nature

THIS WEEK

Editorials

Present danger ▶

There is much hype about predicting and preventing future pandemics, but not enough is being done about a threat sitting under our noses.

Quanundrum ▶

Does reality exist? Fifty years on, Bell’s theorem still divides (and confuses) physicists.

Summer skills ▶

A fledgling neuroscience programme is a rare beacon of research excellence in Romania.

World View

Uprooting researchers can drive them out of science ▶

Making early-career scientists change institutions frequently is disruptive and — with modern technology — unnecessary, says Russell Garwood.

Seven Days

Seven days: 13–19 June 2014 ▶

The week in science: Chile axes giant hydroelectric dams; calls to dismantle RIKEN’s centre for developmental biology; and Europe’s medicines agency frees data on drug trials.

NEWS IN FOCUS

3D images remodel history ▶

Digital-photo software promises to offer unprecedented access to artefacts and sites.

Tree hitched a ride to island ▶

Acacia analysis reveals globetrotting seed trekked 18,000 kilometres from Hawaii to Réunion.

US child study hits buffers ▶

Launch date for cohort study set to be delayed as data problems are identified.

HIV trial attacked ▶

Critics question ethics of allowing pregnant women to receive treatment that falls below the standard in their country.

Irish university labs face external audits ▶

Funding agency aims to affirm best practice with independent checks on research methods.

Features

The parched planet: Water on tap ▶

Researchers are exploring unconventional sources of fresh water to quench the globe's growing thirst.

Scientific publishing: The inside track ▶

Members of the US National Academy of Sciences have long enjoyed a privileged path to publication in the body's prominent house journal. Meet the scientists who use it most heavily.

COMMENT

Stem cells: Taking a stand against pseudoscience ▶

Elena Cattaneo and Gilberto Corbellini are among the academics working to protect patients from questionable stem-cell therapies. Here, they share their experiences and opinions of the long, hard fight for evidence to prevail.

Regulation: Sell help not hope ▶

Stem cells are being used as a wedge in calls to allow unproven medical interventions onto the market, warn Paolo Bianco and Douglas Sipp.

Books and Arts

Evolution: The complexity chronicles ▶

Nancy Moran enjoys a treatise on symbiosis — the intimate association of species that transformed life and Earth.

Books in brief ▶

Correspondence

NIH policy: mandate goes too far R. Douglas Fields | NIH policy: status quo is also costly Louise D. McCullough, Margaret M. McCarthy, Geert J. de Vries | Open access: Sharing your data is easier than you think Stephen Eglen | Citizen campaigns: Justifying embryo research in Europe Joep Geraedts | Colour blindness: Still too many red–green figures S. Colby Allred, William J. Schreiner, Oliver Smithies

RESEARCH

Latest Online

Structural biology: Enzyme assembly line pictured ▶

Peter F. Leadlay

Structural biology: Lipopolysaccharide rolls out the barrel ▶

Russell E. Bishop

Evolutionary developmental biology: Use it or lose it ▶

Bau-lin Huang, Susan Mackem

Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs ▶

Javier Lopez-Rios, Amandine Duchesne, Dario Speziale et al.

The basic five-digit limb of tetrapods has been altered many times during evolution, usually by the progressive loss of digits — this study tracks the molecular underpinnings of this change, showing that in comparison to mouse, the polarized gene expression in the bovine limb bud is progressively lost due to evolutionary alteration of the cis-regulatory sequences that control Ptch1 expression in response to SHH signalling in the digit-forming handplate.

Aryl hydrocarbon receptor control of a disease tolerance defence pathway ▶

Alban Bessede, Marco Gargaro, Maria T. Pallotta et al.

Initial exposure to lipopolysaccharide (LPS) induces endotoxin tolerance, which reduces immunological reactions to LPS; here it is shown that primary LPS challenge is controlled by AhR, TDO2 and IL-10, whereas sustained effects require AhR, IDO1 and TGF-β, allowing for disease tolerance with reduced immunopathology in infections.

Structure of a modular polyketide synthase ▶

Somnath Dutta, Jonathan R. Whicher, Douglas A. Hansen et al.

