal cardiomyocyte cell cycle arrest p.249
The neonatal heart has a high regenerative capacity that is lost in adult life; the transcription factor Meis1 has been identified as a relevant proliferative switch for this transition, providing a potential therapeutic target for adult heart regeneration.
doi: 10.1038/nature12054
細菌学：CRISPR/Cas系は細菌の自然免疫回避と毒性に関与する
A CRISPR/Cas system mediates bacterial innate immune evasion and virulence p.254
The CRISPR/Cas system known to aid bacterial defences by targeting invading DNA can also act to evade eukaryotic defences through a different class of small RNAs downregulating an endogenous immunogenic bacterial lipoprotein.
doi: 10.1038/nature12048
免疫：胸腺由来の制御性T細胞は共生微生物叢に対する寛容に関わっている
Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota p.258
By using high-throughput sequencing of T-cell receptors, this study shows that thymus-derived regulatory T (Treg) cells constitute most Treg cells in all lymphoid and intestinal organs, including the colon, suggesting that thymic Treg cells and not induced Treg cells dominantly control tolerance to the gut’s antigens such as commensal microbiota.
doi: 10.1038/nature12079
細胞：筋芽細胞融合の促進因子であることが新たにわかったホスファチジルセリン受容体BAI1とアポトーシス細胞
Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion p.263
The apoptotic event of phosphatidylserine exposure and its recognition by the receptor BAI1 has an unexpected new role as a signal enhancing mouse myoblast fusion, an insight with relevance to some congenital muscle diseases and muscle injury treatments.
doi: 10.1038/nature12135
構造生物学：Lactobacillus brevis由来の葉酸エネルギー共役因子輸送体の結晶構造
Crystal structure of a folate energy-coupling factor transporter from Lactobacillus brevis p.268
The crystal structure of an inward-facing, nucleotide-free folate energy-coupling factor transporter from Lactobacillus brevis at a resolution of 3 Å suggests a transport model that involves a substantial conformational change of the substrate-specific binding protein, FolT.
doi: 10.1038/nature12046
構造生物学：細菌のエネルギー共役因子輸送体の構造
Structure of a bacterial energy-coupling factor transporter p.272
The crystal structure of a nucleotide-free energy-coupling factor transporter from Lactobacillus brevis at a resolution of 3.5 Å suggests a plausible working model for the transport cycle of such transporters.
doi: 10.1038/nature12045
