| | | Volume 509 Number 7502 | | | | 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 | | | | | | | | | | | | Specials - Outlook: Cancer | | | | | | This overview of the current battles against cancer focuses on some of the hottest areas in current research including personalized treatments, nanodevice drug delivery, and the ever-present threat from environmental carcinogens. ▼ more | | | | | | | | | | Specials - Technology Feature: Proteomics: An atlas of expression | | | | | | The first draft of the complete human proteome has been more than a decade in the making. In the process, the effort has also delivered lessons about technology and biology. ▼ more | | | | | | | | | | Specials - Promotional Feature: 2014 Research Perspectives of the Max Planck Society | | | | | | From nanorobots to exoplanets, the Max Planck Society's 2014 Research Perspectives identify six particularly promising fields which are being prioritized for their potential to make an impact in future. ▼ more | | | | | | | | | | | | | Direct high-precision measurement of the magnetic moment of the proton | | Although large synchrotron experiments capture the headlines, measurements of fundamental constants or atomic properties can still make valuable contributions to the search for new physical laws - if the precision is high enough. An good example is the work of Andreas Mooser et al., a direct measurement of the magnetic moment of the proton with unprecedented precision. In combination with a measurement of the antiproton magnetic moment, this should pave the way for a rigorous test of matter-antimatter symmetry. | | | | | | | | | | | | | Storm-induced sea-ice breakup and the implications for ice extent | | Sea ice is retreating in the Arctic. In the Antarctic it is retreating in places but expanding elsewhere. These changes have not yet been fully explained. New observations from Antarctica show that large waves generated by ocean storms have a much greater impact on the breakup and retreat of sea ice than previously thought. It was assumed that the influence of waves decayed exponentially from the ice edge, but it is now clear that ocean waves can destabilize ice shelves hundreds of kilometres from the ice edge. | | | | | | | | | | | | | A single female-specific piRNA is the primary determiner of sex in the silkworm | | Susumu Katsuma and colleagues have answered a question that has perplexed insect geneticists for more than eight decades — how does the W chromosome determine femaleness in the silkworm Bombyx mori and many other Lepidoptera. The authors show that the feminizing factor is a single W chromosome-derived PIWI-interacting RNA (piRNA). The piRNA silences the product of a gene called Masc, located on the Z chromosome. The silencing is important for the production of female-specific isoforms of the doublesex gene. This is the first experimental evidence showing a piRNA-mediated sex determination process. | | | | | | | | | | | | | | | In this week's podcast: cooking that kills, fears of a post-antibiotic world, and how measuring a proton could help scientists find out where all the antimatter has gone. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | A three-step plan for antibiotics ▶ | | | | If the threat of antibiotic resistance is to be managed, existing drugs must be marshalled more effectively and new medicines must get to market fast. | | | | | | | | | | | | Clean break ▶ | | | | Improved biomass stoves are not popular, people everywhere deserve modern cooking methods. | | | | | | | | | | | | | | | | | | | | | | | | | | | | Seven days: 23–29 May 2014 ▶ | | | | The week in science: Germany announces research windfall; new crater is spotted on Mars; and Pfizer admits defeat in its pursuit of AstraZeneca. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Global health: Deadly dinners ▶ | | | | Polluting biomass stoves, used by one-third of the global population, take a terrible toll. But efforts to clean them up are failing. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Q&A: The space crusader ▶ | | | | US astronomer Neil deGrasse Tyson, director of New York's Hayden Planetarium, currently hosts the television series Cosmos — an update of Carl Sagan's 1980 show — broadcast in 181 countries and 45 languages. As it winds down, Tyson talks about the rich mix of science and pop culture, the 'neurosynaptic snapshot' of public responses to his tweets, and his momentous meeting with Sagan. