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A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

A tethered macrocyclic peptide antibiotic class described here—which shows potent antibacterial activity against carbapenem-resistant Acinetobacter baumannii—blocks the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane through inhibition of the LptB₂FGC complex.

There are big uncertainties in the contribution of irrigation to crop yields. Here, the authors use Bayesian model averaging to combine statistical and process-based models and quantify the contribution of irrigation for wheat and maize yields, finding that irrigation alone cannot close yield gaps for a large fraction of global rainfed agriculture.

Resistive switching in metal oxides is related to the migration of donor defects. Here Baeumer et al. use in operandoX-ray spectromicroscopy to quantify the doping locally and show that small local variations in the donor concentration result in large variations in the device resistance.

IL-36 receptor is crucial for host defense and tissue repair. Here, the authors describe identification and characterization of low molecular weight inhibitors of the IL-36 receptor using encoded library technologies. This represents a rare example of small molecules inhibiting a member of IL-1 receptor family.

In a multicenter, randomized trial, patients with heart failure with preserved ejection fraction who underwent a regimen of combined endurance and resistance exercise training over the course of 1 year did not show a statistically significant improvement in the modified Packer score—the primary efficacy endpoint—as compared to patients who received usual care, but they did show improvements in secondary endpoints for maximal oxygen consumption and NYHA heart failure class.

Here the authors report the cryo-EM structure of a triple-mutant of the anti-microbial peptide plectasin, PPI42, assembling in a pH- and concentration dependent manner into helical non-amyloid fibrils. The fibrils formation is reversible, and follows a sigmoidal kinetics. The fibrils adopt a right-handed helical superstructure composed by two protofilaments, stabilized by an outer hydrophobic ring and an inner hydrophobic centre. These findings reveal that α/β proteins can natively assemble into fibrils.

The presence of an accessory genetic element, tarIJLM—which leads to the production of a S. aureus-type wall teichoic acid—alters the lifestyle of S. epidermidis invasive clones, impairing in vivo mouse colonization but increasing endothelial attachment and host mortality.

The performance of energy materials is affected by structural defects, as well as physicochemical heterogeneity over different length scales. Here the authors map nanoscale correlations between morphological and functional heterogeneity, quantifying the trap states limiting electronic transport in bismuth vanadate thin films.

Hofer et al. show that fasting promotes the synthesis of spermidine, which stimulates eIF5A hypusination to induce autophagy and increase lifespan in various species in a conserved manner.

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.

In this work, authors report a method to describe, evaluate and generate floor plans using hypergraphs. With it, it is shown how spatial efficiency has larger energy saving potential than traditional building upgrade measures and how autogenerated floor plans can increase comfort and building performance.

Cryo-EM structures of Pol III preinitiation complexes are presented, comprising Pol III and the transcription factor TFIIIB bound to a natural promoter in different functional states.

RNA polymerase III (Pol III), the largest eukaryote polymerase yet characterized, transcribes structured small non-coding RNAs; here cryo-electron microscopy structures of budding yeast Pol III allow building of an atomic-level model of the complete 17-subunit complex, both unbound and while elongating RNA.

Here, Dekkers et al. characterize associations of 1528 gut metagenomic species with the plasma metabolome in 8583 participants of the SCAPIS Study, and find that gut microbiota explain up to 58% of the variance of individual plasma metabolites.

Y6, as a non-fullerene acceptor for organic solar cells, has attracted intensive attention because of the low voltage loss and high charge generation efficiency. Here, Zhang et al. find that the delocalization of exciton and electron wavefunction due to strong π-π packing of Y6 is the key for the high performance.

Stomata act to control CO₂ uptake and water loss, integrating endogenous signals with environmental cues to ‘set’ stomatal aperture. Separate closure-inducing signals access unique but partially overlapping, modular gene networks.

Transcription factor TFIIIC plays roles in Pol III transcription and in chromatin organization. CryoEM structure of the yeast TFIIIC subcomplex τA, a negative stain reconstruction of τA bound to the TFIIIB subunits Brf1 and TBP and accompanying biochemistry suggest how τA achieves positioning of TFIIIB upstream of the TSS and remodeling of the TFIIIC complex during assembly of TFIIIB.

A disturbed microbial network characterizes relapsing refractory Crohn’s disease and antedates disease recurrence after surgical removal of the active disease segment.

Myosin A (PfMyoA) is essential for the pathogenesis of Plasmodium falciparum, the causative agent of malaria. Here we decipher the mechanism by which a small molecule inhibitor (KNX-002) of PfMyoA impedes its motor activity.

Acanthaporin is identified as a pore-forming protein from the infectious Acanthamoeba culbertsoni with a previously unknown structure. The newly identified structure includes a pH-dependent histidine switch that controls partitioning between the inactive dimer and the active monomer, which assembles into larger species to cause toxicity.

Steroid units can facilitate membrane permeation and bioavailability in drugs. Here, using a medicinal chemistry program, Krieget al. identify an arylmethylamino steroid that kills Plasmodium parasites, likely through a chelate-based quinone methide mechanism, and has activity against Schistosoma mansoni.

