nature

THIS WEEK

Editorials

Worldwide weapons ▶

Progress towards a United Nations arms-trade treaty is encouraging, but it won't keep weapons out of the hands of human-rights abusers.

Tough choices ▶

Scientists must find ways to make more efficient use of funds — or politicians may do it for them.

On the up ▶

The soaring incidence of diabetes is driving the United Arab Emirates' science ambitions.

World View

Spanish changes are scientific suicide ▶

If research continues to be sidelined, Spain will be left with little domestic expertise, warns Amaya Moro-Martín.

Seven Days

Seven days: 10–16 February 2012 ▶

The week in science: Europe's Vega rocket launches; US approves first new nuclear reactors for three decades; and this year's schedule for the Large Hadron Collider is announced.

NEWS IN FOCUS

Obama shoots for science increase ▶

US president wants to make room for research to grow in 2013 — but faces an uphill battle.

Models hone picture of climate impacts ▶

International programme will improve predictions.

Russians celebrate Vostok victory ▶

Team finally drills into biggest Antarctic subglacial lake.

Sequencing set to alter clinical landscape ▶

Access to whole genomes shifts potential for diagnosis, but poses challenges for doctors and regulators.

Death-rate row blurs mutant flu debate ▶

Even if a 59% mortality rate for H5N1 is too high, the virus could still cause a flu pandemic more serious than that of 1918.

Features

Human evolution: Cultural roots ▶

A South African archaeologist digs into his own past to seek connections between climate change and human development.

Prions and chaperones: Outside the fold ▶

Susan Lindquist has challenged conventional thinking on how misfolded proteins drive disease and may power evolution. But she still finds that criticism stings.

COMMENT

Evolution: Adapted to culture ▶

Mark Pagel proposes that our ability to share and build on ideas is what made us human.

Personalized medicine: Bring clinical standards to human-genetics research ▶

Study protocols need to be rigorous, because more than science is at stake. Sometimes participants' lives depend on the results, writes Gholson J. Lyon.

Health policy: Regulate alcohol for global health ▶

The World Health Organization is the only body that can promote health through the use of international law. It should make alcohol its next target, says Devi Sridhar.

Books and Arts

Evolution: Custom built ▶

Culture is both a product and a driver of human evolution, finds Peter Richerson.

Books in brief ▶

Energy: A crude awakening ▶

John Vidal is gripped by a book that reveals how natural riches can impoverish nations.

Q&A: Transgene curator ▶

Next month in Pittsburgh, Pennsylvania, artist Richard Pell opens the Center for PostNatural History — a museum of bioengineered organisms. He talks about the joys and pitfalls involved in collecting genetically modified maize, mosquitoes and zebrafish.

Correspondence

Medical research: No catch to UK charity funding Mark Walport, Iain Foulkes, Peter Weissberg, Delyth Morgan & Sharmila Nebhrajani | Whaling: Don't trade the moratorium away Mark Peter Simmonds & Sue Fisher | Whaling: Ways to agree on quotas Justin G. Cooke, Russell Leaper & Vassili Papastavrou | Sociology of science: Big data deserve a bigger audience Bernardo A. Huberman | Research integrity: Data audits could curb misconduct J. Leslie Glick

Regulatory RNA ▶

Angela K. Eggleston, Alex Eccleston, Barbara Marte & Claudia Lupp

Functional complexity and regulation through RNA dynamics ▶

Elizabeth A. Dethoff, Jeetender Chugh, Anthony M. Mustoe & Hashim M. Al-Hashimi

RNA-guided genetic silencing systems in bacteria and archaea ▶

Blake Wiedenheft, Samuel H. Sternberg & Jennifer A. Doudna

Modular regulatory principles of large non-coding RNAs ▶

Mitchell Guttman & John L. Rinn

The microcosmos of cancer ▶

Amaia Lujambio & Scott W. Lowe

RESEARCH

Latest Online

Cancer genetics: Evolution after tumour spread ▶

Steven C. Clifford

The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila ▶

Nan Liu, Michael Landreh, Kajia Cao, Masashi Abe, Gert-Jan Hendriks et al.