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Accurate design of co-assembling multi-component protein nanomaterials ▶ | | | | Neil P. King, Jacob B. Bale, William Sheffler et al. | | | | A computational method is reported that can be used to design protein nanomaterials in which two distinct subunits co-assemble into a specific architecture; five 24-subunit cage-like protein nanomaterials are designed, and experiments show that their structures are in close agreement with the computational design models. | | | | | | | | | | | | | | | | Cntnap4 differentially contributes to GABAergic and dopaminergic synaptic transmission ▶ | | | | T. Karayannis, E. Au, J. C. Patel et al. | | | | The molecular relationship between synaptic dysfunction and psychiatric disorders was investigated using a mouse model system; presynaptically localized Cntnap4 is required for the output of two disease-relevant neuronal subpopulations (cortical parvalbumin-positive GABAergic cells and midbrain dopaminergic neurons) and Cntnap4 mutants show behavioural abnormalities which can be pharmacologically reversed. | | | | | | | | | | | | | | | | | | | | | | | | The sonic hedgehog factor GLI1 imparts drug resistance through inducible glucuronidation ▶ | | | | Hiba Ahmad Zahreddine, Biljana Culjkovic-Kraljacic, Sarit Assouline et al. | | | | A new mechanism by which acute myeloid leukaemia patients become resistant to Ara-C and a newer treatment, ribavirin, is uncovered; these drugs can be glucuronidated and thereby inactivated by members of the UDP glucuronosyltransferase family of enzymes activated through GLI1 signalling. | | | | | | | | | | | | | | | | Genomic divergence in a ring species complex ▶ | | | | Miguel Alcaide, Elizabeth S. C. Scordato, Trevor D. Price et al. | | | | Two species may be fully reproductively isolated at the point they meet, but be connected by continuous gene flow by a longer route around the back of a geographical barrier; such a ring species complex exists for the greenish warbler, and genomics shows that there have been several historical breaks in gene flow along the continuum, as well as some introgression between the end forms. | | | | | | | | | | | | RLIM is dispensable for X-chromosome inactivation in the mouse embryonic epiblast ▶ | | | | JongDae Shin, Mary C. Wallingford, Judith Gallant et al. | | | | The ubiquitin ligase RLIM is known to activate the long non-coding RNA Xist, which is crucial for X-chromosome inactivation in female mice; however, unlike imprinted X-chromosome inactivation that requires RLIM for Xist expression, evidence is now provided that during random X-chromosome inactivation Xist expression is regulated by an RLIM-independent pathway in vivo. | | | | | | | | | | | | | | | | Receptor binding by H10 influenza viruses ▶ | | | | Sebastien G. Vachieri, Xiaoli Xiong, Patrick J. Collins et al. | | | | The structure and receptor-binding characteristics are presented of the haemagglutinin (HA) from an avian H10N2 virus that closely resembles an isolate from recent human fatalities; although avian H10 has a marked preference for the avian receptor, it is already able to bind to the human receptor, and its structure in complex with the human receptor shows similarities to HA from pandemic H1 and H7 viruses. | | | | | | Gene therapy: Repair and replace ▶ | | | | Alain Fischer | | | | One approach to treating inherited diseases is repairing the defective genes, but this has proved challenging in stem cells. An optimized protocol has now been developed that allows gene repair in blood-cell precursors. | | | | | | Immunology: When lymphocytes run out of steam ▶ | | | | André Veillette & Dominique Davidson | | | | The finding that absence of the enzyme CTPS1 underlies a form of human immunodeficiency highlights the role of metabolism in immune responses and suggests avenues for treating diseases such as leukaemia. | | | | | | | | | | | | | | | | A draft map of the human proteome ▶ | | | | Min-Sik Kim, Sneha M. Pinto, Derese Getnet et al. | | | | A draft map of the human proteome is presented here, accounting for over 80% of the annotated protein-coding genes in humans; some novel protein-coding regions, including translated pseudogenes, non-coding RNAs and upstream open reading frames, are identified. | | | | | | | | | | | | Mass-spectrometry-based draft of the human proteome ▶ | | | | Mathias Wilhelm, Judith Schlegl, Hannes Hahne et al. | | | | A mass-spectrometry-based draft of the human proteome and a public database for analysis of proteome data are presented; assembled information is used to estimate the size of the protein-coding genome, to identify organ-specific proteins, proteins predicting drug resistance or sensitivity, and many translated long intergenic non-coding RNAs, and to reveal conserved control of protein abundance. | | | | | | | | | | | | | | | | A Palaeozoic shark