医薬品の適応外使用は科学の軽視であり、患者に被害が及ばぬよう、規制する必要がある。
The limits of free speech p.311
Unregulated drug marketing stifles science and harms patients. To suggest otherwise is an affront to liberty — not a protection of it.
doi: 10.1038/492311a
Unregulated drug marketing stifles science and harms patients. To suggest otherwise is an affront to liberty — not a protection of it.
doi: 10.1038/492311a
Despite some shortcomings, a global study of health metrics should be applauded.
doi: 10.1038/492311b
Japanese scientists deserve support in their bid for the next big collider.
doi: 10.1038/492312a
Early results from Atacama telescope signal the opening of a scientific frontier.
doi: 10.1038/492319a
Government plans to close struggling institutions and increase funding to the best.
doi: 10.1038/492320a
Amgen’s deal with deCODE Genetics shows value of combined medical and genetic data.
doi: 10.1038/492321a
Study tracks changes in life expectancy and health burdens.
doi: 10.1038/492322a
Court decision sets precedent for protecting intellectual property.
doi: 10.1038/492323a
This epic year for science saw the discovery of the Higgs boson and Curiosity’s arrival on Mars, but researchers also felt the sting of austerity.
doi: 10.1038/492324a
Disintegrating ice, spectacular sunbursts and minuscule lizards are among 2012’s most striking pictures.
doi: 10.1038/492328a
この1年間、最も注目を浴びた10人とは、どんな顔ぶれだろうか。
doi: 10.1038/492335a
40年以上前に存在が予測されたある熱効果は、それに似たもう1つ別の現象が代わって脚光を浴びたためにほとんど忘れ去られていた。今回、実験的に確認されたこの効果は、熱制御デバイスの開発を後押しするものとなりそうだ。
doi: 10.1038/492358a
RNA結合タンパク質のFMR1は神経発達障害である脆弱X症候群に重要な役割を果たしているが、このタンパク質が標的とするRNAについてはほとんどわかっていなかった。今回行われた解析によって、非常に多数の標的候補が見つかった。
doi: 10.1038/nature11764
心筋細胞は傷害を受けると大量に死ぬが、哺乳類成体の心臓にはこうした細胞を再生する能力がほとんどない。調節性マイクロRNA配列はこのような心筋細胞の自己複製を促進する可能性がある。
doi: 10.1038/nature11763
がん細胞における代謝の変化は腫瘍形成を後押しすることがあるという説は、徐々に受け入れられつつある。SIRT6タンパク質が代謝の調節によって腫瘍形成を抑制するという知見は、この説に重みを加えるものだ。
doi: 10.1038/492362a
Tetタンパク質はDNA中の塩基からメチル基を除去することにより遺伝子発現を調節している。この活性は、精子や卵の細胞を形成するための細胞分裂経路を開始させる促進段階なのかもしれない。
doi: 10.1038/492363a
ヒドロキシルラジカルの1つが数ミリケルビンという温度まで冷却された。この結果は、分子の基底状態におけるボース・アインシュタイン凝縮のような現象の観察へつながる扉を開くものである。
doi: 10.1038/492364a
ポーラーロウ(polar low、極低気圧)として知られる強力な暴風の影響は、普通は気象モデルに取り込まれない。だが、ポーラーロウの海洋循環への影響を評価するシミュレーションは、これをモデルに取り込むべきであることを示唆している。
doi: 10.1038/492365a
今年掲載されたNews & Viewsの中から編集部が選んだ記事の抜粋を集めた。
doi: 10.1038/492366a
Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10
doi: 10.1038/nature11677
In mammals, enlargement of the heart during embryonic development is primarily dependent on the increase in cardiomyocyte numbers. Shortly after birth, however, cardiomyocytes stop proliferating and further growth of the myocardium occurs through hypertrophic enlargement of the existing myocytes. As a consequence of the minimal renewal of cardiomyocytes during adult life, repair of cardiac damage through myocardial regeneration is very limited. Here we show that the exogenous administration of selected microRNAs (miRNAs) markedly stimulates cardiomyocyte proliferation and promotes cardiac repair. We performed a high-content microscopy, high-throughput functional screening for human miRNAs that promoted neonatal cardiomyocyte proliferation using a whole-genome miRNA library. Forty miRNAs strongly increased both DNA synthesis and cytokinesis in neonatal mouse and rat cardiomyocytes. Two of these miRNAs (hsa-miR-590 and hsa-miR-199a) were further selected for testing and were shown to promote cell cycle re-entry of adult cardiomyocytes ex vivo and to promote cardiomyocyte proliferation in both neonatal and adult animals. After myocardial infarction in mice, these miRNAs stimulated marked cardiac regeneration and almost complete recovery of cardiac functional parameters. The miRNAs identified hold great promise for the treatment of cardiac pathologies consequent to cardiomyocyte loss.
