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Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Rare-earth permanent magnets are engineered with a complex microstructure of composition and phase, grains and grain boundaries, and it is this complex structure which leads to the magnetic performance. Here, Giron and coauthors, through thorough microstructural analysis, demonstrate that the grain microstructure, not grain boundaries, are primarily responsible for optimal magnetic properties.

Rhodopsin is a light-activated G-protein-coupled receptor. The structure of its ligand-free state at 2.9 Å resolution was reported recently. This paper describes a similar resolution crystal structure of the same protein bound to a fragment of G-protein and suggests a mechanism by which G-proteins might be activated by G-protein-coupled receptors.

Zangari et al. show that d-cysteine targets NFS1, thus affecting Fe–S cluster biogenesis and impairing tumour growth.

Here the authors show that genetic changes between species often alter gene expression in a cell type-specific manner. Most of this variability is driven by locally functioning cis-acting variation, and this contributes to the speed at which cell types accumulate expression changes.

High binding affinities are usually obtained when ligands are rigidified. Here the authors present flexible peptides binding to Armadillo repeat proteins with femtomolar affinity. They demonstrate that the bound state is characterized by residual dynamics limiting entropic losses upon binding.

The conserved eukaryotic heterotrimeric NatC complex co-translationally acetylates the N-termini of numerous target proteins. Here, the authors provide insights into the catalytic mechanism of NatC by determining the crystal structures of Saccharomyces cerevisiae NatC in the absence and presence of cofactors and peptide substrates and reveal the molecular basis of substrate binding by further biochemical analyses.

The molecular landscape of chromothriptic medulloblastoma remains to be characterised. Here, spatial transcriptomics analysis of 13 chromothriptic and non-chromothriptic medulloblastomas identifies distinct spatial composition patterns and cell communication networks in these tumours.

Chromothripsis (CT) is a type of genome instability which is prevalent in medulloblastoma with germline TP53 mutations (Li-Fraumeni syndrome, LFS). Here the authors combine single-cell genomic and transcriptomic analyses to reveal the clonal heterogeneity and functional consequences of CT in LFS medulloblastoma.

Potthoff and colleagues present a MALDI-MSI-based method that integrates in-source brightfield and fluorescence microscopy, which allows for spatially-resolved analysis of lipids and metabolites at the (sub)cellular level.

Channelrhodopsins’ mechanism of light-gated ion conductance could be engineered for use in optogenetic tools. Here, structures of the slow-cycling mutant of HcKCR1, including an open state structure, provide insight into channel gating and selectivity.

Multiomic factor analysis of blood multiomic data, including single-cell transcriptomics, for individuals with either acute or chronic coronary syndrome identifies immune cell signatures that correlate with treatment outcomes.

Recently discovered kalium channelrhodopsins (KCRs) are optogenetic tools for neuronal silencing. Here, authors report cryo-electron microscopy structures of KCR1 from Hyphochytrium catenoides and a highly homologous but sodium-selective channel from the same organism.

Isolating nanoscale species in liquids permits their scalable manipulation, enabling numerous fundamental and applied processes. Thus, achieving true dissolution of 2D materials is particularly desirable. Now, ionic salts of a range of important layered materials have been shown to spontaneously dissolve, yielding solutions of charged, monodisperse, undamaged and easy-to-manipulate 2D nanosheets.

Numerous genetic variants, including those located in the non-coding regions of the genome, are known to be associated with blood cells traits. Here, Frontini and colleagues investigate their potential regulatory functions using epigenomic data and promoter long-range interactions.

Opsin has recently been shown to equilibrate phospholipids across the photoreceptor disc membranes. Goren et al.demonstrate that the large conformational changes driven by exposure to light are not required for this activity, and provide insight into the potential mechanisms of lipid translocation.

JNJ-1802—a highly potent dengue virus inhibitor—blocks the NS3–NS4B interaction within the viral replication complex, and is highly effective against viral infection with DENV-1 or DENV-2 in non-human primates.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Retinitis pigmentosa is often caused by mutations that affect the activity or transport of rhodopsin, but some mutations cause disease even though an apparently functional protein is produced. Here the authors show that three such enigmatic mutants retain scramblase activity but are unable to dimerize.

The crystal structure of a ligand-free opsin at 2.9 Å resolution is reported; the entrance pathway for 11-cis-retinal and the exit pathway for all-trans-retinal are apparent.

