Volume 523 Issue 7561

Editorials

Prepare farms for the future p.381

Scientists must work closely with farmers to ensure that agriculture can stand up to the ravages of climate change.

doi: 10.1038/523381a

Timeless advice p.381

The best guidance on how to get ahead in science stands the test of time.

doi: 10.1038/523381b

It’s good to talk p.382

Help for those struggling to reproduce results could be just a phone call away.

doi: 10.1038/523382a

News

News Features

Quest for climate-proof farms p.396

Climate change is a major threat to food production, so researchers are working with farmers to make agriculture more resilient.

doi: 10.1038/523396a

News & Views

Pathfinder for DNA constructs p.412

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

doi: 10.1038/523412a

CRISPR for Cryptosporidium p.413

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

doi: 10.1038/nature14636

Feedforward loop for diversity p.414

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

doi: 10.1038/nature14634

Machine learning for 3D microscopy p.416

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.

doi: 10.1038/523416a

Natural polarity inverted p.417

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

doi: 10.1038/523417a

Articles

Speed cells in the medial entorhinal cortex p.419

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.

doi: 10.1038/nature14622

Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy p.431

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.

doi: 10.1038/nature14658

Letters

DNA rendering of polyhedral meshes at the nanoscale p.441

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.

doi: 10.1038/nature14586

Catalytic asymmetric umpolung reactions of imines p.445

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.

doi: 10.1038/nature14617

The ancestry and affiliations of Kennewick Man OPEN p.455

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.

doi: 10.1038/nature14625

Directional dominance on stature and cognition in diverse human populations p.459

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10−300, 2.1 × 10−6, 2.5 × 10−10 and 1.8 × 10−10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months’ less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

doi: 10.1038/nature14618

Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment p.468

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).

doi: 10.1038/nature14569

Engineered CRISPR-Cas9 nucleases with altered PAM specificities p.481

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.

doi: 10.1038/nature14592

Single-cell chromatin accessibility reveals principles of regulatory variation p.486

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.

doi: 10.1038/nature14590