nature

THIS WEEK

Editorials

Struggle for independence ▶

The faculty of the Scripps Research Institute is bucking a national trend with its refusal to merge with the University of Southern California.

Within reach ▶

A redoubling of efforts should swiftly eradicate polio from its last strongholds.

Food for thought ▶

Researchers investigating different farming practices should not have to pick sides.

World View

Misjudgements will drive social trials underground ▶

A Facebook study that manipulated news feeds was not definitively unethical and offered valuable insight into social behaviour, says Michelle Meyer.

Seven Days

Seven days: 11–17 July 2014 ▶

The week in science: Smallpox found in fridge; HIV-rebound dashes hope of ‘cure’; and scandal over faked peer review.

NEWS IN FOCUS

Quantum-hub finalists picked ▶

UK government considers eight proposals for up to six research centres.

Landslide risks rise up agenda ▶

Forum on deadly natural phenomena discusses use of simulation and hazard-mapping technologies.

Scripps merger fiasco highlights US funding woes ▶

Other independent biomedical research institutions have turned to private benefactors.

Charity begins at CERN ▶

Particle-physics lab sets up fund for 'extras' as other big institutes mull similar move.

Correction ▶

Features

Physics: Wave of the future ▶

After two decades and more than half a billion dollars, LIGO, the world's largest gravitational-wave observatory, is on the verge of a detection. Maybe.

Weight-loss surgery: A gut-wrenching question ▶

Gastric-bypass surgery can curb obesity as well as diabetes and a slew of other problems. Researchers are now trying to find out how it works.

COMMENT

Infectious disease: Polio eradication hinges on child health in Pakistan ▶

Boosting basic medical services and routine immunizations — not travel vaccinations — is the key to ending polio worldwide, says Zulfiqar Ahmed Bhutta.

Psychological treatments: A call for mental-health science ▶

Clinicians and neuroscientists must work together to understand and improve psychological treatments, urge Emily A. Holmes, Michelle G. Craske and Ann M. Graybiel.

Books and Arts

History of medicine: Typhus and tyranny ▶

Tilli Tansey ponders a turbulent history of vaccine research in Nazi-occupied Europe.

Correspondence

Policy matters: Editorials should heed social scientists Marcelino Fuentes | Careers: Virtual mobility can drive equality Conor O'Carroll | Teaching: China is closing its rural education gap Xin Miao, Christina W. Y. Wong | European research: Brain project leaders need an open mind Richard Morris

RESEARCH

Latest Online

Structural biology: Corralling a protein-degradation regulator ▶

Raymond J. Deshaies

Malaria: Protein-export pathway illuminated ▶

Sanjay A. Desai, Louis H. Miller

Topoisomerase II mediates meiotic crossover interference ▶

Liangran Zhang, Shunxin Wang, Shen Yin et al.

Topoisomerase II mediates meiotic crossover interference by adjusting the protein/DNA meshwork of chromosome axes.

Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide ▶

Eric S. Fischer, Kerstin Böhm, John R. Lydeard et al.

The crystal structures of thalidomide and its derivatives bound to the E3 ligase subcomplex DDB1–CRBN are shown; these drugs are found to have dual functions, interfering with the binding of certain cellular substrates to the E3 ligase but promoting the binding of others, thereby modulating the degradation of cellular proteins.

Crystal structure of the human COP9 signalosome ▶

Gondichatnahalli M. Lingaraju, Richard D. Bunker, Simone Cavadini et al.

The COP9 signalosome (CSN) complex regulates cullin–RING E3 ubiquitin ligases—the largest class of ubiquitin ligase enzymes, which are involved in a multitude of regulatory processes; here, the crystal structure of the entire human CSN holoenzyme is presented.

Dynamic and static maintenance of epigenetic memory in pluripotent and somatic cells ▶

Zohar Shipony, Zohar Mukamel, Netta Mendelson Cohen et al.

Using a new method to estimate DNA methylation turnover rate, embryonic stem cells are shown to lack clonal transmission of methylation but still maintain a stable epigenetic state, whereas somatic cells transmit methylation clonally but lose epigenetic state coherence owing to the persistence of accumulated methylation errors.

