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Volume 523 Issue 7561, 23 July 2015

Adult zebrafish engineered to act as a novel competitive marrow transplantation system. Haematopoietic stem and progenitor cell (HSPC) transplantation � with infusions of either bone marrow or peripheral blood progenitor cells � is used clinically to treat certain cancers and diseases of the blood and immune system, but we still understand very little about how HSPCs engraft to the host. Leonard Zon and colleagues have developed a competitive marrow transplantation system in adult zebrafish in which engraftment is measured by in vivo fluorescence imaging of the kidney � the adult haematopoietic site. Using this model to screen for engraftment enhancing activity, the authors identify epoxyeicosatrienoic acids, including 11,12-epoxyeicosatrienoic acid (EET) and 14,15-EET, as agents able to enhance engraftment and HSPC specification through the activation of a transcription factor Runx1-mediated expression program. This activity of EET is conserved in mice, indicating possible clinical potential for EET to promote bone marrow transplants. Cover image: Vera Binder & Ellen van Rooijen

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  • Representations of 3D surfaces used in computer graphics have been adopted as templates in an efficient method for making nanoscale objects from DNA, lowering the barriers to applications of DNA nanotechnology. See Letter p.441

    • Tim Liedl
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  • Study of the diarrhoea-causing pathogen Cryptosporidium has been hindered by a lack of genetic-modification and culture tools. A description of genome editing and propagation methods for the parasite changes this picture. See Letter p.477

    • Stephen M. Beverley

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  • DNA-sequence analysis suggests that genetic mutations arise at elevated rates in genomes harbouring high levels of heterozygosity — the state in which the two copies of a genetic region contain sequence differences. See Letter p.463

    • Michael Lynch
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  • Artificial neural networks have been combined with microscopy to visualize the 3D structure of biological cells. This could lead to solutions for difficult imaging problems, such as the multiple scattering of light.

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    • Lei Tian
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  • The concept of umpolung describes the reversal of the naturally occurring electrostatic polarization of chemical groups. It has now been used to make single mirror-image isomers of nitrogen-containing molecules. See Letter p.445

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Article

  • On the basis of neural firing rates a specific class of neuron is identified in the medial entorhinal cortex that linearly encodes information on running speed in a context-independent manner and that is distinct from other functionally specific entorhinal neurons.

    • Emilio Kropff
    • James E. Carmichael
    • Edvard I. Moser
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  • Gram-positive bacteria use peptidase-containing ATP-binding cassette transporters (PCATs) to export quorum-sensing and antimicrobial polypeptides; here, the X-ray crystal structures of PCAT1 from Clostridium thermocellum in the absence and presence of ATP are reported.

    • David Yin-wei Lin
    • Shuo Huang
    • Jue Chen
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  • Here the cis form of tau protein, which disrupts axonal microtubules and transport, spreads to other neurons, and leads to apoptosis in vitro and in vivo, is found to be produced by neurons immediately after traumatic brain injury (TBI); treating TBI mice with cis antibody blocks early production of cis tau, prevents tauopathy and spread and restores brain structural and functional outcomes, and may be further developed to treat TBI and to prevent neurodegeneration after injury.

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Letter

  • A study of the formation of X-ray jets in solar coronal holes suggests that this process does not follow the popular ‘emerging-flux’ model, but instead results from a minifilament eruption akin to the larger-scale filament eruptions that drive larger solar flares and mass ejections.

    • Alphonse C. Sterling
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  • A general method of folding arbitrary polygonal digital meshes in DNA uses a routeing algorithm based on graph theory and a relaxation simulation that traces scaffold strands through the target structures to produce complex structures with an open conformation that are stable under biological assay conditions.

    • Erik Benson
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  • Imines conventionally act as electrophiles towards carbon nucleophiles in the synthesis of amines, but the range of amines could be much extended if the carbon atom of the imine could be rendered electron-rich to allow it to act as a nucleophile toward a carbon electrophile; such a reaction can be promoted by new phase-transfer catalysts, leading to highly efficient asymmetric reactions of imines with enals.

    • Yongwei Wu
    • Lin Hu
    • Li Deng
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  • Kennewick Man, a 8,500-year-old male human skeleton discovered in Washington state, USA, has been the subject of scientific and legal controversy; here a DNA analysis shows that Kennewick Man is closer to modern Native Americans than to any other extant population worldwide.

    • Morten Rasmussen
    • Martin Sikora
    • Eske Willerslev
    Letter Open Access
  • An analysis of 16 health-related quantitative traits in approximately 350,000 individuals reveals statistically significant associations between genome-wide homozygosity and four complex traits (height, lung function, cognitive ability and educational attainment); in each case increased homozygosity associates with a decreased trait value, but no evidence was seen of an influence on blood pressure, cholesterol, or ten other cardio-metabolic traits.

    • Peter K. Joshi
    • Tonu Esko
    • James F. Wilson
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  • Mutation rates vary within genomes; here, by calling mutation events directly using a parent–offspring sequencing strategy in Arabidopsis, replicated in the rice and honey bee genomes, mutation rates are found to be higher in heterozygotes and in proximity to crossover events.

    • Sihai Yang
    • Long Wang
    • Dacheng Tian
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  • An in vivo imaging-based competitive transplant screen in zebrafish identifies epoxyeicosatrienoic acids as enhancers of haematopoietic stem and progenitor cell (HSPC) engraftment; these derivatives of arachidonic acid also promote zebrafish developmental HSPC specification through a PI(3)K-dependent AP-1 and runx1 transcriptional program and their pro-engraftment effect is conserved in mammals (indicating clinical potential).

    • Pulin Li
    • Jamie L. Lahvic
    • Leonard I. Zon
    Letter
  • Cryptosporidium is an important cause of diarrhoeal disease in young children but until now it has been difficult to study; here, the parasite is genetically modified, paving the way for in-depth investigation and the development of effective treatments.

    • Sumiti Vinayak
    • Mattie C. Pawlowic
    • Boris Striepen
    Letter
  • CRISPR-Cas9 nucleases are widely used for genome editing, but the range of sequences that Cas9 can recognize is constrained by the need for a specific protospacer adjacent motif (PAM); here the commonly used Streptococcus pyogenes Cas9 (SpCas9) is modified to recognize alternative PAM sequences, enabling robust editing of endogenous gene sites in zebrafish and human cells not currently targetable by wild-type SpCas9.

    • Benjamin P. Kleinstiver
    • Michelle S. Prew
    • J. Keith Joung
    Letter
  • A single-cell method for probing genome-wide chromatin accessibility has been developed; the results provide insight into the relationship between cell-to-cell variation associated with specific trans-factors and cis-elements, as well insights into the relationship between chromatin accessibility and three-dimensional genome organization.

    • Jason D. Buenrostro
    • Beijing Wu
    • William J. Greenleaf
    Letter
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  • Junior researchers have a lot to learn, but talking to others about their experiences will help to avert nasty surprises.

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