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This is a Protocol for the derivation, expansion and cryopreservation of primary organoids from human amniotic fluid cells. These cells generate lung, kidney tubule and gastrointestinal epithelial organoids autologous to the developing fetus.

Evolution of viruses undermines the efficacy of vaccines and antibody therapies. To overcome this challenge, authors describe a strategy for prefusion-stabilization to provide proof-of-principle for fusion-machinery sarbecovirus vaccines.

SPNS2 exports S1P and FTY720-P to control immune cell migration. Here, the authors use cryo-EM, immunofluorescence, in vitro binding and in vivo S1P export, and MD simulations to uncover the mechanisms of SPNS2’s transport and inhibition.

Homologous to E6AP C-terminus (HECT) E3s forge polyubiquitin chains through multiple reaction steps. A HECT polyubiquitylation cascade was visualized step-by-step, through use of chemical tools and cryo‐EM, and revealed how K48 linkage-specificity is attained by oligomeric UBR5.

Using cryo-EM structures, single-molecule fluorescence and electrophysiological studies, Kern et al. show how LRRC8A:C volume-regulated channels assemble into heteromers and use pore-bound lipids to block conduction in a closed state.

The rhoptry is an apical secretory organelle of apicomplexan parasites that is essential for host cell invasion. Here, Mageswaran et al. provide in situ ultrastructures of rhoptries from two pathogens, revealing a conserved architecture including luminal filaments and a distinct docking mechanism.

The pros and pitfalls of partnering in science, with insights from researchers and beyond.

The pros and pitfalls of collaboration, with insights from researchers and beyond.

We investigate the de novo design of allostery and suggest that it can arise from global coupling of the energetics of protein substructures without optimized allosteric communication pathways, providing a roadmap for the design of switchable molecular systems.

Jee et al. study a cancer hotspot allele of DICER1 that disrupts RNaseIIIb activity. Beyond ablating 5p hairpin cleavage, 3p passenger strands are globally upregulated and active. Thus, this setting induces both loss and gain of miRNA function.

Serotonergic enterochromaffin cells of the intestine exhibit distinct sensory, secretory and physiological properties depending on their location within the complex crypt–villus architecture of the gut.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

The β-barrel assembly machinery (BAM) assists the folding and membrane insertion of bacterial outer membrane proteins. Here, the authors report structural characterization of BAM in lipid environment and in complex with the client protein EspP integrated into the barrel of BamA, providing insight into BAM mechanism of function.

A post eradication polio vaccine should be safe and easy to produce. Here, the authors characterize a recombinant virus-like particle polio vaccine with stabilized capsid proteins and show comparable immunogenicity to the current inactivated polio vaccine.

Structural and biophysical analysis of the Arabidopsis thaliana auxin transporter PIN8 reveal that PIN transporters export auxin using an elevator mechanism.

Ojer et al. use data from the American National Election Studies to map US voters in a two-dimensional ideological space. Democrats and Republicans have grown more polarized over the past 30 years, while partisan sorting has declined since 2010.

A newly developed monoclonal antibody, MARV16, broadly neutralizes all Marburg virus isolates and provides effective protection in guinea pigs with Marburg virus disease.

Antibiotics to treat carbapenem-resistant Acinetobacter baumannii infection are an urgent need. The cerastecins are potent, bactericidal and efficacious in animal models of infection, and may enable new treatment modalities targeting LOS transport.

This pilot trial showed that perioperative treatment with the isocitrate dehydrogenase (IDH) inhibitor safusidenib of patients with low-grade IDH-mutant glioma, with craniotomy and lumbar puncture before and after treatment, is feasible and safe and enabled in-depth translational investigation of safusidenib treatment-induced changes in the tumor, including electrophysiological effects.

Cryo-electron microscopy has undergone a resolution revolution—here, this method has been combined with lipid nanodisc technology to solve structures of TRPV1, the receptor for capsaicin, in a membrane bilayer, revealing mechanisms of lipid and ligand regulation.

Ancient DNA reveals how the explosive expansion of Yamnaya steppe pastoralists began with a small community north of the Black Sea speaking ancestral Indo-European, and detects genetic links with Anatolian speakers, stemming from a common Indo-Anatolian homeland in the North Caucasus–lower Volga region.

Advancements in sequencing technologies and assemblers have enabled us to generate a complete, haplotype-resolved X chromosome in cattle. This study discovers the cattle X centromere is a natural neocentromere and characterises its genetic and epigenetic structure.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

Virus-host competition drives evolution of diverse antiviral defences in bacteria and antidefense systems in their viruses (phages). Here, Silas et al. use a functional screen of phage accessory genes to show how bacterial cell-surface sugars can be major determinants of phage host-range, and how some phage proteins injected into bacterial cells inhibit host immunity.

Upon hyperpolarization, the S4 voltage-sensing segment of sea urchin SLC9C1 moves down, removing inhibition caused by an intracellular helix and enabling Na⁺/H⁺ exchange, leading to pH-dependent activation of sAC and sperm chemotaxis.