Viral tagging reveals discrete populations in Synechococcus viral genome sequence space ▶

Li Deng, J. Cesar Ignacio-Espinoza, Ann C. Gregory et al.

The metagenome of uncultured, Pacific Ocean viruses linked to a ubiquitous cyanobacteria is characterized using viral-tagging, revealing discrete populations in viral sequence space that includes previously cultivated populations and new populations missed in isolate-based studies.

Brain structure resolves the segmental affinity of anomalocaridid appendages ▶

Peiyun Cong, Xiaoya Ma, Xianguang Hou et al.

An anomalocaridid from the Cambrian period of China is so well preserved that its anterior nervous system can be resolved.

Functional polarization of tumour-associated macrophages by tumour-derived lactic acid ▶

Oscar R. Colegio, Ngoc-Quynh Chu, Alison L. Szabo et al.

The growth of tumours is supported by tumour production of lactic acid, which polarizes tumour-associated macrophages to an M2 phenotype through a pathway dependent on hypoxia-inducible factor 1α.

Coordinated regulation of protein synthesis and degradation by mTORC1 ▶

Yinan Zhang, Justin Nicholatos, John R. Dreier et al.

mTORC1 is known to stimulate protein synthesis; now, it is shown to also promote the synthesis of proteasomes, which degrade proteins into the amino acids needed to create new proteins.

Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia ▶

Serkan Kir, James P. White, Sandra Kleiner et al.

Many patients with cancer experience cachexia, a wasting disorder of adipose tissue and skeletal muscle that leads to weight loss and frailty; now, tumour-derived parathyroid-hormone-related protein has been shown to stimulate the expression of genes involved in heat production in adipose tissues and to have an important role in tissue wasting.

Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer ▶

Jae Myoung Suh, Johan W. Jonker, Maryam Ahmadian et al.

Pharmacological fibroblast growth factor 1 (FGF1) normalizes blood glucose in diabetic mice by means of an FGF receptor signalling pathway that is independent of its mitogenic activity.

PTEX is an essential nexus for protein export in malaria parasites ▶

Brendan Elsworth, Kathryn Matthews, Catherine Q. Nie et al.

This paper demonstrates that a protein complex known as PTEX translocates all malaria parasite proteins destined for export into the cytosol of their host red blood cell.

PTEX component HSP101 mediates export of diverse malaria effectors into host erythrocytes ▶

Josh R. Beck, Vasant Muralidharan, Anna Oksman et al.

Plasmodium parasites, the causative agent of malaria, infect and remodel red blood cells by exporting hundreds of proteins into the red blood cell cytosol, a topological conundrum given that the parasite resides in a compartment known as the parasitophorous vacuole; here a dihydrofolate-reductase-based destabilization domain approach is used to inactivate HSP101, part of the Plasmodium translocon of exported proteins, and to demonstrate that it is required for the secretion of all classes of exported Plasmodium proteins.

The alarmin IL-33 promotes regulatory T-cell function in the intestine ▶

Chris Schiering, Thomas Krausgruber, Agnieszka Chomka et al.

The alarmin interleukin-33 is constitutively expressed at barrier sites and released in response to tissue damage; here, the IL-33 receptor ST2 is shown to be preferentially expressed on colonic regulatory T cells, where it promotes regulatory T-cell function and adaptation to the inflammatory tissue environment.

Articles and Letters

Genetics of ecological divergence during speciation ▶

Matthew E. Arnegard, Matthew D. McGee, Blake Matthews et al.

Traits responsible for recent niche divergence between sympatric threespine stickleback species are subjected to forward genetic analysis; additive variation at several loci across the genome accounts for most of the genetic basis of ecological divergence, with a further role for epistatic interactions that disadvantage hybrids.

Reprogramming human endothelial cells to haematopoietic cells requires vascular induction ▶

Vladislav M. Sandler, Raphael Lis, Ying Liu et al.

