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Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

Emissions from croplands are an important source of GHG emissions that can be shaped by management. This study presents maps of emissions globally for different crops, showing that drained peatlands, rice paddies and fertilizer were the main drivers, and highlights differences in emission intensity.

The brain can flexibly perform multiple tasks by compositionally combining task-relevant neural representations.

Bruijns et al. present a modeling tool that enables the tracking of learning dynamics across subjects to reveal how behaviors emerge and adapt. Applying the tool to a decision-making task in mice uncovers similarities and differences across individuals.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Targeting neurons that regulate energy balance may offer new approaches for obesity treatment. Here, authors show that chemogenetic and pharmacological manipulation of GABAergic neurons in the DRN/vlPAG increases adaptive thermogenesis and reduces weight gain in mice fed a highfat diet.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

Fano resonant optical coatings (FROCs) present an ideal platform for structural coloring from thin-film metamaterials. This platform provides full-color gamut coverage at greater than 61% of the CIE gamut, with exceptionally high purity (up to 99%) and high brightness. FROCs exhibit tunable iridescence, cost-effective and scalable manufacturing, and significant advantages over existing structural coloring schemes.

The authors uncover a direct, BAI1-dependent, role for C1q in the control of neural stem cell proliferation and quiescence via MDM2–p53 and p32, a complement cascade-independent mechanism of C1q action that has implications for central nervous system health and disease.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Antibacterial compounds are discovered by combining phenotypic screening with deep learning.

This Perspective discusses current evidence on clonal hematopoiesis dynamics in humans and compares mathematical models used to predict CH progression, highlighting their implications for the clinical management of individuals with precursor states.

The vagus nerve is known to promote rest and digest, to counter physiologic stresses. Here, authors show that insulin signaling plays a critical role in optimizing autonomic function to maintain metabolic and inflammatory homeostasis.

The experimental demonstration of many-body signal amplification in a solid-state, room-temperature quantum sensor is reported.

Implantation of lung tissue into humanized mice enables in vivo study of the human immune response to pathogens.

Constructing nanoparticle assemblies with atomic precision remains a major challenge in nanoscience. Here, the authors realize atomic‐level control over the 1D, 2D and hierarchical 3D assembly of Au nanoparticles by modulating the site‐specific surface ligands and associated counterions.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

Parallel operation of two exchange-only qubits consisting of six quantum dots arranged linearly is shown to be achievable and maintains qubit control quality compared with sequential operation, with potential for use in scaled quantum computing.

Brain-wide recordings in mice reveal that prior expectations are distributed through recurrent loops across all levels of cortical and subcortical processing.

Bond et al. predict mechanism of action of hit compounds from a pooled screen of Mycobacterium tuberculosis mutants underproducing essential proteins by comparing the strain-specific responses of screening hits to those elicited by known antimicrobials.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

Doping a metal nanocluster with heteroatoms dramatically changes its properties, but it remains difficult to dope with single-atom control. Here, the authors devise a strategy to dope single atoms of Ag or Cu into hollow Au nanoclusters, creating precise alloy nanoparticles atom-by-atom.

Engineered pyroptotic vesicles formed during tumour cell pyroptosis and engineered as personalized tumour vaccines can activate a robust antitumour immune response for post-surgical tumour recurrence inhibition.

Uechi et al. found that a small-molecule lipoamide dissolves stress granules (SGs) by targeting SFPQ, a redox-sensitive disordered SG protein, alleviating pathological phenotypes caused by amyotrophic lateral sclerosis-associated FUS and TDP-43 mutants.

A bacterial reverse transcriptase synthesizes polydeoxyadenylate to provide population-level immunity against viral infection.

RNA G-quadruplexes (rG4s) are structures formed in guanine-rich regions of RNA that can serve as crucial regulatory elements in gene expression. Here the authors present an RNA language model for transcriptome-wide prediction of rG4s and genetic variants that disrupt or create them.

In this study, the authors determine the structure of a Type I-A retron from E. coli FORC82 and reveal the functional interplay between Reverse Transcriptases (RTs) and Structural Maintenance of Chromosomes (SMC) ATPases.’

