Volume 518 Issue 7539, 19 February 2015

Science will benefit most from a combination of youthful innovation and hard-won experience.

Messy governance and a lack of long-term planning threaten the success of the European Spallation Source, says Olof Hallonsten.

Researchers are buzzing about a publication that accepts only 'brief ideas'.

The week in science: Europe’s spaceplane soars; transgenic apples given go-ahead for US market; and geoengineering risks are highlighted.

Facility will study biomedical uses at attosecond resolution.

Researchers aim to cut passwords and people out of the data-safety equation.

Analysis of millions of papers finds that junior biomedical researchers tend to work on more innovative topics than their senior colleagues do.

Eurasian region gains ground as birthplace of Indo-European tongues.

Projects aim to mimic human body using networks of simulated organs.

Federal start-up funds inspire investment in ARPA-E technologies.

The idea of two sexes is simplistic. Biologists now think there is a wider spectrum than that.

The billions of specimens in natural-history museums are becoming more useful for tracking Earth's shrinking biodiversity. But the collections also face grave threats.

Corruption is a barrier to innovation, warns Alina Mungiu-Pippidi. Greater scrutiny of public spending is needed if science and technology are to fulfil their potential.

Douwe Draaisma enjoys the autobiography of Michael Gazzaniga, who has studied split brains for half a century.

Barbara Kiser reviews five of the week's best science picks.

Robert P. Crease examines Steven Weinberg's radical retelling of the story of science.

Philip Ball sees something of Macbeth in a play about J. Robert Oppenheimer, leader of the Manhattan Project.

Discoverer of the repeating organization of neurons in the mammalian cortex.

Neurons in the brain's visual cortex receive inputs from thousands of other neurons. But it now emerges that each is strongly connected to only a few others: those most similar to itself. See Letter p.399

The contribution of explosions known as novae to the lithium content of the Milky Way is uncertain. Radioactive beryllium, which transforms into lithium, has been detected for the first time in one such explosion. See Letter p.381

The most powerful oxidant found in nature is compound Q, an enzymatic intermediate that oxidizes methane. New spectroscopic data have resolved the long-running controversy about Q's chemical structure. See Letter p.431

An ensemble of climate models predicts that winds along the world's coasts will intensify because of global warming, inducing more ocean upwelling — a process that will affect the health of coastal marine ecosystems. See Letter p.390

A package of papers investigates the functional regulatory elements in genomes that have been obtained from human tissue samples and cell lines. The implications of the project are presented here from three viewpoints. See Articles p.317, p.331, p.337 & p.344 and Letters p.350, p.355, p.360 & p.365

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

An analysis of genome-wide chromatin interactions during human embryonic stem cell differentiation reveals changes in chromatic organization and simultaneously identifies allele-resolved chromatin structure and differences in gene expression during differentiation.

Genome-wide association studies combined with data from epigenomic maps for immune cells have been used to fine-map causal variants for 21 autoimmune diseases; disease risk tends to be linked to single nucleotide polymorphisms in cell-type-specific enhancers, often in regions adjacent to transcription factor binding motifs.

Lineage-specific transcription factors and signalling pathways cooperate with pluripotency regulators to control the transcriptional networks that drive cell specification and exit from an embryonic stem cell state; here, we report genome-wide binding data for 38 transcription factors combined with analysis of epigenomic and gene expression data during the differentiation of human embryonic stem cells into the three germ layers.

As part of the Epigenome Roadmap project, this study uses a chromosome-spanning haplotype reconstruction strategy to construct haplotype-resolved epigenomic maps for a diverse set of human tissues; the maps reveal extensive allelic biases in chromatin state and transcription, which vary across individuals due to genetic backgrounds.

The integrative analysis of epigenetic footprints along consecutive stages of neural progenitors derived from human ES cells reveals regulatory mechanisms that orchestrate stage-specific differentiation.

An analysis of cell-type-specific epigenomic features reveals a relationship between epigenomic and mutational profiles; chromatin characteristics can explain a large proportion of mutational variance in cancer genomes and the mutational distribution can identify the probable cell type from which a given cancer originated from.

Analysis of transcriptional and epigenomic changes in the hippocampus of a mouse model of Alzheimer’s disease shows that immune function genes and regulatory regions are upregulated, whereas genes and regulatory regions involved in synaptic plasticity, learning and memory are downregulated; genetic variants associated with Alzheimer’s disease are only enriched in orthologues of upregulated immune regions, suggesting that dysregulation of immune processes may underlie Alzheimer’s disease predisposition.