with osteichthyan-like branchial arches ▶ | | | | Alan Pradel, John G. Maisey, Paul Tafforeau et al. | | | | A description of the gill skeleton of a very early fossil shark-like fish shows that it bears more resemblance to gill skeletons from bony fishes rather than to those from modern cartilaginous fishes, suggesting that modern sharks are not anatomically primitive, as previously thought. | | | | | | | | | | | | Bacterial phylogeny structures soil resistomes across habitats ▶ | | | | Kevin J. Forsberg, Sanket Patel, Molly K. Gibson et al. | | | | Functional metagenomic selections for resistance to 18 antibiotics in 18 different soils reveal that bacterial community composition is the primary determinant of soil antibiotic resistance gene content. | | | | | | | | | | | | 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. | | | | | | | | | | | | Scalable control of mounting and attack by Esr1+ neurons in the ventromedial hypothalamus ▶ | | | | Hyosang Lee, Dong-Wook Kim, Ryan Remedios et al. | | | | Activation of Esr1+ neurons of the mouse ventromedial hypothalamus initiates graded social behavioural responses–weak activation triggers close investigation (sniffing) during a social encounter that often leads, with continued stimulation, to mounting behaviours by males towards either gender; mounting behaviour transitions to aggressive attacks with greater stimulation intensity. | | | | | | | | | | | | A single female-specific piRNA is the primary determiner of sex in the silkworm ▶ | | | | Takashi Kiuchi, Hikaru Koga, Munetaka Kawamoto et al. | | | | It is known that in the silkworm (Bombyx mori), males have two Z sex chromosomes whereas females have Z and W and the W chromosome has a dominant role in female determination; here a single female-specific W-chromosome-derived PIWI-interacting RNA is shown to be the feminizing factor in B. mori. | | | | | | | | | | | | | | | | Dichloroacetate prevents restenosis in preclinical animal models of vessel injury ▶ | | | | Tobias Deuse, Xiaoqin Hua, Dong Wang et al. | | | | During development of myointimal hyperplasia in human arteries, smooth muscle cells have hyperpolarized mitochondrial membrane potential (ΔΨm), high proliferation and apoptosis resistance; PDK2 is a key regulatory protein whose activation is necessary for myointima formation, and its blockade with dichloroacetate prevents Δψm hyperpolarization, facilitates apoptosis and reduces myointima formation in injured arteries, without preventing vessel re-endothelialization, possibly representing a novel strategy to prevent proliferative vascular diseases. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |  | | | Nature Partner Journals is a new series of online open access journals published in collaboration with world-renowned international partners. Each partnership in the portfolio brings together strong editorial leadership with world-class publication systems to deliver high-quality, peer-reviewed original research. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Cntnap4 differentially contributes to GABAergic and dopaminergic synaptic transmission ▶ | | | | T. Karayannis, E. Au, J. C. Patel et al. | | | | The molecular relationship between synaptic dysfunction and psychiatric disorders was investigated using a mouse model system; presynaptically localized Cntnap4 is required for the output of two disease-relevant neuronal subpopulations (cortical parvalbumin-positive GABAergic cells and midbrain dopaminergic neurons) and Cntnap4 mutants show behavioural abnormalities which can be pharmacologically reversed. | | | | | | | | | | | | The sonic hedgehog factor GLI1 imparts drug resistance through inducible glucuronidation ▶ | | | | Hiba Ahmad Zahreddine, Biljana Culjkovic-Kraljacic, Sarit Assouline et al. | | | | A new mechanism by which acute myeloid leukaemia patients become resistant to Ara-C and a newer treatment, ribavirin, is uncovered; these drugs can be glucuronidated and thereby inactivated by members of the UDP glucuronosyltransferase family of enzymes activated through GLI1 signalling. | | | | | | | | | | | | | | | | Receptor binding by H10 influenza viruses ▶ | | | | Sebastien G. Vachieri, Xiaoli Xiong, Patrick J. Collins et al. | | | | The structure and receptor-binding characteristics are presented of the haemagglutinin (HA) from an avian H10N2 virus that closely resembles an isolate from recent human fatalities; although avian H10 has a marked preference for the avian receptor, it is already able to bind to the human receptor, and its structure in complex with the human receptor shows similarities to HA from pandemic H1 and H7 viruses. | | | | | | | | | | | | | | | | Dichloroacetate