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Crystal structures of the σ₂ receptor are determined and used to perform a docking screen of nearly 500 million molecules, identifying σ₂-selective ligands and providing insight into the role of σ₂ in neuropathic pain.

A radio signal detected in the direction of Proxima Centauri in a Breakthrough Listen programme is analysed for signs that it was transmitted by extraterrestrial intelligent life, using a newly developed framework. However, the signal ‘blc1’ is likely to be terrestrial radio-frequency interference.

Post-translational site-selective formation of boronoalanine in proteins enables applications of boron for binding partner capture, footprinting of interactions with reactive oxygen species, proteolytic control and mapping of transient structures.

He et al. develop a network-based metric of amyloid-β burden by integrating individualized brain connectomes with amyloid-PET imaging. This approach improves prediction of future cognitive decline in older adults and may support earlier identification of individuals at risk of dementia.

Crystal structures of BAK core domain dimers suggest a mechanism by which lipids contribute to the oligomerization of BAK, which is essential for BAK-mediated permeabilization of the mitochondrial outer membrane.

Studies of the genetic association between vitamin D and cancer risk have typically been underpowered. Here the authors analyse this using Mendelian Randomisation with more than 70 vitamin D variants obtained from the UK Biobank and large-scale data from various consortia, confirming null associations between vitamin D and most cancers.

Drug efflux through ABC transporters is a common mechanism leading to chemoresistance in cancer. Here, the authors show that mitochondrial respiration provides ATP to allow ABC transporters activity so mitochondrial respiration inhibition overcomes chemoresistance in preclinical cancer models.

The structure of the yeast nuclear pore complex, determined at sub-nanometre precision using an integrative approach that combines a wide range of data, reveals details of its architecture, transport mechanism and evolutionary origins.

The transcription factor c-Myc is a master regulator of cellular metabolism and has an important role in tumorigenesis. Phanet al. show that 14-3-3σ, an inhibitor of cell cycle progression, also suppresses tumour-promoting metabolic programmes by promoting the degradation of c-Myc.

The CNV analysis group of the Psychiatric Genomic Consortium analyzes a large schizophrenia cohort to examine genomic copy number variants (CNVs) and disease risk. They find an enrichment of CNV burden in cases versus controls and identify 8 genome-wide significant loci as well as novel suggestive loci conferring either risk or protection to schizophrenia.

Climate change poses both practical and theoretical problems for coastal managers, who have to make and implement plans that cope with a highly uncertain, and therefore inherently risky, future. This Perspective uses three examples of ecological engineering — marshes, mangroves, and oyster reefs — to illustrate the synergistic effects and benefits of this approach.

Previous studies identified an association between the 2q35 locus and breast cancer. Here, the authors show that a SNP at 2q35, rs4442975, is associated with oestrogen receptor positive disease and suggest that this effect is mediated through the downregulation of a known breast cancer gene, IGFBP5.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

The rich transmission spectrum of exoplanet WASP-189 b reveals its dynamical atmosphere with a three-dimensional thermochemical stratification, requiring the unification of dynamical, thermal and chemical models for its study.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Defined levels of SARS-CoV-2-specific binding and neutralizing antibodies elicited by the COVID-19 vaccine ChAdOx1 nCoV-19 are identified as correlates of protection against symptomatic infection.

During embryogenesis, the cytoplasmic protein Myomarker (MYMK) mediates muscle fibre formation by fusion of myoblasts. Here, the authors identify autosomal recessive mutations in MYMK that cause Carey-Fineman-Ziter syndrome in humans, and model the disease variants in zebrafish.

Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.

A low-mass star that is just 12 parsecs away from Earth is shown to be transited by an Earth-sized planet, GJ 1132b, which probably has a rock/iron composition and might support a substantial atmosphere.

The heterogeneity of androgen receptor (AR) gene alterations across metastases in prostate cancer remains unresolved. Here, the authors characterise AR genomic complexity across spatially separated lethal metastases from 10 prostate cancer patients and investigate how AR alterations evolve.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

Simulations of early galaxy formation suggest that the dynamics of structure formation, rather than the Lyman–Werner flux, drives the formation of massive black holes in the early Universe.

This is the first report of the sequencing of the nearly complete nuclear genome of an extinct animal, the woolly mammoth. 4.1 billion bases of high quality sequence from several mammoth species are reported, including 3.3 billion bases from the woolly mammoth. Nuclear-genome sequencing of extinct species and its comparison with the extant relatives (in this case African elephant) provide insights into elephantid evolution and population differences.

Many physiological functions of helicases depend on their ability to unwind nucleic acid duplexes in an ATP-dependent fashion. Here, Özeş et al. describe a fluorescence assay to monitor in real time RNA duplex unwinding by DEAD-box helicases.

Structure-based docking screens of compound libraries are common in early drug and probe discovery. This protocol outlines best practices and control calculations to evaluate docking parameters prior to undertaking a large-scale prospective screen.

The genome of the southeast Asian orang-utan has been sequenced. The draft assembly of a Sumatran individual alongside sequence data from five Sumatran and five Bornean orang-utan genomes is presented. The resources and analyses described offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.

David Goldstein, Mohamad Mikati and colleagues report identification of de novo mutations in ATP1A3 in alternating hemiplegia of childhood, which is a rare neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurologic manifestations.