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In this study, the authors uncover how diverse inhibitory interneurons in the amygdala flexibly contribute to fear and safety learning, revealing a key role for inhibition in emotional memory and adaptive circuit plasticity.

Here the authors perturb genes linked to schizophrenia risk in human neurons. They find that single perturbations share common downstream effects on gene networks, while joint perturbations result in downstream effects being saturated.

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.

Time-lapse imaging studies of more than a day in the fly brain have been infeasible until now. Here the authors present a laser microsurgery approach to create a permanent window in the fly cuticle to enable time-lapse imaging of neural architecture and dynamics for up to 10–50 days.

PU.1^low CD28-expressing microglia may act as suppressive cells in Alzheimer’s disease, mitigating its progression by reducing neuroinflammation and amyloid plaque load, indicating potential immunotherapeutic approaches for treatment.

Walmsley and colleagues report that systemic hypoxia induces persistent loss of histone H3K4me3 marks and epigenetic reprogramming in neutrophil progenitors, resulting in long-term impairment of subsequent neutrophil effector functions.

Research on sustainable diets has primarily focused on human and planetary health, neglecting workers in food value chains. This study quantifies the risk of forced labour embedded in five different diets in the USA, underscoring the need to integrate such risk in sustainable diet transition efforts.

Vaccination-induced antibody responses wane, but protection from infection often lasts longer. Here the authors boost-immunize rhesus macaques with pre-existing hybrid immunity using new bivalent SARS-CoV-2 vaccine, and find that protection from subsequent infection correlates with immune infiltration in the lung.

Using dual-color mesoscopic imaging in the neocortex of awake mice, the authors show that cholinergic release and neuronal activity exhibit distinct spatiotemporal patterns that are differentially linked to spontaneous fluctuations in behavioral state.

We find that leptin-target neurons expressing basonuclin 2 in the arcuate nucleus that acutely suppress appetite by directly inhibiting agouti-related protein neurons are a key component of the neural circuit that maintains energy balance.

Stress-associated catecholamines promote CD8⁺ T cell exhaustion through the β₁-adrenergic receptor, and blocking β-adrenergic signalling may help restore anti-tumour functions.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Vector-borne pathogens are known to elicit immune response upon mosquito biting the host which is critically linked to the establishment of infection and pathogenesis of disease, yet the impact of the mosquito bite itself is not immunologically well-appreciated. Here the authors characterize the immune response to the mosquito vector Aedes aegypti in a controlled human in vivo challenge model and show the induction of a range of immune pathways and cell types.

Mitochondrial DNA heteroplasmy associates with context-specific nuclear CpG methylation, supported by a cell model. Heteroplasmy–CpG scores relate to mortality and cardiovascular risk, though direction and mechanisms remain unclear.

Sugar-sweetened beverages (SSBs) have adverse effects on health and the environment, but comprehensive and sustained strategies to curb their intake are lacking. While several countries have implemented policies, a broad suite of effective approaches has been challenging to enact and evaluate due to insufficient administrative or political capacity and strong influence from transnational corporations. Continued research, advocacy and support are needed to successfully implement, monitor, evaluate and revise strategies to reduce SSB intakes worldwide.

The vCA1-BA projection is enriched in shock responsive neurons, which are necessary for fear memory encoding and become correlated with a network of neurons during retrieval. Here the authors show that the magnitude of vCA1 correlated activity is proportional to memory strength and requires the shock response during encoding.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Akbar and colleagues show that sestrins induce the reprogramming of non-proliferative, senescent-like CD27^–CD28^–CD8⁺ T cells to acquire an innate-like killing activity modulated by the NK receptor NKG2D and the adaptor molecule DAP12.

An IgE antibody recognising Folate Receptor-alpha has been tested in clinical trials for ovarian cancer and preclinical studies show macrophage involvement in the anti-tumoural functions of IgE. Here the authors demonstrate that IgE induces proinflammatory activation of ovarian cancer patient macrophages, which reverses their immunosuppressive induction of Treg cells and promotes CD8⁺ T cell function.

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.

This study presents 11 new hornwort (Anthocerotophyta) genomes that clarify the structure and evolution of sex and accessory chromosomes in bryophytes and shed new light on the early evolution of land plants.

The elimination of forced labour (Sustainable Development Goal 8.7) is a priority for the sustainability of food systems. Using data on production, trade, labour intensity and risk, this study estimates the risk of forced labour embedded in the US land-based food supply across product category, country of origin and supply chain stage.

Potassium channels in the ventral tegmental area are known to regulate resilience against stress-induced depression. Here, the authors show over expression of KCNQ3 channels in VTA dopaminergic neurons or treatment with KCNQ channel openers normalizes depressive behaviours in mouse models.

The role of the immune system in tissue regeneration remains poorly understood. Here, in bone marrow transplantation and organoid culture models, T-cell-derived Interferon-γ is shown to promote STAT1-dependent intestinal stem cell c-MYC expression and epithelial regeneration.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

Long-term BA.5-specific efficiency of booster vaccination is incompletely understood. Here, analyzing immunity to and efficacy of various COVID-19 vaccination regimens in Syrian hamster, the authors found that heterologous boosting provides more durable immunity and that NVX-CoV2373 provides the strongest boosting effect.

Whole tissue RNA profiling can help identify altered molecular pathways underlying neurodegenerative disease, but often masks cell type-specific transcriptional changes. Here, the authors compare transcriptomes of neurons, astrocytes, and microglia from Alzheimer's disease model brains and identify hundreds of cell-type specific changes.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

The authors construct a time-calibrated phylogeny spanning >90% of spiny-rayed fishes to explore patterns of body shape disparity within acanthomorphs. They find a trend of steady accumulation of lineages from the Cenozoic, with an increase in morphological disparity following the Cretaceous–Palaeogene event, facilitating the radiation of diverse morphotypes that characterize acanthomorphs’ widespread ecological success today.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.