prevents restenosis in preclinical animal models of vessel injury ▶ | | | | Tobias Deuse, Xiaoqin Hua, Dong Wang et al. | | | | During development of myointimal hyperplasia in human arteries, smooth muscle cells have hyperpolarized mitochondrial membrane potential (ΔΨm), high proliferation and apoptosis resistance; PDK2 is a key regulatory protein whose activation is necessary for myointima formation, and its blockade with dichloroacetate prevents Δψm hyperpolarization, facilitates apoptosis and reduces myointima formation in injured arteries, without preventing vessel re-endothelialization, possibly representing a novel strategy to prevent proliferative vascular diseases. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Accurate design of co-assembling multi-component protein nanomaterials ▶ | | | | Neil P. King, Jacob B. Bale, William Sheffler et al. | | | | A computational method is reported that can be used to design protein nanomaterials in which two distinct subunits co-assemble into a specific architecture; five 24-subunit cage-like protein nanomaterials are designed, and experiments show that their structures are in close agreement with the computational design models. | | | | | | | | | | | | | | | | | | | | Three regimes of extrasolar planet radius inferred from host star metallicities ▶ | | | | Lars A. Buchhave, Martin Bizzarro, David W. Latham et al. | | | | Analysis of the metallicities of more than 400 stars hosting 600 candidate extrasolar planets shows that the planets can be categorized by size into three populations — terrestrial-like planets, gas dwarf planets with rocky cores and hydrogen–helium envelopes, and ice or gas giant planets — on the basis of host star metallicity. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Climate science: How Antarctic ice retreats ▶ | | | | Trevor Williams | | | | New records of iceberg-rafted debris from the Scotia Sea reveal episodic retreat of the Antarctic Ice Sheet since the peak of the last glacial period, in step with changes in climate and global sea level. | | | | | | | | | | | | | | | | | | | | Storm-induced sea-ice breakup and the implications for ice extent ▶ | | | | A. L. Kohout, M. J. M. Williams, S. M. Dean et al. | | | | Concurrent observations at multiple locations indicate that storm-generated ocean waves propagating through Antarctic sea ice can transport enough energy to break first-year sea ice hundreds of kilometres from the ice edge, which is much farther than would be predicted by the commonly assumed exponential wave decay. | | | | | | | | | | | | Bacterial phylogeny structures soil resistomes across habitats ▶ | | | | Kevin J. Forsberg, Sanket Patel, Molly K. Gibson et al. | | | | Functional metagenomic selections for resistance to 18 antibiotics in 18 different soils reveal that bacterial community composition is the primary determinant of soil antibiotic resistance gene content. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Statistics: Attacking an epidemic ▶ | | | | Despite a huge amount of funding and research, regional and individual differences in cancer trends make it a hard disease to wipe out. By Mike May. | | | | | | | | | | | | Therapy: This time it's personal ▶ | | | | Tailoring cancer treatment to individual and evolving tumours is the way of the future, but scientists are still hashing out the details. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Perspective: Learning to share ▶ | | | | Genomics can provide powerful tools against cancer — but only once clinical information can be made broadly available, says John Quackenbush. | | | | | | | | | | | | Biology: Three known unknowns ▶ | | | | Even as cancer therapies improve, basic questions about drug resistance, tumour spread and the role of normal tissue remain unanswered. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Proteomics: An atlas of expression ▶ | | | | The first draft of the complete human proteome has been more than a decade in the making. In the process, the effort has also delivered lessons about technology and biology. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | JSH Guidelines for the Management of Hypertension 2014 -just published in Hypertension Research
Hypertension Research is proud to feature The Japanese Society of Hypertension Guidelines for the Management of Hypertension 2014 (JSH 2014) in conjunction with a compilation of clinical and population studies related to the treatment of hypertension. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Careers related news & comment | | | | | | | | | | | | | | | | | | | | | | 
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