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Phage-plasmids are bacterial extrachromosomal elements that act both as plasmids and as viruses. Here, Shan et al. show that segregational drift and loss-of-function mutations play key roles in the infection dynamics of a cosmopolitan phage-plasmid, allowing it to create continuous productive infections in marine bacteria.

The 2.4 Å structure of the Ca²⁺-bound calpain 2 heterodimer bound to one of the four inhibitory domains of calpastatin. Calpastatin seems to inhibit calpain by occupying both the primed and unprimed sides of the active site cleft. This crystal structure also reveals the conformational changes that calpain undergoes upon binding calcium, which include opening of the active site cleft and movement of the domains relative to each other to produce a more compact enzyme.

CRISPRi-based screen identifies enhancers that nonlinearly regulate lineage-specifying transcription factors during definitive endoderm differentiation. A new CTCF-loop-constrained Interaction Activity (CIA) model is better at predicting functional enhancers than previous Hi-C-based enhancer–promoter contact frequency models.

SARS-CoV-2 seroprevalence surveys aim to estimate the proportion of the population that has been infected, but their accuracy depends on the characteristics of the test assay used. Here, the authors use statistical models to assess the impact of the use of different assays on estimates of seroprevalence in the United States.

The Micrarchaeota lineage includes poorly characterized archaea with reduced genomes that likely depend on host interactions for survival. Here, the authors report a stable co-culture of a member of the Micrarchaeota and its host, and use multi-omic and physiological analyses to shed light on this symbiosis.

Eric Schadt and colleagues report the construction of yeast regulatory networks from multiple sources of large-scale functional genomic data, and show that a network constructed from the integration of genotypic, transcription factor binding site, and protein–protein interaction data is the most predictive.

Shining intense laser light onto a thin aluminium foil creates a relativistic plasma aperture—and diffraction. As a result, an electron beam is generated with a spatial structure that can be changed by varying the characteristics of the laser pulse.

A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.

Pierre Guermonprez and colleagues have worked out how a subset of dendritic cells expands in individuals with severe malaria. Plasmodium infection causes an accumulation of xanthine in infected red blood cells. The researchers found that type I interferon triggers an increase in the enzyme that metabolizes xanthine to uric acid. Uric acid then acts on mast cells to release Flt3 ligand, an important regulator of dendritic cells, which in turn stimulate T cells to respond to the infection.

Nitrogen fixation by diazotrophs is critical for marine primary production. Using Tara Oceans datasets, this study combines a quantitative image analysis pipeline with metagenomic mining to provide an improved global overview of diazotroph abundance, diversity and distribution.

Using single-molecule imaging and manipulation, the authors show linker histone H1 preferentially forms phase-separated droplets with single-stranded nucleic acids over double-stranded DNA and nucleosomes, suggesting a noncanonical nuclear function.

Specific neurons in the fan-shaped body of the Drosophila brain convert translational information in relation to the fly’s body to externally referenced coordinates for navigation.

Nephropathic cystinosis is a lysosomal storage disease characterized by proximal tubular cell dysfunction. Here Festa and colleagues show that these lysosomal alterations lead to defective autophagic clearance of mitochondria and increased oxidative stress that, in turn, activates the transcription factor ZONAB leading to impaired cell differentiation.

Analyses from the gut microbiome of over 1,000 individuals from the PREDICT 1 study, for which detailed long-term diet information as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements are available, unveil new associations between specific gut microbes, dietary habits and cardiometabolic health.

The mechanisms of thermosensing in the Drosophila brain are elucidated by the identification of distinct classes of projection neurons which are excited either by external cooling or warming, or both; the neurons that are excited by warming participate in complex circuits that incorporate crossover inhibition from cool receptor neurons.

A variant telomerase template demonstrates that human telomeres can tolerate significant degeneracy and remain functional. Once incorporated by telomerase, variant sequences can influence telomere length dynamics.

How ribosomes differ in composition and function to regulate gene expression is poorly understood. Here, the authors show that ribosome composition changes during stem cell differentiation and identify a ribosomal protein that regulates production of the mesoderm lineage.

A new Burden of Proof meta-analytic method that accounts for between-study heterogeneity and corrects for bias between different study designs is used to interpret the strength of evidence between different pairs of risk factors and health outcomes.

Monocytes recruited to skin infection are not involved in bacterial clearance but instead regulate local angiogenesis and healing.

Retinal pigment epithelium (RPE) plays an important role in diabetic retinopathy (DR) progression. Here, the authors show AKT1 and AKT2 are reciprocally regulated in the RPE of DR donor tissue and diabetic mice, reducing Akt2 in RPE causing a compensatory increase in Akt1 and attenuating DR.

Future changes and regional differences in snowpacks are unclear. Here the American Cordillera mountain range, spanning the Americas, is estimated to lose snow faster in the southern midlatitudes—global warming should be limited to below 2.5 °C to prevent low-to-no-snow conditions across the range.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

It is important to understand dwell fatigue that has been implicated in several uncontained jet engine failures. Here the authors observe stress bursts due to slip intermittency in a Ti alloy using synchrotron x-ray diffraction microscopy to understand the roles of precipitates and trace oxygen.

