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A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

A key hypothesis for the evolution of division of labour in social insects is that a shared set of genes – a genetic toolkit - regulates reproductive castes across species. Here, the authors analyze brain transcriptomes from nine species of social wasps to identify the factors that shape this toolkit.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Interpreting untargeted mass spectrometry (MS) data is challenging due to incomplete reference libraries. Here, the authors created the nearest neighbor suspect spectral library from largescale public MS data, significantly enhancing the ability to hypothesize structures for unknown mass spectra.

Despite its prevalence, the function of dermal photoreception in color-changing animals remains poorly understood. Here, the authors describe an optical mechanism in hogfish skin, suggesting that one function is to obtain sensory feedback about color change performance.

Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.

Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

Charlotte Sumner and colleagues report that mutations in the ankyrin repeat region of TRPV4 cause Charcot-Marie-Tooth disease type 2C. Their functional studies indicate that the mutations result in increased channel activity.

Prediabetes refers to individuals with blood glucose levels above the normal levels but below the thresholds for a diabetes mellitus diagnosis. In this Primer, Mohan and colleagues discuss the increasing prevalence of prediabetes, its pathophysiology and diagnosis as well as the importance of early intervention to improve adverse outcomes in patients.

Analysis of monkeypox virus (MPXV) isolates circulating in Nigeria before the 2022 global outbreak of MPXV sheds light on the diversification of the virus that eventually gave rise to the 2022 MPXV lineage.

Markov, Ren, Senkow and colleagues report that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterized patients who recovered, whereas responses against nonstructural proteins and activation of NF-κB were associated with poor outcomes.

Low efficiency of target DNA integration remains a challenge in genome engineering. Here the authors perform large-scale compound library and genetic screens to identify targets that enhance gene editing: they see that combined DNA-PK and Polϴ inhibition with potent compounds increases editing efficiency and precision.

The high resolution structure of the new therapeutic target, cathepsin K, complexed with the potent mechanism-based inhibitor, APC3328, reveals the substrate-binding sites of this cysteine proteinase and validates the binding mode for this inhibitor class.

GPR61 is an orphan GPCR of interest for treatment of appetite disorders, such as obesity and cachexia. Here, the authors report structures of GPR61 in its active and inactive states, including with a G protein-competitive small molecule inverse agonist.

A computational approach to generate reference-free protein families from the sequence space in metagenomes reveals an enormously diverse functional space.

Metabolomics is improved by using a reference library of both known and unknown molecules.

The structure of human cathepsin K, a potential target for treatment of osteoporosis, reveals active site differences with homologous cysteine proteinases that should enable the design of cathepsin K selective inhibitors.

Deep learning-based methods to generate new molecules can require huge amounts of data to train. Skinnider et al. show that models developed for natural language processing work well for generating molecules from small amounts of training data, and identify robust metrics to evaluate the quality of generated molecules.

NMR resonances of backbone nuclei have been assigned for >95% of the residues in oxidized, substrate-free, perdeuterated ¹³C/¹⁵N-labelled MurB (347 residues). A novel approach utilizing minimum chemical shift changes was employed to localize the NADP⁺ binding site on MurB.

Identifying a chemical substance using mass spectrometry without knowing its structure is challenging. To help detect novel designer drugs from their mass spectra, Skinnider et al. describe a generative model that is biased towards creating potentially psychoactive molecules and thus helps identify potential candidates for a specific sample.

The authors analyse 9 years of time-lapse surveys in Bute Inlet, British Columbia (CA), to show how an active submarine channel evolves. They show how channel evolution is controlled by fast upstream-migration of steep knickpoints, which are similar to waterfalls in rivers.

PTSD has been associated with DNA methylation of specific loci in the genome, but studies have been limited by small sample sizes. Here, the authors perform a meta-analysis of DNA methylation data from 10 different cohorts and identify CpGs in AHRR that are associated with PTSD.

Liquid water on equatorial Mars is inconsistent with large-scale climatic conditions. Humidity and temperature measurements by the Curiosity rover support the formation of subsurface liquid brines by hydration of perchlorates during the night.

Biallelic mutations in the sorbitol dehydrogenase gene SORD are identified as a common cause of hereditary neuropathy. Functional studies suggest that SORD deficiency may be treatable with aldose reductase inhibitors.

Th17 cells are involved in the pathogenesis of several inflammatory diseases. Here, the authors show that inhibitors of the pro-inflammatory cytokine TNF, used in patients undergoing anti-inflammatory treatment, might mediate the acquisition of anti-inflammatory properties by these typically pathogenic cells.

The structure of turbidity currents has remained unresolved mainly due to lack of observations. Here the authors present data from a high-resolution monitoring array deployed for 18 months over Monterey Bay, that suggests turbidity currents are driven by dense near-bed layers.

The authors infer that pelvic skeleton reduction in a fossil sequence of the Miocene stickleback fish, Gasterosteus doryssus, proceeds through the same gene of large effect and a similar suite of genes of small effect as in a closely related extant species, Gasterosteus aculeatus.

Combining data on sea-surface chlorophyll-a with a regional ocean model and diatom abundance from sediment grabs, the authors determine the strength of pelagic–benthic coupling across the George V region in East Antarctica.

Efficient nanoparticle delivery into tumours has been a challenge in the field. It is now shown that the efficiency can be improved substantially when the dose breaches a specific threshold.