The conserved microRNA miR-34 regulates age-associated events and long-term brain integrity in Drosophila, providing a molecular link between ageing and neurodegeneration.

Clonal selection drives genetic divergence of metastatic medulloblastoma ▶

Xiaochong Wu, Paul A. Northcott, Adrian Dubuc, Adam J. Dupuy, David J. H. Shih et al.

In a mouse model and in human medulloblastoma patients, the metastases in an individual have similar genomic alterations and DNA methylation patterns, but these patterns are highly divergent from those of the primary tumour, indicating that therapies will need to be tailored to fit the molecular alterations present in the primary tumour and/or the metastases.

IDH mutation impairs histone demethylation and results in a block to cell differentiation ▶

Chao Lu, Patrick S. Ward, Gurpreet S. Kapoor, Dan Rohle, Sevin Turcan et al.

Cancer-associated IDH mutants that produce 2-hydroxyglutarate are shown to prevent the histone demethylation that is required for lineage-specific progenitor cells to differentiate into terminally differentiated cells.

IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype ▶

Sevin Turcan, Daniel Rohle, Anuj Goenka, Logan A. Walsh, Fang Fang et al.

Mutation of isocitrate dehydrogenase 1 (IDH1) is shown to induce DNA hypermethylation and to remodel the epigenome to resemble that of gliomas with the CpG island methylator phenotype.

Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation ▶

Peppi Koivunen, Sungwoo Lee, Christopher G. Duncan, Giselle Lopez, Gang Lu et al.

The (R)-enantiomer of 2-hydroxyglutarate, which is produced when IDH is mutated in human tumours, is shown to stimulate the activity of the EGLN prolyl 4-hydroxylases, leading to diminished levels of HIF and enhanced human astrocyte proliferation.

Structural basis for iron piracy by pathogenic Neisseria ▶

Nicholas Noinaj, Nicole C. Easley, Muse Oke, Naoko Mizuno, James Gumbart et al.

Structural analysis reveals the iron scavenging mechanism used by Neisseria species, involving TbpA and TbpB proteins, and sheds light on how human transferrin is specifically targeted.

The same pocket in menin binds both MLL and JUND but has opposite effects on transcription ▶

Jing Huang, Buddha Gurung, Bingbing Wan, Smita Matkar, Natalia A. Veniaminova et al.

Crystal structures of menin in its free form and in complexes with MLL1 or with JUND, or with an MLL1–LEDGF heterodimer, show that menin contains a deep pocket that binds short peptides of MLL1 or JUND in the same manner, but produces opposite effects on transcription.

Control of ground-state pluripotency by allelic regulation of Nanog ▶

Yusuke Miyanari & Maria-Elena Torres-Padilla

Tight regulation of Nanog dose at the chromosome level is important for the acquisition of pluripotency during development.

Articles and Letters

Eutrophication causes speciation reversal in whitefish adaptive radiations ▶

P. Vonlanthen, D. Bittner, A. G. Hudson, K. A. Young, R. Müller et al.

Historical and contemporary data of whitefish radiations from pre-alpine European lakes and reconstruction of changes in whitefish genetic species differentiation through time show that species diversity may have evolved in response to ecological opportunity, and that eutrophication, by diminishing this opportunity, has driven extinctions through speciation reversal and demographic decline.

Prions are a common mechanism for phenotypic inheritance in wild yeasts ▶

Randal Halfmann, Daniel F. Jarosz, Sandra K. Jones, Amelia Chang, Alex K. Lancaster et al.

Previously thought to be rare laboratory artefacts or diseases of yeast, prions are actually found in one third of 700 wild strains; the prions give their hosts beneficial traits that can be transmitted epigenetically to the next generation, and then fixed in the genome.

Crystal structure of the channelrhodopsin light-gated cation channel ▶

Hideaki E. Kato, Feng Zhang, Ofer Yizhar, Charu Ramakrishnan, Tomohiro Nishizawa et al.

