Turning point p.295

The result of next week’s crucial UK referendum on whether or not to remain in the European Union will have worldwide repercussions.

doi: 10.1038/534295a

Full Text


Under the sea p.296

If life in the oceans is to be preserved, people must get to know the wonders of the deep.

doi: 10.1038/534296a

Full Text


Nature distilled p.296

We need your views on an experiment to convey the latest research in digestible form.

doi: 10.1038/534296b

Full Text



Stem cells for Snoopy: pet medicines spark a biotech boom p.303

Firms chase a new breed of advanced veterinary care, from antibodies to cell therapies.

doi: 10.1038/534303a

Full Text


France launches massive meteor-spotting network p.304

Tracking space rocks that reach Earth will give insight into the early Solar System.

doi: 10.1038/nature.2016.20070

Full Text


Promising gene therapies pose million-dollar conundrum p.305

Economists, investors and medical insurers can’t figure out how to pay for cutting-edge drugs.

doi: 10.1038/534305a

Full Text


Boon or burden: what has the EU ever done for science? p.307

More than 500 million people and 28 nations make up the European Union. It will lose one of its richest, most populous members, if the United Kingdom votes to leave on 23 June. Ahead of a possible ‘Brexit’, Nature examines five core ways that the EU shapes the course of research.

doi: 10.1038/534307a

Full Text

News Features


How iPS cells changed the world p.310


doi: 10.1038/534310a

Full Text


Can you teach old drugs new tricks? p.314


doi: 10.1038/534314a

Full Text

News & Views


Genomics: The language of flowers p.328


doi: 10.1038/nature18445

Full Text


Immunotherapy: Cancer vaccine triggers antiviral-type defences p.329


doi: 10.1038/nature18443

Full Text


Computational materials science: Predictions of pinning p.331


doi: 10.1038/534331a

Full Text


Cell reprogramming: Brain versus brawn p.332


doi: 10.1038/nature18444

Full Text



Stem cell function and stress response are controlled by protein synthesis p.335

The protein translation rate is low in tissue stem cells and tumour-initiating cells, and genetically preventing cytosine-5 methylation on transfer RNA in skin tumours is shown to favour the maintenance of a state of translational inhibition in mice, with tumour-initiating cells in this state becoming more sensitive to cytotoxic stress.

doi: 10.1038/nature18282

日本語要約 | Full Text | PDF


Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells p.341

Leukaemic stem cells (LSCs) are responsible for BCR–ABL-driven chronic myeloid leukaemia relapse; here, p53 and MYC signalling networks are shown to regulate LSCs concurrently, and targeting both these pathways has a synergistic effect in managing the disease.

doi: 10.1038/nature18288

日本語要約 | Full Text | PDF


TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action p.347

Cryo-electron microscopy has undergone a resolution revolution—here, this method has been combined with lipid nanodisc technology to solve structures of TRPV1, the receptor for capsaicin, in a membrane bilayer, revealing mechanisms of lipid and ligand regulation.

doi: 10.1038/nature17964

日本語要約 | Full Text | PDF



Fission and reconfiguration of bilobate comets as revealed by 67P/Churyumov–Gerasimenko p.352

A modelling study of the bilobate nucleus of comet 67P/Churyumov–Gerasimenko reveals that it has spun much faster in the past, but that its chaotically changing spin rate has so far prevented it from splitting; eventually the two lobes will separate, but they will be unable to escape each other and will ultimately merge again—a situation that seems to be common among cometary nuclei.

doi: 10.1038/nature17670

日本語要約 | Full Text | PDF


Mean first-passage times of non-Markovian random walkers in confinement p.356

An analytical method of determining the mean first-passage time (the time taken by a random walker in confinement to reach a target point) is presented for a Gaussian non-Markovian random walker, thus revealing the importance of memory effects in first-passage statistics.

doi: 10.1038/nature18272

日本語要約 | Full Text | PDF


Intrinsic ferroelectric switching from first principles p.360

Molecular dynamics simulations of 90° domain walls in PbTiO3 are used to construct a nucleation-and-growth-based analytical model that quantifies the dynamics of many types of domain walls in various ferroelectrics, suggesting intrinsic domain-wall motion as a universal mechanism for ferroelectric switching.

doi: 10.1038/nature18286

日本語要約 | Full Text | PDF


Self-assembly of microcapsules via colloidal bond hybridization and anisotropy p.364

The self-assembly of colloidal particles into hollow micrometre-scale capsules is achieved through the combination of anisotropic particle morphology, deformable surface ligands that re-distribute on binding and the mutual attraction between particles, suggesting a design strategy for colloidal self-assembly

doi: 10.1038/nature17956

日本語要約 | Full Text | PDF


Concerted nucleophilic aromatic substitution with 19F and 18F p.369

Nucleophilic aromatic substitution (SNAr) is widely used by organic chemists to functionalize aromatic molecules, and it is the most commonly used method to generate arenes that contain 18F for use in positron-emission tomography (PET) imaging. A wide range of nucleophiles exhibit SNAr reactivity, and the operational simplicity of the reaction means that the transformation can be conducted reliably and on large scales. During SNAr, attack of a nucleophile at a carbon atom bearing a ‘leaving group’ leads to a negatively charged intermediate called a Meisenheimer complex. Only arenes with electron-withdrawing substituents can sufficiently stabilize the resulting build-up of negative charge during Meisenheimer complex formation, limiting the scope of SNAr reactions: the most common SNAr substrates contain strong π-acceptors in the ortho and/or para position(s). Here we present an unusual concerted nucleophilic aromatic substitution reaction (CSNAr) that is not limited to electron-poor arenes, because it does not proceed via a Meisenheimer intermediate. We show a phenol deoxyfluorination reaction for which CSNAr is favoured over a stepwise displacement. Mechanistic insights enabled us to develop a functional-group-tolerant 18F-deoxyfluorination reaction of phenols, which can be used to synthesize 18F-PET probes. Selective 18F introduction, without the need for the common, but cumbersome, azeotropic drying of 18F, can now be accomplished from phenols as starting materials, and provides access to 18F-labelled compounds not accessible through conventional chemistry.

