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An inherently explainable AI trained on 1,015 expert-annotated prostate tissue images achieved strong Gleason pattern segmentation while providing interpretable outputs and addressing interobserver variability in pathology.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

JWST/NIRSpec observations of the 49 Ceti debris disk reveal spatially resolved, fluorescently excited CO emission, indicating a secondary origin of the gas in debris disks (that is, from the collision of volatile-rich bodies).

Natural products inspire the development of pseudo-natural products through combinations of fragments of compound classes that are chemically and biologically distinct. Here, the authors report a library of 244 pseudo-natural products, evaluate them in the cell painting essays and identify the phenotypic role of individual fragments.

This study discovers human SERF2 as a key partner in stress granule formation by binding specific RNA G-quadruplexes. SERF2 and these RNAs provide a detailed structural model of protein-RNA interactions driving liquid-liquid phase separation in condensates.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

Sperry et al. used machine learning approaches to investigate profiles of mood instability and create a prediction model for clinical and functioning outcomes using data from the Prechter Longitudinal Study of Bipolar Disorder.

The HIV-1 RNA-binding protein rev facilitates nuclear export of viral RNA. Here, the authors use native mass spectrometry to study the interactions between rev-derived peptides and rev response elements of HIV-1 RNA, providing mechanistic insights into rev recognition and recruitment.

Researchers reveal widespread, newly formed seafloor seeps along Antarctica’s Ross Sea coast. Methane-rich flows alter local ecosystems and may influence warming. The drivers remain unknown, warranting coordinated study.

Individuals with schizophrenia show reduced structural similarity in temporal, cingulate, and insular lobes, especially those with worse cognition and symptoms, affecting late maturing association areas with low metabolism and high neurotransmission.

Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

Social norms approaches are widely applied in health promotion. This pre-registered systematic review and meta-analysis of RCTs using social norms messaging in developed countries aimed to evaluate their effectiveness for changing health behaviours. An initial small effect disappeared when controlling for publication bias.

Military personnel face increased exposure to pandemic-related stressors, yet their mental health impacts remain underexplored. Here, the authors analyze data from the STARRS Longitudinal Study, revealing significant increases in mental health issues among soldiers during COVID-19, particularly among vulnerable groups, underscoring the need for targeted support during pandemics.

Despite being a virulence factor, candidalysin toxin is essential for Candida albicans to penetrate the oral epithelium to establish and maintain non-infectious colonization

Observed 730 Myr after the Big Bang, a little red dot is found to anchor an overdensity of eight galaxies and seems to be embedded in a massive host dark matter halo.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

ChatGPT provides a way of teaching people about climate change. This research reveals that conversations between climate sceptics and ChatGPT reduced climate scepticism, but these effects are modest, inconsistent across studies and prone to decay over time.

Simulations show that the Solar System’s gas disk shaped how and where primitive bodies were implanted in the asteroid belt, revealing different arrival times for CM and CI parent bodies and identifying CM bodies as likely sources of Earth’s water.

Basal cells, rather than neuroendocrine cells, have been identified as the probable origin of small cell lung cancer and other neuroendocrine–tuft cancers, explaining neuroendocrine–tuft heterogeneity and offering new perspectives for targeting lineage plasticity.

CSF total tau (t-tau), often used as a marker of neuronal damage, is more strongly linked to synaptic degeneration. Here, the authors show that t-tau better reflects synaptic dysfunction than axonal or neuronal loss in Alzheimer’s disease.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Genome-wide association meta-analyses of attention-deficit/hyperactivity disorder symptom measures and clinical diagnoses identify new risk loci, highlight putative effector genes and yield improved polygenic risk scores.

TCR-TRANSLATE, a deep learning framework adapting machine translation to immune design, demonstrates the successful generation of a functional T cell receptor sequence for a cancer epitope from the target sequence alone.

By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding interdomain misfolding.

Individual proteins tend to adopt preferred orientations when subjected to vitrification for cryo-electron microscopy analysis. A laser flash melting procedure followed by rapid revitrification provides a simple approach to mitigate this issue, reducing the number of micrographs required for successful structure determination at high-resolution.

An evaluation framework isolates perturbation-specific effects in perturbation datasets.

