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Non-alcoholic steatohepatitis (NASH) is characterized by lipid accumulation within hepatocytes and fibrosis. Seitz et al. show that the GTPase protein Rab24 is increased in the livers of people who are obese or have NASH.

The active zone is a brain signaling hub critical for synaptic information transfer and the encoding of behaviors. The authors identify Blobby as an assembly factor required for proper active zone nanoscale protein architecture and memory formation.

Species-specific gaze shifts with natural stimuli drive correlated spiking in retinal ganglion cells.

Here, Schubert et al. investigate the metabolic requirements for Salmonella Typhimurium colonization using a barcoded mutant pool across five different mouse models with varying microbiome complexity and identify several monosaccharides that are utilized in a context-(in)dependent manner.

Cerebral malaria can lead to fatal brain swelling. Oelschlegel et al. find infected red blood cells and reduced flow in large draining cerebral veins in mouse model of cerebral malaria, suggesting that impaired venous efflux could cause the swelling.

Commensal bacteria such as Lactobacillus rhamnosus can inhibit the pathogenicity of the fungus Candida albicans. Here, Alonso-Roman et al. investigate the interplay between C. albicans, L. rhamnosus and intestinal epithelial cells, showing that changes in the metabolic environment, induced by the bacteria, trigger adaptations in C. albicans that reduce fungal pathogenicity.

Single-molecule fluorescence currently requires specialized imaging equipment due to the low signal of a single emitter. Here the authors introduce NanoAntennas with Cleared HOtSpots (NACHOS) to boost the signal sufficient for detection of a single emitter by a smartphone, opening the door to point-of-care applications.

Spontaneous parthenogenesis in sunflower has been used to develop a scalable doubled haploid breeding system.

Proteins are inserted into the outer mitochondrial membrane by the mitochondrial sorting and assembly machinery, two structural forms of which are presented here, suggesting the mechanism involved.

The role of cortical PV neurons in the regulation of sleep architecture and homeostatic sleep rebound is not fully understood. Here, the authors show that CaMKII-mediated control of cortical parvalbumin-neuron activity regulates the homeostatic sleep rebound in mice.

Here the authors present a syntrophic vesicle system for selective transport of adenine nucleotides between ATP-producing and ATP-consuming nanoreactors. The platform can sustain synthetic cells, bionanoreactors and life-like entities with ATP.

The targeted development of proteome-wide selective covalent probes remains a challenge. Here, the authors show the exploration of the natural product Sulphostin as a starting point for dipeptidyl peptidase 8 and 9 inhibitor development.

Therapeutic antibodies with enhanced resistance to the evolution of SARS-CoV-2 can be identified via deep mutational learning by screening a combinatorial library of receptor-binding domains for antibody binding and escape.

A new asymmetric non-fullerene acceptor, P2EH-1V, is designed and synthesized for constructing devices demonstrating record-high efficiencies of 26.7% (certified at 26.4%) over an aperture area greater than 1 cm² in perovskite–organic tandem solar cells.

Cachexia is associated with poor prognosis in heart failure. Here the authors show that mice and patients with cardiac cachexia display reduced skeletal muscle expression and circulating levels of Musclin. Musclin ablation in skeletal muscle worsens, while its muscle-specific overexpression ameliorates heart failure in mice.

Germ layer specification during zygotic genome activation is regulated by chromatin state. Here, the authors use single-cell multiome profiling in Drosophila to show that H3K27me3 and H3K27ac at cis-regulatory elements control cell type-specific gene expression and developmental progression.

Antimicrobial peptide LL37 can bind nucleic acids and potentiate their sensing by endosomal TLRs. Here the authors show that LL37 binds to RNA from neutrophil extracellular traps (NETs), which amplifies inflammation and production of more LL37 and NETs via TLR8/13, suggesting that LL37 contribution to psoriasis may be fueled by NET-associated RNA.

How gut microbiota affect systemic responses to viral infection is still unclear. Here the authors use LCMV mouse infection model to show that a low complexity 12-strains community but not germ-free condition potentiates anti-viral immunity against LCMV beyond that of specific pathogen-free mice, but also aggravates LCMV-induced diseases.

Kiourtis et al. show that liver senescence triggers senescence and dysfunction in other organs through TGFβ secretion from the liver.

