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Summaries of newsworthy papers: Nature: A big deletion, Medicine: Platelets promote closure of vessels in newborns, Neuroscience: To boldly go, Geoscience: Sensitive climate and Nature: The good fight

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE For papers that will be published online on 06 December 2009 This press release is copyrighted to the Nature journals mentioned below. This press release contains: · Summaries of newsworthy papers: Nature: A big deletion Genetics: Environment and ethnicity influence gene expression Medicine: Platelets promote closure of vessels in newborns Neuroscience: To boldly go Geoscience: Sensitive climate And finally…Nature: The good fight · Mention of papers to be published at the same time with the same embargo · Geographical listing of authors PDFs of all the papers mentioned on this release can be found in the relevant journal’s section of http://press.nature.com. Press contacts for the Nature journals are listed at the end of this release. Warning: This document, and the Nature journal papers to which it refers, may contain information that is price sensitive (as legally defined, for example, in the UK Criminal Justice Act 1993 Part V) with respect to publicly quoted companies. Anyone dealing in securities using information contained in this document, or in advance copies of a Nature journal’s content, may be guilty of insider trading under the US Securities Exchange Act of 1934. PICTURES: To obtain artwork from any of the journals, you must first obtain permission from the copyright holder (if named) or author of the research paper in question (if not). NOTE: Once a paper is published, the digital object identifier (DOI) number can be used to retrieve the abstract and full text from the journal web site (abstracts are available to everyone, full text is available only to subscribers). To do this, add the DOI to the following URL: http://dx.doi.org/ (For example, http://dx.doi.org/10.1038/ng730). For more information about DOIs and Advance Online Publication, see http://www.nature.com/ng/aop/. HYPE: We take great care not to hype the papers mentioned on our press releases, but are sometimes accused of doing so. If you ever consider that a story has been hyped, please do not hesitate to contact us at press@nature.com, citing the specific example. PLEASE CITE THE SPECIFIC NATURE JOURNAL AND WEBSITE AS THE SOURCE OF THE FOLLOWING ITEMS. IF PUBLISHING ONLINE, PLEASE CARRY A HYPERLINK TO THE APPROPRIATE JOURNAL’S WEBSITE. [1] Nature: A big deletion DOI: 10.1038/nature08689 The first demonstration of copy number variation making a significant contribution to the genetic architecture of human obesity is reported online this week in Nature. The progressive dissection of the genetic basis for human obesity has not only medical but also social implications to help remove the stigma of this disorder. Copy number variation is caused by the deletion or duplication of sections of DNA in the genome, leading to a difference in the number of copies of genes that a person has. Sadaf Farooqi and colleagues identify several large, rare genetic deletions in 300 patients with severe early-onset obesity compared with over 7,000 healthy individual of the same ancestry. The most prevalent of these deletions spans a region that includes the gene SH2B1, which is known to be involved in insulin signalling. Individuals with this deletion eat more and have severe insulin resistance that is disproportionate for the degree of obesity. Obesity is a highly heritable disorder but the genetic associations that have been reported so far account for only a small percentage of the inherited variation in body mass index. This study marks the first report of a copy number variation associated with obesity. Author contact Sadaf Farooqi (University of Cambridge, UK) Tel: +44 1223 762634; E-mail: isf20@cam.ac.uk [2] Genetics: Environment and ethnicity influence gene expression DOI: 10.1038/ng.495 Both genetic and environmental factors influence variation in gene expression, according to a study published online in this week’s Nature Genetics. Gene expression is commonly used by researchers to gauge levels of gene activity, as misregulation of gene expression can often contribute to disease and disrupt developmental processes. In addition, rural and urban lifestyles are associated with differences in incidence of numerous diseases, including asthma, diabetes and cancer. In order to investigate the genetic and geographical effects on gene expression, Greg Gibson and colleagues analyzed gene expression variation in blood leukocyte samples from 194 Arab and Amazigh individuals from an urban city and two rural villages in southern Morocco. They found that environmental location had a substantial effect