Designing soft magnets with yield strengths exceeding one gigapascal while remaining ductile to prevent irreversible deformation for safe and efficient operation is challenging. The authors address this challenge by employing a nanostructuring strategy with morphologically anisotropic precipitates.

Here Mukherjee et al. characterize the bidirectional communication between adipose tissue and ovarian cancer cells and show that adipocytes instruct cancer cells to divert glycolytic glycerol-3-phosphate towards lipid synthesis, thus promoting metastasis.

Fluorine nuclear magnetic resonance spectroscopy of the stimulatory heterotrimeric G protein reveals a conformational landscape shaped by interactions with nucleotides, the lipid bilayer and a G-protein-coupled receptor.

The measurement of the total cross-section of proton–proton collisions is of fundamental importance for particle physics. Here, the first measurement of the inelastic cross-section is presented for proton–proton collisions at an energy of 7 teraelectronvolts using the ATLAS detector at the Large Hadron Collider.

High-performance magnets are essential for energy conversion, but rare earth dependence and brittleness limit their use. Here, authors develop a rare earth-free magnet with enhanced magnetic and mechanical properties by introducing nano-lamellar structures via thermo-magnetic processing.

Aberrant activation of the TGF-β pathway leads to fibrotic disease. Distler and colleagues show that TGF-β-mediated fibrosis requires the decrease of Dickkopf-1, an antagonist of canonical Wnt signalling, suggesting that the two pathways interact for the manifestation of this disease.

Anterior Uveitis is a common inflammatory eye disease that can result in vision loss. Here, the authors perform GWAS and whole-exome analyses of Anterior Uveitis to identify the underlying genetics of HLA-B*27 positive and negative forms of the disease.

The cryo-electron microscopy structure of human rhodopsin bound to the inhibitory G_i protein-coupled receptor provides insights into ligand–receptor–G-protein interactions.

A single-cell spatial transcriptomic and proteomic study of immune cells in the human CNS border compartments reveals differences in CNS-associated macrophages across age, perturbation and disease.

Mammalian mitoribosomes feature dramatically reduced ribosomal RNAs and follow mitochondria specific assembly pathways. Here the authors describe the process of human mitochondrial ribosome maturation that results in the formation of the ribosomal active site region, including the peptidyl transferase loop and the two tRNA-binding loops.

Hutchinson–Gilford progeria syndrome causes premature aging. Here the authors show that activation of the DNA damage response at dysfunctional telomeres and transcription of telomeric non-coding RNAs contributes to the pathogenesis, which can be ameliorated by treatment with sequence-specific telomeric antisense oligonucleotides.

When expressed in neurons, channelrhodopsin proteins allow the cells' electrical activity to be controlled by light. The structure of one such protein will guide efforts to make better tools for controlling neurons. See Article p.369

Whole-genome sequencing of tumour and germline DNA samples from 92 patients with high-grade serous ovarian cancer identifies frequent gene breakages that inactivate the tumour suppressors RB1, NF1, RAD51B and PTEN, and contribute to chemotherapy resistance; acquired resistance was associated with diverse mechanisms such as reversions of germline BRCA1/2 mutations and overexpression of the drug efflux pump MDR1.

Chip-scale modular components are important for nanophotonic applications. Here, the authors demonstrate post-processing of a silicon-on-insulator waveguide into an integrated hybrid plasmonic circuit, consisting of a plasmonic rotator and a nanofocusser module, which together result in nanoscale nonlinear wavelength conversion.

Alexander Schramm, Johannes Schulte and colleagues characterize 16 paired samples from patients with neuroblastoma at diagnosis and relapse using whole-exome sequencing, mRNA expression profiling, array CGH and DNA methylation analysis. Their data show the frequency, identity and evolution of genetic alterations in neuroblastoma.

A 256 × 256 pixel scintillator-based X-ray detector that improves resolution by limiting optical cross-talk is made using terbium-doped gadolinium oxysulfide scintillator particles in an organic photodetector matrix.

Platten and colleagues find that tryptophan metabolism by myeloid cells contributes to immunosuppressive microenvironment uniquely in IDH-mutant gliomas, which can be overcome by inhibiting this pathway in murine tumor models.

The kinase RIPK3 initiates necroptosis, which has been reported to promote inflammation in various pathological conditions. Here, the authors show that genetic ablation of Ripk3results in adipocyte apoptosis and white adipose tissue inflammation in obese mice, which promotes glucose intolerance.