Polyketide synthases are multidomain enzymes that produce polyketides, which form the basis of many therapeutic agents; here, electron cryo-microscopy is used to establish the structure of a bacterial full-length module, and to elucidate the structural basis of both intramodule and intermodule substrate transfer.

Structural basis for outer membrane lipopolysaccharide insertion ▶

Haohao Dong, Quanju Xiang, Yinghong Gu et al.

Lipopolysaccharide, an essential component of the outer membranes of Gram-negative bacteria, is inserted by LptD–LptE, a protein complex with a unique ‘barrel and plug’ architecture; the structure, molecular dynamics simulations and functional assays of the LptD–LptE complex of Salmonella typhimurium suggest that lipopolysaccharide may pass through the barrel and is then inserted into the outer leaflet of the outer membrane through a lateral opening between two β-strands of LptD.

Patterning and post-patterning modes of evolutionary digit loss in mammals ▶

Kimberly L. Cooper, Karen E. Sears, Aysu Uygur et al.

A study of limb development in multiple mammals reveals that evolutionary digit loss has occured in many different ways—at different stages and by different mechanisms, such as regulation of Shh in initial digit specification events or by removal of digits through cell death.

Structural rearrangements of a polyketide synthase module during its catalytic cycle ▶

Jonathan R. Whicher, Somnath Dutta, Douglas A. Hansen et al.

Polyketide synthases (PKSs) are multidomain enzymes that produce polyketides, which form the basis of many therapeutic agents; here, electron cryo-microscopy is used to probe the structure of an intact module of a multi-enzyme PKS in different functional states.

Historical contingency and its biophysical basis in glucocorticoid receptor evolution ▶

Michael J. Harms, Joseph W. Thornton

By characterizing a very large number of might-have-been evolutionary trajectories starting from a resurrected ancestral protein, the authors show that the evolution of an essential modern protein was contingent on extremely unlikely historical mutations.

A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes ▶

Ida Moltke, Niels Grarup, Marit E. Jørgensen et al.

An association mapping study of type-2-diabetes-related quantitative traits in the Greenlandic population identified a common variant in TBC1D4 that increases plasma glucose levels and serum insulin levels after an oral glucose load and type 2 diabetes risk, with effect sizes several times larger than any previous findings of large-scale genome-wide association studies for these traits.

Structural basis for lipopolysaccharide insertion in the bacterial outer membrane ▶

Shuai Qiao, Qingshan Luo, Yan Zhao et al.

Lipopolysaccharide, an essential component of the Gram-negative bacteria outer membrane, is inserted by LptD–LptE, a protein complex with a unique ‘barrel and plug’ architecture; the structure of the LptD–LptE complex of Shigella flexneri determined here shows LptD forming a 26-stranded β-barrel with LptE located inside the barrel of LptD, the first two β-strands are distorted by two proline residues, creating a potential portal in the barrel wall that might allow lateral diffusion of lipopolysaccharide into the outer membrane.

Articles and Letters

The genome of Eucalyptus grandis OPEN ▶

Alexander A. Myburg, Dario Grattapaglia, Gerald A. Tuskan et al.

The Eucalyptus grandis genome has been sequenced, revealing the greatest number of tandem duplications of any plant genome sequenced so far, and the highest diversity of genes for specialized metabolites that act as chemical defence and provide unique pharmaceutical oils; genome sequencing of the sister species E. globulus and a set of inbred E. grandis tree genomes reveals dynamic genome evolution and hotspots of inbreeding depression.

Single-cell RNA-seq reveals dynamic paracrine control of cellular variation ▶

Alex K. Shalek, Rahul Satija, Joe Shuga et al.

Large-scale single-cell RNA-seq of stimulated primary mouse bone-marrow-derived dendritic cells highlights positive and negative intercellular signalling pathways that promote and restrain cellular variation.

The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy ▶

Baris Bingol, Joy S. Tea, Lilian Phu et al.

Damaged mitochondria are removed by mitophagy, and defects in mitophagy are linked to Parkinson’s disease; here it is shown that USP30, a deubiquitinase localized to mitochondria, antagonizes mitophagy by removing the ubiquitin tags put in place by Parkin, USP30 inhibition is therefore potentially beneficial for Parkinson’s disease by promoting mitochondrial clearance and quality control.

mTORC1 controls the adaptive transition of quiescent stem cells from G₀ to G_Alert ▶

Joseph T. Rodgers, Katherine Y. King, Jamie O. Brett et al.

