nature

THIS WEEK

Editorials

A ripe time for gaining ground ▶

After three years of heated debate, the advocates and critics of gain-of-function research must work to agree on how best to regulate the work.

The ice bucket ▶

Social-media fun for medical research bypasses animal sensitivities.

Toxic influence ▶

Europe must act to stop livestock drugs from wiping out its vulture populations.

World View

Stormy outlook for long-term ecology studies ▶

The closure of a 40-year project to understand and protect seabirds shows the false priorities of funders, warns Tim Birkhead.

Seven Days

Seven days: 17–23 October 2014 ▶

The week in science: Snail discovery revives publishing spat; proposed nuclear-waste site passes key US safety evaluation; and biopharmaceutical firm AbbVie cools on US$54-billion takeover deal.

NEWS IN FOCUS

US suspends risky disease research ▶

Government to cease funding gain-of-function studies that make viruses more dangerous, pending a safety assessment.

US midterm elections offer little hope for science ▶

November vote is unlikely to break a political stalemate that has squeezed research funding.

Oldest-known human genome sequenced ▶

DNA shows a group of modern humans roamed across Asia.

Sun’s stroke keeps Kepler online ▶

Space telescope beats mechanical failures to begin a second mission that will trace new celestial targets.

Data bank struggles as protein imaging ups its game ▶

Hybrid methods to solve structures of molecular machines create a storage headache.

Features

Human-subjects research: The ethics squad ▶

Bioethicists are setting up consultancies for research — but some scientists question whether they are needed.

The discovery of Homo floresiensis: Tales of the hobbit ▶

In 2004, researchers announced the discovery of Homo floresiensis, a small relative of modern humans that lived as recently as 18,000 years ago. The ‘hobbit’ is now considered the most important hominin fossil in a generation. Here, the scientists behind the find tell its story.

COMMENT

Human evolution: Small remains still pose big problems ▶

Ten years after the publication of a remarkable find, Chris Stringer explains why the discovery of Homo floresiensis is still so challenging.

Emergency planning: Be prepared ▶

Scenario-based training for disasters is better than just drawing up a paper plan, say Jennifer K. Pullium and colleagues.

Books and Arts

In retrospect: On the Connexion of the Physical Sciences ▶

Richard Holmes finds Mary Somerville's breakthrough science best-seller thrillingly fresh, 180 years on.

Correspondence

Warming goal: still the best indicator Michael Oppenheimer | Warming goal: clear link to emissions H. Damon Matthews | China: Open access to Earth land-cover map Chen Jun, Yifang Ban, Songnian Li | Sustainability: root targets in consensus Sean Maxwell | European Science Foundation: Stop the cuts, not the evaluations Jean-Claude Worms, Jane Swift

RESEARCH

Latest Online

Palaeontology: Mystery of the horrible hands solved ▶

Thomas R. Holtz Jr

Cancer: Metastasis risk after anti-macrophage therapy ▶

Ioanna Keklikoglou, Michele De Palma

Developmental biology: Cells unite by trapping a signal ▶

James Sharpe

Structure and insights into the function of a Ca²⁺-activated Cl⁻ channel ▶

Veronica Kane Dickson, Leanne Pedi, Stephen B. Long

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.

Hepatitis A virus and the origins of picornaviruses ▶

Xiangxi Wang, Jingshan Ren, Qiang Gao et al.

Hepatitis A virus is a picornavirus that causes significant morbidity but remains poorly understood; this paper now provides high-resolution crystal structures of both the mature and the empty hepatitis A virus particle, which show that the three-dimensional structure resembles insect picorna-like viruses.

Productivity limits and potentials of the principles of conservation agriculture ▶

Cameron M. Pittelkow, Xinqiang Liang, Bruce A. Linquist et al.

A global meta-analysis of conservation agriculture principles indicates that the potential contribution of no-till to the sustainable intensification of agriculture is more limited than often assumed.