doi: 10.1038/nature17667

日本語要約 | Full Text | PDF


Seafloor geodetic constraints on interplate coupling of the Nankai Trough megathrust zone p.374

Seafloor geodetic data from the Nankai Trough, off southwestern Japan, show that most offshore sites in this earthquake-prone region have high slip-deficit rates, revealing previously unknown locations that could be important for the mitigation of future earthquake- and tsunami-associated disasters.

doi: 10.1038/nature17632

日本語要約 | Full Text | PDF

神経科学:in vivoでの単一血管の血行動態応答の神経相関

Neural correlates of single-vessel haemodynamic responses in vivo p.378

Functional imaging techniques use changes in blood flow to infer neural activity, but how strongly the two are correlated is a subject of debate; here, vascular and neural responses to a range of visual stimuli are imaged in cat and rat primary visual cortex, revealing that vascular signals are partially decoupled from local neural signals.

doi: 10.1038/nature17965

日本語要約 | Full Text | PDF


Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease p.383

Preclinical evaluation and optimization of mitochondrial replacement therapy reveals that a modified form of pronuclear transfer is likely to give rise to normal pregnancies with a reduced risk of mitochondrial DNA disease, but may need further modification to eradicate the disease in all cases.

doi: 10.1038/nature18303

日本語要約 | Full Text | PDF


Co-repressor CBFA2T2 regulates pluripotency and germline development p.387

A co-repressor protein, CBFA2T2, oligomerizes to stabilize its binding partner PRDM14 and the pluripotency factor OCT4 on chromatin, thus facilitating the transcriptional landscape underpinning the germline and pluripotent fate.

doi: 10.1038/nature18004

日本語要約 | Full Text | PDF


Dissecting direct reprogramming from fibroblast to neuron using single-cell RNA-seq p.391

The transcriptome changes driving the conversion of fibroblasts to neurons at the single-cell level are reported, revealing that early neuronal reprogramming steps are homogenous, driven by the proneural pioneer factor Ascl1; the expression of myogenic genes then has a dampening effect on efficiency, which needs to be counteracted by the neuronal factors Myt1l and Brn2 for more efficient reprogramming.

doi: 10.1038/nature18323

日本語要約 | Full Text | PDF


Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy p.396

The development of a nanoparticle RNA vaccine is reported that preferentially targets dendritic cells after systemic administration, and is shown to provide durable interferon-α-dependent antigen-specific immunity in mouse tumour models; initial results in advanced melanoma patients indicate potential efficacy in humans.

doi: 10.1038/nature18300

日本語要約 | Full Text | PDF


Aberrant PD-L1 expression through 3′-UTR disruption in multiple cancers p.402

Successful treatment of many patients with advanced cancer using antibodies against programmed cell death 1 (PD-1; also known as PDCD1) and its ligand (PD-L1; also known as CD274) has highlighted the critical importance of PD-1/PD-L1-mediated immune escape in cancer development. However, the genetic basis for the immune escape has not been fully elucidated, with the exception of elevated PD-L1 expression by gene amplification and utilization of an ectopic promoter by translocation, as reported in Hodgkin and other B-cell lymphomas, as well as stomach adenocarcinoma. Here we show a unique genetic mechanism of immune escape caused by structural variations (SVs) commonly disrupting the 3′ region of the PD-L1 gene. Widely affecting multiple common human cancer types, including adult T-cell leukaemia/lymphoma (27%), diffuse large B-cell lymphoma (8%), and stomach adenocarcinoma (2%), these SVs invariably lead to a marked elevation of aberrant PD-L1 transcripts that are stabilized by truncation of the 3′-untranslated region (UTR). Disruption of the Pd-l1 3′-UTR in mice enables immune evasion of EG7-OVA tumour cells with elevated Pd-l1 expression in vivo, which is effectively inhibited by Pd-1/Pd-l1 blockade, supporting the role of relevant SVs in clonal selection through immune evasion. Our findings not only unmask a novel regulatory mechanism of PD-L1 expression, but also suggest that PD-L1 3′-UTR disruption could serve as a genetic marker to identify cancers that actively evade anti-tumour immunity through PD-L1 overexpression.

doi: 10.1038/nature18294

日本語要約 | Full Text | PDF


Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma p.407

The stem cell determinant Musashi (Msi) is a key mediator of pancreatic cancer progression and therapy resistance.

doi: 10.1038/nature17988

日本語要約 | Full Text | PDF


The bacterial DnaA-trio replication origin element specifies single-stranded DNA initiator binding p.412

The bacterial chromosome replication origin contains an indispensable element composed of a repeating trinucleotide motif, termed the DnaA-trio, that stabilizes DnaA binding on single-stranded DNA.

doi: 10.1038/nature17962

日本語要約 | Full Text | PDF


Structural basis for amino acid export by DMT superfamily transporter YddG p.417

The X-ray structure of the drug/metabolite transporter (DMT) protein YddG from Starkeya novella reveals a new membrane transport topology, with ten transmembrane segments in an outward-facing state and two pseudo-symmetric inverted structural repeats.

doi: 10.1038/nature17991

日本語要約 | Full Text | PDF

「Journal home」に戻る