Alterations of therapeutic pressures have been shown to affect clonal evolution of resistance. Here, the authors conducted a single arm, phase 2 trial consisting of alternating osimertinib and gefitinib in non-small cell lung cancer, and found ctDNA dynamics were predictive of response.

Ricca et al discover a new family of tubular pili in Microcystis aeruginosa, a harmful algal bloom-forming cyanobacterium. These pili are crucial for buoyancy by forming cell micro-colonies, which increases drag and prevents sinking. The pili also enrich microcystin and co-localize with iron-enriched extracellular matrix components, suggesting a vital role in bloom proliferation.

Early detection could improve prognosis for preeclampsia and fetal growth restriction, major causes of maternal/fetal morbidity and mortality. Here they show that Leptin and Pappalysin2 cell free RNAs are elevated in maternal plasma in cases of PE + FGR.

The Akt-mTOR axis influences cell activation, differentiation and metabolism. Jordan and colleagues show that thymic and inducible T_H17 cells exhibit different requirements for mTORC1 and mTORC2 as well as Akt isoforms.

This pilot trial showed that perioperative treatment with the isocitrate dehydrogenase (IDH) inhibitor safusidenib of patients with low-grade IDH-mutant glioma, with craniotomy and lumbar puncture before and after treatment, is feasible and safe and enabled in-depth translational investigation of safusidenib treatment-induced changes in the tumor, including electrophysiological effects.

Silane, which is a precursor to the sandy surfaces of rocky planets and dusty clouds on gas giants, is seen directly in another world—a low-metallicity brown dwarf in which oxidation is slow and gas mixing is fast.

Two high-redshift post-starburst galaxies are in the process of quenching, although their quasars remain active, indicating the complex co-evolution between black hole activity and star formation.

The role of the tumour microenvironment in the response to immune checkpoint inhibitors in metastatic melanoma remains poorly understood. Here, single cell profiling of metastatic melanoma samples identifies associations of the mature dendritic enriched in immunoregulatory molecules subtype with immunotherapy response.

Meltwater ponding reduces Greenland Ice Sheet albedo, but this process is not included in models. This study uses drone imagery to show that small streams and ponds, often missed by satellites, considerably increase the energy available for melt.

New field measurements and modeling show meltwater refreezing in Greenland’s bare ice may reduce runoff to surrounding oceans, highlighting a process climate models can incorporate for improved predictions of future sea-level rise.

pOXA-48 plasmids have emerged as key vectors of carbapenem resistance within Enterobacteriaceae. In this study, the authors use a transposon sequencing (Tn-seq) approach to identify genetic determinants critical for plasmid stability and conjugative transfer.

Net-zero bioplastics are possible when combined with high recycling rates. This study presents a mixed polyester recycling process integrated with monomer separation and purification for both fossil- and bio-based plastics. Techno-economic and life cycle analyses confirm its environmental and commercial advantages, advancing the path toward circular, low-emission polyester plastics.

Free energy calculations are an essential tool to identify targets for individual proteins. Here, authors describe free energy perturbation (FEP+) calculations to optimise on target and off-target potencies for the discovery of potent Wee1 inhibitors with kinome-wide selectivity.

Ventures focusing on gene therapy, adoptive T-cell therapy, protein homeostasis and the microbiome are among those selected by the editors in 2013's crop of startups.

Our understanding of how post-translational modification—protein phosphorylation—impacts the complexity of eukaryotic signalling pathways is continuously expanding. Now, protein oligophosphorylation has been characterized as an additional phosphorylation mode. Structural and mass spectrometry methods revealed that NME1 catalysed its own oligophosphorylation, leading to altered protein–protein interactions.

Sarah-Maria Fendt received her doctoral degree from ETH Zurich, Switzerland, and she conducted her postdoctoral research at the Massachusetts Institute of Technology, USA. She is currently a principal investigator at the VIB Center for Cancer Biology and a full professor at KU Leuven, Belgium.

A survey across 90 societies reveals that variation and change in everyday norms are explained by a single value dimension: the priority societies place on individualizing versus binding moral concerns.

Zaman, Yang and Huang et al. demonstrate MDK’s suppressive effect on amyloid-β and its impact on amyloid burden and microglial activation in Alzheimer disease mice, highlighting its protective role in pathogenesis.