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Liver fibrosis is a consequence of the sustained inflammatory processes underpinning chronic liver disease. Here authors show that autophagy in CD4 T cells is an important process in preventing the emergence of pathogenic Th17 cells, which are causal to the progression of liver fibrosis.

Here, the authors identify a conformational switch in the amino-terminal transactivation domain of c-MYC, termed coreMYC, which cycles between a closed, inactive state and an open, active conformation. Polyphenol epigallocatechin gallate (EGCG) is used to modulate the conformational landscape of coreMYC, stabilizing the closed and inactive conformation.

COMPLEXES of manganese(ii) with bipyridine (bpy) have the potential to act as catalysts for oxidation of alkanes and alkenes when the complex is oxidized in acidic conditions^1–6. But their catalytic activity in solution is limited by their catalase activity⁷—their tendency to decompose H₂O₂. Because of their polynuclear nature such complexes cannot induce epoxidation of alkenes, and other epoxidation catalysts suffer from self-oxidation and side reactions^8–11. Moreover, all of these homogeneous catalytic processes require phase-transfer conditions. Here we report that, when encapsulated in the supercages of zeolites X and Y, cis-[Mn(bpy)₂]²⁺ complexes can catalyse selective epoxidation of alkenes without complications from competing processes such as self-oxidation or catalase activity. Epoxidation of cycloalkenes is followed by acid-catalysed ring-opening, carbon–carbon bond cleavage and formation of alkenedioic acids (Fig. 1). All of the various intermediates in the process can be obtained selectively by controlling the reaction conditions and zeolite acidity. Thus this supramolecular system provides a clean, one-step heterogeneous catalytic route to useful industrial products.

The interplay between continental subduction exhumation dynamics and the obduction of ophiolite sheets remains enigmatic. Here, the authors show that the extrusion of the subducted continental upper crust triggers the necking and breaking of the oceanic upper plate and leads to far-travelled ophiolite sheet emplacement.

A large international panel of experts reach consensus on a new standard for reporting settings in psychedelic trials, identifying 30 key non-pharmacological factors to strengthen the rigor of psychedelic research.

Murcy et al. show that increasing the plasma glutamine-to-glutamate ratio in atherosclerosis can distally reprogram transcriptional and post-transcriptional remodeling of the aorta by GLS2-dependent hepatic glutaminolysis.

Low-latitude planktonic foraminifera are coping with rapid ocean warming, acidification and nutrient shifts by migrating to deeper water-column depths or polewards, displacing higher-latitude species and reducing low-latitude diversity, ultimately being unable to adapt fast enough to survive in situ.

Three closely related proline-based ligands give rise to different catalytic systems in asymmetric dialkylzinc addition reactions. Mechanistic studies reveal that monomeric, dimeric and product–catalyst complexes and aggregates larger than dimers are all catalytically active.

High-throughput screening and hit optimization have led to the development of a small molecule, CIM-834, that targets the SARS-CoV-2 membrane protein and blocks assembly of the virus.

The vascular, cellular and molecular changes underlying sex differences in mood disorders are unclear. Here, the authors show that blood-brain barrier dysfunction modulates anxiety- and depressive-like behaviors in female mice and endothelium-specific changes associated with maladaptive responses compared to resilience to stress.

Nanobodies recognizing class-II major-histocompatibility-complex molecules and conjugated to relevant self-antigens confer protection against autoimmune diseases in mice.

Calcium-permeable AMPA receptors are identified to have a role in maintaining low feature selectivity in a specific population of inhibitory interneurons, and this function is conserved across ferrets, rodents, marmosets and humans.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

HnRNP A1 dysfunction is associated with neurodegeneration in multiple sclerosis (MS). Herein, advanced RNA sequencing and CLIPseq of MS brains and relevant models demonstrated that hnRNP A1 binding of target RNAs and RNA splicing were altered, precipitating neurodegeneration.

Here, integrating ribosome profiling, RNA-seq and proteomics to reveal transcriptional and post-translational regulation in HIV-infected T cells, the authors show that non-AUG translation of viral upstream ORFs elicits distinct immune responses and regulates viral gene expression in a DDX3-dependent manner.

Differential DNA methylation and the long-range effects of chromatin organization lead to pronounced differences in recombination landscape between males and females.

Over half the world’s rivers dry periodically, yet little is known about the biological communities in dry riverbeds. This study examines biodiversity across 84 non-perennial rivers in 19 countries using DNA metabarcoding. It finds that nutrient availability, climate and biotic interactions influence the biodiversity of these dry environments.

A first-order, disorder-driven, superconductor–insulator phase transition is demonstrated. This is in contrast with the usually observed second-order transition and highlights the role of Coulomb interactions between preformed Cooper pairs.

Deciphering patterns of histone modifications that modulate chromatin structure and function is important, but remains challenging. Here the authors describe a method to uncover patterns of site-specific histone acetylation by deconvolution of overlapping peptide isomer mass spectra.

Natural populations of Saccharomyces paradoxus in which rapid evolution of chromosome architecture and contact between nascent species drove the formation of a new species through homoploid hybrid speciation.

Lateralization of hippocampal function has been observed in CA1-3, but the extent to which there is lateralization in the dentate gyrus is less clear. Using 2-photon calcium imaging of granule cells over five days in mice, the authors explore differences in spatial encoding between the left and right dentate gyrus.