Copulation in antiarch placoderms and the origin of gnathostome internal fertilization ▶

John A. Long, Elga Mark-Kurik, Zerina Johanson et al.

The discovery of claspers in fossils of antiarch placoderms, an ancient group of armoured fish, suggests that internal fertilization was the ancestral type of reproduction for all jawed vertebrates: this contrasts with the current understanding that external fertilization must be the ancestral state.

Allosteric activation of the RNF146 ubiquitin ligase by a poly(ADP-ribosyl)ation signal ▶

Paul A. DaRosa, Zhizhi Wang, Xiaomo Jiang et al.

Structural and biochemical approaches are used to show how RNF146 activity is allosterically regulated by the binding of poly(ADP-ribose) ligand, and how substrate specificity is achieved with protein poly(ADP-ribosyl)ation and ubiquitination occurring in the same protein complex.

Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile ▶

Charlie G. Buffie, Vanni Bucci, Richard R. Stein et al.

A fraction of the intestinal microbiota as precise as a single bacterial species confers infection resistance by synthesizing Clostridium difficile-inhibiting metabolites from host-derived bile salts.

Identification of multipotent mammary stem cells by protein C receptor expression ▶

Daisong Wang, Cheguo Cai, Xiaobing Dong et al.

Using transplantation and lineage-tracing strategies, protein C receptor is identified as a marker of mammary stem cells in mice, with potential implications for understanding the initiation of breast cancer.

Luminal signalling links cell communication to tissue architecture during organogenesis ▶

Sevi Durdu, Murat Iskar, Celine Revenu et al.

Groups of cells within a migrating collective assemble shared luminal cavities that trap and concentrate the signalling molecule fibroblast growth factor, providing a self-organising mechanism to focus and coordinate cell communication within tissues.

Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis ▶

Laura Bonapace, Marie-May Coissieux, Jeffrey Wyckoff et al.

In mouse models of breast cancer, anti-CCL2 therapy—thought to be potentially useful in treating cancer—is shown to accelerate the growth of lung metastases on discontinuation due to a surge of recruitment of bone marrow monocytes and increased interleukin-6-dependent vascularization of the lung metastatic environment.

Resolving the long-standing enigmas of a giant ornithomimosaur Deinocheirus mirificus ▶

Yuong-Nam Lee, Rinchen Barsbold, Philip J. Currie et al.

Two almost complete skeletons are presented for the theropod dinosaur Deinocheirus mirificus, revealing a humpbacked form with a duckbill-like skull.

Reductive dehalogenase structure suggests a mechanism for B12-dependent dehalogenation ▶

Karl A. P. Payne, Carolina P. Quezada, Karl Fisher et al.

X-ray crystallography and EPR spectroscopy are used to characterize a soluble, oxygen-tolerant reductive dehalogenase from Nitratireductor pacificus pht-3B; the data suggest that the cobalt in the cobalamin cofactor ligates the halogen atom of the substrate, directly abstracting the halogen atom via an oxidative addition.

In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system ▶

Danilo Maddalo, Eusebio Manchado, Carla P. Concepcion et al.

The CRISPR/Cas system has been used to induce the Eml4–Alk chromosomal inversion in mice, a characteristic chromosomal rearrangement seen in human non-small cell lung cancers; the mice developed lung cancer and responded to the ALK inhibitor crizotinib, which is used to treat lung cancer patients with the EML4–ALK rearrangement; this general strategy can be used to engineer other disease-associated chromosomal rearrangements in mice and potentially in other organisms.

Rapid modelling of cooperating genetic events in cancer through somatic genome editing ▶

Francisco J. Sánchez-Rivera, Thales Papagiannakopoulos, Rodrigo Romero et al.

The CRISPR/Cas system has been used in mice for genome editing to introduce genetic alterations found in human lung tumours, and these genome modifications resulted in mouse lung tumours showing different histopathologies depending on the genes altered; the CRISPR/Cas system offers improved and faster ways to create animal models of human diseases such as cancer.