on gene expression. However, further work is necessary to determine how these expression differences might be relevant to different health risks in urban and rural locations. The team also analyzed the genomes of the 194 individuals and found that there were a few hundred genetic variants that influenced gene expression levels in all sampled locations. The study shows that in addition to genetic factors, environmental factors also contribute to gene expression variation. Author contact: Greg Gibson (Queensland Institute of Medical Research, Brisbane, Queensland, Australia) Tel: +61 7 3365 2194; E-mail: ggibson.uq@gmail.com [3] Medicine: Platelets promote closure of vessels in newborns DOI: 10.1038/nm.2060 Platelets are crucial for the closure of a blood vessel that, if left open after birth, can lead to disease, according to a report online this week in Nature Medicine. The finding helps to advance our understanding of an important disorder which is seen in newborns. The ductus arteriosus is a fetal blood vessel that is essential during embryonic development and closes promptly after birth. If it doesn’t close, patients develop pulmonary hypertension and heart failure. How the ductus arteriosus manages to close has remained unclear, but Steffen Massberg and his colleagues show that platelets — the cells responsible for blood clotting — play an essential role in its closure in mice. The team found that platelets are recruited to the ductus arteriosus during closure, promoting the formation of a clot as this blood vessel contracts. In mice with defective platelet function, the ductus arteriosus failed to close, resulting in a condition similar to that found in the human disease: increased blood flow in the lung and excessive growth of the right ventricle of the heart. They also showed, in a clinical study in premature babies, that not having enough platelets in the blood was associated with a failure of the ductus arteriosus to close. Author contact: Steffen Massberg (Technische Universität Munich, Germany) Tel: +49 89 1218 4012; E-mail: massberg@dhm.mhn.de [4] Neuroscience: To boldly go DOI: 10.1038/nn.2453 Neurons in the frontal pole cortex area of the brain are important for encoding actions that produce successful outcomes, finds a paper online in Nature Neuroscience this week. The work reports the first direct neuronal recordings in this region, and suggests that the area, which was thought to be very complex, actually has very simple response patterns. Satoshi Tsujimoto and colleagues recorded the responses of frontal pole neurons while monkeys performed a decision making task. They found that the neurons encoded the monkey’s earlier decision, but only at the time when the monkey was receiving feedback as to whether it had made the correct response. The simple response properties of the neurons are surprising because neurons in other frontal areas typically show more complex patterns of activity. However, these responses have important implications. We need to learn to repeat the actions that have successful outcomes, but figuring out which specific action is successful can be difficult to tease out, especially if there is a lot of other intervening behaviour between when the action occurs and when the consequences of our actions are evident. This work shows that the frontal pole is responsible for providing information about earlier decisions, ensuring that the correct decision receives credit for the successful outcome. Author contact: Satoshi Tsujimoto (National Institutes of Mental Health and Kobe University, Hyogo, Japan) Tel: +81 78 803 7741; E-mail: tsujimoto@ruby.kobe-u.ac.jp [5] Geoscience: Sensitive climate DOI: 10.1038/ngeo706 Three to five million years ago, global temperatures were significantly higher than expected from atmospheric carbon dioxide levels at the time, according to a study published online this week in Nature Geoscience. The authors conclude that the higher long-term sensitivity of the Earth system should be taken into account when defining dangerous anthropogenic climate change. Daniel Lunt and colleagues combine a global climate model with a reconstruction of the Earth’s environment three to five million years ago, when temperatures were 3 to 5° C warmer than today. They use the model to separate various contributions to global temperatures, and find that atmospheric carbon dioxide concentrations caused more warming than would be expected from the estimates of climate sensitivity that are used for future climate projections. They conclude that the discrepancy arises because in the earlier period the Earth system had a long time to adjust to the environmental conditions, whereas climate models for future projections do not fully include feedbacks that involve slowly changing parts of the system, such as ice sheets or