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Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

New methods for targeted covalent protein modification at low reactivity aspartates and glutamates are of high interest. Here, the authors report a technique inspired by the HaloTag technology, which employs a covalent conjugation reaction between ligands with a reactive chloroalkane linker and a specific aspartic acid, and use it to covalently modify lipoprotein chaperone PDEδ at a binding site glutamic acid.

Estimating rates of pertussis infections is challenging due to the large proportion of asymptomatic infections and lack of a reliable serological correlate of protection. Here, the authors develop a transmission model to evaluate the reliability of pertussis serosurveys for quantifying recent infections.

Demand-side food policies show small average effects, with effectiveness varying across intervention types. Targeted strategies and a better understanding of how context and population influence outcomes can advance food system sustainability.

Sivanandan, Leitmann, and colleagues present the CellPaint-POSH platform, which combines pooled CRISPR screening with Cell Painting. Using self-supervised deep learning on cell images, the method enables discovery of gene function and biological networks.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

This research finds a strong recency bias in information gathering, attenuated in those on the OCD spectrum—a possible mechanism for indecisiveness. Behavioural and MEG data show reduced evidence updating in high-OC individuals.

In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.

Nonninger et al. identify the TFEB–TGFβ signaling axis as a regulator of stem cell resilience that protects against a senescence-like state during the adult diapause in Caenorhabditis elegans, a mechanism conserved in vertebrate aging and mammalian cancer.

Spatial transcriptomics (ST) technologies link tissue morphology with gene expression, but remain expensive to use; furthermore, models that predict ST data from histopathology images possess considerable limitations. Here, the authors develop STimage, a deep learning probabilistic framework for ST prediction from histopathology images while prioritising robustness and interpretability.

Induction of CD11b-positive regulatory B cells and low expression of CD40 in melanoma cells have been associated with resistance to agonist CD40 (aCD40) and immune checkpoint blockade (ICB). Here the authors show that the addition of RAS/MEK/PI3K inhibitors to aCD40 abrogates these effects and reverses ICB resistance in preclinical melanoma models.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

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.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Current single-cell RNA sequencing methods struggle to comprehensively profile transcriptomes, with many lowly expressed transcripts remaining undetected. Here authors present a workflow for enhancing the detection of both transcripts and regions of interest in combination with a standard transcriptome profile.

Virtual nature exposure reduces self-reported pain and is associated with decreased brain responses linked to somatosensory and nociceptive processing, providing new insights into the underlying mechanisms of nature-induced analgesia.

Here, the authors present genome-wide aDNA from 138 Early Bronze Age individuals from Lower Austria. Their findings point to a patrilocal society with non-strict female exogamic practices and long-distance genetic connections across Central Europe.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

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.

Stronger links between researchers who work on Earth’s and other planets’ atmospheres, and between the experimental, modelling and observational communities, will help to interpret the astronomical data now at our fingertips.

Noradrenergic circuits support and balance aggressive behavioural states in predatory nematodes, distinguish predatory from non-predatory nematode species and are associated with the evolution of complex behavioural traits.

A martensitic alloy with a tensile strength exceeding 3 GPa and a fracture elongation of 5.13% is developed. These mechanical properties arise from interface complexes interacting with dense dislocation networks, which is a mechanism shown to be applicable to other compositions.

In this study, the authors reveal two hippocampal neuron subpopulations that encode time or distance via opposing ramping dynamics. These populations form parallel circuits controlled by distinct interneurons, PV for initiation and SST for maintenance of encoding.

Different agonists produce equilibria of at least four distinct active states of the G-protein-bound M2 muscarinic acetylcholine receptor, each with a different ability to activate G proteins.

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.

In social settings, people need to establish how much they contribute to shared outcomes. Here, the authors show that people strategically alter their actions to establish their level of control and identify neural activity underlying this process.

Candida auris can scavenge carbon dioxide from microenvironments through Nce103 to sustain fitness when colonizing human skin.

This paper develops the Risk Analysis – Perception framework to analyze a national survey and public health metrics for public perceptions of extreme heat risk in the US, finding substantial misalignments between assessed and perceived risk.