Articles and Letters

Genome sequence of a 45,000-year-old modern human from western Siberia ▶

Qiaomei Fu, Heng Li, Priya Moorjani et al.

The high-quality genome sequence of a 45,000-year-old modern human from Siberia reveals that gene flow from Neanderthals into the ancestors of this individual had already occurred about 7,000 to 13,000 years earlier; genomic comparisons show that he belonged to a population that lived close in time to the separation of populations in east and west Eurasia and that may represent an early modern human radiation out of Africa that has no direct descendants today.

Pulmonary macrophage transplantation therapy ▶

Takuji Suzuki, Paritha Arumugam, Takuro Sakagami et al.

This study reports the correction of pulmonary alveolar proteinosis (PAP) in Csf2rb–/– mice by a single transfer of either wild-type or gene-corrected macrophages directly to the lungs — the transplanted macrophages persisted for at least 1 year; this transplantation strategy obviated the need for myeloablation and immunosuppression and should be a feasible therapy for humans with hereditary PAP.

Structure and immune recognition of trimeric pre-fusion HIV-1 Env ▶

Marie Pancera, Tongqing Zhou, Aliaksandr Druz et al.

A crystal structure of the human immunodeficiency virus Env trimer, used by the virus to infect cells, is determined here; the new structure, which shows the pre-fusion form of Env, increases our understanding of the fusion mechanism and of how the conformation of Env allows the virus to evade the immune response.

Producing more grain with lower environmental costs ▶

Xinping Chen, Zhenling Cui, Mingsheng Fan et al.

In an experiment across China to test integrated soil–crop system management for rice, wheat and maize against current practice, improvements in grain yield are equivalent to high-input techniques, but nutrient use, nutrient loss and greenhouse gas emissions are lower than current practice.

A Hox regulatory network of hindbrain segmentation is conserved to the base of vertebrates ▶

Hugo J. Parker, Marianne E. Bronner, Robb Krumlauf

Nested Hox expression domains are found in jawed vertebrates and in non-vertebrate chordates, but it is unclear whether there is a link between brain regionalization and Hox expression in jawless vertebrates; here, Hox expression is shown to be integrated with hindbrain segmentation in lampreys.

Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis ▶

Kirsten I. Bos, Kelly M. Harkins, Alexander Herbig et al.

Three 1,000-year-old mycobacterial genomes from Peruvian human skeletons reveal that a member of the Mycobacterium tuberculosis complex derived from seals caused human disease before contact in the Americas.

Dendritic cells control fibroblastic reticular network tension and lymph node expansion ▶

Sophie E. Acton, Aaron J. Farrugia, Jillian L. Astarita et al.

During inflammation, the lymph node stromal compartment is shown to accommodate high numbers of infiltrating lymphocytes by relaxing the cytoskeleton of fibroblastic reticular cells, allowing the latter to stretch and the lymph node to expand.

Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers ▶

Simona Chera, Delphine Baronnier, Luiza Ghila et al.

An investigation of the influence of age on the generation of insulin-producing cells after β-cell loss in mice reveals that, whereas α-cells can reprogram to produce insulin from puberty to adulthood, efficient reconstitution in the very young is through δ-cell reprogramming, leading to complete diabetes recovery.

High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity ▶

Manon D. Schulz, Çiğdem Atay, Jessica Heringer et al.

A high-fat diet promotes intestinal tumorigenesis independently of obesity in a mouse model with oncogene activation, by changing the composition of the gut microbiota and altering immune regulation.

Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia ▶

Panagiotis Ntziachristos, Aristotelis Tsirigos, G. Grant Welstead et al.

T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with a poor prognosis and no available targeted therapies; now two histone H3 lysine 27 demethylases, JMJD3 and UTX, are shown to have contrasting roles in human T-ALL cells and a mouse model of the disease, and a small molecule demethylase inhibitor is found to inhibit the growth of T-ALL cell lines, introducing a potential therapeutic avenue for acute leukaemia.

