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Here, the authors used electronic healthcare records to analyse the genetic basis of variation in 42 routinely-acquired quantitative blood tests among up to 40,000 British South Asian volunteers from the Genes and Health study. By combining their results with genetic findings from UK Biobank, they explore similarities and differences between ancestries in the genetic basis of these traits.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

Despite widespread use of azides across material science and various areas across chemistry, the underlying biosynthetic pathways for its formation have so far been unknown. Now, a promiscuous ATP-utilizing enzyme, Tri17, capable of synthesizing various azide molecules has been identified. Biochemical, structural and computational analyses support a potential molecular mechanism for azide formation by Tri17.

Mechanistic analysis of α-synuclein binding clarifies the roles of lipid packing defects and charge in regulating membrane interactions.

Abdel-Wahab and colleagues perform immunophenotyping of AML cells to identify AML-specific surface antigens and show that the RNA helicase U5 snRNP200 represents a therapeutic target for antibody therapy with optimized Fc receptor binding.

Here, the authors identify a third component of the outer membrane LPS translocon in Escherichia coli called LptM. Biochemical analysis and structural modelling reveal that LptM binds the LPS translocon by mimicking its native substrate, so stabilising an active conformation of the complex.

Bacterial type IV pili are filamentous cell surface structures and candidate targets for vaccine development. Here, authors determine how antibodies interact with pili at the structural level providing insight into immune escape mechanisms and potential countermeasures.

AI methods can discover new antibiotics but existing methods have limitations. Swanson et al. develop a generative AI model that learns to design molecules that are easy to synthesize. The authors apply the model to design and validate novel antibiotics against the bacterial pathogen Acinetobacter baumannii.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Spontaneous jumping of condensing droplets holds promise for antifogging, but is generally inhibited for microdroplets. Lecointre et al. show that antifogging ability of cone structures at nanoscales is universal over a large range of cone sizes, shapes, apex angles and even truncation.

KCNQ1 channels are active in heart, brain and gut. Functional loss causes epilepsy and sudden arrhythmic death. Here, authors describe a key activator drug binding site, explaining isoform and drug selectivity, and point the way for new drug design.

Organic biocrystals play crucial roles in biological processes and diseases, yet the molecular mechanisms of their formation remain poorly understood. Here, the authors reveal that hematin crystal nucleation in malaria parasites follows a nonclassical pathway and can be modulated by solute-modifier interactions, offering a strategy to control crystal formation in a variety of systems, including for malaria treatment.

Jungnickel, Guelle et al. use metabolomics, electrophysiology and cryo-EM approaches to show that MFSD1 is a lysosomal dipeptide uniporter, which provides an additional route to recycle lysosomal proteolysis products to lysosomal amino acid exporters.

Determining dynamic ensembles of biomolecules is still challenging. Here the authors present an approach for rapid RNA ensemble determination that combines RNA structure prediction tools and NMR residual dipolar coupling data and use it to determine atomistic ensemble models for a variety of RNAs.

Here, the authors combine single-molecule atomic force spectroscopy measurements and molecular dynamics simulations to investigate the binding of spike proteins from four SARS-CoV-2 variants of concern (VoC) to the human ACE2 receptor. They observe an increase in the RBD-ACE2 complex stability for several of the VoCs and derive how the mutations affect the kinetic, thermodynamic and structural properties of complex formation.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Mechanically interlocked molecules and molecular cages are two important themes in supramolecular chemistry. Here, the authors combine these concepts to construct a giant [13]rotaxane built around a palladium capsule, one of the most complex metallosupramolecular assemblies yet.

Gloeobacter proton-gated ion channel (GLIC) is a convenient model of pentameric ligand-gated ion channels. Here, Bharambe & Li et al. report structures and simulations of GLIC with insights into the role of lipids in GLIC gating mechanism.

A massively parallel computational and experimental approach for de novo designing and screening small hyperstable proteins targeting influenza haemagglutinin and botulinum neurotoxin B identifies new therapeutic candidates more robust than traditional antibody therapies.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Collagen is an important structural protein in connective tissue, but the effect of location and type of micro-ruptures in the structure on the overall tissue is not well understood. Here, the authors use scale-bridging simulations to determine the breakage points in collagen, and how the failure mode helps to prevent material ageing

Bacterial cell shape is dependent on the formation of the extracellular sugar polymer called peptidoglycan. Here the authors describe RodA-PBP2, the enzymatic core of the elongasome, which is the complex responsible peptidoglycan synthesis, and utilize an integrated approach to investigate the mechanism of peptidoglycan biosynthesis.

