| | Volume 511 Number 7509 | | | nature | | The science that matters. Every week. | | | | | | | |  | | EPIGENETICS FUNDING OPPORTUNITY - Cutting edge science is all about collaboration. That's why EpiCypher is offering FIVE FULLY-FUNDED Epigenetic Peptide Array Screening & Services Grants. Eligible projects include any effort studying the role of histone modifications or chromatin biology in physiologic or pathologic processes. Apply online today or call 855-374-2461. | | | | | | | Jump to the content that matters to you | | | | | | | | | | Genome sequencing identifies major causes of severe intellectual disability | Intellectual disability is known to be linked to genetic variance but the majority of cases remain undiagnosed. This uses whole-genome sequencing to identify genetic alterations in patients with severe intellectual disability. Sequencing of 50 patients with severe intellectual disability — and with no family history of the condition — produced a conclusive genetic diagnosis in 21 patients. The results suggest that de novo copy number variations and single-nucleotide variations affecting the coding region are a major cause of severe intellectual disability. | | | | | | | | | Ramp compression of diamond to five terapascals | Knowledge of the behaviour of matter under extreme pressure is essential for describing the interior state of giant planets such as Jupiter. The National Ignition Facility (NIF) at Lawrence Livermore National Laboratory in California is pursuing laboratory astrophysics at up to 50 million atmospheres pressure. Working with the NIF at temperatures below those used in fusion experiments, Raymond Smith and colleagues have achieved a new experimental benchmark in the replication of conditions deep within giant planets. | | | | | | | | | Declines in insectivorous birds are associated with high neonicotinoid concentrations | The use of neonicotinoid pesticides has been linked to declines in bees and other pollinators. New data from the Netherlands show a correlation between declines in insectivorous farmland bird populations and water concentrations of imidacloprid, a neonicotinoid. The spatial connection remains once other land-use changes have been accounted for. The researchers suggest that neonicotinoids may have a cascading effect on ecosystem that should be taken into account in future legislation on insecticide usage. | | | | | | | | |  | | APPLY TODAY for the 2014 ONCOLOGY RESEARCH GRANT. Together with Illumina, we're giving two deserving researchers the power to tap into the wealth of genomic data locked within FFPE samples using an innovative technique developed by EA | Quintiles using Illumina's RNA Access method. Unleash the power of your research with RNA-seq and DNA Methylation. | | | | | | | | | | | | In this week's podcast: the protein behind a wasting disorder affecting half of cancer patients, squeezing diamond to learn about the insides of giant planets, and an exhibition about finding your way on the high seas. Plus, the best science news from outside Nature. | | | | | | | | | | | | | | | | | | | | | | | | 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. | | | | | | | | | | | | | | | | | 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. | | | | | | | | | | | | | | | | | | | | Charity begins at CERN ▶ | | | Particle-physics lab sets up fund for 'extras' as other big institutes mull similar move. | | | | | | | | | | | | | | 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. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 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. | | | | | | | | | | | | | | | | | | | | 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. | | | | | | | | | | | | | | 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. | | | | | | | | | | | 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. | | | | | | | | | | | 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. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Nature Outlook Vaccines Waging a global battle to prevent disease Access the Outlook free online for six months. Produced with support from the New Venture Fund, United Nations Children's Fund (UNICEF), and GAVI Alliance, with additional support from the Bill & Melinda Gates Foundation. | | | | | | | | | | | | | | | | | | | | | | 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. | | | | | | | | | | | | | | 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. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 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. | | | | | | | | | | | 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 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. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Scientific Data is an open-access, peer-reviewed publication and exists to help you publish, discover and reuse research data. 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