This study describes the conversion of human fetal and adult vascular endothelial cells into engraftable haematopoietic progenitors by transduction with some transcription factors and then culture on a vascular niche feeder layer; the haematopoietic progenitors may be useful for the generation of engraftable healthy and long-lasting haematopoietic cells for treatment of inherited and acquired blood disorders.

The cancer glycocalyx mechanically primes integrin-mediated growth and survival ▶

Matthew J. Paszek, Christopher C. DuFort, Olivier Rossier et al.

Metastatic cancer cells are shown to have a tendency towards forming a bulky glycocalyx owing to the production of large glycoproteins, and this cancer-associated glycocalyx has a mechanical effect on the spatial organization of integrins — by funnelling integrins into adhesions, integrin clustering and signalling is promoted, which leads to enhanced cell survival and proliferation.

Declines in insectivorous birds are associated with high neonicotinoid concentrations ▶

Caspar A. Hallmann, Ruud P. B. Foppen, Chris A. M. van Turnhout et al.

The water concentrations of imidacloprid, a neonicotinoid pesticide, correlate with declines in farmland bird populations in the Netherlands.

Genome sequencing identifies major causes of severe intellectual disability ▶

Christian Gilissen, Jayne Y. Hehir-Kwa, Djie Tjwan Thung et al.

Whole-genome sequencing is used to identify genetic alterations in patients with severe intellectual disability for whom all other tests, including array and exome sequencing, returned negative results; de novo single-nucleotide and copy number variations affecting the coding region seem to be a major cause of this disorder.

Engineering a memory with LTD and LTP ▶

Sadegh Nabavi, Rocky Fox, Christophe D. Proulx et al.

A rodent study using optogenetics to induce long-term potentiation and long-term depression provides a causal link between synaptic plasticity and memory.

ABCB5 is a limbal stem cell gene required for corneal development and repair ▶

Bruce R. Ksander, Paraskevi E. Kolovou, Brian J. Wilson et al.

The loss of limbal stem cells (LSCs) due to injury or disease is one of the leading causes of blindness; here, the ABCB5 protein is identified as a marker of LSCs in mouse and human eye, and shown to be functionally required for LSC maintenance, corneal development and repair.

WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis ▶

Hong Ouyang, Yuanchao Xue, Ying Lin et al.

p63 and PAX6 act to specify limbal stem or progenitor cells (LSCs), and WNT7A controls corneal epithelium differentiation through PAX6; loss of WNT7A or PAX6 induces LSCs into epithelium, and transduction of PAX6 in skin epithelial stem cells converts them to LSC-like cells and transplantation in a rabbit corneal injury model can replenish corneal epithelial cells and repair damaged corneal surface.

BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor PCID2 ▶

Vaibhav Bhatia, Sonia I. Barroso, María L. García-Rubio et al.

BRCA2, the breast cancer susceptibility gene factor, interacts with TREX-2, a protein complex involved in the biogenesis and export of messenger ribonucleoprotein, to process DNA–RNA hybrid structures called R-loops that can trigger genome instability; these may be a central cause of the stress occurring in early cancer cells that drives oncogenesis.

The structural basis of transfer RNA mimicry and conformational plasticity by a viral RNA ▶

Timothy M. Colussi, David A. Costantino, John A. Hammond et al.

RNA molecules can perform multiple functions, which can be driven by different conformational states; here, the crystal structure of the transfer-RNA-like structure of the turnip yellow mosaic virus is solved, providing insight into the structural basis of RNA multifunctionality.

News & Views

Ecology: Pesticides linked to bird declines ▶

Dave Goulson

Neurobiology: Keeping a lid on it ▶

Gina Turrigiano

Cancer: Sugar-coated cell signalling ▶

Andrew J. Ewald, Mikala Egeblad

Stem cells: Reprogramming finds its niche ▶

Daniel Lucas, Paul S. Frenette

Structural biology: Corralling a protein-degradation regulator ▶

Raymond J. Deshaies

Malaria: Protein-export pathway illuminated ▶

Sanjay A. Desai, Louis H. Miller

Corrigendum

Corrigendum: Sustained translational repression by eIF2α-P mediates prion neurodegeneration ▶

Julie A. Moreno, Helois Radford, Diego Peretti et al.