Genome release of enteroviruses relies on exposure to acidic pH, but the mechanism of uncoating remains unclear. Here, Buchta et al. show that echovirus 18 loses one to three adjacent capsid-protein pentamers, resulting in an opening of more than 120 Å for genome release.

The transition between conducting and non-conducting states of K⁺ channels has been explained by conformational changes at the intracellular entrance to the conduction pathway. Here authors demonstrate that control over K⁺ currents in Kir channels is not explained by the canonical pore-gating model, as conduction is not impaired by a constricted inner helix bundle.

New data on brain-wide circuits centred around two interconnected hypothalamic neuron populations provide significant mechanistic insights into the emergence of social need during social isolation and the satiation of social need during social reunion.

Malaysia's research system is closed and isolated. What are scientists with a yen for rigorous research to do? David Cyranoski finds out.

Sodium glucose transporters are critical for maintaining glucose homeostasis. Here, authors provide a detailed framework for how SGLTs utilize cellular membrane potentials to stabilize their substrate accepting conformation leading to accelerated transport.

HPV’s E6 protein promotes cancer by degrading p53. This study reveals the cryoEM structure of HPV16 E6 in complex with E6AP and p53, highlighting their picomolar affinity and large protein-protein interaction interface.

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.

NHA2 exchanges sodium ions for protons across cell membranes, and its activity is linked to the pathogenesis of diabetes mellitus and essential hypertension in humans. Drew et al. report the cryo-EM structure of NHA2 in detergent and nanodiscs.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Glycine receptors (GlyR) are a critical postsynaptic component of spinal neurons. Here, the auhtors present cryo-EM structures of a heteromeric GlyR in the presence of an antagonist, agonist and agonist with a positive allosteric modulator.

The condensation of RNA polymerase II (Pol II) into transcriptionally active clusters is critical for eukaryotic gene regulation and pre-mRNA transcription. Here the authors show that a tight network of tyrosine-proline interactions imparts temperature and concentration-dependent self-coacervation of Pol II’s C-terminal domain (CTD).

An exciting genome-wide association study in the British population for seven common diseases. This analysis confirms previously identified loci and provides strong evidence for many novel disease susceptibility loci.

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.

Cryo-electron microscopy structures of three different serotonin receptors in complex with serotonin and other agonists provide insights into the role of lipids in regulating these receptors and the structural basis of ligand recognition.

Cryo-electron microscopy structures of PCFT in a substrate-free state and bound to the antifolate drug pemetrexed provide insights into how this protein recognizes folates and mediates their transport into cells.

Human disease mutations affect protein–protein interfaces in a three-dimensional structurally resolved interaction network. Predicted oncoPPIs in cancer correlate with survival and drug sensitivity, and affect growth in vitro, supporting their relevance to disease pathogenesis.

The intrinsic disorder of histone tails poses challenges in their characterization. Here the authors apply extensive molecular dynamics simulations of the full nucleosome to show reversible binding to DNA with specific binding modes of different types of histone tails, where charge-altering modifications suppress tail-DNA interactions and may boost interactions between nucleosomes and nucleosome-binding proteins.

The uptake of hydrophobic molecules by bacterial FadL channels is implicated in quorum sensing, interactions with eukaryotic hosts and biodegradation of many pollutants. Insights into monoaromatic hydrocarbon uptake by TodX and CymD channels suggest that all FadL channels mediate substrate uptake via lateral diffusion.

John Perry, Ken Ong and colleagues analyze genotype data on ∼370,000 women and identify 389 independent signals that associate with age at menarche, implicating ∼250 genes. Their analyses suggest causal inverse associations, independent of BMI, between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men.

Despite advances in GPCR structures and peptide design, creating high-affinity ligands remains a challenge. Here the authors develop a computational method, successfully identifying peptide-based molecules for KOR: their platform shows promise for streamlined GPCR ligand discovery.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

A cooperative insertion mechanism for CO₂ adsorption is shown to generate highly efficient adsorbents for carbon capture applications.