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In a zebrafish model of human cutaneous and acral melanomas, CRKL amplification causes tumours to favour a fin location, indicating that tumour location is determined by both the driver oncogenes and the pre-existing positional identity gene program.

This study demonstrates that the extracellular matrix (ECM) of the developing brain stabilizes recently born synapses. The authors identify a microglial metalloprotease that digests the ECM to increase the plasticity of these newborn synapses.

u-Segment3D is a universal framework that translates and enhances 2D instance segmentations to a 3D consensus instance segmentation without training data. It performs well across diverse datasets, including cells with complex morphologies.

An in vivo imaging-based competitive transplant screen in zebrafish identifies epoxyeicosatrienoic acids as enhancers of haematopoietic stem and progenitor cell (HSPC) engraftment; these derivatives of arachidonic acid also promote zebrafish developmental HSPC specification through a PI(3)K-dependent AP-1 and runx1 transcriptional program and their pro-engraftment effect is conserved in mammals (indicating clinical potential).

Swarte, Zhang and colleagues review the microbiome in solid-organ transplantation and allogeneic haematopoietic-stem-cell transplantation recipients, considering the effects of the intestinal environment, interactions between the microbiota and immunosuppressive drugs, and effects of dysbiosis on transplantation outcomes. The potential of microbiome-targeted interventions to improve transplantation outcomes is also discussed.

Seegren et al. demonstrate that the mitochondrial calcium uptake complex is a key molecular apparatus that links age-related changes in mitochondrial physiology to systemic macrophage-mediated age-associated inflammation.

Cerebrospinal fluid (CSF) is essential for brain development. Here, the authors use gold nanoparticle enhanced X-ray microtomography to map CSF distribution in post-natal rodents and describe particle size-dependent CSF pathways that transport CSF into the brain parenchyma of rodents.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

Dietary protein restriction in healthy, lean men elicits an increased energy intake to maintain body weight, which is driven, at least in part, by FGF21-mediated alterations to adipose tissue mitochondria.

Microglia drastically change their morphology when reacting to pathological stimuli. Here, the authors study the molecular responses to stimulation and unravel cytoskeleton remodeling pathways that induce morphological and functional changes.

Here, Swarte et al. use metagenomics to investigate the association between the gut microbiome and Health-Related Quality of Life (HRQoL) in kidney transplant recipients, showing evidence for the association of multiple taxonomic, metabolic and neuroactive pathways (gut brain modules) with lower HRQoL, together suggesting potential modifiable gut microbial factors to improve HRQoL.

This genome-wide association study identifies 162 genetic loci linked to income, shedding light on the complex interplay between genetics, income, education and health.

This study presents a predictive equation for total energy expenditure derived from doubly labelled water measurements. Applying this equation to two large datasets (the National Diet and Nutrition Survey and National Health and Nutrition Examination Survey) shows that the misreporting of total energy intake is greater than 50%, with important implications for macronutrient availability.

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

Roy et al. describe a generalized method for computationally designing miniproteins selective for a single integrin heterodimer and conformational state. The designed αvβ6 inhibitor remains monomeric and maintains biological activity following aerosolization and shows excellent efficacy in bleomycin induced lung fibrosis.

Longitudinal profiling of the nasal and faecal microbiomes of 66 dairy farmers and 166 dairy cows over a year-long period shows that microbes acquired from cow microbiomes introduce clinically relevant antimicrobial resistance genes to farmer guts.

Genomic analysis of 118 cervical tumors from Ugandan individuals identifies HPV-clade-specific differences in tumor DNA methylation, regulatory-region-associated histone marks, gene expression and pathway dysregulation.

The mechanisms that control activation of the AIM2 inflammasome by cytosolic bacteria are unclear. Kanneganti and colleagues demonstrate that a pathway involving the transcription factor IRF1 is required for the activation of AIM2.

Adaptive light-sheet microscopy improves imaging of live organisms by correcting for optical aberrations in real time.

Human brain structure changes throughout the lifespan. Brouwer et al. identified genetic variants that affect rates of brain growth and atrophy. The genes are linked to early brain development and neurodegeneration and suggest involvement of metabolic processes.

An examination of motor cortex in humans, marmosets and mice reveals a generally conserved cellular makeup that is likely to extend to many mammalian species, but also differences in gene expression, DNA methylation and chromatin state that lead to species-dependent specializations.

Synthetic promoters can be superior to native ones but the design is challenging without knowledge of gene regulation. Here the authors develop a pipeline that allows for screening a synthetic promoter library to identify high performance promoters in potentially any given cell state of interest.

Here the authors present results from a randomized, double-blinded Phase 1 clinical trial, testing a thermostable presentation of a clinical-stage adjuvanted subunit tuberculosis vaccine candidate. The vaccine candidate is safe and well tolerated, and elicits comparable or improved immune responses compared to the non-thermostable presentation.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Protein O-fucosyltransferase 1 (Pofut1) regulates Notch activity by adding O-fucose residues to its extracellular domain. Fucose analogs were identified that inhibited Delta-mediated Notch binding and activation but spared Jagged1-mediated signaling.

The authors describe an integrated atlas of the diverse cell types in the mouse primary motor cortex.

A six-letter sequencing workflow can simultaneously detect genetic and epigenetic bases.

Fungi have the potential to produce sustainable foods for a growing population, but current products are based on a small number of strains with inherent limitations. Here, the authors develop genetic tools for an edible fungus and engineer its nutritional value and sensory appeal for alternative meat applications.

A robust acoustic droplet ejection–drop-on-tape method delivers samples to an X-ray free-electron laser source for combined serial femtosecond crystallography and X-ray emission spectroscopy analysis, providing detailed insights into macromolecular reaction dynamics.

The oxygen-evolving complex in Photosystem II (PSII) catalyzes the light-driven oxidation of water to oxygen and it is still under debate how the water reaches the active site. Here, the authors analyse time-resolved XFEL-based crystal structures of PSII that were determined at room temperature and report the structures of the waters in the putative channels surrounding the active site at various time-points during the reaction cycle and conclude that the O1 channel is the likely water intake pathway and the Cl1 channel the likely proton release pathway.

Itaconate is an immunomodulatory macrophage metabolite. Mesaconate, a structurally similar molecule, is shown to be synthesized from itaconate in inflammatory macrophages and shows similar immunomodulatory effects, despite not repressing tricarboxylic acid cycle activity nor inhibiting succinate dehydrogenase activity.

Detection of primary aldosteronism, the most common form of secondary arterial hypertension, is essential for targeted management and prevention of cardiovascular complications. Here, the authors identify genetic loci associated with primary aldosteronism, suggesting new mechanisms of disease.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Quantum electrodynamics predicts a rare process in which light is scattered by light. The ATLAS Collaboration reports signs of this elusive effect in the collisions of ultra-relativistic lead ions.

Anoxic lake sediments are thought to be the major source of the high amount of methane emitted from freshwaters. Here Günthel and colleagues find unexpected quantities of this greenhouse gas are produced in lake surfaces, indicating an overlooked global importance from oxygenated sources.