Volume 542 Number 7642



Researchers should reach beyond the science bubble p.391

Scientists in the United States and elsewhere ought to address the needs and employment prospects of taxpayers who have seen little benefit from scientific advances.

doi: 10.1038/542391a


Gene editing in legal limbo in Europe p.392

The European Union is dragging its feet on gene-editing rules and scientists should push the issue.

doi: 10.1038/542392a


Pluto could be staging a comeback — and it’s not alone p.392

A proposal to massively expand the number of bodies called planets raises interesting questions.

doi: 10.1038/542392b



Inside the Chinese lab poised to study world's most dangerous pathogens p.399

Maximum-security biolab is part of plan to build network of BSL-4 facilities across China.

doi: 10.1038/nature.2017.21487


Broad Institute wins bitter battle over CRISPR patents p.401

The US Patent and Trademark Office issues a verdict in legal tussle over rights to genome-editing technology.

doi: 10.1038/nature.2017.21502


Giant crack in Antarctic ice shelf spotlights advances in glaciology p.402

Rift through Larsen C ice shelf has grown to 175 kilometres, and collapse of nearby ice shelves could offer a glimpse of its future.

doi: 10.1038/nature.2017.21507


Delay in hiring science advisers intensifies Brexit worries p.403

Policy experts want scientists at the table when government decides on environmental protection and membership of international collaborations.

doi: 10.1038/nature.2017.21511


The race to map the human body — one cell at a time p.404

A host of detailed cell atlases could revolutionize understanding of cancer and other diseases.

doi: 10.1038/nature.2017.21508


Collapse of Aztec society linked to catastrophic salmonella outbreak p.404

DNA of 500-year-old bacteria is first direct evidence of an epidemic — one of humanity's deadliest — that occurred after Spanish conquest.

doi: 10.1038/nature.2017.21485

News Features


An epigenetics gold rush: new controls for gene expression p.406


doi: 10.1038/542406a

News & Views


Systems neuroscience: Diversity in sight p.418


doi: 10.1038/nature21498


Climate science: Predictable ice ages on a chaotic planet p.419


doi: 10.1038/542419a


Molecular biology: RNA editing packs a one-two punch p.420


doi: 10.1038/542420a


Astronomy: Earth's seven sisters p.421


doi: 10.1038/542421a


Materials science: Organic analogues of graphene p.423


doi: 10.1038/nature21503


Cancer: A targeted treatment with off-target risks p.424


doi: 10.1038/nature21504



A simple rule to determine which insolation cycles lead to interglacials p.427

A simple model, based on only summer insolation energy and time since the previous deglaciation, correctly predicts the deglaciation history of the past 2.6 million years, including the change in frequency of glacial–interglacial cycles about one million years ago.

doi: 10.1038/nature21364

遺伝学:発達障害におけるde novo変異の保有率と構造

Prevalence and architecture of de novo mutations in developmental disorders p.433

Whole-exome analysis of individuals with developmental disorders shows that de novo mutations can equally cause loss or altered protein function, but that most mutations causing altered protein function have not yet been described.

doi: 10.1038/nature21062


Inhibition decorrelates visual feature representations in the inner retina p.439

The functional diversity of bipolar cells, which split visual inputs into different excitatory channels within the retina, arises from centre–surround interactions in their receptive fields that tune both spatial and temporal signalling.

doi: 10.1038/nature21394


Sterile protection against human malaria by chemoattenuated PfSPZ vaccine p.445

Immunization with Plasmodium falciparum sporozoites under chemoprophylaxis can protect against controlled human malaria infection with the same strain for at least 10 weeks, and protection correlates with polyfunctional T-cell memory.

doi: 10.1038/nature21060


Adipose-derived circulating miRNAs regulate gene expression in other tissues p.450

Adipose tissue is a major source of circulating exosomal miRNAs, which contribute to the regulation of gene expression in distant tissues and organs.

doi: 10.1038/nature21365



Seven temperate terrestrial planets around the nearby ultracool dwarf star TRAPPIST-1 p.456

Last year, three Earth-sized planets were discovered to be orbiting the nearby Jupiter-sized star TRAPPIST-1; now, follow-up photometric observations from the ground and from space show that there are at least seven Earth-sized planets in this star system, and that they might be the right temperature to harbour liquid water on their surfaces.

doi: 10.1038/nature21360


Static non-reciprocity in mechanical metamaterials p.461

Suitably engineered mechanical metamaterials show static non-reciprocity—that is, the transmission of motion from one side to the other depends on the direction of that motion.

doi: 10.1038/nature21044


Onset of the aerobic nitrogen cycle during the Great Oxidation Event p.465

Nitrogen isotope data from sediments deposited during the earliest stage of the Great Oxidation Event show evidence for the emergence of a pervasive aerobic marine nitrogen cycle.