SimuFLUX, a user-friendly simulator, accepts commercial MINFLUX microscope configuration files and implements detailed models of point spread functions, fluorophore dynamics, and optical mechanics to optimize and assess feasibility of MINFLUX experiments.

In daily life, light exposure influences cognitive performance in 58 UK adults: brighter, more stable days are linked to better vigilance, memory, and visual search, while recent bright light reduces sleepiness and reaction times.

Plant traits drive ecosystem dynamics yet are challenging to map globally due to sparse measurements. Here, the authors combine crowdsourced biodiversity observations with Earth observation data to accurately map 31 plant traits at 1 km² resolution.

An autonomous laboratory, the A-Lab, is presented that combines computations, literature data, machine learning and active learning, which discovered and synthesized 41 novel compounds from a set of 58 targets after 17 days of operation.

The viscosity of tumour cells is shown to govern their ability to disseminate through the bloodstream and extravasate, establishing a key biomechanical factor of metastasis.

Mendelian genetics posits equal transmission of alleles, but selfish alleles can bias the transmission of large genomic regions or entire chromosomes. This study reveals the evolution of large amplicons as a distinct genetic feature of chromosomes with selfish alleles.

Tau protein has been observed to form condensates in various contexts. Here, the authors show that tau can form DNA-anchored droplets that organize nearby microtubules, pointing to a role in mitosis.

Here, the authors present archaeology of the Namorotukunan site in Kenya’s Turkana Basin that demonstrates adaptive shifts in hominin tool-making behaviour spanning 300,000 years and increasing environmental variability. They contextualize these findings with paleoenvironmental proxies, dating, and geological descriptions.

Bessler et al. developed a human organoid model for H3.3K27M-altered diffuse midline glioma that recapitulates key tumor features and demonstrated its utility for modeling CAR T cell and microglia functions.

Myotonic dystrophy type 1 affects both muscle and neuronal function, but its synaptic pathology is poorly understood. Here, the authors show that upregulation of FasII (NCAM1) in both pre- and postsynaptic cells synergistically drives neuropathological and behavioral DM1 phenotypes, which can be rescued by FasII knockdown or specific isoform modulation.

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

This research quantifies hospital admissions in Shanghai for mental and behavioral disorders linked to humid heat, projecting a 68.2% increase by the 2090s under high greenhouse gas emissions and emphasizing the importance of mitigation strategies to reduce future morbidity burdens.

A preinfusion circulatory inflammation biomarker-based signature predicts the likelihood of treatment failure in patients with non-Hodgkin lymphoma who were treated with CAR-T cell therapy, with an inflammatory cluster assignment being prognostic of clinical response and survival outcomes.

u-Segment3D is a universal framework that translates and enhances 2D instance segmentations to a 3D consensus instance segmentation without training data. It performs well across diverse datasets, including cells with complex morphologies.

Synaptic vesicle fusion is essential for neuronal communication, yet its nanoscale sequence has not been directly confirmed. Here, the authors use timed in situ cryo-electron tomography to visualize the full fusion process and its link to vesicle resupply.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Reproduction in numerous marine organisms is timed to specific moon phases, but the mechanisms for sensing moon phases are incompletely understood. Here the authors report that an ancient, light-sensitive protein L-Cryptochrome in a marine bristle worm can discriminate between sun- and moonlight, enabling the animals to properly decode moon phases.

Hepatocyte organoids derived directly from human tissue enable long-term hepatocyte expansion and can be combined with portal mesenchyme and cholangiocyte organoids to form a donor-specific periportal liver assembloid system.

Analyses of ancient human DNA show that cultural and political transformations in Central Europe during the second half of the first millennium ce were associated with movements of Slavic populations into Germany, Poland and Croatia.

Interwoven magnetic and non-magnetic layers in TbTi₃Bi₄ overcome kagome frustration, producing coupled elliptical-spiral magnetic and spin-density-wave orders and a very large anomalous Hall effect driven by strong electron–magnetic field interactions.

DynamicAtlas integrates fixed and live imaging data to generate a morphodynamic atlas of Drosophila development.