LARGE1 glycosyltransferase synthesizes matriglycan (xylose-glucuronate)_n on dystroglycan, and short matriglycan can cause neuromuscular disorders. Authors show that LARGE1 processively polymerizes matriglycan of defined length on prodystroglycan.

Designed novel protein nanoparticle technology integrates antibody targeting and responds to changes in environmental conditions to release protected molecular cargoes, opening new applications for precision medicine.

Proteins in the fungal plasma membrane are key antifungal targets but their native structure and spatial distribution are poorly understood. Here, Jiang et al. use proteomics and cryo-electron tomography to investigate the organisation of membrane proteins in the fungal plasma membrane and how this is affected by antifungal drugs.

Structures of the yeast replisome associated with the FACT complex and an evicted histone hexamer offer insights into the mechanism of replication-coupled histone recycling for maintaining epigenetic inheritance.

A new computational method for design of pseudosymmetric self-assembling protein nanomaterials has resulted in purification of cage-like protein assemblies containing 960 subunits with a diameter of 96 nm.

Here, the authors apply genome-scale metabolic network reconstructions to metagenomic data obtained from human vaginal swabs to identify bacterial vaginosis-associated bacterial metabolic interactions, and validate in vitro microbial metabolites implicated in host estrogen receptor binding.

The SIT1-ACE2 complex transports the amino acid proline and is the receptor of SARS-CoV-2. Here, the authors identify specific sequence requirements for proline transport and explain for how a missense mutation causes iminoglycinuria.

N-glycosylation is vital for biological processes but difficult to analyse. Here, the authors introduce a scalable method to profile N-glycans across 20 mouse tissues, revealing tissue-specific glycosylation patterns and novel N-glycan structures, offering new insights into glycobiology.

Crohn’s disease is associated with altered intestinal microbiota. Here, the authors show that the microbe Atopobium parvulumis associated with Crohn’s disease patients, triggers colitis in a mouse model, and that scavenging microbe-induced hydrogen sulfide improved symptoms in mice.

A structural and functional analysis of the systems involved in oligosaccharide uptake in gut Bacteroidetes describes multicomponent complexes termed utilisomes that include pre-processing and transport subunits.

Na+ /H+ exchangers regulate intracellular pH, sodium levels, and cell volume. Cryo-EM structures reveal lipid coordination at the dimer interfaces of NhaA with cardiolipin and endosomal NHE9 with PI(3,5)P2. These findings demonstrate how specific lipids can regulate ion-exchange activity by stabilizing dimerization with physiological ramifications.

Cryogenic electron ptychography (Cryo-EPty) is an emerging method for imaging the structure of biomacromolecules. Here, authors develop single particle analysis based on cryo-EPty phase for high contrast, wide spatial frequency-band 3D imaging.

The molecular mechanisms of cell entry for the recently identified highly pathogenic feline coronavirus FCoV-23 are characterized in detail.

A high-resolution electron cryo-microscopy structure of the rat transient receptor potential (TRP) channel TRPV1 in its ‘closed’ state is presented; the overall structure of this ion channel is found to share some common features with voltage-gated ion channels, although several unique, TRP-specific features are also characterized.

Nucleotide excision repair is a conserved DNA repair system. Here, the authors explore the structural details of damage identification by UvrA and reveal the UvrA-UvrB-DNA complex architecture at varying stoichiometries. They propose a model for damage recognition by UvrA and lesion hand-off to UvrB.

In their study, Ezuz et al. show that the aged spleen contributes to T cell aging through hemolytic stress and an increasingly heme- and iron-rich microenvironment. T cells adapt by limiting their iron levels. This protective response impairs cell function but can be reversed in vivo by iron supplementation during activation.

Tilt-corrected bright-field scanning transmission electron microscopy offers enhanced cryogenic electron microscopy contrast and substantial improvement in dose efficiency for thick samples such as bacterial cells and large organelles, while still being able to perform single-particle analysis.

By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding interdomain misfolding.

It is unclear why C. elegans continues to produce large quantities of yolk after reproduction. Here the authors show that post-reproductive C. elegans mothers vent yolk which supports their offspring’s growth, serving as a form of primitive lactation.

Here the authors use a range of approaches to examine the interplay between genetic variants linked to risk for polygenic skin diseases and transcription factors (TFs) important for skin homeostasis. The findings implicate dysregulated binding of specific TF families in risk for diverse skin diseases.

A quantum algorithm is introduced that performs Markov chain Monte Carlo to sample from the Boltzmann distribution of Ising models, demonstrating, through experiments and simulations, a polynomial speedup compared with classical alternatives.

We present a protocol for the analysis of polar and ionic metabolites by using anion-exchange chromatography–tandem mass spectrometry (AEC-MS/MS) with an untargeted or semi-targeted workflow for the identification of metabolites in biological samples.

The SLC45A4 gene encodes a neuronal polyamine transporter and is linked to pain response in humans and mice.