Erratum

Erratum: CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation ▶

Emmanuel Martin, Noé Palmic, Sylvia Sanquer et al.

Retraction

Retraction: Generation of cell polarity in plants links endocytosis, auxin distribution and cell fate decisions ▶

Pankaj Dhonukshe, Hirokazu Tanaka, Tatsuaki Goh et al.

Research Highlights

Cancer: Roving tumour cells tracked down | Ecology: Ocean reserves miss key target | Neurodegeneration: Antibodies fight Parkinson's | Vision: Prism of the eye guides light | Virology: What makes HIV fit to spread | Cognition: Chimp intelligence partly inherited | Bigfoot sighted on Twitter

NEWS & COMMENT

Infectious disease: Polio eradication hinges on child health in Pakistan | Psychological treatments: A call for mental-health science | History of medicine: Typhus and tyranny | European research: Brain project leaders need an open mind

More Biological Sciences ▶

RESEARCH

Latest Online

Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide ▶

Eric S. Fischer, Kerstin Böhm, John R. Lydeard et al.

The crystal structures of thalidomide and its derivatives bound to the E3 ligase subcomplex DDB1–CRBN are shown; these drugs are found to have dual functions, interfering with the binding of certain cellular substrates to the E3 ligase but promoting the binding of others, thereby modulating the degradation of cellular proteins.

Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia ▶

Serkan Kir, James P. White, Sandra Kleiner et al.

Many patients with cancer experience cachexia, a wasting disorder of adipose tissue and skeletal muscle that leads to weight loss and frailty; now, tumour-derived parathyroid-hormone-related protein has been shown to stimulate the expression of genes involved in heat production in adipose tissues and to have an important role in tissue wasting.

Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer ▶

Jae Myoung Suh, Johan W. Jonker, Maryam Ahmadian et al.

Pharmacological fibroblast growth factor 1 (FGF1) normalizes blood glucose in diabetic mice by means of an FGF receptor signalling pathway that is independent of its mitogenic activity.

Articles and Letters

The cancer glycocalyx mechanically primes integrin-mediated growth and survival ▶

Matthew J. Paszek, Christopher C. DuFort, Olivier Rossier et al.

Metastatic cancer cells are shown to have a tendency towards forming a bulky glycocalyx owing to the production of large glycoproteins, and this cancer-associated glycocalyx has a mechanical effect on the spatial organization of integrins — by funnelling integrins into adhesions, integrin clustering and signalling is promoted, which leads to enhanced cell survival and proliferation.

ABCB5 is a limbal stem cell gene required for corneal development and repair ▶

Bruce R. Ksander, Paraskevi E. Kolovou, Brian J. Wilson et al.

The loss of limbal stem cells (LSCs) due to injury or disease is one of the leading causes of blindness; here, the ABCB5 protein is identified as a marker of LSCs in mouse and human eye, and shown to be functionally required for LSC maintenance, corneal development and repair.

BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor PCID2 ▶

Vaibhav Bhatia, Sonia I. Barroso, María L. García-Rubio et al.

BRCA2, the breast cancer susceptibility gene factor, interacts with TREX-2, a protein complex involved in the biogenesis and export of messenger ribonucleoprotein, to process DNA–RNA hybrid structures called R-loops that can trigger genome instability; these may be a central cause of the stress occurring in early cancer cells that drives oncogenesis.

News & Views

Cancer: Sugar-coated cell signalling ▶

Andrew J. Ewald, Mikala Egeblad

Erratum

Erratum: CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation ▶

Emmanuel Martin, Noé Palmic, Sylvia Sanquer et al.

Research Highlights

Cancer: Roving tumour cells tracked down | Neurodegeneration: Antibodies fight Parkinson's

NEWS & COMMENT

Infectious disease: Polio eradication hinges on child health in Pakistan | Psychological treatments: A call for mental-health science

More Health Sciences ▶

RESEARCH

Latest Online

Tracking photon jumps with repeated quantum non-demolition parity measurements ▶

L. Sun, A. Petrenko, Z. Leghtas et al.

The quantized changes in the photon number parity of a microwave cavity can be tracked on a short enough timescale, and with sufficiently little interference with the quantum state, for this parity observable to be used to monitor the occurrence of error in a recently proposed protected quantum memory.

