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The activity of the membrane-bound enzyme pMMO depends on copper but the location of the copper centers is still under debate. Here, the authors reconstitute pMMO in nanodiscs and use native top-down MS to localize its copper centers, providing insights into which sites are essential for activity.

Gender-based violence is widespread, affecting women and men worldwide. Stein et al. use a meta-analysis and the Burden of Proof methodology to evaluate associations between gender-based violence and eight health outcomes, including major depressive disorder, substance use and reproductive health.

Around the world, more than a billion children are regularly exposed to violence or neglect. Flor et al. systematically review evidence that links childhood physical violence, psychological violence and neglect to increased risks for 14 health outcomes.

Prostate cancer growth depends on de novo lipogenesis controlled by the mitochondrial pyruvate dehydrogenase complex (PDC). Here the authors find that a histone methyltransferase KMT9 is localized in the mitochondria of prostate cancer cells to regulate PDC activity by methylating its subunit DLAT.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Ibogaine is a natural substance that interrupts opioid addiction but has cardiac risks. This article introduces novel ibogaine analogs that show reduced cardiac risk and enhanced neuroplasticity and therapeutic-like effects in models of opioid use disorder.

Topochemical polymerization reactions produce ultra-high molecular weight crystalline polymers. Here the authors show a family of para-azaquinodimethane compounds that undergo facile visible light and thermally initiated polymerization in the solid state and the crystal structure has been resolved via cryoelectron microscopy.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Terman and colleagues employed a genetic screen in Drosophila to identify the SelR methionine sulfoxide reductase as the enzyme responsible for reversing the Mical-mediated oxidation of actin. Thus, SelR antagonizes the effects of Semaphorin–Plexin–Mical-dependent signalling in vivo.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Most kimberlites erupting in the past billion years on Earth did so about 30 million years after continental breakup, with dynamical and analytical models suggesting a control from rifting-related mantle delamination.

Gene discovery and polygenic predictions from a genome-wide association study of educational attainment in 1.1 million individuals.

In plants, light-dependent activation fatty acid synthesis (FAS) is mediated in part by acetyl-CoA carboxylase (ACCase). Here the authors identify a family of genes encoding carboxyltransferase interactors that attenuate FAS in the light by docking acetyl-CoA carboxylase to the plastid envelope.

H9T, an engineered IL-2 partial agonist, promotes the expansion of T cells while maintaining a stem-cell-like state, leading to improved efficacy of adoptive cell therapy in mouse models of melanoma and acute lymphoblastic leukaemia.

Reductions in air pollution in the United States over the past two decades have led to positive results for forest growth and survival. However, further measures are needed to protect sensitive tree species and bolster forest biodiversity

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

Products of the mevalonate pathway support plant development. Here the authors show that the extracellular ATP receptor P2K1 phosphorylates mevalonate kinase and this affects the mevalonate pathway.

There is a genetic component to the risk of severe COVID-19, but the genetic effects are difficult to separate from social constructs that covary with genetic ancestry. To address this, the authors identify determinants of COVID-19 severity using admixture mapping, viral phylodynamics, and host immune and metagenomic sequencing.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

Materials with correlated localisation of percolating particles and emergent conductive paths can realise sharp transitions and high conductivities characteristic of the explosively-grown network. Here the authors exploit explosive percolation to realize a low-loading composite material with enhanced electrical properties by in-situ reduction of graphene oxide.

Patient-derived xenografts provide a resource for basic and translational cancer research. Here, the authors generate multiple pediatric high-grade glioma xenografts, use omics technologies to show that they are representative of primary tumours and use them to assess therapeutic response.

A meta-analysis using the burden of proof risk function identified consistent evidence supporting harmful associations between the exposure to intimate partner violence against women and childhood sexual abuse on health outcomes.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

A streamlined sequencing process enables identification of disease-causing variants in the clinic within 8 hours.

The optical detection of two virulence factors of Mycobacterium tuberculosis on extracellular vesicles in blood allowed for the diagnosis of tuberculosis in paediatric cases that were missed by clinical microbiological assays.

An analysis of over 2,000 genomes from Human Microbiome Project metagenomic data led to the identification of several extended- and narrow-spectrum antibiotics against clinical multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci.

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.

This paper reports the identification of high-frequency deletions in the Ikaros gene in acute lymphoblastic leukaemia cases that are characterized by BCR-ABL1 translocations. In contrast, BCR-ABL1 CML is not associated with Ikaros deletions in chronic phase patients, but are often acquired during progression to blast crisis. These deletions lead to expression of altered transcripts. In contrast to previous models suggesting that these transcripts result from aberrant alternative splicing, it is shown that the deletions found are due to aberrant RAG-mediated recombination.

Daniel Benjamin, Meike Bartels, Philipp Koellinger and colleagues report a genome-wide association meta-analysis of subjective well-being, depressive symptoms and neuroticism. The study leverages a large sample size together with genetic correlations between the phenotypes to identify, with high confidence, loci associated with each phenotype.

COVID-19 booster immunizations aimed at spike protein from new SARS-CoV-2 variants induce robust germinal centre B cell responses against the original spike protein, as well as de novo B cell responses against the variant spike protein.

A genome-wide, high-resolution single nucleotide polymorphism array analysis of a large number of acute lymphoblastic leukaemia samples identifies a number of genomic changes. These include alterations in the genes encoding Pax5 and other regulators of B-cell development and differentiation.

A clinical decision support system for diagnosis of myocardial infarction, based on machine learning models that use a single measurement of high-sensitivity troponin, outperforms clinical guidelines that use fixed cardiac troponin thresholds for diagnosis.

The monolithic integration of electronic and plasmonic technologies can be used to create electro-optic transmitters capable of symbol rates beyond 100 GBd.

A genome-wide association study in 293,723 individuals identifies 74 genetic variants associated with educational attainment, which, although only explaining a small proportion of the variation in educational attainment, highlights candidate genes and pathways for further study.

Lower olefins are mainly produced from fossil resources and the methanol-to-olefins process offers a new sustainable pathway. Here, the authors show a new zeolite containing tantalum and aluminium centres which shows simultaneously high propene selectivity, catalytic activity, and stability for the synthesis of propene.