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This study examines how multimodal large language models evaluate hate speech. Larger models can make context-sensitive decisions aligned with human judgement. However, pervasive demographic and lexical biases remain, and visual identity cues may amplify disparities.

Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody drug conjugate. Through integrated laboratory and clinical studies, the authors identify significant ERBB2 (the gene that encodes the HER2 protein) mutational heterogeneity in patients with urothelial cancer and co-mutation and amplification of ERBB2 as a potential biomarker of exceptional response to T-DXd.

AvrPm4 is a chimeric powdery mildew effector that is recognized by the wheat kinase fusion resistance protein Pm4. The pathogen can evade Pm4 recognition by expressing the suppressor SvrPm4, an RNase-like effector with multiple roles.

Rare loss-of-function mutations in SETD1A are associated with schizophrenia, but how SETD1A haploinsufficiency leads to disease phenotypes remains unknown. Here, authors show that SETD1A regulates genes at common schizophrenia risk loci regulating genomic stability and synaptic function.

Caspase 8 protein expression is largely absent in small cell lung cancer (SCLC) patients. Here, the authors generate a caspase 8 deletion SCLC mouse model and show that it promotes a neuronal progenitor-like cell state and pre-tumoral immunosuppression triggered by necroptosis that promotes metastasis.

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).

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

Breakage of both chromosomal DNA strands creates unique problems for DNA repair. Here, Luthman et al. show that for some broken ends, the two strand breaks are repaired in parallel, while for other ends one strand must be repaired before the other.

Acute respiratory infections (ARI) account for substantial morbidity and mortality in adults, and can be a common cause for antibiotic overuse, due to unknown microbial etiology. In this work, authors present their 4-gene signature, capable of discriminating bacterial and non-bacterial illness in adults hospitalized with ARI.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

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.

How warning colours arise from camouflage is a long-standing puzzle. This study finds that elapid snakes with cryptic upper sides but bright ventral patches often precede aposematism, and these colours co-evolve with behaviours that reveal them.

CNS toxicity was unexpectedly observed for anti-miR-17 RGLS4326 in nonclinical studies. Here, authors identify AMPA receptor inhibition as the likely culprit. Replacement of 3’-terminus guanine to adenine leads to discovery of farabursen (RGLS8429) that is devoid of CNS toxicity.

Distinct neuron subtypes compartmentalize specific functions by differentially localizing and translating specific RNAs. This work identifies dynamic subtype- and stage-specific growth cone molecular machinery during neocortical circuit development.

This study explores pathways of emissions and mitigation compatible with four climate boundaries—planetary boundaries for the climate system. The results highlight the importance of peak emission timing, limitation of carbon budgets as a sole indicator and trade-offs between mitigation options.

This work uses gene expression and single cell analyses to group extrapulmonary tuberculosis patients into three immune types, revealing immune pathways driving pathogenesis and markers that could improve diagnosis and guide tailored treatments.

CRISPR activators are powerful tools for controlling gene expression, but they suffer from inconsistent efficacy and high toxicity. Here, authors develop a high-throughput method to test thousands of CRISPR activators, revealing distinct principles of activator biology and delivering improved tools.

Hidden catalysis plagues catalyst development and occurs when an impurity or species generated in situ facilitates the reaction instead of the intended catalyst. Current methods to identify hidden catalysis require time-consuming, labour-intensive mechanistic analyses, so limiting widespread use. A colorimetric indicator has been developed that enables rapid, visual detection of hidden borane catalysis.

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.

In this work, researchers address a key question for maternal group B Streptococcus (GBS) vaccine assessment: What newborn antibody concentrations protect against invasive infant GBS disease? They present serologic thresholds by age at onset and serotype based on a large U.S. case-control study.

The somitic mesoderm is seen as the main source of brown adipose tissue, although some depots are of partially unknown origin. Here, the authors show that Osr1 labels multipotent dorsal aorta progenitors at E9.5 that contribute to cartilage, muscle, and adipose tissues, revealing a non-somitic contribution to several brown adipose depots.

Bacterial biofilms include viscous extracellular polymeric matrices such as extracellular DNA (eDNA). Here, Mugunthan et al. show that protein RecA generates three-stranded nucleic acid structures known as R-loops, which contribute to formation of the viscoelastic eDNA matrix as part of bacterial stress responses.