Structure and mechanism of Zn²⁺-transporting P-type ATPases ▶

Kaituo Wang, Oleg Sitsel, Gabriele Meloni et al.

The X-ray crystal structures of a zinc-ion-transporting P-type ATPase are solved in a zinc-free, phosphoenzyme ‘ground’ state and in a transition state of dephosphorylation, characterizing these transporters of an essential micronutrient that is needed for many biological processes but is cytotoxic when free.

News & Views

HIV: A stamp on the envelope ▶

Rogier W. Sanders, John P. Moore

Lung disease: Treatment by cell transplant ▶

Mary Jane Thomassen, Mani S. Kavuru

Physiology: Relax and come in ▶

Kari Vaahtomeri, Michael Sixt

HIV: Potency needs constancy ▶

Alexandra Trkola

Palaeontology: Mystery of the horrible hands solved ▶

Thomas R. Holtz Jr

Cancer: Metastasis risk after anti-macrophage therapy ▶

Ioanna Keklikoglou, Michele De Palma

Developmental biology: Cells unite by trapping a signal ▶

James Sharpe

Brief Communications Arising

The ‘mitoflash’ probe cpYFP does not respond to superoxide ▶

Markus Schwarzländer, Stephan Wagner, Yulia G. Ermakova et al.

Cheng et al. reply ▶

Heping Cheng, Wang Wang, Xianhua Wang et al.

Tryptophan catabolism is unaffected in chronic granulomatous disease ▶

Ghassan J. Maghzal, Susann Winter, Bettina Wurzer et al.

Romani & Puccetti reply ▶

L. Romani, P. Puccetti

Research Highlights

Pros and cons of the PhD glut | Microbiology: Obesity link to jet-lagged microbes | Conservation: Horn trade could save rhinos | Stem cells: Cell transplants enhance vision | Neuroscience: Molecule boosts brain rewiring | Palaeontology: Strange fossil is a vertebrate cousin | Cancer: Immunotherapy beats leukaemia

NEWS & COMMENT

A ripe time for gaining ground | The ice bucket | US suspends risky disease research | Oldest-known human genome sequenced | Data bank struggles as protein imaging ups its game | Human evolution: Small remains still pose big problems | Toxic influence | Stormy outlook for long-term ecology studies

More Biological Sciences ▶

RESEARCH

Latest Online

Cancer: Metastasis risk after anti-macrophage therapy ▶

Ioanna Keklikoglou, Michele De Palma

Hepatitis A virus and the origins of picornaviruses ▶

Xiangxi Wang, Jingshan Ren, Qiang Gao et al.

Hepatitis A virus is a picornavirus that causes significant morbidity but remains poorly understood; this paper now provides high-resolution crystal structures of both the mature and the empty hepatitis A virus particle, which show that the three-dimensional structure resembles insect picorna-like viruses.

Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile ▶

Charlie G. Buffie, Vanni Bucci, Richard R. Stein et al.

A fraction of the intestinal microbiota as precise as a single bacterial species confers infection resistance by synthesizing Clostridium difficile-inhibiting metabolites from host-derived bile salts.

Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis ▶

Laura Bonapace, Marie-May Coissieux, Jeffrey Wyckoff et al.

In mouse models of breast cancer, anti-CCL2 therapy—thought to be potentially useful in treating cancer—is shown to accelerate the growth of lung metastases on discontinuation due to a surge of recruitment of bone marrow monocytes and increased interleukin-6-dependent vascularization of the lung metastatic environment.

In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system ▶

Danilo Maddalo, Eusebio Manchado, Carla P. Concepcion et al.

The CRISPR/Cas system has been used to induce the Eml4–Alk chromosomal inversion in mice, a characteristic chromosomal rearrangement seen in human non-small cell lung cancers; the mice developed lung cancer and responded to the ALK inhibitor crizotinib, which is used to treat lung cancer patients with the EML4–ALK rearrangement; this general strategy can be used to engineer other disease-associated chromosomal rearrangements in mice and potentially in other organisms.

