Volume 516 Number 7530

Editorials

Room for growth p.143

The European Commission’s plans to allow individual countries a veto on the farming of genetically modified crops, although a compromise, should enable the technology to move forward.

doi: 10.1038/516143a

Ethical overkill p.143

Institutions should take a unified look at protections for research on human subjects.

doi: 10.1038/516143b

Protect and serve p.144

Nations must keep expanding conservation efforts to avoid a biodiversity crisis.

doi: 10.1038/516144a

News

Tsunami alerts fall short p.151

Ten years after the devastating Sumatra earthquake, warnings for the Indian Ocean go out, but often do not reach the people most at risk.

doi: 10.1038/516151a

News Features

Life – a status report p.158

Species are disappearing quickly — but researchers are struggling to assess how bad the problem is.

doi: 10.1038/516158a

The black box of reprogramming p.162

Scientists have been reprogramming adult cells into embryonic ones for decades — but they are only now getting to grips with the mechanics.

doi: 10.1038/516162a

News & Views

A designer's guide to pluripotency p.172

Pluripotent stem cells, which give rise to almost all cell types, can be engineered from mature cells. A thorough analysis of the process has led to the characterization of a new type of pluripotent cell. See Articles p.192 & p.198

doi: 10.1038/516172a

Breakthrough for protons p.173

The atomically thin material called graphene is impermeable to atoms as small as helium. The finding that protons can pass through it might enable new kinds of membrane to be developed and aid research into fuel cells. See Letter p.227

doi: 10.1038/nature14074

A beacon for bacterial tubulin p.175

The protein FtsZ forms a ring structure that constricts to allow bacterial cells to divide. A second protein, MapZ, has now been found to guide FtsZ to the correct mid-cell position in the bacterium Streptococcus pneumoniae. See Letter p.259

doi: 10.1038/nature14071

Calcium-activated proteins visualized p.176

The first crystal structures of bestrophin and lipid scramblase proteins cast light on how these protein families transport very different substrates across membranes, yet are both activated by calcium ions. See Articles p.207 & p213

doi: 10.1038/nature13944

The virtues of tiling p.178

A cracked metal film on an elastic substrate has been shown to provide ultrahigh sensitivity in detecting mechanical vibrations. The result draws inspiration from principles of tiling that apply to many biological systems. See Letter p.222

doi: 10.1038/516178a

When wells run dry p.179

A global analysis reveals growing societal dependence on the use of non-renewable freshwater resources that depletes groundwater reserves and undermines human resilience to water scarcity in a warming world.

doi: 10.1038/516179a

Review

Catalytic enantioselective synthesis of quaternary carbon stereocentres p.181

Carbon atoms to which four distinct carbon substituents are attached — quaternary carbon stereocentres — are common features of molecules found in nature; in this Review, the authors discuss catalytic enantioselective reactions that have been developed during the past decade for synthesizing organic molecules containing such carbon atoms.

doi: 10.1038/nature14007

Articles

Divergent reprogramming routes lead to alternative stem-cell states p.192

The forced expression of key transcription factors can induce somatic cells to acquire pluripotency characteristics; here high levels of reprogramming factors are used to induce mouse embryonic fibroblasts to a stable alternative pluripotent state with low intercellular adhesion.

doi: 10.1038/nature14047

Genome-wide characterization of the routes to pluripotency p.198

This study presents an extensive molecular characterization of the reprograming process by analysis of transcriptomic, epigenomic and proteomic data sets describing the routes to pluripotency; it finds distinct routes towards two stable pluripotent states characterized by distinct epigenetic events.

doi: 10.1038/nature14046

X-ray structure of a calcium-activated TMEM16 lipid scramblase p.207

The authors describe the structure of a Ca2+-activated lipid scramblase which catalyses the passive movement of lipids between the two leaflets of a lipid bilayer; the structure reveals the location of a regulatory calcium-binding site embedded within the membrane and the presence of a hydrophilic membrane-traversing cavity that is exposed to the lipid bilayer, where catalysis is likely to occur.

doi: 10.1038/nature13984

Structure and insights into the function of a Ca2+-activated Cl channel p.213

The X-ray crystal structure of a eukaryotic Ca2+-activated chloride channel, BEST1, and its function in liposomes are described; the structure shows that Ca2+ binds to the cytosolic region of this pentameric channel and reveals that the pore is approximately 95 Å long with at least 15 distinct anion-binding sites.

doi: 10.1038/nature13913

Letters

H2D+ observations give an age of at least one million years for a cloud core forming Sun-like stars p.219

