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Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Bacterial transcription with σ^N requires activation by specialized AAA+ ATPases. Here, the authors visualize transient structural intermediates and engineer a biochemical assay to show that these ATPases partially unfold σ^N to initiate transcription.

Coupling live-cell imaging, machine learning and genomic sequencing, the MAGIC platform enables investigation of the cellular context, mutation rates and triggers of spontaneous chromosomal abnormality formation, shedding light on fundamental determinants of chromosomal instability.

Voltage-modulated scanning probe microscopy may elucidate important processes at solid–liquid interfaces, but it is complicated by the presence of mobile ions. By incorporating force sensitivity into a multidimensional measurement approach, Collins et al.present a technique that overcomes these limitations.

mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.

The Mass Spectrometry Query Language (MassQL) is an open-source language that enables instrument-independent searching across mass spectrometry data for complex patterns of interest via concise and expressive queries without the need for programming skills.

This study explores four decades of biodiversity change across the tree of life in Germany’s terrestrial and aquatic ecosystems by sequencing standardized biota samples from a long-term pollution monitoring archive.

Meshworks of claudin polymers control the paracellular transport and barrier properties of epithelial tight junctions. Here, the authors show different claudin nanoscale organization principles, finding that claudin segregation enables barrier formation and paracellular ion flux across tight junctions.

Biological nitrogen fixation may impose stronger constraints on the carbon sink in natural terrestrial biomes and represent a larger source of agricultural nitrogen than is generally considered in analyses of the global nitrogen cycle.

On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

Here, Shaban et al. show that coronaviruses modulate ER stress and the unfolded protein response. The ER stress inducer thapsigargin exerts potent antiviral effects, partially reverses the virus-induced translational shut-down, reprograms the host proteome and suppresses autophagic flux, thereby inhibiting coronavirus replication at multiple levels.

Sequences of 137 ancient and 502 modern human genomes illuminate the population history of the Eurasian steppes after the Bronze Age and document the replacement of Indo-European speakers of West Eurasian ancestry by Turkic-speaking groups of East Asian ancestry.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Dendritic cells play intricate roles in engaging a range of immune cells. Here, the authors establish a role for the transcription factor RelB in dendritic cells as a molecular rheostat that controls the level of immune tolerance by limiting the number of regulatory T cells.

Mutations in the RNA-binding protein roquin-1 are known to result in humoral autoimmunity. Heissmeyer and colleagues show that MALT1 cleavage of roquin and regnase-1 downstream of TCR signaling releases cooperatively repressed targets to promote T_H17 cell differentiation

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Laser spectroscopy measurements of the fermium isotopic chain show a smooth trend in the nuclear size of heavy actinide elements, and diminishing shell effects on the size evolution compared with lighter nuclei.

Large genes require dual adeno-associated viral (AAV) vectors for in vivo delivery/expression, but current methods have limitations. Here the authors develop and functionally evaluate REVeRT, an efficient and flexible dual AAV vector technology based on reconstitution via mRNA trans-splicing.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

It is unclear whether trait trade-offs and optimality principles observed at the individual level scale up to the ecosystem level. Here, the authors show that plant trait coordination principles also predict patterns between community-level traits and ecosystem-scale processes.

Three key axes of variation of ecosystem functional changes and their underlying causes are identified from a dataset of surface gas exchange measurements across major terrestrial biomes and climate zones.

The bacterial pathogen Helicobacter pylori is known for its ability to induce DNA double-strand breaks in the genome of its target cells. Here, we show that H. pylori-induced DNA damage and replication stress occurs in S-phase cells as a result of R-loop-mediated transcription/replication conflicts that are triggered by activation of the ALPK1/TIFA/NF-κB signaling axis.

Genomic analysis of 491 medulloblastoma samples, including methylation profiling of 1,256 cases, effectively assigns candidate drivers to most tumours across all molecular subgroups.

CRISPR/Cas9 technology has been used for genome engineering in vivo. Here, the authors use a transfection technique to deliver multiple guide RNAs to the pancreas of adult mice, allowing genetic screening and chromosome engineering in pancreatic cancer.

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.

Two related papers show that cells disseminated from malignant lesions at early time points during tumorigenesis can contribute to metastases at distant organs and provide insights into the molecular basis of dissemination.

Here, the authors perform a meta-analysis in 26,699 people with seizures and 492,324 controls to identify 25 genome-wide significant copy-number variants. The discovered loci point to known disease genes and associations with clinical annotations.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

The integrated and indivisible nature of the SDGs is facing implementation challenges due to the silo approaches. We present the three interconnected foci (SDG interactions, modeling, and tools) at the science-policy interface to address these challenges. Accounting for them will support accelerated SDG progress, operationalizing the integration and indivisibility principles.

Analysis of changes in functional groups of species and potential drivers of environmental change for protected areas across the world’s major tropical regions reveals large variation between reserves that have been effective and those experiencing an erosion of biodiversity, and shows that environmental changes immediately outside reserves are nearly as important as those inside in determining their ecological fate.

The authors provide protocols for rapid and scalable genome engineering in somatic cells of the liver and pancreas through both viral and nonviral delivery of CRISPR components into living mice.

The penis is a diverse and rapidly evolving structure, much more complex than its fundamental function — sperm transfer — would seem to require. In this Review, experts in the field discuss the drivers of penis evolution, and consider how the penis might be an ideal characteristic on which to focus in studies to link phenotype with genotype.

Damaged erythrocytes accumulate in various pathological conditions, such as hemolytic anemia, anemia of inflammation, and sickle cell disease. In mice challenged with damaged erythorcytes, a monocyte subset migrates to the liver (but not to the spleen), and this subset differentiates into a transient macrophage population that removes the damaged erythrocytes, thus preventing organ damage.

Christel Depienne, Eric LeGuern and colleagues report the identification of 5 de novo missense mutations in HCN1 in individuals with early-onset epileptic encephalopathy. Functional studies confirmed the pathogenic nature of these mutations.

Johannes Lemke, Holger Lerche and colleagues report the identification of de novo mutations in the potassium channel gene KCNA2 in patients with epileptic encephalopathies. The authors confirm in vitro that two mutations cause dominant loss of channel function, whereas the other two mutations induce gain-of-function effects, leading to permanently open channels.