Channelrhodopsins are light-gated cation channels used in optogenetics; here, the high-resolution crystal structure of a channelrhodopsin from Chlamydomonas reinhardtii is determined.

DNase I sensitivity QTLs are a major determinant of human expression variation ▶

Jacob F. Degner, Athma A. Pai, Roger Pique-Regi, Jean-Baptiste Veyrieras, Daniel J. Gaffney et al.

In human lymphoblastoid cell lines, 8,902 loci were identified at which genetic variation is significantly associated with local DNase I sensitivity; these variants are responsible for a large fraction of expression quantitative trait loci.

Extrathymically generated regulatory T cells control mucosal T_H2 inflammation ▶

Steven Z. Josefowicz, Rachel E. Niec, Hye Young Kim, Piper Treuting, Takatoshi Chinen et al.

Selective impairment of peripheral regulatory T-cell differentiation is found to result in spontaneous allergic T_H2-type inflammation in the intestine and lungs, demonstrating the functional heterogeneity of regulatory T cells generated in the thymus and extrathymically in controlling immune mediated inflammation and disease.

Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting ▶

Hirokazu Matsushita, Matthew D. Vesely, Daniel C. Koboldt, Charles G. Rickert, Ravindra Uppaluri et al.

Exome analysis of chemical-carcinogen-induced mouse tumours provides evidence for T-cell-mediated immunoselection as a mechanism of immunoediting.

Expression of tumour-specific antigens underlies cancer immunoediting ▶

Michel DuPage, Claire Mazumdar, Leah M. Schmidt, Ann F. Cheung & Tyler Jacks

This paper illustrates that immunosurveillance and immunoediting can occur in an oncogene-driven endogenous tumour model provided that the tumours carry strong neoantigens not present in the host.

Outgrowth of single oncogene-expressing cells from suppressive epithelial environments ▶

Cheuk T. Leung & Joan S. Brugge

The earliest stages of tumorigenesis are mimicked in a three-dimensional model of mammary epithelial cells, showing that oncogenes that can promote cell translocation can also drive clonal outgrowth.

Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion ▶

Teresa L. M. Thurston, Michal P. Wandel, Natalia von Muhlinen, Ágnes Foeglein & Felix Randow

Galectin 8, a cytosolic lectin, is shown to function as a danger receptor that detects damaged vesicles and protects cells from bacterial infection by inducing autophagy.

Brassinosteroid regulates stomatal development by GSK3-mediated inhibition of a MAPK pathway ▶

Tae-Wuk Kim, Marta Michniewicz, Dominique C. Bergmann & Zhi-Yong Wang

Brassinosteroid inhibits stomatal development by alleviating GSK3-mediated inhibition of a MAPK module, revealing a link between a plant MAPKKK and its upstream regulators, and between brassinosteroid and a specific developmental output.

Single-molecule imaging of DNA pairing by RecA reveals a three-dimensional homology search ▶

Anthony L. Forget & Stephen C. Kowalczykowski

The search for DNA homology is vital to recombinational DNA repair and occurs by intersegment contact sampling wherein the three-dimensional conformational state of the double-stranded DNA target and the length of the homologous RecA–single-stranded DNA filament have important roles.

News & Views

Molecular biology: RNA discrimination ▶

Monika S. Kowalczyk, Douglas R. Higgs & Thomas R. Gingeras

Biodiversity: Species choked and blended ▶

Jeffrey S. McKinnon & Eric B. Taylor

Microbiology: A sweet way of sensing danger ▶

Ju Huang & John H. Brumell

Structural biology: Ion channel in the spotlight ▶

Oliver P. Ernst & Thomas P. Sakmar

Cancer genetics: Evolution after tumour spread ▶

Steven C. Clifford

Research Highlights

Microbiology: Seal corpses shelter Antarctic microbes | Behavioural science: Sex is spread across the genes | Ecology: Fish figures hint at past extinctions | Zoology: Stripes from shifting cells | Immunology: T-cell retreat in chronic hepatitis C