Rapid modelling of cooperating genetic events in cancer through somatic genome editing ▶

Francisco J. Sánchez-Rivera, Thales Papagiannakopoulos, Rodrigo Romero et al.

The CRISPR/Cas system has been used in mice for genome editing to introduce genetic alterations found in human lung tumours, and these genome modifications resulted in mouse lung tumours showing different histopathologies depending on the genes altered; the CRISPR/Cas system offers improved and faster ways to create animal models of human diseases such as cancer.

Articles and Letters

Structure and immune recognition of trimeric pre-fusion HIV-1 Env ▶

Marie Pancera, Tongqing Zhou, Aliaksandr Druz et al.

A crystal structure of the human immunodeficiency virus Env trimer, used by the virus to infect cells, is determined here; the new structure, which shows the pre-fusion form of Env, increases our understanding of the fusion mechanism and of how the conformation of Env allows the virus to evade the immune response.

Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers ▶

Simona Chera, Delphine Baronnier, Luiza Ghila et al.

An investigation of the influence of age on the generation of insulin-producing cells after β-cell loss in mice reveals that, whereas α-cells can reprogram to produce insulin from puberty to adulthood, efficient reconstitution in the very young is through δ-cell reprogramming, leading to complete diabetes recovery.

High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity ▶

Manon D. Schulz, Çiğdem Atay, Jessica Heringer et al.

A high-fat diet promotes intestinal tumorigenesis independently of obesity in a mouse model with oncogene activation, by changing the composition of the gut microbiota and altering immune regulation.

Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia ▶

Panagiotis Ntziachristos, Aristotelis Tsirigos, G. Grant Welstead et al.

T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with a poor prognosis and no available targeted therapies; now two histone H3 lysine 27 demethylases, JMJD3 and UTX, are shown to have contrasting roles in human T-ALL cells and a mouse model of the disease, and a small molecule demethylase inhibitor is found to inhibit the growth of T-ALL cell lines, introducing a potential therapeutic avenue for acute leukaemia.

News & Views

HIV: A stamp on the envelope ▶

Rogier W. Sanders, John P. Moore

Lung disease: Treatment by cell transplant ▶

Mary Jane Thomassen, Mani S. Kavuru

Cancer: Metastasis risk after anti-macrophage therapy ▶

Ioanna Keklikoglou, Michele De Palma

Research Highlights

Stem cells: Cell transplants enhance vision | Cancer: Immunotherapy beats leukaemia

NEWS & COMMENT

A ripe time for gaining ground | The ice bucket

More Health Sciences ▶

RESEARCH

Latest Online

Astrophysics: Secret ingredient exposed ▶

Christopher M. Johns-Krull

Suppression of cooling by strong magnetic fields in white dwarf stars ▶

G. Valyavin, D. Shulyak, G. A. Wade et al.

Cool white dwarf stars often have mysteriously strong magnetic fields (because their coolness suggests that they are old, and magnetic fields should decline in strength with age) and unexplained brightness variations; here the magnetic field is shown to suppress atmospheric convection, inhibiting cooling evolution and causing dark spots.

Spatially resolved magnetic field structure in the disk of a T Tauri star ▶

Ian W. Stephens, Leslie W. Looney, Woojin Kwon et al.

Measurements of polarized 1.25-mm continuum emission from the accretion disk of the T Tauri star HL Tau show that the magnetic field inside the disk cannot be dominated by a vertical component, and that a purely toroidal field also does not fit the data; this suggests that the role of the magnetic field in the accretion of a T Tauri star is more complex than the current theoretical understanding.

Articles and Letters

Two families of exocomets in the β Pictoris system ▶

F. Kiefer, A. Lecavelier des Etangs, J. Boissier et al.

Statistical analysis of over a thousand spectra of the star β Pictoris reveals that it has two kinds of exocomets circling it: old exhausted comets trapped in mean-motion resonance with a massive planet, and fragments of comets.