Analysis of eleven Sulfolobus strains reveals that chromosome organization affects mutation rates in this species.

In a replicated ecosystem-scale natural experiment across ten islands in the Indian Ocean, invasive black rats disrupted nutrients provided by seabirds, leading to a coral reef fish having larger territories and investing less time in aggression than on rat-free islands.

Analysis of rare protein-truncating, damaging missense and copy number variants from exome sequencing of 63,237 individuals identifies 72 genes associated with autism spectrum disorder.

The design of solution-processed thermoelectric nanomaterials with efficient, stable performance remains a challenge. Here, the authors report an in-situ doping method based on nanoscale interface engineering to realize n-type thermoelectric nanowires with high performance and stability.

Over the past five decades, breakthroughs in device design and advances in material and growth technologies have transformed semiconductor lasers from laboratory curiosities into practical devices with real-world applications.

Targeting conserved secondary structure of RNA viruses offers the potential for a customizable therapeutic approach to viral variants.

In a series of experiments, Jangraw et al. show that people’s mood declines over time in common psychological tasks and during rest periods, but not in freely chosen behaviours.

Simultaneous single-cell protein and transcriptome analysis identifies a baseline immune circuit associated with antibody responses to vaccination in healthy individuals and the severity of disease flares in patients with a subtype of systemic lupus erythematosus.

MATR3 is an ALS-linked gene. Here the authors describe a mutant MATR3 knockin mouse, which mimics some aspects of early-stage ALS.

Xiao, Woodham, Cui, et al. apply machine learning to brain MRI data from major depression and the UK Biobank. They identify two neuroanatomical dimensions, one linked to preserved brain structure and healthier outcomes, and the other to reduced volumes, impaired cognition, self-harm, and adverse metabolic and genetic profiles.

Exposing Caenorhabditis elegans to non-coding small RNAs from pathogenic Pseudomonas aeruginosa induces avoidance behaviours in treated worms and their progeny, which reveals how C. elegans discriminates between bacterial species in its microbial environment.

Human aging is characterized by an elevated basal inflammatory state. Gilroy and colleagues use a tractable in vivo human inflammation model to demonstrate a mechanism whereby efferocytosis is impaired in the elderly but is reversible by p38 inhibition.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

Sung et al. provide a powerful pipeline based on deep mutational scanning to elucidate the molecular mechanisms of mitochondrial complex I assembly and predict pathogenicity of mutations in complex I assembly factors.

A framework to break the inherent trade-off barrier between spectral resolution and operational bandwidth of integrated optical spectrometers is developed and demonstrated on thin-film lithium niobate without sacrificing the compact footprint.

Dynamins are required at nascent endosomes to promote membrane fission. Here, the authors use super-resolution microscopy to show that dynamin-1 recruitment relies on pre-existing nanoclusters and trapping of molecules laterally diffusing on the plasma membrane.

Congenital myasthenic syndromes are rare inherited neuromuscular disorders. Here, the authors attempt to explain diverse disease severity seen in 20 patients with shared CHRNE gene mutations with a multilayer network analysis that identifies individual-level impairments at the neuromuscular junction.

Systemic lupus erythematosus is associated with neurological impairment. Here the authors show that exposure of hippocampal neurons to lupus autoantibodies in mice initiates a neuroinflammatory state sustained by continuous HMGB1:RAGE signaling that can be reversed with an ACE inhibitor.

A black hole at the centre of a quasar at a redshift of z = 4 is accreting the mass of the Sun every day. The quasar’s extreme luminosity is equivalent to 50,000 times that of the Milky Way. Its broad-line region should be resolvable observationally and will provide an important test for broad-line region size–luminosity relationships.

The esterification of butyrate to serine makes for an odourless and tasteless oral prodrug that ameliorated disease severity and reduced inflammatory responses in mouse models of rheumatoid arthritis and multiple sclerosis.

Here the authors show that the telomere repeat-containing RNA (TERRA) undergoes phase separation with the lysine-specific demethylase 1A (LSD1) to promote R-loop formation for homology-directed telomere DNA synthesis in the alternative lengthening of telomere (ALT) pathway.

An analysis of eight ultra-faint galaxies during the epoch of reionization with absolute magnitudes between −17 mag and −15  mag shows that most of the photons that reionized the Universe come from dwarf galaxies.

Single-cell RNA sequencing analysis of over 800,000 human adult breast cells from 55 female donors identifies 41 cell subtypes and highlights age- and parity-dependent effects. Samples from healthy women with germline mutations in BRCA1 or BRCA2 showed signs of T cell exhaustion.

Land use intensification is a major driver of biodiversity change. Here the authors measure diversity across multiple trophic levels in agricultural grassland landscapes of varying management, finding decoupled responses of above- and belowground taxa to local factors and a strong impact of landscape-level land use.