doi: 10.1038/nature11739
Fragile X syndrome (FXS) is a multi-organ disease that leads to mental retardation, macro-orchidism in males and premature ovarian insufficiency in female carriers. FXS is also a prominent monogenic disease associated with autism spectrum disorders (ASDs). FXS is typically caused by the loss of fragile X mental retardation 1 (FMR1) expression, which codes for the RNA-binding protein FMRP. Here we report the discovery of distinct RNA-recognition elements that correspond to the two independent RNA-binding domains of FMRP, in addition to the binding sites within the messenger RNA targets for wild-type and I304N mutant FMRP isoforms and the FMRP paralogues FXR1P and FXR2P (also known as FXR1 and FXR2). RNA-recognition-element frequency, ratio and distribution determine target mRNA association with FMRP. Among highly enriched targets, we identify many genes involved in ASD and show that FMRP affects their protein levels in human cell culture, mouse ovaries and human brain. Notably, we discovered that these targets are also dysregulated in Fmr1
doi: 10.1038/nature11737
Protease-activated receptor 1 (PAR1) is the prototypical member of a family of G-protein-coupled receptors that mediate cellular responses to thrombin and related proteases. Thrombin irreversibly activates PAR1 by cleaving the amino-terminal exodomain of the receptor, which exposes a tethered peptide ligand that binds the heptahelical bundle of the receptor to affect G-protein activation. Here we report the 2.2-Å-resolution crystal structure of human PAR1 bound to vorapaxar, a PAR1 antagonist. The structure reveals an unusual mode of drug binding that explains how a small molecule binds virtually irreversibly to inhibit receptor activation by the tethered ligand of PAR1. In contrast to deep, solvent-exposed binding pockets observed in other peptide-activated G-protein-coupled receptors, the vorapaxar-binding pocket is superficial but has little surface exposed to the aqueous solvent. Protease-activated receptors are important targets for drug development. The structure reported here will aid the development of improved PAR1 antagonists and the discovery of antagonists to other members of this receptor family.
doi: 10.1038/nature11701
Globular clusters can be grouped into a few distinct families on the basis of the radial distribution of ‘blue stragglers’, stars with masses greater than those at the turn-off point on the main sequence; this grouping can yield a direct measure of the cluster’s dynamical age purely from observed properties.
doi: 10.1038/nature11686
Evaporative cooling of molecules has not been achieved so far, owing to unfavourable collision properties and trap losses; microwave-forced evaporative cooling of hydroxyl molecules loaded in a magnetic quadrupole trap is now reported.
doi: 10.1038/nature11718
A thermal analogue of a superconducting quantum interference device (SQUID, widely used to measure small magnetic fields) is realized, in which the flow of heat between the superconductors is dependent on the quantum phase difference between them.
doi: 10.1038/nature11702
Neutron scattering measurements on single-crystal samples of the mineral herbertsmithite, which is a spin-1/2 kagome-lattice antiferromagnet, provide evidence of fractionalized spin excitations at low temperatures, indicating that the ground state of herbertsmithite may be a quantum spin liquid.
doi: 10.1038/nature11659
Results on light scattering from metal hole arrays show the relative importance of surface plasmon polaritons and quasi-cylindrical waves in extraordinary optical transmission.
doi: 10.1038/nature11669
Measurements of the viscous anisotropy of highly deformed polycrystalline olivine find it to be approximately an order of magnitude larger than that predicted by grain-scale simulations; the maximum degree of anisotropy is reached at geologically low shear strain, such that deforming regions of the Earth’s upper mantle should exhibit significant viscous anisotropy.
doi: 10.1038/nature11671
Critical transitions in experimental and theoretical systems can be anticipated on the basis of specific warning signs, with ‘critical slowing down’ being the best studied; long-term data from a real system, a Chinese lake, now show that a flickering phenomenon can be observed up to 20 years before the critical transition to a eutrophic state.
doi: 10.1038/nature11655
The Gossypium genus is used to investigate emergent consequences of polyploidy in cotton species; comparative genomic analyses reveal a complex evolutionary history including interactions among subgenomes that result in genetic novelty in elite cottons and provide insight into the evolution of spinnable fibres.
doi: 10.1038/nature11798
High-speed tracking of effortful responses and neuronal activity in rats during a forced swim test identifies medial prefrontal cortex (mPFC) neurons that respond during escape-related swimming but not normal locomotion, and optogenetics shows that mPFC neurons projecting to the brainstem dorsal raphe nucleus, which is implicated in depression, modulate this behavioural response to challenge.
doi: 10.1038/nature11617
Dopamine is synonymous with reward in mammals but associated with aversive reinforcement in insects, where reward seems to be signalled by octopamine; here it is shown that flies have discrete populations of dopamine neurons representing positive or negative values that are coordinately regulated by octopamine.
doi: 10.1038/nature11614
A whole-genome and transcriptome analysis of 20 human induced pluripotent stem-cell lines shows that reprogramming does not necessarily add de novo copy number variants to what is already present in the somatic cells from which they originated.
doi: 10.1038/nature11629
A loss-of-function approach in mice is used to show that the methylcytosine dioxygenase Tet1 has a role in regulating meiosis and meiotic gene activation in female germ cells; Tet1 deficiency does not greatly affect genome-wide demethylation but has a more specific effect on the expression of a subset of meiotic genes.
doi: 10.1038/nature11709
The crystal structure of the Mediator head module from the fission yeast Schizosaccharomyces pombe is solved at 3.4 Å resolution.
doi: 10.1038/nature11670
GABA-releasing neurons from the ventral tegmental area that project to the nucleus accumbens are shown to block the firing of cholinergic accumbal interneurons, affecting learning in mice.
doi: 10.1038/nature11657