NEWS & COMMENT

On the up | Sequencing set to alter clinical landscape | Death-rate row blurs mutant flu debate | Human evolution: Cultural roots | Prions and chaperones: Outside the fold | Evolution: Adapted to culture | Personalized medicine: Bring clinical standards to human-genetics research | Health policy: Regulate alcohol for global health | Evolution: Custom built | Books in brief | Q&A: Transgene curator | Whaling: Ways to agree on quotas Justin G. Cooke, Russell Leaper & Vassili Papastavrou

CAREERS

Allen school expanding

More Biological Sciences ▶

RESEARCH

Latest Online

Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation ▶

Peppi Koivunen, Sungwoo Lee, Christopher G. Duncan, Giselle Lopez, Gang Lu et al.

The (R)-enantiomer of 2-hydroxyglutarate, which is produced when IDH is mutated in human tumours, is shown to stimulate the activity of the EGLN prolyl 4-hydroxylases, leading to diminished levels of HIF and enhanced human astrocyte proliferation.

Structural basis for iron piracy by pathogenic Neisseria ▶

Nicholas Noinaj, Nicole C. Easley, Muse Oke, Naoko Mizuno, James Gumbart et al.

Structural analysis reveals the iron scavenging mechanism used by Neisseria species, involving TbpA and TbpB proteins, and sheds light on how human transferrin is specifically targeted.

The same pocket in menin binds both MLL and JUND but has opposite effects on transcription ▶

Jing Huang, Buddha Gurung, Bingbing Wan, Smita Matkar, Natalia A. Veniaminova et al.

Crystal structures of menin in its free form and in complexes with MLL1 or with JUND, or with an MLL1–LEDGF heterodimer, show that menin contains a deep pocket that binds short peptides of MLL1 or JUND in the same manner, but produces opposite effects on transcription.

Articles and Letters

Brassinosteroid regulates stomatal development by GSK3-mediated inhibition of a MAPK pathway ▶

Tae-Wuk Kim, Marta Michniewicz, Dominique C. Bergmann & Zhi-Yong Wang

Brassinosteroid inhibits stomatal development by alleviating GSK3-mediated inhibition of a MAPK module, revealing a link between a plant MAPKKK and its upstream regulators, and between brassinosteroid and a specific developmental output.

Single-molecule imaging of DNA pairing by RecA reveals a three-dimensional homology search ▶

Anthony L. Forget & Stephen C. Kowalczykowski

The search for DNA homology is vital to recombinational DNA repair and occurs by intersegment contact sampling wherein the three-dimensional conformational state of the double-stranded DNA target and the length of the homologous RecA–single-stranded DNA filament have important roles.

News & Views

Analytical chemistry: Ultrasensitive radiocarbon detection ▶

Richard N. Zare

Brief Communications Arising

Isotope fractionation in silicate melts ▶

Daniel J. Lacks, James A. Van Orman & Charles E. Lesher

Dominguez et al. reply ▶

G. Dominguez, G. Wilkins & M. H. Thiemens

More Chemical Sciences ▶

RESEARCH

Latest Online

Abrupt acceleration of a ‘cold’ ultrarelativistic wind from the Crab pulsar ▶

F. A. Aharonian, S. V. Bogovalov & D. Khangulyan

Observations of γ-rays from the Crab pulsar suggest that the energy of the pulsar wind changes from electromagnetic to kinetic over a relatively short distance close to the light cylinder of the pulsar.

Articles and Letters

Light echoes reveal an unexpectedly cool η Carinae during its nineteenth-century Great Eruption ▶

A. Rest, J. L. Prieto, N. R. Walborn, N. Smith, F. B. Bianco et al.

Light echoes from the massive binary star η Carinae reveal it to have been much cooler than models suggest during its Great Eruption in 1840 but the cause of the eruption remains unknown.

Magnetic reconnection from a multiscale instability cascade ▶

Auna L. Moser & Paul M. Bellan

Laboratory observations show how a macroscopic magnetohydrodynamic plasma instability drives a fine-scale secondary instability that is associated with magnetic reconnection.

