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Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

Pasha and Turner review recent insights into the role of intratumoral heterogeneity in therapeutic resistance in metastatic breast cancer and discuss forward-looking strategies to overcome this hurdle.

The recent development of a broad range of biocatalysts that can be applied in organic synthesis has brought into focus the need to rethink the way in which organic target molecules might be constructed in the future. To aid synthetic chemists in identifying where biocatalysts might be usefully applied, we propose that guidelines and rules for 'biocatalytic retrosynthesis' be developed and that this new approach be embedded in the future training and education of organic chemists.

High contiguity human genomes can be assembled de novo in 6 h using nanopore long-read sequences and the Shasta toolkit.

An artificial transfer hydrogenase, based on the incorporation of a biotinylated iridium-piano-stool complex in streptavidin, is shown to be fully compatible with a range of biocatalysts. The location of the active metal centre inside the protein scaffold efficiently prevents mutual inactivation processes and enables the concurrent interplay with oxidative enzymes.

Individuals over eighty years of age are less likely to mount a good immune response against SARS-CoV-2 (measured by neutralization titres) after the first dose of the BNT162b2 mRNA vaccine, but achieve good neutralization after the second dose.

Typhoid fever is caused by Salmonella enterica serovar Typhi (S. Typhi). This study examines ∼2,000 clinical isolates of S. Typhi to show highly structured/geographically restricted genomes except rapidly disseminating H58 subclade, and design a genotyping framework for tracking the disease.

Transmission spectroscopy observations from the James Webb Space Telescope show the detection of carbon dioxide in the atmosphere of the gas giant exoplanet WASP-39b.

David van Heel and colleagues report results of a large genome-wide association study of celiac disease. Most of the associated loci contain genes with immune functions, and over half harbor risk variants that are correlated with variation in cis gene expression.

Structural characterization of carboxylic acid reductase in multiple didomain configurations, coupled with mutagenesis, reveals how the enzyme transitions into a catalytically competent orientation and prevents over-reduction of its aldehyde product.

ESR1 mutations occur in endocrine-resistant patients but have not yet been reported in in vitro models of breast cancer. Here, the authors report the discovery of naturally occurring ESR1 ^Y537Cand ESR1 ^Y537S mutations in two breast cancer cell lines after acquisition of resistance to long-term-estrogen-deprivation.

A single dose of the ChAdOx1 nCoV-19 vaccine elicits antibodies and cytokine-producing T cells that might help control or prevent SARS-CoV-2 infection.

Amyotrophic Lateral Sclerosis (ALS) is highly heritable but the mechanisms of sporadic ALS are not fully understood. In this study, the authors identify drivers of variation and disease-relevant changes in the epigenomic profile of iPSC-derived motor neuron lines generated from ALS patients and healthy controls as part of the Answer ALS program.

John Chambers and colleagues report genome-wide association studies to several ECG measurements, identifying an association of SCN10A to PR interval. They find that Scn10a^−/− mice show a shorter PR interval.

Flavin-dependent halogenases catalyse the regioselective formation of carbon–chlorine and carbon–bromine bonds using oxygen and inorganic halide salts. Now, genome mining has led to the discovery of a previously unknown viral halogenase that catalyses the iodination of arenes, thereby providing a rare biocatalytic tool for the formation of carbon–iodine bonds.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

ADHD is often found to be comorbid with disruptive behavior disorders, but the genetic loci underlying this comorbidity are unknown. Here, the authors have performed a GWAS meta-analysis of ADHD with disruptive behavior disorders, finding three genome-wide significant loci in Europeans, and replicating one in a Chinese cohort.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

An analysis of 21 coral reefs in the Indian Ocean using data across 17 years that spanned a major climatic disturbance reveals factors that predispose a coral reef to recovery or regime shift from hard corals to macroalgae; these results could foreshadow the likely outcomes of tropical coral reefs to the effects of climate change, informing management and adaptation plans.

Mudd, Ellebedy and colleagues integrate single-cell transcriptomics and TCR sequencing to characterize the spike-specific CD4⁺ T_FH cell response in the lymph nodes and blood of BNT162b2-vaccinated and SARS-CoV-2-infected individuals up to 6 months after vaccination or infection.

A nanopore DNA sequencer is used for real-time genomic surveillance of the Ebola virus epidemic in the field in Guinea; the authors demonstrate that it is possible to pack a genomic surveillance laboratory in a suitcase and transport it to the field for on-site virus sequencing, generating results within 24 hours of sample collection.

Aortic dissection is a medical emergency that occurs when the layers of the aortic wall are forced apart by bleeding, creating a false route of blood flow. Important risk factors for aortic dissection include hypertension and connective tissue disorders.

Ecologists and space agencies must forge a global monitoring strategy, say Andrew K. Skidmore, Nathalie Pettorelli and colleagues.

How γδ TCRs bind antigen presented by antigen-presenting molecules remains unclear. Godfrey and colleagues describe a population of human γδ T cells that interacts with CD1d and provide a molecular basis for how a γδ TCR binds CD1d–α-GalCer.

Answer ALS is a resource of patient-derived iPS cell lines, multi-omic data derived from iPS neurons and longitudinal clinical and smartphone data from over 1,000 patients with ALS. This serves as a foundation to identify distinct disease subgroups.

Deregulation of fibroblast growth factor (FGF) signalling is observed in several types of cancer, which makes this pathway a highly promising potential therapeutic target. However, aberrant FGF receptor (FGFR) signalling can be challenging. In this Review, Babinaet al. discuss the differences between diverse mechanisms of oncogenic activation of FGFR, and the factors that determine response and resistance to FGFR targeting.

Fibroblast growth factors (FGFs) and their receptors have been shown to drive tumorigenesis and tumour progression. However, FGF signalling can also be tumour suppressive, and understanding the mechanisms that underlie these context-specific effects will be important to rationally target FGF signalling for therapeutic benefit.

During a pandemic, trust in leaders is affected by how they resolve moral dilemmas. Across 22 countries, leaders’ endorsement of instrumental harm reduced public trust, while endorsement of impartial beneficence increased trust.

Paul Thompson and colleagues report a genome-wide association study for hippocampal, intracranial and total brain volume. They identify a locus at 12q24 associated with hippocampal volume and a locus at 12q14 associated with intracranial volume.