The nasal commensal bacterium Staphylococcus lugdunensis produces a novel cyclic peptide antibiotic, lugdunin, that inhibits colonization by S. aureus in animal models and is associated with a significantly reduced S. aureus carriage rate in humans, suggesting that human commensal bacteria could be a valuable resource for the discovery of new antibiotics.

TREM-1 is a receptor that amplifies acute pro-inflammatory responses in infection. Here the authors show that TREM-1 plays an important role in atherosclerosis, a chronic and non-infectious disease, by critically skewing myelopoiesis towards preferential monocyte differentiation and by contributing to CD36-driven cellular lipid accumulation.

The authors measure numerous ecosystem functions across an elevational gradient on Mt Kilimanjaro and find that species richness impacts function more than species turnover across sites. They also show that variation in species richness impacts ecosystem functioning more strongly at the landscape scale than at the local scale.

The heparan sulfate proteoglycan-binding cytokine APRIL has a protective role against atherosclerotic disease.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Production of polyphosphate polymers is a ubiquitous trait of bacteria. Here, the authors investigate the role of bacterial long polyphosphates in host immune suppression and show that long polyphosphates produced by E. coli inhibit LPS-mediated inflammation and bacterial clearance in mice.

Multidimensional spectroscopic tools are important to explore the details of molecular dynamics. Here the authors use shaped pulses to demonstrate a 3D fluorescence spectroscopy method to extract the fourth and higher-order nonlinear responses in light-molecule interaction.

G protein-coupled receptors are a major class of drug targets. Here, the authors develop a method whereby their biophysical and functional properties can be altered through directed evolution in mammalian cells, leading to variants exhibiting features such as high stability and expression, or increased allosteric coupling.

In ice-rich Siberian permafrost sediments deposited during the Pleistocene, 33-74% of the organic carbon is mineral-bound favoured by the presence of reactive iron, which can reduce microbial CO₂ production after thawing

A number of disease-causing human transthyretin (TTR) mutations are known to lead to amyloid formation. Here the authors combine neutron crystallography, native mass spectrometry and modelling studies to characterize the T119M and S52P-TTR mutants, providing mechanistic insights into TTR amyloidosis.

Group 3 innate lymphoid cells (ILC3s) promote T cell activation in the spleen but suppress it in the gut. Here, the authors show that this distinct regulation is mediated by gut microbiota-induced IL-23 and IFN-γ, respectively, and, along with the article by Rao et al, this work elucidates how cytokines set context specificity of ILC-T cell crosstalk by regulating ILC antigen presentation.

In contrast to previously reported findings, M2-like polarized macrophages are not a source of catecholamines and do not contribute to browning of the fat.

A 3.3-Å-resolution cryo-EM structure of yeast Maf1 bound to RNA polymerase III (Pol III) explains the molecular mechanism for Pol III inhibition.

Many chromatin modifying proteins, including BRDT, contain bromodomains, which are known to interact with nucleosomes. Here, the authors find that BRDT interacts with nucleosomes via only one of its two bromodomains, and that the interaction involves contacts with DNA as well as acetylated histones.

Patients with partial recombination-activating gene (RAG) deficiency (pRD) present variable late-onset autoimmune clinical phenotypes. Walter and colleagues identified a restricted primary B cell antigen receptor repertoire enriched for autoreactivity and clonal persistence in pRD. They described dysregulated B cell maturation with expansion of T-bet⁺ B cells revealing how RAG impacts stringency of tolerance and B cell fate in the periphery.

Here the authors structurally investigate elongating human RNA polymerase I at 2.7 Å using cryo-electron microscopy, as well as an RNA polymerase I open complex at 3.3 Å and bound to initiation factor RRN3 at 3.2 Å.

Measuring the mass of individual microbial cells remains challenging. Here, the authors present a cell balance to monitor the proliferation of single budding yeast cells under culture conditions in real time, showing that single cells increase total mass in multiple linear segments of constant growth rates.

Oncogenic dosage variation along distinct evolutionary routes defines fundamental aspects of pancreatic cancer biology and phenotypic diversification.

The helical bundle structure of the CC1 ___domain of STIM1 of the store-activated calcium channel CRAC is crucial to maintaining the channel resting state, and helix–helix interactions can be manipulated to normalize a disease-linked STIM1 mutant.

Cryo-EM structures of human Pol III in both apo- and elongating states reveal metazoan-specific differences in the regulation of transcription termination and identify mutations relevant to human disease.

Acinic cell carcinoma (AciCC) is a rare salivary gland carcinoma that is poorly understood. Here the authors perform genomic, transcriptomic and epigenomic profiling of AciCC and find highly recurrent and specific rearrangements [t(4;9)(q13;q31)], which lead to enhancer hijacking that activates oncogenic transcription factor NR4A3.

An online approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups has been developed to help to improve current diagnostic standards.