vegetation patterns. Author contact: Daniel Lunt (University of Bristol, UK) Tel: +44 117 3317483; Email: d.j.lunt@bristol.ac.uk [6] Nature: The good fight DOI: 10.1038/nature08678 Researchers identify the pheromone and sensory neuron responsible for aggressive behaviour in male fruitflies, reported in Nature this week. The discovery could enable a better understanding of the brain circuits involved in this evolutionarily conserved, innate social behaviour. Aggressive behaviour has been previously associated with pheromones in some animals, including certain insects and mice. This is the first study to determine the specific pheromone responsible and its sensory neuron in any species. Liming Wang and David Anderson demonstrate that exposure to the pheromone cVA — a male-specific volatile chemical compound — vigorously promotes male–male aggression in fruitflies. It seems to work through the same neurons that are involved in sensing smell, and it is dependent on the expression of protein receptors that recognise cVA. Although the findings reveal interesting information about the control of aggression in fruitflies, there is as yet no conclusive evidence that the same mechanisms are at work in humans. The research offers the first step to unravelling the genetics of this complex but conserved social behaviour. Author contact David Anderson (California Institute of Technology, Pasadena, CA, USA) Tel: +1 626 395 6821; E-mail: wuwei@caltech.edu ******************************************** Items from other Nature journals to be published online at the same time and with the same embargo: NATURE CELL BIOLOGY (http://www.nature.com/naturecellbiology) [7] Rab27a and Rab27b control different steps of the exosome secretion pathway DOI: 10.1038/ncb2000 [8] Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure DOI: 10.1038/ncb2002 [9] An actomyosin-based barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos DOI: 10.1038/ncb2005 NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio) [10] Reduced histone deacetylase 7 activity restores function to misfolded CFTR in cystic fibrosis DOI: 10.1038/nchembio.275 [11] Relating diffusion along the substrate tunnel and oxygen sensitivity in hydrogenase DOI: 10.1038/nchembio.276 NATURE GENETICS (http://www.nature.com/naturegenetics) [12] Skp2 is required for survival of aberrantly proliferating Rb1-deficient cells and for tumorigenesis in Rb1+/- mice DOI: 10.1038/ng.498 [13] A restricted spectrum of NRAS mutations causes Noonan syndrome DOI: 10.1038/ng.497 [14] The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes DOI: 10.1038/ng.493 NATURE GEOSCIENCE (http://www.nature.com/ngeo) [15] Towards absolute plate motions constrained by lower-mantle slab remnants DOI: 10.1038/ngeo708 [16] Plagioclase breakdown as an indicator for shock conditions of meteorites DOI: 10.1038/ngeo704 NATURE IMMUNOLOGY (http://www.nature.com/natureimmunology) [17] B cell–specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers DOI: 10.1038/ni.1829 NATURE MATERIALS (http://www.nature.com/naturematerials) [18] Three-dimensional structure and multistable optical switching of triple-twisted particle-like excitations in anisotropic fluids DOI: 10.1038/nmat2592 [19] High-performance polymer semiconducting heterostructure devices by nitrene-mediated photocrosslinking of alkyl side chains DOI: 10.1038/nmat2594 [20] A silicon-based electrical source of surface plasmon polaritons DOI: 10.1038/nmat2595 Nature MEDICINE (http://www.nature.com/naturemedicine) [21] A mitotic transcriptional switch in polycystic kidney disease DOI: 10.1038/nm.2068 [22] NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation DOI: 10.1038/nm.2069 NATURE METHODS (http://www.nature.com/nmeth) [23] Engineering a polarity sensitive biosensor for time-lapse imaging of apoptotic processes and degeneration DOI: 10.1038/nmeth.1405 [24] Floxin, a resource for genetically engineering mouse embryonic stem cells DOI: 10.1038/nmeth.1406 [25] High-throughput generation of selected reaction monitoring assays for proteins and proteomes DOI: 10.1038/nmeth.1408 NATURE NANOTECHNOLOGY (http://www.nature.com/nnano) [26] Atomic force microscopy as a tool for atom manipulation DOI: 10.1038/nnano.2009.347 [27] Highly conductive self-assembled nanoribbons of coordination polymers DOI: 10.1038/nnano.2009.354 [28] Single donor ionization energies in a nanoscale CMOS channel DOI: 10.1038/nnano.2009.373 Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience) [29] Dissecting differential gene expression within the circadian neuronal circuit of Drosophila DOI: 10.1038/nn.2451 [30] The corticothalamocortical circuit drives higher-order cortex in the mouse DOI: 10.1038/nn.2449 [31] Spike integration and cellular memory in a rhythmic network from Na+/K+ pump current dynamics DOI: 10.1038/nn.2444 [32] Collective dynamics in human and monkey sensorimotor cortex: Predicting Single Neuron Spikes DOI: 10.1038/nn.2455 [33] The slow (<1 Hz) rhythm of NREM sleep: a dialogue between three cardinal oscillators DOI: 10.1038/nn.2445 Nature PHYSICS (http://www.nature.com/naturephysics) [34] Interference-induced terahertz transparency in a semiconductor magneto-plasma DOI: 10.1038/nphys1480 [35] Back-action-evading measurements of nanomechanical motion DOI: 10.1038/nphys1479 Nature STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol) [36] A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4–DDB1 ubiquitin ligase machinery DOI: 10.1038/nsmb.1719 [37] Role of the RNA polymerase trigger loop in catalysis and pausing DOI: 10.1038/nsmb.1732 [38] A sequence similar to tRNA3Lys gene is embedded in HIV-1 U3–R and promotes minus-strand transfer DOI: 10.1038/nsmb.1687 [39] Catalysis of the microtubule on-rate is the major parameter regulating the depolymerase activity of MCAK DOI: 10.1038/nsmb.1728 [40] Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates DOI: 10.1038/nsmb.1705 [41] ATP-dependent human RISC assembly pathways DOI: 10.1038/nsmb.1733 ****************************************** GEOGRAPHICAL LISTING OF AUTHORS The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details. AUSTRALIA Brisbane: 2 Perth: 15 Queensland: 2 CANADA: Edmonton: 40 Montreal: 10, 35 CZECH REPUBLIC Praha: 13 FRANCE Grenoble: 11, 28 Marseille: 11 Paris: 7, 21 Toulouse: 11 Tours: 18 GERMANY Berlin: 13, 25 Dortmund: 13 Dusseldorf: 13 Erlangen: 13 Frankfurt: 13 Freiburg: 13 Hamburg: 13 Heidelberg: 3 Leipzig: 25 Magdeburg: 13 Munich: 3 Neuherberg: 3 ITALY Bologna: 13 Chieti: 13 Modena: 27 Rome: 4, 13 Turin: 13 JAPAN Fukuoka: 12, 16 Hyogo: 16 Ibaraki: 26 Kobe: 4 Kyoto: 17 Miyagi: 7 Mito: 16 Osaka: 26, 29 Saitama: 41 Sendai: 12 Tokyo: 41 Tsukuba: 16 Yokohama: 17 MOROCCO Agadir: 2 NETHERLANDS Amsterdam: 20 Enschede: 20 Rijswijk: 15 Utrecht: 15 NORWAY Oslo: 15 Trondheim: 15 PORTUGAL Lisbon: 7 Oeiras: 7 SINGAPORE Singapore: 19 SPAIN Madrid: 26, 27 SOUTH AFRICA Johannesburg: 15 SWITZERLAND Bern: 29 Geneva: 36 Zurich: 25 UNITED KINGDOM Birmingham: 3 Bristol: 1, 5 Cardiff: 33 Cambridge: 1, 5, 9, 14, 19, 24 Leeds: 5 Liverpool: 22 London: 7, 13 Manchester: 1 Newcastle: 5 Oxford: 22 UNITED STATES OF AMERICA Alabama Birmingham: 10 California Berkeley: 8, 13 La Jolla: 10, 12 Los Angeles: 23 Pasadena: 6, 35 San Francisco: 24 Stanford: 24 Colorado Boulder: 18 Illinois Abbott Park: 30 Evanston: 29 Chicago: 24, 30 Maryland Baltimore: 8 Bethesda: 4 College Park: 35 Rockville: 13 Massachusetts Boston: 3, 13, 32 Cambridge: 7, 12 Charlestown: 7 Waltham: 29, 31 Minnesota Rochester: 38 New Mexico Los Alamos: 34 New York Bronx: 12 Ithaca: 35 New York: 5, 12, 13, 40 North Carolina Cary: 2 Chapel Hill: 10 Durham: 2 Raleigh: 2 Oregon Portland: 10 Pennsylvania Pittsburgh: 10 Rhode Island Providence: 32 Texas College Station: 34 Dallas: 10, 21, 41 Houston: 34 Virginia Reston: 5 Washington Seattle: 25, 36, 37, 39 Wisconsin Madison: 37 PRESS CONTACTS… For media inquiries relating to embargo policy for all the Nature Research Journals: Rachel Twinn (Nature London) Tel: +44 20 7843 4658; E-mail: r.twinn@nature.com Neda Afsarmanesh (Nature New York) Tel: +1 212 726 9231; E-mail: n.afsarmanesh@us.nature.com Ruth Francis (Head of Press, Nature, London) Tel: +44 20 7843 4562; E-mail: r.francis@nature.com For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually: Nature Cell Biology (London) Sowmya Swaminathan Tel: +44 20 7843 4656; E-mail: cellbio@nature.com Nature Chemical Biology (Boston) Andrea Garvey Tel: +1 617 475 9241, E-mail: chembio@us.nature.com Nature Genetics (New York) Myles Axton Tel: +1 212 726 9324; E-mail: natgen@us.nature.com Nature Geoscience (London) Heike Langenberg Tel: +44 20 7843 4042; E-mail: h.langenberg@nature.com Nature Immunology (New York) Laurie Dempsey Tel: +1 212 726 9372; E-mail: immunology@us.nature.com Nature Materials (London) Vincent Dusastre Tel: +44 20 7843 4531; E-mail: materials@nature.com Nature Medicine (New York) Juan Carlos Lopez Tel: +1 212 726 9325; E-mail: medicine@us.nature.com Nature Methods (New York) Hugh Ash Tel: +1 212 726 9627; E-mail: methods@us.nature.com Nature Nanotechnology (London) Peter Rodgers Tel: +44 20 7014 4019; Email: p.rodgers@nature.com Nature Neuroscience (New York) Kalyani Narasimhan Tel: +1 212 726 9319; E-mail: neurosci@us.nature.com Nature Physics (London) Alison Wright Tel: +44 20 7843 4555; E-mail: a.wright@nature.com Nature Structural & Molecular Biology (New York) Michelle Montoya Tel: +1 212 726 9326; E-mail: nsmb@us.nature.com About Nature Publishing Group (NPG): Nature Publishing Group (NPG) is a publisher of high impact scientific and medical information in print and online. 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