Characterizing and predicting the magnetic environment leading to solar eruptions ▶

Tahar Amari, Aurélien Canou, Jean-Jacques Aly

Modelling the solar magnetic field using observations of the photospheric field in the four-day period preceding a coronal mass ejection shows that the formation and later ejection of a twisted rope of magnetic flux provides the physical mechanism responsible for the ejection.

Piezoelectricity of single-atomic-layer MoS₂ for energy conversion and piezotronics ▶

Wenzhuo Wu, Lei Wang, Yilei Li et al.

The two-dimensional semiconducting material molybdenum disulphide shows strong piezoelectricity in its single-layered form, suggesting possible applications in nanoscale electromechanical devices for sensing and energy harvesting.

Identification of an iridium-containing compound with a formal oxidation state of IX ▶

Guanjun Wang, Mingfei Zhou, James T. Goettel et al.

The tetrahedral iridium tetroxide cation [IrO₄]+, which has an iridium 5d0 valence electron configuration and a formal oxidation state of IX, is generated in the gas phase, identified by infrared photodissociation spectroscopy, and predicted, by quantum chemical calculations, to be the most stable of all possible [IrO₄]+ isomers.

News & Views

Astronomy: Hurling comets around a planetary nursery ▶

Aki Roberge

Astrophysics: Secret ingredient exposed ▶

Christopher M. Johns-Krull

Research Highlights

Solar Physics: Solar atmosphere is a hotbed of activity | Photonics: Laser moves items long distances

NEWS & COMMENT

In retrospect: On the Connexion of the Physical Sciences | Sun’s stroke keeps Kepler online

More Physical Sciences ▶

RESEARCH

Articles and Letters

Methane dynamics regulated by microbial community response to permafrost thaw ▶

Carmody K. McCalley, Ben J. Woodcroft, Suzanne B. Hodgkins et al.

The abundance of key microbial lineages can be used to predict atmospherically relevant patterns in methane isotopes and the proportion of carbon metabolized to methane during permafrost thaw, suggesting that microbial ecology may be important in ecosystem-scale responses to global change.

Limited impact on decadal-scale climate change from increased use of natural gas ▶

Haewon McJeon, Jae Edmonds, Nico Bauer et al.

It has been hoped that making abundant natural gas available by hydraulic fracturing (fracking) would reduce greenhouse gas emissions but now modelling shows that increased consumption will have limited effect on climate change.

News & Views

Climate change: A crack in the natural-gas bridge ▶

Steven J. Davis, Christine Shearer

Astronomy: Hurling comets around a planetary nursery ▶

Aki Roberge

Research Highlights

Meteorology: Tornadoes growing more clustered

NEWS & COMMENT

Warming goal: still the best indicator | Warming goal: clear link to emissions | China: Open access to Earth land-cover map | Sustainability: root targets in consensus | Toxic influence

More Earth & Environmental Sciences ▶

Career changes: Open for business ▶

A master's in business can offer scientists extra flexibility or whole new career paths.

Turning point: Andrew Dove ▶

Curiosity about catalysis leads to biomaterials career.

Careers related news & comment

The ice bucket | Seven days: 17–23 October 2014 | US suspends risky disease research Sara Reardon | European Science Foundation: Stop the cuts, not the evaluations Jean-Claude Worms, Jane Swift | Stormy outlook for long-term ecology studies Tim Birkhead | US midterm elections offer little hope for science Lauren Morello | Human-subjects research: The ethics squad Elie Dolgin

Fellowships of NCT Heidelberg School of Oncology (NCT HSO)

National Center for Tumor Diseases (NCT) Heidelberg  

Two PhD Positions

ETH Zurich 

Postdoctoral Researcher

NUI Galway 

Post-Doctoral Fellowship : Clinical Genomics

CEA French Atomic and Alternative Energies Commission 

International Symposium Bone Regeneration

11.06.15 Berlin, Germany