Comprehensive genome sequencing of 120 individuals representing all of the Darwin’s finch species and two close relatives reveals important discrepancies with morphology-based taxonomy, widespread hybridization, and a gene, ALX1, underlying variation in beak shape.

Mediator is the key transcription co-activator complex that enables basal and regulated transcription initiation by RNA polymerase (Pol) II; here a 15-subunit yeast core Mediator bound to a core Pol II initiation complex is reconstituted and its structure determined by cryo-electron microscopy at subnanometre resolution.

The origin of lithium is key to understanding the enrichment history of the Universe; now the classical nova V339 Del (Nova Delphini 2013) reveals that nova explosions could have been contributing to the recent rapid increase of the amount of lithium in the Universe.

Time-resolved X-ray solution scattering is used to visualize and probe the dynamics of the individual steps in the formation of a gold trimer complex, including covalent bond formation, with a time resolution of ∼500 femtoseconds.

An ensemble of climate models shows that by the end of the twenty-first century the coastal upwelling season near the eastern boundaries of the Atlantic and Pacific oceans will start earlier, end later and become more intense at high latitudes, thus becoming more homogeneous; these changes may affect the geographical distribution of marine biodiversity.

Tomographically derived seismic velocities are used to infer the distribution of partial melt below the Lau Basin, revealing an unexpected relationship between the amount of in situ melt and the water content of the magma, indicating that subducted water enhances melt extraction.

In complex networks of the cerebral cortex, the majority of connections are weak and only a minority strong, but it is not known why; here the authors show that excitatory neurons in primary visual cortex follow a rule by which strong connections are sparse and occur between neurons with correlated responses to visual stimuli, whereas only weak connections link neurons with uncorrelated responses.

Regeneration and plasticity after spinal cord injury are limited by inhibitory proteoglycans; here, modulation of a receptor for proteoglycans in rats is shown to lead to functional recovery after injury.

Angelman syndrome is a neurodevelopmental disorder caused by disrupted function of the maternal copy of the imprinted UBE3A gene; here, targeting a long non-coding RNA that is responsible for silencing the paternal copy of UBE3A with antisense oligonucleotides is shown to partially restore UBE3A expression in the central nervous system and correct some cognitive deficits in a mouse model of the disease.

If deprived of exogenous glutamine, naive mouse embryonic stem cells are shown to be capable of generating the amino acid from other sources to enable their proliferation; the stem cells use glutamine and glucose catabolism to maintain a high level of intracellular α-ketoglutarate and promote demethylation of chromatin and ensure sufficient expression of pluripotency-associated genes.

The deubiquitinase enzyme DUBA is shown to act as a negative regulator of interleukin-17A (IL-17A) in T_H17 cells; DUBA interacts with and stabilizes the ubiquitin ligase UBR5, which in turn targets RORγt for degradation in the proteaseome, thus limiting IL-17A production.

Deep-genome and single-cell sequencing analyses of patient-derived breast cancer xenografts reveal extensive, dynamic and reproducible changes in intra-tumoral mutational clonal composition on engraftment and serial propagation.

Four different XNAs — polymers with backbone chemistries not found in nature, namely, arabino nucleic acids, 2′-fluoroarabino nucleic acids, hexitol nucleic acids and cyclohexene nucleic acids — are found to be able to support the evolution of synthetic enzymes (XNAzymes) that catalyse several chemical reactions.

Time-resolved resonance Raman vibrational spectroscopy was used to study the mechanism of soluble methane monooxygenase and obtain structural information on the key reaction cycle intermediate, compound Q, which contains a unique dinuclear Fe^IV cluster that breaks the strong C-H bond of methane and inserts an oxygen atom (from O₂) to form methanol.

The X-ray crystal structure of the human cytoplasmic dynein-2 motor bound to the ATP-hydrolysis transition state analogue ADP.vanadate is described.

Cutting-edge tools that can identify the characteristics of cells are helping researchers to develop more-effective vaccines.

Of all of the hazards faced by researchers, the biggest threat may be the human element.

Genomicist reaches top rank as middle author.

Study on scientific paperwork might cut red tape.

US academia shows bias against motherhood.

Improving times fill schools coffers.

Complete control.