doi: 10.1038/nature20826


Theory of chaotic orbital variations confirmed by Cretaceous geological evidence p.468

Cretaceous astrochronologic evidence reveals a resonance transition associated with the orbits of Mars and the Earth, confirming predicted chaotic Solar System behaviour and enabling an improvement in the geological timescale.

doi: 10.1038/nature21402


Ancestral morphology of crown-group molluscs revealed by a new Ordovician stem aculiferan p.471

Presence of a radula in Calvapilosa kroegeri confirms the molluscan affinity of sachitids, and the single shell plate reveals the ancestral condition for all crown molluscs and early evolution of the multi-plated body plan characteristic of Aculifera.

doi: 10.1038/nature21055


m6A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition p.475

The maternal-to-zygotic transition (MZT) is one of the most profound and tightly orchestrated processes during the early life of embryos, yet factors that shape the temporal pattern of vertebrate MZT are largely unknown. Here we show that over one-third of zebrafish maternal messenger RNAs (mRNAs) can be N6-methyladenosine (m6A) modified, and the clearance of these maternal mRNAs is facilitated by an m6A-binding protein, Ythdf2. Removal of Ythdf2 in zebrafish embryos decelerates the decay of m6A-modified maternal mRNAs and impedes zygotic genome activation. These embryos fail to initiate timely MZT, undergo cell-cycle pause, and remain developmentally delayed throughout larval life. Our study reveals m6A-dependent RNA decay as a previously unidentified maternally driven mechanism that regulates maternal mRNA clearance during zebrafish MZT, highlighting the critical role of m6A mRNA methylation in transcriptome switching and animal development.

doi: 10.1038/nature21355


Metabolic gatekeeper function of B-lymphoid transcription factors p.479

The B-lymphoid transcription factors PAX5 and IKZF1 restrict the supply of glucose and energy to B cells to levels that are not enough to fuel a driver-oncogene, thereby acting as tumour suppressors and sensitizing acute lymphoblastic leukaemia B cells to glucocorticoid therapy.

doi: 10.1038/nature21076


Synthetic essentiality of chromatin remodelling factor CHD1 in PTEN-deficient cancer p.484

The gene CHD1 is synthetic essential in PTEN-deficient prostate and breast cancers.

doi: 10.1038/nature21357

がん:B細胞でのホスファチジルイノシトール 3-キナーゼδの遮断はゲノム不安定性を上昇させる

Phosphatidylinositol 3-kinase δ blockade increases genomic instability in B cells p.489

Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglobulin genes to initiate class switch recombination and somatic hypermutation. In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. AID expression is tightly regulated in B cells and its overexpression leads to enhanced genomic instability and lymphoma formation. The phosphatidylinositol 3-kinase δ (PI3Kδ) pathway regulates AID by suppressing its expression in B cells. Drugs for leukaemia or lymphoma therapy such as idelalisib, duvelisib and ibrutinib block PI3Kδ activity directly or indirectly, potentially affecting AID expression and, consequently, genomic stability in B cells. Here we show that treatment of primary mouse B cells with idelalisib or duvelisib, and to a lesser extent ibrutinib, enhanced the expression of AID and increased somatic hypermutation and chromosomal translocation frequency to the Igh locus and to several AID off-target sites. Both of these effects were completely abrogated in AID-deficient B cells. PI3Kδ inhibitors or ibrutinib increased the formation of AID-dependent tumours in pristane-treated mice. Consistently, PI3Kδ inhibitors enhanced AID expression and translocation frequency to IGH and AID off-target sites in human chronic lymphocytic leukaemia and mantle cell lymphoma cell lines, and patients treated with idelalisib, but not ibrutinib, showed increased somatic hypermutation in AID off-targets. In summary, we show that PI3Kδ or Bruton’s tyrosine kinase inhibitors increase genomic instability in normal and neoplastic B cells by an AID-dependent mechanism. This effect should be carefully considered, as such inhibitors can be administered to patients for years.

doi: 10.1038/nature21406


Editing and methylation at a single site by functionally interdependent activities p.494

The C-to-U deamination at position 32 of tRNAThr in Trypanosoma brucei requires two enzymatic activities and proceeds via formation of a 3-methylcytosine intermediate, supporting the notion of a coupled modification system.

doi: 10.1038/nature21396


Basis of catalytic assembly of the mitotic checkpoint complex p.498

The near-complete in vitro reconstitution of the mitotic spindle assembly checkpoint reveals how the assembly of its effector, the mitotic checkpoint complex, is catalysed.

doi: 10.1038/nature21384

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