The identification of T cell epitopes is a critical step in understanding the immune response to infection and in designing vaccine based approaches. Here the authors introduce a frame work of antigen discovery called MHCvalidator and Epitrack to identify new antigenic features for T-cell COVID-19 vaccines and characterise a novel non-canonical epitope from a truncated Spike variant and mutation of an immunodominant epitope in the BNT162b4 vaccine.

Callixylon wood from the Late Devonian (approximately 360 Myr ago) is found to contain tyloses, swellings of parenchyma cells into adjacent water-conducting cells that develop in response to embolism and pathogen infection.

Authors apply theory and microbial ecology modelling to a wastewater sample, and show that antimicrobial resistance carrying plasmids interact with a higher number and more diverse range of bacteria than plasmids that do not carry resistance genes.

Oxide-based lithium/sodium-rich antiperovskites are regarded as promising solid electrolytes. Here, authors report a series of antiperovskites with a soft lattice containing hydride (H^–) and chalcogenide (S^2–, Se^2–, Te^2–) anions, enabling the fast Li⁺ /Na⁺ transport assisted by rotational phonon modes.

Non-perennial rivers and streams are mapped globally, showing that more than half of rivers worldwide experience no flow for at least one day per year.

PTEN is a key cell signaling lipid phosphatase that is regulated by C-terminal phosphorylation. Biophysical methods were used to illuminate the structural basis for PTEN regulation, which involves a dynamic N-terminal helix that influences catalysis.

The Middle Ordovician icehouse has been suggested to be sparked by extra-terrestrial dust associated with an asteroid break-up. Here, the authors use an astronomically calibrated timescale to decouple millennia-scale climate and biodiversity change from the meteorite shower 468.4 million years ago.

Bacteria can synthesize and secrete cellulosic polymers using membrane-associated multiprotein complexes consisting of cellulose synthases and accessory subunits. Here, Anso et al. use cryogenic electron microscopy to shed light on the mechanisms underlying accessory subunit recruitment and function within the Bcs macrocomplex for phosphoethanolamine-modified cellulose secretion in E. coli.

A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.

PIAS1 is an E3 SUMO ligase involved in various cellular processes. Here, the authors use quantitative proteomics to identify potential PIAS1 substrates in human cells and elucidate the biological consequences of PIAS1-mediated SUMOylation of vimentin.

Spondyloarthritis pathology is manifested by increased myeloid infiltration of the joints. Here the authors show that in a mouse model of spondyloarthritis, a single dose of a microbial ligand curdlan induces persistent extramedullary myelopoiesis in the spleen and joints, which is driven by GM-CSF and can be amplified by exogenous IL-33.

The nature and role of insular interhemispheric communications remains underexplored in social anxiety processing. Here the authors show that insular neurons play a role in social preference encoding during acute social isolation.

Improving the performance of 2D transistors is essential to enable their future application for beyond-silicon electronics. Here, the authors report a method to induce localized tensile strain in monolayer MoS₂ transistors, leading to enhanced electron mobilities up to 185 cm²/Vs and an 8-fold increase of the on-state current densities.

Lysine ubiquitination, catalysed by E3 ubiquitin ligases, is pivotal for regulating protein stability and cell signalling. Using protein semisynthesis, the roles of the C-terminal carboxylate and conformational interconversion in HECT-domain E3 catalysis are now characterized, revealing evolutionary plasticity in side chain versus backbone utilization.

Analysis of genomic data from 25 distantly related plant species shows signatures of selection on the same gene families and functions that repeatedly contributed to local adaptation to climate.

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

Liver cirrhosis is characterised by extensive fibrosis of the liver, and understanding the underpinning immunological processes is important in designing intervention. Here authors show that Mucosal-Associated Invariant T cells are instrumental to controlling the balance between profibrogenic and restorative macrophages and inhibiting their activation might reverse liver fibrosis.

Improvements in European freshwater biodiversity occurred mainly before 2010 but have since plateaued, and communities downstream of dams, urban areas and cropland were less likely to experience recovery.

ON-target genotoxicity in gene editing is generally underestimated. Here the authors report Fluorescence-Assisted Megabase-scale Rearrangements Detection (FAMReD) systems to detect and characterize rare large loss of heterozygosity: they show that ON-target genotoxicity can be prevented by p53 and cell cycle arrest.

The quest to improve transparent conductors is a balance between increasing electrical conductivity and optical transparency. Here the authors demonstrate that both can be fulfilled by separating the optical and electrical conductivity directionality.

The ubiquitin–proteasome system clears misfolded proteins to maintain cellular homeostasis. Mayor and colleagues identify the ubiquitin ligase Hul5 as a critical component of the heat-shock response and show that it selectively targets misfolded cytosolic proteins for degradation.

Cryptic translation of the 'non-coding' genome is increasingly recognised, however its biological significance remains unclear. Laumont et al.employ proteogenomic techniques to map the human immunoproteome, and find that approximately 10% of MHC class I-associated peptides are cryptic.

Ubiquitylation and SUMOylation are two important related post-translational modifications. Here the authors present an approach for the simultaneous identification and quantification of protein-wide SUMO and ubiquitin sites from a single sample, uncovering widespread crosstalk between the two modifications.

Mass spectrometry (MS) has furthered our understanding of MHC class I-associated peptides (MIPs), but the technique is inadequate for studying MIP-associated polymorphisms. Here, the authors combine high-throughput MS with exome and transcriptome sequencing to identify polymorphic MIPs from two female siblings.