A mouse study reveals that the stem cell quiescent state is composed of two distinct phases, G₀ and G_Alert; stem cells reversibly transition between these two phases in response to systemic environmental stimuli acting through the mTORC1 pathway.

The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR ▶

Randall M. Chin, Xudong Fu, Melody Y. Pai et al.

Ageing in the worm Caenorhabditis elegans is shown to be delayed by supplementation with α-ketoglutarate, an effect that is probably mediated by ATP synthase—which is identified as a direct target of α-ketoglutarate—and target of rapamycin (TOR).

PTEN action in leukaemia dictated by the tissue microenvironment ▶

Cornelius Miething, Claudio Scuoppo, Benedikt Bosbach et al.

A mouse model of T-cell leukaemia is used to test whether PTEN loss is required for tumour maintenance as well as initiation; although it had little effect on tumour load in haematopoietic organs, PTEN reactivation reduced the CCR9-dependent tumour dissemination to the intestine that was amplified on PTEN loss, exposing the importance of tumour microenvironment in PTEN-deficient settings.

Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer ▶

Khaled Ali, Dalya R. Soond, Roberto Piñeiro et al.

The kinase PI(3)Kδ is shown to be required for the immunosuppressive function of regulatory T cells; inactivation of PI(3)Kδ in these cells leads to enhanced cytotoxic T-cell function and restricts tumour growth and metastasis in a variety of mouse tumour models.

CFIm25 links alternative polyadenylation to glioblastoma tumour suppression ▶

Chioniso P. Masamha, Zheng Xia, Jingxuan Yang et al.

CFIm25 is identified as a factor that prevents messenger RNAs being shortened due to altered 3′ polyadenylation, which typically occurs when cells undergo high proliferation and correlates with increased tumorigenic activity in glioblastoma tumours.

Persistent gut microbiota immaturity in malnourished Bangladeshi children ▶

Sathish Subramanian, Sayeeda Huq, Tanya Yatsunenko et al.

Bacterial species whose representation defines healthy postnatal assembly of the gut microbiota in Bangladeshi children during their first 2 years are identified, and a model is constructed to compare healthy children to those with severe acute malnutrition (SAM); results show that SAM is associated with microbiota immaturity that is only partially ameliorated by existing nutritional interventions.

Ribosomal oxygenases are structurally conserved from prokaryotes to humans ▶

Rasheduzzaman Chowdhury, Rok Sekirnik, Nigel C. Brissett et al.

Crystal structures of human and prokaryotic ribosomal oxygenases reported here, with and without their ribosomal protein substrates, support their assignments as hydroxylases, and provide insights into the evolution of the JmjC-domain-containing hydroxylases and demethylases.

Co-opting sulphur-carrier proteins from primary metabolic pathways for 2-thiosugar biosynthesis ▶

Eita Sasaki, Xuan Zhang, He G. Sun et al.

How sulphur is incorporated into sulphur-containing secondary metabolites is poorly understood; here, the bacterium Amycolatopsis orientalis is shown to co-opt sulphur-carrier proteins from primary metabolic pathways to facilitate the biosynthesis of sulphur-containing natural products.

News & Views

Cancer: Natural-born killers unleashed ▶

Emilio Hirsch, Francesco Novelli

Population health: Immaturity in the gut microbial community ▶

Elizabeth K. Costello, David A. Relman

Cell biology: Balancing act ▶

Alban Ordureau, J. Wade Harper

Structural biology: Enzyme assembly line pictured ▶

Peter F. Leadlay

Structural biology: Lipopolysaccharide rolls out the barrel ▶

Russell E. Bishop

Evolutionary developmental biology: Use it or lose it ▶

Bau-lin Huang, Susan Mackem

Research Highlights

Zoology: How ants link up to build bridges | Ecology: Stick together to fight disease | Molecular biology: Genome editing of stem cells | Regenerative biology: Love hormone revitalizes muscles | Animal behaviour: Apes cooperate on their own

NEWS & COMMENT

Present danger | Tree hitched a ride to island | Evolution: The complexity chronicles | NIH policy: mandate goes too far | Citizen campaigns: Justifying embryo research in Europe | 3D images remodel history | US child study hits buffers | HIV trial attacked | Stem cells: Taking a stand against pseudoscience | Regulation: Sell help not hope

More Biological Sciences ▶

RESEARCH

Latest Online

A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes ▶

Ida Moltke, Niels Grarup, Marit E. Jørgensen et al.