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.

The nucleus accumbens (NAc) controls reward learning and motivated behaviors. Here, authors show that the neuropeptide gastrin-releasing peptide regulates the excitability of subpopulations of NAc neurons and modulates motivated behavior in mice.

Like cells in a body, social insects cooperate to maintain colony health. This study reveals that ants have evolved a chemical signalling system that alerts nestmates when their own immunity is insufficient to overcome infection, enabling efficient colony-level disease defence.

Homologous recombination rearranges genetic information during meiosis to generate new combinations in the genome. Here, the authors report direct, single-individual detection of recombination in primates and humans using long-read sequencing.

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.

Dykes are the main magma pathway through the Earth crust. Dykes are assumed to form by hydraulic fracturing through elastic rocks. We show how dykes emplaced in the deep ductile crust grow through very rapid ductile deformation of their host rocks.

To simulate physical systems on a quantum computer, their degrees of freedom must be encoded into qubits. This Review assesses the different methods that exist to allow quantum calculation of fermionic systems.

Here a mechanism for nitrogen fixation maintenance is identified in Medicago truncatula where two polygalacturoneases are expressed in nodules and secreted into the symbiosome space for clearing of excessive un-esterified pectins.

Recently published results from a Phase I trial showed the blood brain barrier could be transiently opened in glioblastoma patients using low-intensity ultrasound and microbubbles. Here, the authors develop a microfluidic chip to capture tumour-derived extracellular vesicles and particles in response to paclitaxel treatment.

Yong et al. highlight how sampling conditions affect metabolic profile in renal cancer, showing that prolonged ischemic exposure disrupts tissue metabolome stability and masks important phenotypes, such as suppressed gluconeogenesis.

Hepatitis C virus (HCV) variability and its phenotypic consequences aren’t well studied in relation to viral replication fitness and disease severity. Here, the authors identify a replication-enhancing domain in non-structural protein 5A, linking high replication fitness to severe disease outcomes, with implications for understanding HCV pathogenesis in immunocompromised patients.

Nordvall et al. use a cohort study design to study causal effects of the COVID-19 vaccine on childbirth rates in a representative Swedish population. They show that COVID-19 vaccination has no association with either childbirth rates or miscarriages.

Somatic mutations in blood cells (CHIP) are linked to diseases like heart disease, but the mechanisms are unclear. Here, the authors show that different CHIP driver genes alter unique sets of plasma proteins, some of which are validated in mouse models.

The mitochondrial β-barrel assembly machinery exhibits conformational dynamics in the absence of substrate. The antibiotic darobactin A stabilizes the open confirmation of the Sam50 lateral gate and inhibits SAM complex function in vitro.

In a quasi-experimental analysis of emergency calls in California communities, Dee and Pyne find that having mental health first responders accompany police on qualified calls reduces the number of individuals placed in involuntary psychiatric detentions.

The study advances the use of serological surveys to guide trachoma elimination program decisions and provides a way to set thresholds for whether or not to continue an intervention program.

In an integrated analysis of transcriptomic data from the SUBSPACE consortium and public datasets of patients with sepsis, acute respiratory distress syndrome, trauma and burns, dysregulation within four consensus molecular clusters related to myeloid and lymphoid cells is associated with mortality and illness severity.

How the nervous system controls social behaviours of bees is poorly understood. This study finds that social feeding of male honeybees is hardwired into the nervous system by the fruitless (fru) gene, and that expression of this transcription factor is restricted to the nervous system of males.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

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.

Vigilance involves the activation of orexinergic neurons in the lateral hypothalamus (LH-ox). Here the authors report the functional role of a monosynaptically connected circuit with orexinergic neurons connected to noradrenergic neurons in the locus coeruleus which target lateral amygdala neurons and enhance fear expression and generalization.

As Nature Aging celebrates its fifth anniversary, the journal asks some of the researchers who contributed to the journal early on to reflect on the past and the future of aging and age-related disease research, the impact of the field on human health now and in the future, and what challenges need to be addressed to ensure sustained progress.

The impact of ACKR3 constitutive activity is unknown. Here, the authors suppress basal ACKR3 activity using inverse agonistic nanobodies to stabilize an inactive conformation and revealing a role for ACKR3 in basal cell motility.