Articles in 2016

Structural studies shed light on the function and stoichiometry of the Ton complex, which harnesses the proton motive force across the bacterial inner membrane to transduce energy to the outer membrane.

Deep whole-genome sequencing of 300 individuals from 142 diverse populations provides insights into key population genetic parameters, shows that all modern human ancestry outside of Africa including in Australasians is consistent with descending from a single founding population, and suggests a higher rate of accumulation of mutations in non-Africans compared to Africans since divergence.

Computational methods for the de novo design of conformationally restricted peptides produce exceptionally stable short peptides stabilized by backbone cyclization and/or internal disulfide bonds that are promising starting points for a new generation of peptide-based drugs.

Structures of the human P2X₃ receptor in its open, closed, desensitized and antagonist-bound states show the receptor’s gating mechanism and the basis of antagonist binding.

Identification and characterization, using a comprehensive embryonic phenotyping pipeline, of 410 lethal alleles during the generation of the first 1,751 of 5,000 unique gene knockouts produced by the International Mouse Phenotyping Consortium.

Insights into the genomic architecture of heterosis for grain yield in rice are presented, and further mapping of grain yield loci resolves candidate genes that could be useful for breeding.

The bicyclic azetidines, a class of potent, well-tolerated antimalarial compounds that is active against multiple stages of the Plasmodium life-cycle, has been discovered following screens against libraries of compounds reminiscent of natural products.

The methylation of adenosine residues on the long non-coding RNA XIST is essential for X-chromosome transcriptional repression during female mammalian development.

A light-actuated liquid crystal polymer material system precisely manipulates liquid drops through capillary forces, and can be formed into a variety of shapes.

Projections from the locus coeruleus, an area typically defined by noradrenergic signalling, to the hippocampus drive novelty-based memory enhancement through possible co-release of dopamine.

The X-ray crystal structures of human endothelin type B receptor in the ligand-free form and in complex with the endogenous agonist endothelin-1.

The cryo-electron microscopy structure of the rabbit voltage-gated calcium channel Ca_v1.1 complex at a nominal resolution of 3.6 ångströms.

Aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ, reduces soluble and insoluble Aβ in the brain, an action accompanied by a dose-dependent slowing of clinical decline in treated patients.

Careful study of the famous fossil ‘Lucy’, a hominin who died over 3 million years ago, suggests that she died as a result of multiple injuries sustained in a fall–probably out of a tall tree.

Reconstructions of ocean and land temperatures since ad 1500 indicate that sustained, industrial-era warming of land areas in the Northern Hemisphere and tropical oceans began earlier than previously thought, around the mid-nineteenth century.

Using a single-cell sequencing analysis in monkey embryos, and comparing the genes expressed during early development in this species with those in mice and in human pluripotent stem cells, the authors define characteristics of pluripotency ontogeny across mammalian species.

Computational docking to the the μ-opioid-receptor identifies PZM21, a novel selective biased agonist that generates substantial affective analgesia in mice without altering respiration or inducing drug reinforcement.

An integrated computational approach that explores the viral content of more than 3,000 metagenomic samples collected globally highlights the existing global viral diversity, increases the known number of viral genes by an order of magnitude, and provides detailed insights into viral distribution across diverse ecosystems and into virus–host interactions.

Exome sequencing data from 60,706 people of diverse geographic ancestry is presented, providing insight into genetic variation across populations, and illuminating the relationship between DNA variants and human disease.