An association mapping study of type-2-diabetes-related quantitative traits in the Greenlandic population identified a common variant in TBC1D4 that increases plasma glucose levels and serum insulin levels after an oral glucose load and type 2 diabetes risk, with effect sizes several times larger than any previous findings of large-scale genome-wide association studies for these traits.

Articles and Letters

The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy ▶

Baris Bingol, Joy S. Tea, Lilian Phu et al.

Damaged mitochondria are removed by mitophagy, and defects in mitophagy are linked to Parkinson’s disease; here it is shown that USP30, a deubiquitinase localized to mitochondria, antagonizes mitophagy by removing the ubiquitin tags put in place by Parkin, USP30 inhibition is therefore potentially beneficial for Parkinson’s disease by promoting mitochondrial clearance and quality control.

PTEN action in leukaemia dictated by the tissue microenvironment ▶

Cornelius Miething, Claudio Scuoppo, Benedikt Bosbach et al.

A mouse model of T-cell leukaemia is used to test whether PTEN loss is required for tumour maintenance as well as initiation; although it had little effect on tumour load in haematopoietic organs, PTEN reactivation reduced the CCR9-dependent tumour dissemination to the intestine that was amplified on PTEN loss, exposing the importance of tumour microenvironment in PTEN-deficient settings.

Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer ▶

Khaled Ali, Dalya R. Soond, Roberto Piñeiro et al.

The kinase PI(3)Kδ is shown to be required for the immunosuppressive function of regulatory T cells; inactivation of PI(3)Kδ in these cells leads to enhanced cytotoxic T-cell function and restricts tumour growth and metastasis in a variety of mouse tumour models.

CFIm25 links alternative polyadenylation to glioblastoma tumour suppression ▶

Chioniso P. Masamha, Zheng Xia, Jingxuan Yang et al.

CFIm25 is identified as a factor that prevents messenger RNAs being shortened due to altered 3′ polyadenylation, which typically occurs when cells undergo high proliferation and correlates with increased tumorigenic activity in glioblastoma tumours.

News & Views

Cancer: Natural-born killers unleashed ▶

Emilio Hirsch, Francesco Novelli

Population health: Immaturity in the gut microbial community ▶

Elizabeth K. Costello, David A. Relman

Cell biology: Balancing act ▶

Alban Ordureau, J. Wade Harper

NEWS & COMMENT

Present danger | NIH policy: mandate goes too far | US child study hits buffers | HIV trial attacked | Stem cells: Taking a stand against pseudoscience | Regulation: Sell help not hope

More Health Sciences ▶

RESEARCH

Latest Online

Fundamental constants: A cool way to measure big G ▶

Stephan Schlamminger

Normal-state nodal electronic structure in underdoped high-T_c copper oxides ▶

Suchitra E. Sebastian, N. Harrison, F. F. Balakirev et al.

Quantum oscillation measurements in the underdoped copper oxide YBa₂Cu₃O_6 + x reveal a nodal electronic structure from charge order, which helps to characterize the normal state out of which superconductivity emerges in the underdoped regime.

Precision measurement of the Newtonian gravitational constant using cold atoms ▶

G. Rosi, F. Sorrentino, L. Cacciapuoti et al.

Determination of the gravitational constant G using laser-cooled atoms and quantum interferometry, a technique that gives new insight into the systematic errors that have proved elusive in previous experiments, yields a value that has a relative uncertainty of 150 parts per million and which differs from the current recommended value by 1.5 combined standard deviations.

Articles and Letters

Contextuality supplies the ‘magic’ for quantum computation ▶

Mark Howard, Joel Wallman, Victor Veitch et al.

Quantum computing promises advantages over classical computing for certain problems; now ‘quantum contextuality’ — a generalization of the concept of quantum non-locality — is shown to be a critical resource that gives the most promising class of quantum computers their power.

