Volume 523 Number 7559

Editorials

The HIV epidemic can be stopped p.127

Mounting evidence that rapid treatment with antiretroviral drugs dramatically reduces HIV transmission must be acted on fast if a target date for curbing the epidemic is to be met.

doi: 10.1038/523127a

A numbers game p.127

Institutions must be plain about research metrics if academics are to engage with them.

doi: 10.1038/523127b

Cloud cover p.128

Opposition to storing vast scientific data sets on cloud-computing platforms is weakening.

doi: 10.1038/523128a

News

News Features

How to beat HIV p.146

Scientists have the tools to end the epidemic. They just need better ways to use them.

doi: 10.1038/523146a

News & Views

Iron's voyage from the abyss p.160

An iron-rich plume of water from a hydrothermal vent has been found to extend more than 4,000 kilometres through the ocean. The finding has implications for the productivity of marine algae, and therefore for climate. See Letter p.200

doi: 10.1038/523160a

Diagnosis by extracellular vesicles p.161

The detection of a single molecule anchored to circulating extracellular vesicles allows late-stage pancreatic cancer to be identified from just one drop of a patient's blood. See Article p.177

doi: 10.1038/nature14626

Hidden impacts of logging p.163

A meta-analysis of changes in the abundance of tropical-forest birds reveals that the effect of selective timber harvesting varies with logging practices and species traits. The results offer a framework for managing impacts on biodiversity.

doi: 10.1038/523163a

A twist in the tale of γ-ray bursts p.164

An unusually long burst of γ-rays zapped Earth in December 2011, lasting 4 hours. The cause of this burst is now proposed to be a peculiar supernova produced by a spinning magnetic neutron star. See Letter p.189

doi: 10.1038/523164b

How to build a microbial eye p.166

Dissection of the subcellular eye of microorganisms called warnowiid dinoflagellates reveals that this structure is composed of elements of two cellular organelles — the plastid and the mitochondrion. See Letter p.204

doi: 10.1038/nature14630

Another action of a thalidomide derivative p.167

Lenalidomide effectively treats a blood disorder caused by the 5q chromosomal deletion. A study shows that the drug binds to its target, CRBN, to promote the breakdown of an enzyme encoded by a gene in the 5q region. See Article p.183

doi: 10.1038/nature14628

Review

Feedback in low-mass galaxies in the early Universe p.169

Feedback in the form of galactic-scale outflows of gas from star-forming, low-mass galaxies allowed ionizing radiation to escape from galaxies when the Universe was about 500 million years old, changing the hydrogen between galaxies from neutral to ionized.

doi: 10.1038/nature14454

Articles

Letters

A very luminous magnetar-powered supernova associated with an ultra-long γ-ray burst p.189

A new class of ultra-long-duration (more than 10,000 seconds) γ-ray bursts has recently been suggested. They may originate in the explosion of stars with much larger radii than those producing normal long-duration γ-ray bursts or in the tidal disruption of a star. No clear supernova has yet been associated with an ultra-long-duration γ-ray burst. Here we report that a supernova (SN 2011kl) was associated with the ultra-long-duration γ-ray burst GRB 111209A, at a redshift z of 0.677. This supernova is more than three times more luminous than type Ic supernovae associated with long-duration γ-ray bursts, and its spectrum is distinctly different. The slope of the continuum resembles those of super-luminous supernovae, but extends further down into the rest-frame ultraviolet implying a low metal content. The light curve evolves much more rapidly than those of super-luminous supernovae. This combination of high luminosity and low metal-line opacity cannot be reconciled with typical type Ic supernovae, but can be reproduced by a model where extra energy is injected by a strongly magnetized neutron star (a magnetar), which has also been proposed as the explanation for super-luminous supernovae.

doi: 10.1038/nature14579

Basin-scale transport of hydrothermal dissolved metals across the South Pacific Ocean p.200

Hydrothermal dissolved iron, manganese, and aluminium from the southern East Pacific Rise is transported several thousand kilometres westward across the South Pacific Ocean; global hydrothermal dissolved iron input is estimated to be more than four times what was previously thought and modelling suggests it must be physically or chemically stabilized in solution.

doi: 10.1038/nature14577

Unusual biology across a group comprising more than 15% of domain Bacteria p.208

More than 15% of the bacterial domain consists of a radiation of phyla about which very little is known; here, metagenomics is used to reconstruct 8 complete and 789 draft genomes from more than 35 of these phyla, revealing a shared evolutionary history, metabolic limitations, and unusual ribosome compositions.

doi: 10.1038/nature14486

Human body epigenome maps reveal noncanonical DNA methylation variation OPEN p.212

As part of the Epigenome Roadmap Project, genome-wide maps of DNA methylation and transcriptomes together with genomic DNA sequencing of 18 different primary human tissue types from 4 individuals are presented; analysis reveals widespread differential methylation of CG sites between tissues, and the presence of non-CG methylation in adult tissues.

doi: 10.1038/nature14465

Global circulation patterns of seasonal influenza viruses vary with antigenic drift p.217

The analysis of more than 9,000 haemagglutinin sequences of human seasonal influenza viruses over a 12-year time period shows that the global circulation patterns of A/H1N1 and B viruses are different from those of the well characterised A/H3N2 viruses; in particular the A/H1N1 and B viruses are shown to persist locally across several seasons and do not display the same degree of global movement as the H3N2 viruses.

doi: 10.1038/nature14460

Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity p.231

Melanoma treatment is being revolutionized by the development of effective immunotherapeutic approaches. These strategies include blockade of immune-inhibitory receptors on activated T cells; for example, using monoclonal antibodies against CTLA-4, PD-1, and PD-L1 (refs 3, 4, 5). However, only a subset of patients responds to these treatments, and data suggest that therapeutic benefit is preferentially achieved in patients with a pre-existing T-cell response against their tumour, as evidenced by a baseline CD8+ T-cell infiltration within the tumour microenvironment. Understanding the molecular mechanisms that underlie the presence or absence of a spontaneous anti-tumour T-cell response in subsets of cases, therefore, should enable the development of therapeutic solutions for patients lacking a T-cell infiltrate. Here we identify a melanoma-cell-intrinsic oncogenic pathway that contributes to a lack of T-cell infiltration in melanoma. Molecular analysis of human metastatic melanoma samples revealed a correlation between activation of the WNT/β-catenin signalling pathway and absence of a T-cell gene expression signature. Using autochthonous mouse melanoma models we identified the mechanism by which tumour-intrinsic active β-catenin signalling results in T-cell exclusion and resistance to anti-PD-L1/anti-CTLA-4 monoclonal antibody therapy. Specific oncogenic signals, therefore, can mediate cancer immune evasion and resistance to immunotherapies, pointing to new candidate targets for immune potentiation.

doi: 10.1038/nature14404

Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication p.236

In Caulobacter crescentus, oscillating levels of the second messenger cyclic-di-GMP drive the cell cycle through regulation of the essential cell cycle kinase CckA; as its levels increase during the G1–S transition, cyclic-di-GMP binds to CckA to inhibit kinase and stimulate phosphatase activity, thereby enabling replication initiation.

doi: 10.1038/nature14473