| | | Volume 508 Number 7495 | | | | nature | | The science that matters. Every week. | | | | | | | | | | |  | |
CRISPR/Cas Plasmids and Protocols
Addgene's non-profit resource gives you access to nearly 300 published CRISPR plasmids created by over 20 of the world's leading research labs. This is accompanied by protocols, expert tips, and more. Easily knock-down/activate gene expression, edit genomic DNA, or conduct genome-wide screens. | | | | | | | | Jump to the content that matters to you | | | | | | | | | | | | | | | Thermal fatigue as the origin of regolith on small asteroids | | Small asteroids are covered by a dust- or gravel-like layer called the regolith, thought until recently to consist of debris from micrometeorite impacts. Recent calculations showing that such impacts would be of sufficient force to throw debris away from, rather down to the asteroid, put paid to that idea. Marco Delbo et al. now show that thermal fatigue is a more likely explanation. Experiments on centimetre-scale samples of the Murchison (CM2) and Sahara 97210 meteorites indicate that such rocks would break up more rapidly through thermal fragmentation induced by diurnal temperature variations than as a result of micrometeoroid impacts. | | | | | | | | | | | | | Dynamics of continental accretion | | Subduction zones, where one plate dives under another, become congested when they try to accommodate buoyant, exotic crust. Louis Moresi et al. describe new numerical models of continental accretion that follow the entire process from the initial collision state, through a period of plate margin instability, to the re-establishment of a stable convergent margin. The models illustrate how significant curvature of the orogenic system develops, as well as the mechanism for tectonic escape of the back arc region. | | | | | | | | | | | | | Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity | | Nicotinamide N-methyltransferase (NNMT), an enzyme that methylates nicotinamide (vitamin B3) using S-adenosylmethionine (SAM) as a methyl donor, is present at high levels in adipose tissue and is increased in some cancers, neurodegenerative diseases, obesity and diabetes. This study shows that NNMT is elevated in adipose tissue and liver in obese and diabetic mice. of NNMT knock-down in adipose tissue protects against diet-induced obesity and its metabolic consequences such as glucose intolerance and fatty liver. These findings identify NNMT as a potential target for treating obesity and type-2 diabetes. | | | | | | | | | | | | | | | | | | | | In this week's podcast: a nasty parasite that eats gut cells alive, a grand ecological experiment floods the Colorado River delta, and the strain of being an IPCC contributor and how to make it better. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Look back in wonder ▶ | | | | The launch of the first Sentinel satellite heralds an era in which detailed data on everything from earthquakes to urbanization will be freely available to anyone interested in Earth’s future. | | | | | | | | | | | | Political science ▶ | | | | Russia deserves to be sanctioned, but halting scientific collaboration is not the way to do it. | | | | | | | | | | | | Copper rewired ▶ | | | | Two Nature papers signal new roles for this ancient metal in catalysis and cancer therapy. | | | | | | | | | | | | | | | | | | | | | | | | Seven days: 4–10 April 2014 ▶ | | | | The week in science: Chile hit by magnitude-8.2 quake; US unveils most accurate atomic clock; and European Parliament votes for clinical-trial transparency. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Climate policy: Streamline IPCC reports ▶ | | | | As the Intergovernmental Panel on Climate Change asks how its assessment process should evolve, Dave Griggs argues for decadal updates and eased workloads. | | | | | | | | | | | | | | | | | | | | | | | | Ecology: Wilson in Africa ▶ | | | | Stuart Pimm enjoys a fellow naturalist's first visit to sub-Saharan Africa, and the global lessons drawn from it. | | | | | | | | | | | | | | | | | | | | | | | | Drugs: Gut response ▶ | | | | Maryn McKenna finds much to digest in a warning about the demise of our bodily bacteria. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Homologue engagement controls meiotic DNA break number and distribution ▶ | | | | Drew Thacker, Neeman Mohibullah, Xuan Zhu et al. | | | | DNA double-stranded breaks (DSBs) are shown to form in greater numbers in yeast cells lacking ZMM proteins, which are traditionally regarded as acting strictly downstream of DSB formation; these findings shed light on how cells balance the beneficial and deleterious outcomes of DSB formation. | | | | | | | | | | | | | | | | | | | | Copper is required for oncogenic BRAF signalling and tumorigenesis ▶ | | | | Donita C. Brady, Matthew S. Crowe, Michelle L. Turski et al. | | | | Tumorigenesis driven by the oncogene BRAFV600E is shown both to depend on the BRAF substrates MEK1/2 associating with copper, and to be sensitive to copper-chelating drugs, suggesting merit in testing such drugs for the treatment of BRAF mutation-positive cancers. | | | | | | | | | | | | Rapid and tunable post-translational coupling of genetic circuits ▶ | | | | Arthur Prindle, Jangir Selimkhanov, Howard Li et al. | | | | Protease competition is used to produce rapid and tunable coupling of genetic circuits, enabling a coupled clock network that can encode independent environmental cues into a single time series output, a form of frequency multiplexing in a genetic circuit context. | | | | | | | | | | | | Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion ▶ | | | | Katherine S. Ralston, Michael D. Solga, Nicole M. Mackey-Lawrence et al. | | | | Entamoeba histolytica, the causative agent of fatal diarrhoeal disease in children in the developing world, is shown here to kill human cells by biting off and ingesting pieces of cells, in a process reminiscent of the trogocytosis seen between immune cells; ingestion of bites is required for killing and this mechanism is used both in tissue culture and during invasion of intestinal explants. | | | | | | | | | | | | Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors ▶ | | | | Srdjan Maksimovic, Masashi Nakatani, Yoshichika Baba et al. | | | | The cellular basis of touch has long been debated, in particular the relationship between sensory neurons and non-neuronal cells; a mouse study uses optogenetics to identify their distinct and collaborative roles, with skin-derived Merkel cells both transducing touch and actively tuning responses of touch-sensitive neurons. | | | | | | | | | | | | Piezo2 is required for Merkel-cell mechanotransduction ▶ | | | | Seung-Hyun Woo, Sanjeev Ranade, Andy D. Weyer et al. | | | | A mouse study shows that non-neuronal epidermal Merkel cells aid fine-touch perception in the skin through their expression of the Piezo2 mechanosensitive cation channel which then actively tunes the response to touch in adjacent somatosensory neurons. | | | | | | | | | | | | | | | | Transcriptional landscape of the prenatal human brain ▶ | | | | Jeremy A. Miller, Song-Lin Ding, Susan M. Sunkin et al. | | | | A spatially resolved transcriptional atlas of the mid-gestational developing human brain has been created using laser-capture microdissection and microarray technology, providing a comprehensive reference resource which also enables new hypotheses about the nature of human brain evolution and the origins of neurodevelopmental disorders. | | | | | | | | | | | | A mesoscale connectome of the mouse brain ▶ | | | | Seung Wook Oh, Julie A. Harris, Lydia Ng et al. | | | | In mouse, an axonal connectivity map showing the wiring patterns across the entire brain has been created using an EGFP-expressing adeno-associated virus tracing technique, providing the first such whole-brain map for a vertebrate species. | | | | | | | | | | | | MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool ▶ | | | | Helge Gad, Tobias Koolmeister, Ann-Sofie Jemth et al. | | | | In order to find a general treatment for cancer, this study found that MTH1 activity is essential for the survival of transformed cells, and isolated two small-molecule inhibitors of MTH1, TH287 and TH588 in the presence of these inhibitors, damaged nucleotides are incorporated into DNA only in cancer cells, causing cytotoxicity and eliciting a beneficial response in patient-derived mouse xenograft models. | | | | | | | | | | | | Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy ▶ | | | | Kilian V. M. Huber, Eidarus Salah, Branka Radic et al. | | | | A chemoproteomic screen is used here to identify MTH1 as the target of SCH51344, an experimental RAS-dependent cancer drug; a further search for inhibitors revealed (S)-crizotinib as a potent MTH1 antagonist, which suppresses tumour growth in animal models of colon cancer, and could be part of a new class of anticancer drugs. | | | | | | | | | | | | Structure of the LH1RC complex from Thermochromatium tepidum at 3.0 ▶ | | | | Satomi Niwa, Long-Jiang Yu, Kazuki Takeda et al. | | | | The near-atomic-level structure of a complete bacterial light-harvesting antennareaction centre (LH1RC) complex is described here; the structure reveals how energy is transferred from the LH1 to the RC in a highly efficient way and suggests how ubiquinone might cross a closed LH1 barrier. | | | | | | | | | | | | Detection and replication of epistasis influencing transcription in humans ▶ | | | | Gibran Hemani, Konstantin Shakhbazov, Harm-Jan Westra et al. | | | | Epistasis has rarely been shown among natural polymorphisms in human traits; this research using advanced computation and gene expression data reveals many instances of epistasis between common single nucleotide polymorphisms in humans, with epistasis and the direction of its effect replicating in independent cohorts. | | | | | | | | | | | | A synchronized global sweep of the internal genes of modern avian influenza virus ▶ | | | | Michael Worobey, Guan-Zhu Han, Andrew Rambaut | | | | A local molecular clock approach shows that most genetic diversity in avian influenza virus (AIV) arose in a recent global sweep and that avian strains are the sister group to equine H7N7; most of the 1918 pandemic viruss genes originated from the resulting western hemispheric AIV lineage. | | | | | | | | | | | | Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity ▶ | | | | Daniel Kraus, Qin Yang, Dong Kong et al. | | | | Nicotinamide N-methyltransferase (NNMT) expression is increased in white adipose tissue and liver of obese and diabetic mice, Nnmt knockdown protects against diet-induced obesity by altering the availability of adipose S-adenosylmethionine and NAD+, rendering Nnmt a novel target for treating obesity and type 2 diabetes. | | | | | | | | | | | | | | | | Direct measurement of local oxygen concentration in the bone marrow of live animals ▶ | | | | Joel A. Spencer, Francesca Ferraro, Emmanuel Roussakis et al. | | | | Here, using two-photon phosphorescence lifetime microscopy, the local oxygen tension in the bone marrow of live mice is found to be quite low, with spatiotemporal variations depending on the blood vessel type, distance to the endosteum, and changes in cellularity after stress. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | nature.com webcasts
Macmillan Science Communication presents a custom webcast: Determining the natural variation of lipids Wednesday April 16th at 1pm SGT/AWST/CST / 2pm JST / 3pm AEST | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Copper is required for oncogenic BRAF signalling and tumorigenesis ▶ | | | | Donita C. Brady, Matthew S. Crowe, Michelle L. Turski et al. | | | | Tumorigenesis driven by the oncogene BRAFV600E is shown both to depend on the BRAF substrates MEK1/2 associating with copper, and to be sensitive to copper-chelating drugs, suggesting merit in testing such drugs for the treatment of BRAF mutation-positive cancers. | | | | | | | | | | | | | | | | MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool ▶ | | | | Helge Gad, Tobias Koolmeister, Ann-Sofie Jemth et al. | | | | In order to find a general treatment for cancer, this study found that MTH1 activity is essential for the survival of transformed cells, and isolated two small-molecule inhibitors of MTH1, TH287 and TH588 in the presence of these inhibitors, damaged nucleotides are incorporated into DNA only in cancer cells, causing cytotoxicity and eliciting a beneficial response in patient-derived mouse xenograft models. | | | | | | | | | | | | Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy ▶ | | | | Kilian V. M. Huber, Eidarus Salah, Branka Radic et al. | | | | A chemoproteomic screen is used here to identify MTH1 as the target of SCH51344, an experimental RAS-dependent cancer drug; a further search for inhibitors revealed (S)-crizotinib as a potent MTH1 antagonist, which suppresses tumour growth in animal models of colon cancer, and could be part of a new class of anticancer drugs. | | | | | | | | | | | | A synchronized global sweep of the internal genes of modern avian influenza virus ▶ | | | | Michael Worobey, Guan-Zhu Han, Andrew Rambaut | | | | A local molecular clock approach shows that most genetic diversity in avian influenza virus (AIV) arose in a recent global sweep and that avian strains are the sister group to equine H7N7; most of the 1918 pandemic viruss genes originated from the resulting western hemispheric AIV lineage. | | | | | | | | | | | | Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity ▶ | | | | Daniel Kraus, Qin Yang, Dong Kong et al. | | | | Nicotinamide N-methyltransferase (NNMT) expression is increased in white adipose tissue and liver of obese and diabetic mice, Nnmt knockdown protects against diet-induced obesity by altering the availability of adipose S-adenosylmethionine and NAD+, rendering Nnmt a novel target for treating obesity and type 2 diabetes. | | | | | | | | | | | | | | | | Direct measurement of local oxygen concentration in the bone marrow of live animals ▶ | | | | Joel A. Spencer, Francesca Ferraro, Emmanuel Roussakis et al. | | | | Here, using two-photon phosphorescence lifetime microscopy, the local oxygen tension in the bone marrow of live mice is found to be quite low, with spatiotemporal variations depending on the blood vessel type, distance to the endosteum, and changes in cellularity after stress. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Enantioselective construction of remote quaternary stereocentres ▶ | | | | Tian-Sheng Mei, Harshkumar H. Patel, Matthew S. Sigman | | | | A catalytic and enantioselective intermolecular Heck-type reaction of trisubstituted-alkenyl alcohols with aryl boronic acids provides direct access to quaternary stereocentres remote from a carbonyl group. | | | | | | | | | | | | | | | | | | | | | | | | A quantum gate between a flying optical photon and a single trapped atom ▶ | | | | Andreas Reiserer, Norbert Kalb, Gerhard Rempe et al. | | | | Quantum gates in which stationary quantum bits are combined with flying quantum bits, that is, photons will be essential in quantum networks; such a gate, between a laser-trapped atomic quantum bit and a single photon, is now reported. | | | | | | | | | | | | Nanophotonic quantum phase switch with a single atom ▶ | | | | T. G. Tiecke, J. D. Thompson, N. P. de Leon et al. | | | | Strongly coupling a photon to a single atom trapped in the near field of a nanoscale photonic crystal cavity results in a light switch which can be turned on and off with a single photon. | | | | | | | | | | | | Dynamics of continental accretion ▶ | | | | L. Moresi, P. G. Betts, M. S. Miller et al. | | | | Three-dimensional dynamic computer models show how accretionary tectonic margins evolve from the initial plate-collision state, through a period of plate margin instability, and then re-establish a stable convergent margin; the models illustrate how significant curvature of the orogenic system develops, as well as the mechanism for tectonic escape of the back-arc region. | | | | | | | | | | | | Direct measurement of local oxygen concentration in the bone marrow of live animals ▶ | | | | Joel A. Spencer, Francesca Ferraro, Emmanuel Roussakis et al. | | | | Here, using two-photon phosphorescence lifetime microscopy, the local oxygen tension in the bone marrow of live mice is found to be quite low, with spatiotemporal variations depending on the blood vessel type, distance to the endosteum, and changes in cellularity after stress. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Plate tectonics, damage and inheritance ▶ | | | | David Bercovici, Yanick Ricard | | | | Lithospheric damage, combined with transient mantle flow and migrating proto-subduction, is proposed to explain the apparent emergence of plate tectonics three billion years ago; modelling confirms that tectonic plate boundaries and fully formed tectonic plates can arise under conditions characteristic of Earth but not of Venus. | | | | | | | | | | | | | | | | | | | | Dynamics of continental accretion ▶ | | | | L. Moresi, P. G. Betts, M. S. Miller et al. | | | | Three-dimensional dynamic computer models show how accretionary tectonic margins evolve from the initial plate-collision state, through a period of plate margin instability, and then re-establish a stable convergent margin; the models illustrate how significant curvature of the orogenic system develops, as well as the mechanism for tectonic escape of the back-arc region. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |  | | | Nature Genetics, Chinese Academy of Medical Sciences and Anhui Medical University are pleased to present:
Genome Variation in Precision Medicine May 15-17, 2014 Radegast Lake View Hotel Beijing Click here for more information or to register for this conference today! | | | | | | | | | | | | | | | | | | | | | | | | A guide for the innovator ▶ | | | | Researchers with product-worthy ideas can follow various, often under-appreciated, paths towards commercialization, says Peter Fiske. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Grant obstacles ▶ | | | | Australian researchers decry oppressive grant-application process. | | | | | | | | | | | | Careers related news & comment | | | | | | | | | | | | | | | | | | | | | | 
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