Hegazy and colleagues demonstrate that epithelial oncostatin M receptor expression drives gut inflammation and tumor formation.

Glioblastoma—the deadliest form of brain cancer—alters the calvarial bone and its marrow components, pushing it toward producing more myeloid cells and contributing to an immunosuppressive environment.

Oncologic tumour resection is not fully accurate. Here the authors report a label-free virtual histological imaging method based on a non-contact, reflection-mode ultraviolet photoacoustic remote sensing and scattering microscope, combined with unsupervised deep learning using a cycle-consistent GAN.

On the basis of data from >329,000 migratory birds, this study presents multispecies migratory connectivity as a parameter representing exposure to global change and shows that connections between breeding regions in Canada and non-breeding regions in South America are at greatest risk from global change.

The metabolically driven maturation of geometrically aligned human cardiac microtissues on a microfabricated chip reduces cell-phenotype-dependent variabilities in the action-potential morphology and calcium handling of the cardiomyocytes.

Certain antimetabolites used to treat cancer are more neurotoxic than others, and it is now shown that this is due to their greater tendency to generate DNA double-stranded breaks, whereas less neurotoxic agents induce single-stranded breaks.

The M-cluster in the active site of nitrogenase is derived from an 8Fe core assembled via coupling and rearrangement of two [Fe₄S₄] clusters concomitant with the insertion of an interstitial carbon and a ninth sulfur. Now, by combining synthetic [Fe₄S₄] clusters and assembly with a protein template, it has been shown that sulfite gives rise to the ninth sulfur that is inserted into the nitrogenase cofactor after the radical SAM-dependent carbide insertion and cofactor core rearrangement.

Modulating mitochondrial NAD⁺ levels by changing the expression of the mitochondrial NAD⁺ transporter, SLC25A51, Mukherjee et al. demonstrate that mitochondrial, rather than cytosolic or nuclear, NAD⁺ levels are a key determinant of the rate of liver regeneration.

Noel et al. show aberrant updating of expectations in three distinct mouse models of autism spectrum disorder. Brain-wide neurophysiology data suggest this stems from excess units encoding deviations from prior mean and a lack of sensory prediction errors in frontal areas.

Structural and functional studies highlight the molecular regulation of assembling the mitochondrial division machinery. The core unit is closed, and specific interactions open this unit to facilitate assembly at the right place and time in cells.

Here, the authors reveal the protonation of a single membrane embedded glutamate residue within the homodimer of the efflux transporter EmrE modulates the structure and dynamics in an allosteric manner using NMR spectroscopy.

Lightning Pose is an efficient pose estimation approach that requires few labeled training data owing to its semi-supervised learning strategy and ensembling.

The Zika viral protease NS2B-NS3 is a crucial target for antiviral drug development due to its role in processing viral polyproteins. Here, the authors utilize crystallographic fragment screening and deep mutational scanning to identify binding sites for resistance-resilient inhibitors.

Natural products discovery remains an ongoing challenge. Now, halide depletion offers a complementary approach to discover natural products whose biosynthesis requires halides, including products of cryptic halogenation. Halide depletion reveals that nostochlorosides, the products of an orphan biosynthetic gene cluster in Nostoc punctiforme, are polymerized by a halide-displacing etherifying enzyme.

The authors develop Kausal, a deep learning framework that combines causal discovery with Koopman operator theory to study complex, nonlinear systems. They show that it accurately identifies causal signals and successfully detects major El Niño and La Niña events, outperforming existing methods.

The molecular etiology of hypertensive disorders of pregnancy is largely unknown. Here the authors show from a prospective study of diverse pregnancies that the disease can be split into molecular subtypes based on RNA data and validated a classifier for individuals with no preexisting high risk factors.

Fungal infections are severely underestimated as a cause of mortality, and alternative drugs are urgently needed. Here, Schaefer et al. show that a synthetic polymer mimicking defensins shows different, but synergistic activity with known antifungals.

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

Structural and functional studies reveal how viral proteins trigger the phage antirestriction induced system (PARIS) to degrade host tRNA and how viral tRNAs suppress the PARIS nuclease and thereby overcome this phage defense system.