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When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

Most advanced triple-negative breast cancers remain resistant to immunotherapy. Here, the authors discover that RIPK1-driven necroptosis in both tumor and stromal compartments is essential for effective immunogenic cell death-based therapy and immune checkpoint blockade.

In this study, long-read RNA sequencing achieves accurate single-nucleotide polymorphism calling, haplotype phasing and allele-specific expression analysis.

The mediobasal hypothalamus plays a central role in integrating nutritional and sex-related signals to regulate energy homeostasis. Here, through snRNA-seq of the mediobasal hypothalamus in female and male mice across nutritional states, authors show that Agrp neurons are nutrition-sensitive, DA neurons exhibit transcriptional differences in a sex-dependent manner, and KNDy neurons are responsive to both sex and nutrition.

Hodgson, Huang, Lang et al. show that TDP-43 limits ribonucleoprotein particle condensation into paraspeckles in a concentration- and polymerization-dependent manner. They also link paraspeckle condensation to stress response and neuroprotection.

Rare coding variants that reduce the activity of a protein can have a beneficial impact on health. Here, researchers identify rare genetic variants in the CHRNB3 gene that associate with reduced cigarette smoking across diverse populations.

Leveraging pythons as an extreme model of feeding and fasting behaviour, this study uncovers para-tyramine-O-sulphate as a conserved postprandial metabolite that links nutrient intake to energy balance by activating hypothalamic neurons and suppressing food intake in pythons and mice.

Crystalline materials for optical applications are synthesized in living dinoflagellates.

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.

Despite rapid exploitation of the opportunities that contextualization of brain maps affords, potential limitations have received little attention. In this Roadmap, Royer et al. provide practical guidelines operating at the level of study design, analysis pipelines and interpretation of findings to encourage the development of best practices in data contextualization in neuroscience.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Amyloid plaques are a hallmark of Alzheimer’s disease. Better understanding of their biochemistry can inspire new biomarkers and therapeutics. Using multimodal mass spectrometry imaging, this work reveals surprising lipid heterogeneity in plaque microenvironments across the brain.

Peroxidases have long been considered to use ferryl heme intermediates (Fe(IV) = O) to catalyze oxidative chemistries. Here, Williams et al. find that ferric-oxyl (Fe^III–O^•–) excited states exist along the catalytic reaction coordinate of a peroxidase.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

Repurposing existing drugs to target new disease-associated genes is a promising strategy, but identifying these targets can be challenging. Here, the authors develop GenT, an approach that uses GWAS data to identify disease-associated druggable genes.

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.

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).

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Heparan sulfate proteoglycans facilitate the assembly of clusters of glycoRNAs and cell surface RNA-binding proteins, which negatively modulate VEGF-A signalling and angiogenesis.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

The high-plasticity cell state (HPCS) is a critical hub that enables reciprocal transitions between cancer cell states, and targeting the HPCS may suppress cancer progression and eradicate treatment resistance.

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.

Several recent publications have attempted to detect novel unannotated microproteins using mass spectrometry proteomics. Here, the authors reassess these claimed microprotein detections, finding that many are poorly supported, while a subset represents likely genuine discoveries of novel proteins.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

popEVE is a proteome-wide deep generative model to identify and predict pathogenicity of missense mutations causing genetic disorders.

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.

¹³⁴Ce and ¹³⁴La have great potential as companion diagnostic isotopes for radiotherapeutics labelled with α-emitting ²²⁵Ac and ²²⁷Th. Now, by controlling the Ce^III/Ce^IV redox couple, the large-scale production, purification and characterization of ¹³⁴Ce- and ¹³⁴La-based radiolabels has been achieved and their use for in vivo positron emission tomography is demonstrated.

Gut bacteria digest dietary fiber and release molecules as energy for the host. Here, Yu et al. find that the ability of certain gut bacteria to digest different fibers influences host consumption of food containing these fibers.

Multiomic single-cell analyses of 15 Down syndrome fetal cortical samples identify widespread disruption of neurodevelopmental transcriptional programs, driven by three dosage-sensitive chromosome 21 transcription factors.

In this study, the authors assess the global response to the toxic aldehyde glyoxal (GO) in Pseudomonas aeruginosa, suggesting that GO controls quorum sensing during infection through a mechanism involving a novel protein, ArqI.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

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

The neural substrates of depression may differ by sex. Here the authors show that depression is associated with distinct brain connectivity changes in men and in women that are explained by sex-specific transcriptomic signatures involving genes previously implicated in synapse function, immune signalling, and depression risk.

A silicon-germanium integrated homodyne detector with a footprint of 0.84 mm² is fabricated to enhance the speed performance of quantum light measurement. It can measure the spectrum of squeezing from 100 MHz to 9 GHz of a squeezed light source.

This study presents an analytic framework to link imaging-derived brain phenotypes to gene expression. In the future, this approach may facilitate in vivo pharmacotranscriptomics and the development of personalized (pharmacological) interventions.

Antimicrobial resistance poses a significant global health threat, necessitating swift and precise diagnostic solutions. Here, the authors introduce a culture-free diagnostic platform integrating microfluidic cell enrichment, single-cell Raman spectroscopy, and deep learning, that identifies bacterial and fungal infections directly from clinical samples within 20 minutes.

The authors analyze the Allen Institute Brain Observatory Ca²⁺ imaging data, focusing on mouse visual cortex during locomotive and quiescent states. They find that locomotion increases neural coding fidelity, regardless of whether population activity increases or decreases in response to the population’s preferred stimuli.

Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

An exploratory analysis of the phase 3 ECOSPOR III trial shows that a higher dosage of the oral microbiome therapeutic VOWST led to enhanced pharmacokinetics, increased species engraftment and altered microbiome and metabolite profiles, providing mechanistic insights into how it may prevent Clostridioides difficile infection recurrence.