Realization of three-qubit quantum error correction with superconducting circuits ▶

M. D. Reed, L. DiCarlo, S. E. Nigg, L. Sun, L. Frunzio et al.

A controlled-controlled NOT, or Toffoli, gate is used to develop a fast, high-fidelity, three-qubit error correction protocol with the potential to correct arbitrary single-qubit errors.

Origin of Columbia River flood basalt controlled by propagating rupture of the Farallon slab ▶

Lijun Liu & Dave R. Stegman

A model of subduction that reveals a long tear under Oregon and Nevada provides a new mechanism for the origin of Columbia River flood basalt, resolving previous hypotheses.

News & Views

Analytical chemistry: Ultrasensitive radiocarbon detection ▶

Richard N. Zare

Earth science: Intraplate volcanism ▶

Cin-Ty A. Lee & Stephen P. Grand

Astrophysics: Echoes from an old outburst ▶

Noam Soker & Amit Kashi

Research Highlights

Climate modelling: A rainy signal from noise | Materials: Nanoscale shells trap light | Climate change: More super-hot summers ahead | Materials science: Six-faced particles

NEWS & COMMENT

Models hone picture of climate impacts | Books in brief

More Physical Sciences ▶

RESEARCH

Articles and Letters

Eutrophication causes speciation reversal in whitefish adaptive radiations ▶

P. Vonlanthen, D. Bittner, A. G. Hudson, K. A. Young, R. Müller et al.

Historical and contemporary data of whitefish radiations from pre-alpine European lakes and reconstruction of changes in whitefish genetic species differentiation through time show that species diversity may have evolved in response to ecological opportunity, and that eutrophication, by diminishing this opportunity, has driven extinctions through speciation reversal and demographic decline.

Origin of Columbia River flood basalt controlled by propagating rupture of the Farallon slab ▶

Lijun Liu & Dave R. Stegman

A model of subduction that reveals a long tear under Oregon and Nevada provides a new mechanism for the origin of Columbia River flood basalt, resolving previous hypotheses.

News & Views

Earth science: Intraplate volcanism ▶

Cin-Ty A. Lee & Stephen P. Grand

Brief Communications Arising

Isotope fractionation in silicate melts ▶

Daniel J. Lacks, James A. Van Orman & Charles E. Lesher

Dominguez et al. reply ▶

G. Dominguez, G. Wilkins & M. H. Thiemens

Research Highlights

Climate modelling: A rainy signal from noise | Climate change: More super-hot summers ahead

NEWS & COMMENT

Models hone picture of climate impacts | Russians celebrate Vostok victory | Human evolution: Cultural roots | Energy: A crude awakening | Whaling: Don't trade the moratorium away Mark Peter Simmonds & Sue Fisher

More Earth & Environmental Sciences ▶

Funding: Got to get a grant ▶

A great idea will get applicants only so far. But there are other strategies that can add to the chances of success.

Charity supports science ▶

US philanthropy is increasing.

Tax credit for research ▶

Chilean government hopes to spur scientific investment.

Allen school expanding ▶

Donation will support hiring of global-health researchers.

Careers related news & comment

Tough choices | Energy: A crude awakening | Medical research: No catch to UK charity funding Mark Walport, Iain Foulkes, Peter Weissberg, Delyth Morgan & Sharmila Nebhrajani | Whaling: Ways to agree on quotas Justin G. Cooke, Russell Leaper & Vassili Papastavrou | Research integrity: Data audits could curb misconduct J. Leslie Glick

Director of Anatomic Pathology

Northwestern University 

Research Associate in Molecular Evolution

European Bioinformatics Institute (EBI) 

Postdoctoral Fellow in Cancer Research

European Bioinformatics Institute (EBI) 

Post-Doctoral Scientist

MRC, NIMR 

Metabolomics for Biomedical Research: Where do we Stand?

02.-04.04.12 Bordeaux, France