Articles and Letters

Rapid formation of large dust grains in the luminous supernova 2010jl ▶

Christa Gall, Jens Hjorth, Darach Watson et al.

The formation of dust in the dense circumstellar medium of the bright supernova 2010jl is at first rapid and produces very large grains, which resist destruction, whereas later the dust production rate increases, meaning its source is ejecta; this links early and late dust mass evolution in supernovae with dense circumstellar media.

Ramp compression of diamond to five terapascals ▶

R. F. Smith, J. H. Eggert, R. Jeanloz et al.

New laboratory techniques for applying enormous pressures allow diamond to be compressed to 50 million atmospheres, providing insight into the interiors of planets and theoretical implications.

A low-cost non-toxic post-growth activation step for CdTe solar cells ▶

J. D. Major, R. E. Treharne, L. J. Phillips et al.

MgCl₂ is shown to be a cheap and non-toxic replacement for the costly and environmentally unfriendly salt CdCl₂ that has long been used as the ‘activation’ step in the production of cadmium telluride solar cells.

A deep crust–mantle boundary in the asteroid 4 Vesta ▶

Harold Clenet, Martin Jutzi, Jean-Alix Barrat et al.

Data on Vesta’s surface material provided by the Dawn probe and impacts modelling reveals that Vesta’s crust–mantle boundary must be deeper than 80 kilometres below the surface.

News & Views

High-pressure physics: Piling on the pressure ▶

Chris J. Pickard, Richard J. Needs

Astrophysics: Survival of the largest ▶

Haley Gomez

Materials science: A superelastic organic crystal ▶

Tomiki Ikeda, Toru Ube

Research Highlights

Applied physics: Phone powers electronic label

More Physical Sciences ▶

RESEARCH

Latest Online

Climate science: Cold carbon storage ▶

Sebastian Sobek

A shift of thermokarst lakes from carbon sources to sinks during the Holocene epoch ▶

K. M. Walter Anthony, S. A. Zimov, G. Grosse et al.

Observations and modelling show that the deep thermokarst lakes that formed in Siberia and Alaska when the permafrost warmed in the Holocene epoch changed from climate-warming methane sources to climate-cooling carbon sinks about 5,000 years ago.

Articles and Letters

Pathway from subducting slab to surface for melt and fluids beneath Mount Rainier ▶

R. Shane McGary, Rob L. Evans, Philip E. Wannamaker et al.

Magnetotelluric data from the state of Washington, USA, are used to image the fluid–melt phase of volcanic subduction in Mt Rainier, revealing fluid release at or near the top of the slab, and its migration into the overlying mantle.

News & Views

Ecology: Pesticides linked to bird declines ▶

Dave Goulson

50 & 100 Years Ago ▶

Climate science: Cold carbon storage ▶

Sebastian Sobek

Research Highlights

Agriculture: Global warming could hurt crops | Planetary science: Titan's sea is super salty

More Earth & Environmental Sciences ▶

Interdisciplinary research: Break out ▶

Researchers working at the interface of disciplines can pursue insights without sacrificing career progress.

Turning point: Drew Purves ▶

Computer scientist models global ecology.

Careers related news & comment

Psychological treatments: A call for mental-health science Emily A. Holmes, Michelle G. Craske, Ann M. Graybiel | Careers: Virtual mobility can drive equality Conor O'Carroll | Teaching: China is closing its rural education gap Xin Miao, Christina W. Y. Wong | European research: Brain project leaders need an open mind Richard Morris

Postdoctoral Fellow

UT MD Anderson Cancer Center 

Research Fellow

University of Portsmouth 

Postdoctoral Fellowships

Cells in Motion - Cluster of Excellence 

Project Leader for Underground Research

ETH Zurich 

15th Annual G Protein-Coupled receptor (GPCR) retreat

02.10.14 Bromont, Canada