Activatable fluorophores are of interest for a wide range of applications but the need for caging groups complicates their development and application. Here, the authors report on a photoactivatable silicon rhodamine derivative and its application in live cell imaging and single-particle tracking.

Studying cilia in human neural development is key to understanding ciliopathies. Here, using stem cell-derived human and mouse spinal organoids, the authors reveal inter-species differences for ciliopathy genes and a role for cilia in human axial patterning.

KDM4C regulates cathepsin L-mediated histone H3 N-terminal tail clipping through grainyhead-like 2 (GRHL2) methylation in breast cancer. This link between the cellular redox state and chromatin remodeling might represent a therapeutic target in KDM4C-amplified tumors.

The filamentous fungus expression system Thermothelomyces heterothallica (C1) is a protein expression system that may be useful for large scale antibody production. Here the authors characterise the production of a human monoclonal antibody that neutralises SARS-CoV-2 and compare functional properties in vitro and in animal models to antibodies produced using other methods.

Protons are pumped across the inner mitochondrial membrane, and their return by diffusion through ATP synthase complexes generates ATP. Rieger et al. detect a lateral proton gradient between regions in which pumps or ATP synthase are concentrated, suggesting that the intra-cristae compartment is not at equilibrium.

Bacterial-fungal interactions can stimulate the production of specialised microbial metabolites. Here, Richter et al. use co-culture experimental evolution to show that the presence of a fungus selects for increased surfactin production in the bacterium Bacillus subtilis, which inhibits fungal growth and facilitates the competitive success of the bacterium.

Deep learning holds a great promise for the discovery and design of bioactive peptides, but experimental approaches to validate candidates in high throughput and at low cost are needed. Here, the authors combine deep learning and cell free biosynthesis for antimicrobial peptide (AMP) development and identify 30 functional AMPs, of which six with broad-spectrum activity against drug-resistant pathogens.

This study presents a large-scale analysis of microbial diversity in deep-sea sponges. They show that sponge microbial abundance status, geographic distance, sponge phylogeny and the physical-biogeochemical environment drive microbiome composition, in descending order of relevance. The uniqueness of each deep-sea sponge ground stresses the need for their strategic preservation.

Studying GnRH neuroendocrine cells in the mouse olfactory bulb (GnRH^OB neurons), Decoster et al. show that these cells respond to female odors and their activation regulates males’ female-odor preference and mating behavior.

Zhang et al. identify unimodal neural representations in the spinal cord of cutaneous mechanical and heat stimuli gated by a shared feed-forward local inhibitory neuron type and a neural transition during neuropathy, with increased excitatory drive.

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.

Mechanical stress during muscle contraction constantly threatens the proteome. Here, Kutzner et al. present the OptIMMuS model and identify the TRIM E3 ligase NHL-1 to regulate myosin levels and function upon mechanical stress.

Venomous animals typically disrupt nervous, locomotor, and cardiovascular systems to incapacitate prey, but certain fish-hunting cone snails evolved toxins that specifically target glucose homeostasis. Here, the authors show the combinatorial nature of weaponized insulin and somatostatin mimetics, exemplifying the use of combinatorial chemical mimicry for prey capture.

The nuclear periphery is linked with transcriptional repression, but MyoD1 remains active during myoblast proliferation despite being in this compartment. Here, the authors show that WFS1 tethers MyoD1 to the nuclear periphery via active enhancers.

RNA-binding proteins orchestrate many aspects of plant development and environmental responses. This protocol describes an optimized plant individual-nucleotide-resolution cross-linking and immunoprecipitation method for genome-wide identification of RNA-binding protein binding sites on their cognate RNAs at single-nucleotide resolution.

The RNA-binding ubiquitin E3 ligase TRIM25 plays a critical role in antiviral immunity. Here the authors identify key RNA-binding residues of TRIM25, link RNA binding to antiviral activity, reveal RNA structural and sequence preferences, and investigate binding to the viral genome.

The mechanisms of intratumoral subtype heterogeneity in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, the authors analyse PDAC tumours and preclinical models using multi-omics and imaging; they demonstrate that AP1 dichotomy influences tumor plasticity, heterogeneity, and immune response, with potential therapeutic implications.

This study describes sensing of circulating cell-free DNA after stroke as the mechanism leading to recurrent ischemic events.

Expression of TMPRSS2—a protease that activates SARS-CoV-2 for entry into cells—renders SARS-CoV-2 insensitive to chloroquine.