The age of dense interstellar cloud cores, where stars and planets form, is a crucial parameter in star formation and difficult to measure. Some models predict rapid collapse, whereas others predict timescales of more than one million years (ref. 3). One possible approach to determining the age is through chemical changes as cloud contraction occurs, in particular through indirect measurements of the ratio of the two spin isomers (ortho/para) of molecular hydrogen, H2, which decreases monotonically with age. This has been done for the dense cloud core L183, for which the deuterium fractionation of diazenylium (N2H+) was used as a chemical clock to infer that the core has contracted rapidly (on a timescale of less than 700,000 years). Among astronomically observable molecules, the spin isomers of the deuterated trihydrogen cation, ortho-H2D+ and para-H2D+, have the most direct chemical connections to H2 (refs 8, 9, 10, 11, 12) and their abundance ratio provides a chemical clock that is sensitive to greater cloud core ages. So far this ratio has not been determined because para-H2D+ is very difficult to observe. The detection of its rotational ground-state line has only now become possible thanks to accurate measurements of its transition frequency in the laboratory, and recent progress in instrumentation technology. Here we report observations of ortho- and para-H2D+ emission and absorption, respectively, from the dense cloud core hosting IRAS 16293-2422 A/B, a group of nascent solar-type stars (with ages of less than 100,000 years). Using the ortho/para ratio in conjunction with chemical models, we find that the dense core has been chemically processed for at least one million years. The apparent discrepancy with the earlier N2H+ work arises because that chemical clock turns off sooner than the H2D+ clock, but both results imply that star-forming dense cores have ages of about one million years, rather than 100,000 years.

doi: 10.1038/nature13924

Proton transport through one-atom-thick crystals p.227

Measurements show that monolayers of graphene and hexagonal boron nitride are unexpectedly highly permeable to thermal protons and that their conductivity rapidly increases with temperature, but that no proton transport is detected for few-layer crystals.

doi: 10.1038/nature14015

Formation and properties of ice XVI obtained by emptying a type sII clathrate hydrate p.231

Gas hydrates are ice-like solids that have guest species encaged within a crystalline water framework, making the empty hydrate a natural — though long assumed to be inaccessible — point of reference; it is now shown that several days of continuous vacuum pumping removes all guests from neon hydrate, and the physical properties of the empty hydrate have been determined.

doi: 10.1038/nature14014

Isotopic constraints on marine and terrestrial N2O emissions during the last deglaciation p.234

Gas hydrates are ice-like solids that have guest species encaged within a crystalline water framework, making the empty hydrate a natural — though long assumed to be inaccessible — point of reference; it is now shown that several days of continuous vacuum pumping removes all guests from neon hydrate, and the physical properties of the empty hydrate have been determined.

doi: 10.1038/nature13971

An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons p.242

The authors show that two primate-specific genes encoding KRAB domain containing zinc finger proteins, ZNF91 and ZNF93, have evolved during the last 25 million years to repress retrotransposon families that emerged during this time period; according to the new data KZNF gene expansion limits the activity of newly emerged retrotransposons, which subsequently mutate to evade repression.

doi: 10.1038/nature13760

Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma p.254

Germinal centre B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common malignancy, yet the signalling pathways that are deregulated and the factors leading to its systemic dissemination are poorly defined. Work in mice showed that sphingosine-1-phosphate receptor-2 (S1PR2), a Gα12 and Gα13 coupled receptor, promotes growth regulation and local confinement of germinal centre B cells. Recent deep sequencing studies of GCB-DLBCL have revealed mutations in many genes in this cancer, including in GNA13 (encoding Gα13) and S1PR2 (refs 5,6, 7). Here we show, using in vitro and in vivo assays, that GCB-DLBCL-associated mutations occurring in S1PR2 frequently disrupt the receptor’s Akt and migration inhibitory functions. Gα13-deficient mouse germinal centre B cells and human GCB-DLBCL cells were unable to suppress pAkt and migration in response to S1P, and Gα13-deficient mice developed germinal centre B-cell-derived lymphoma. Germinal centre B cells, unlike most lymphocytes, are tightly confined in lymphoid organs and do not recirculate. Remarkably, deficiency in Gα13, but not S1PR2, led to germinal centre B-cell dissemination into lymph and blood. GCB-DLBCL cell lines frequently carried mutations in the Gα13 effector ARHGEF1, and Arhgef1 deficiency also led to germinal centre B-cell dissemination. The incomplete phenocopy of Gα13- and S1PR2 deficiency led us to discover that P2RY8, an orphan receptor that is mutated in GCB-DLBCL and another germinal centre B-cell-derived malignancy, Burkitt’s lymphoma, also represses germinal centre B-cell growth and promotes confinement via Gα13. These findings identify a Gα13-dependent pathway that exerts dual actions in suppressing growth and blocking dissemination of germinal centre B cells that is frequently disrupted in germinal centre B-cell-derived lymphoma.

doi: 10.1038/nature13765

Programmable RNA recognition and cleavage by CRISPR/Cas9 p.263

In the presence of a short DNA oligonucleotide containing a protospacer adjacent motif, a guide-RNA-programmed Cas9 is able to specifically bind and/or cleave single-stranded RNA—this system can be used to isolate specific endogenous RNA transcripts from a cell lysate without any tag or modification.

doi: 10.1038/nature13769

Regulation of RNA polymerase II activation by histone acetylation in single living cells p.272

The interplay of histone acetylation and RNA polymerase II activity is investigated using fluorescence microscopy; acetylation of H3 at Lys 27 enhances the recruitment of a transcriptional activator and accelerates the transition of RNA polymerase II from initiation to elongation, thus indicating that histone acetylation has a causal effect on two distinct steps in transcription activation.

doi: 10.1038/nature13714