Single-cell RNA-seq reveals dynamic paracrine control of cellular variation ▶

Alex K. Shalek, Rahul Satija, Joe Shuga et al.

Large-scale single-cell RNA-seq of stimulated primary mouse bone-marrow-derived dendritic cells highlights positive and negative intercellular signalling pathways that promote and restrain cellular variation.

Measurement of the magnetic interaction between two bound electrons of two separate ions ▶

Shlomi Kotler, Nitzan Akerman, Nir Navon et al.

The magnetic interaction between two electrons is measured at the micrometre scale, exhibiting spin entanglement generation over 15 seconds of coherent evolution; varying the inter-electron separation shows a distance dependence consistent with the inverse-cube law.

Ultrafast X-ray probing of water structure below the homogeneous ice nucleation temperature ▶

J. A. Sellberg, C. Huang, T. A. McQueen et al.

Femtosecond X-ray laser pulses are used to probe the structure of liquid water in micrometre-sized droplets that have been cooled below the homogeneous ice nucleation temperature, revealing the existence of metastable bulk liquid water down to temperatures of 227 kelvin.

Metastable liquid–liquid transition in a molecular model of water ▶

Jeremy C. Palmer, Fausto Martelli, Yang Liu et al.

A stable crystal phase and two metastable liquid phases of the ST2 model of water exist at the same deeply supercooled condition, and the two liquids undergo a first-order liquid–liquid transition that meets stringent thermodynamic criteria.

News & Views

Applied mathematics: How chaos forgets and remembers ▶

P.-M. Binder, R. M. Pipes

Quantum computing: Powered by magic ▶

Stephen D. Bartlett

Quantum physics: Feel the force ▶

Ferdinand Schmidt-Kaler

Fundamental constants: A cool way to measure big G ▶

Stephan Schlamminger

Corrigendum

Corrigendum: Fuel gain exceeding unity in an inertially confined fusion implosion ▶

O. A. Hurricane, D. A. Callahan, D. T. Casey et al.

Research Highlights

Electronics: Stretchy battery woven into fabric | Physics: Global quantum clock proposed | Particle physics: Exotic four-quark particle confirmed

NEWS & COMMENT

Quanundrum | Books in brief | Open access: Sharing your data is easier than you think | The parched planet: Water on tap

More Physical Sciences ▶

RESEARCH

Articles and Letters

Possible control of subduction zone slow-earthquake periodicity by silica enrichment ▶

Pascal Audet, Roland Bürgmann

Seismic data from subduction zones that exhibit slow earthquakes reveal that the ratio of compressional-wave to shear-wave velocity of the overriding forearc crust is linearly related to the average recurrence time of slow earthquakes and that this may be associated with quartz enrichment within the forearc crust.

Corrigendum

Corrigendum: Sea-level and deep-sea-temperature variability over the past 5.3 million years ▶

E. J. Rohling, G. L. Foster, K. M. Grant et al.

Research Highlights

Glaciology: Refrozen water warms glacier

NEWS & COMMENT

Books in brief | The parched planet: Water on tap

More Earth & Environmental Sciences ▶

Laboratory careers: Catalysts for efficient science ▶

A good lab manager can smooth the running of a laboratory, saving time and money.

Careers related news & comment

Summer skills | Seven days: 13–19 June 2014 | Scientific publishing: The inside track Peter Aldhous | Uprooting researchers can drive them out of science Russell Garwood | NIH policy: mandate goes too far R. Douglas Fields | NIH policy: status quo is also costly Louise D. McCullough, Margaret M. McCarthy, Geert J. de Vries | US child study hits buffers Heidi Ledford | Irish university labs face external audits Richard Van Noorden

Group leader positions in Development & Stem Cells

IGBMC (Institute of Genetics & Molecular & Cellular Biology)/ CERBM GIE 

Postdoctoral Research Scientist

Wellcome Trust Centre for Human Genetics 

Wissenschaftliche / r Mitarbeiter / in / Postdoctoral research fellow

Robert Koch - Institut 

Professor

Helmholtz Institute Erlangen-Nürnberg 

Paediatric Drug Development

8 July London, UK