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The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Stabilization of continental crust requires temperatures of over 900 °C, establishing a link between ultrahigh-temperature metamorphism and craton formation, according to a study of U and Th concentrations in metasedimentary and metaigneous rocks.

The CPLANE complex is essential for ciliogenesis, and mutations to all but one subunit have been associated with ciliopathies. Here they identify three familial mutations in the final subunit, RSG1, that cause ciliopathy and add to our understanding of ciliary transition zone assembly.

The translation of transgenes is regulated using RNA sensors.

The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights.

The understudied lipid kinase PIP4K2C binds SARS-CoV-2 nonstructural protein 6 and regulates virus-induced autophagic flux impairment, suppressing viral protein degradation. PIP4K2C inhibition is a candidate strategy to combat emerging viruses.

Peter Gluckman finds US presidential science adviser John Marburger's posthumous collection enigmatic.

An epicardial device that enables sustained and repeated administration of small molecules, macromolecules and cells directly to the epicardium provides therapeutic benefits in a rat model of myocardial infarction.

Repair of muscle damage requires muscle stem cells, which lose regenerative capacity with aging. Here, the authors show that a sensory organelle, the primary cilium, is critical for muscle stem cell proliferation during regeneration and lost with aging.

A systematic census at 1,636 sites around Australia from 2008 to 2021 finds that more than 30% of shallow invertebrate species in cool latitudes exhibit a high extinction risk due to declining populations and oceanic barriers, but tropical coral species remain relatively stable.

Magnetic resonance imaging of swollen tendons suggests that the elasticity and stress relaxation of extracellular matrix depend on electrostatic repulsions between proteoglycans rather than on hydration-associated changes.

Plant community responses to climate change tend to be lagged in forests, but could be faster in grasslands. Here, the authors integrate long-term experimental data with >1 million occurrence records for >300 species, finding grassland community shifts towards species associated with warmer and drier conditions at a pace that aligns with that of climate change.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

Uhlhaas and Singer outline the evidence that schizophrenia is associated with deficits in neural oscillations. They discuss the possible underlying mechanisms and how these impairments might contribute to the pathophysiology of the disorder.

E2F transcription factors are regulators of cell division and cell fate decisions. Here the authors show that E2F4 is important for proliferation and survival of mouse ESCs, independent of the RB family, and that E2F4 interacts with chromatin regulators associated with gene activation.

The Cancer Genome Atlas Network describe their multifaceted analyses of primary breast cancers, shedding light on breast cancer heterogeneity; although only three genes (TP53, PIK3CA and GATA3) are mutated at a frequency greater than 10% across all breast cancers, numerous subtype-associated and novel mutations were identified.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

The actin severing factor cofilin is activated by the slingshot phosphatases. Phosphorylation of slingshot 1L by protein kinase D is found to block the association of slingshot 1L with actin, thereby inhibiting cofilin activation and directed cell migration.

A lack of clinical investigation, which has arguably become more pronounced in the past decade, currently hinders progress in cancer surgery research, and ultimately the treatment of patients with cancer. This Perspectives describes the major barriers to progress in surgical oncology, and how improvements might be made in this important, but often overlooked, aspect of cancer treatment.

The development of fully defined culture conditions for human embryonic stem cells (hESCs) should enhance experimental reproducibility, reduce unwanted contaminants and facilitate scale-up production. Melkoumian et al. show that a substrate made of peptides derived from extracellular matrix proteins supports long-term culture of hESCs and differentiation to cardiomyocytes.

Increasing population size and per capita impacts are making sustainability a difficult to goal to achieve; this Review explores possibilities for sustainable development.

Integrating Australian Aboriginal art and narratives with soil excavation data suggests that the regularly spaced bare circles in Australian arid grasslands (sometimes known as ‘fairy circles’) are in fact linyji or mingkirri, termite pavement nests used by Aboriginal people for domestic and sacred purposes over generations.

The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.

A report on the results of the first large-scale community-based critical assessment of protein function annotation (CAFA) experiment.

Ontologies are powerful tools that facilitate the integration of large and disparate data sets. Here, researchers from the Kidney Precision Medicine Project provide an introduction to ontologies, including those developed by the consortium, describing how these will be used to improve the annotation of kidney-relevant data, eventually leading to new definitions of kidney disease in support of precision medicine.

Ptacin et al. utilize a semi-synthetic microbial platform with an expanded genetic code to discover a PEGylated IL-2 compound that stimulates Tregs, with minimal effects on effector populations. Studies in mice and primates demonstrate Treg stimulation and support development of this compound for the potential treatment of autoimmune diseases.