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A study reveals a gut–brain sensory pathway through which the microbial component flagellin activates neuropod cells in the colon to signal the brain and reduce feeding in mice.

R-loops formed by RNA hybridization to DNA template strand during transcription influence HIV-1 integration into the CD4⁺ T cell genome. The unwinding of R-loops by splicing helicase Aquarius facilitates integration into speckle-associated domains.

G49, a dual glucagon/glucagon-like peptide-1 receptor agonist, triggers an inter-organ crosstalk between adipose tissue, pancreas and liver, leading to brown fat activation with the final outcomes of increased energy expenditure and body weight loss.

This multisite study detects a link between brain dynamic functional network connectivity and current and future post-traumatic stress symptom severity with a stronger effect in the female group.

In the proof-of-concept phase 2 ROME trial, comprehensive genomic profiling followed by molecular tumor board evaluation and randomization of patients with metastatic solid cancer to receive personalized therapy or standard of care led to a significantly higher objective response rate and longer progression-free survival in patients who received personalized therapy.

There are currently no licensed vaccines to prevent Group A Streptococcus (GAS) infections. In this study, the authors evaluate the immune response and preclinical efficacy of a multicomponent mRNA lipid-nanoparticle vaccine against GAS.

Single-cell transcriptomic analysis of mouse hypothalamus and behavioural experiments show that specific hypothalamic networks regulate conflicting feeding versus parenting behaviours of female mice.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

mRNA COVID-19 vaccines have been updated to the SARS-CoV-2 KP.2 variant of concern, due to its emergence in early 2024. Using data from the US Veterans Affairs Healthcare System, the authors here estimate that the BNT162b2 KP.2-adapted vaccine is 56‒68% effective at preventing a range of COVID-19 outcomes during the early part of the 2024–2025 respiratory virus season.

Interact-omics, a high-throughput cytometry-based framework, resolves the cellular interaction landscape.

In schistosomiasis-endemic regions, the cyclical nature of infection and treatment complicates understanding of host immune responses. Repeated controlled human Schistosoma mansoni infection, designed to reflect the reinfection cycles common in endemic areas, shows that repeated exposure induces mixed worm-specific CD4⁺ T cell responses similar to those seen in endemic infection.

Foamy macrophages are a pathological hallmark of demyelinating brain disorders. Here, the authors identify the molecular mechanisms underlying the faulty regulation of lipid efflux that cause accumulation, suggesting a promising strategy to enhance central nervous system repair.

Brown adipose tissue (BAT) is key for metabolic balance. Here, the authors show that RAP250 deficiency enhances BAT activity. Under these conditions, BAT-derived neuritin-1 regulates thermogenesis and fat metabolism, showing therapeutic promise for obesity and metabolic disorders.

Beyond its known role in stabilizing microtubules, it is now shown that tau protein actively promotes lattice defect repair by enhancing tubulin turnover at topological defects.

A somatic niche embraces the female germline in cereal ovules. MADS31 precisely maintains developmental progression of this niche to support the germline by repressing the post-fertilization programme.

Mechanical confinement of cancer cells at the tumour–microenvironment interface induces phenotype switching through chromatin remodelling by HMGB2, leading to a more invasive and drug-resistant state in melanoma.

Sinclair et al. explore the contribution of chronic inflammation to cardiovascular symptoms associated with post-acute sequelae of SARS-CoV-2 infection (PASC-CVS). The authors identify trace levels of inflammatory cytokines in individuals with PASC-CVS that impair the function of cardiomyocytes derived from induced pluripotent stem cells.

Parkinson’s disease (PD) involves toxic protein buildup and energy failure in neurons. Continuously breathing low-oxygen air protected mice from PD-like neuronal loss and reversed symptoms, even after they began, suggesting that hypoxia may protect neurons.

Though the complement system is pivotal in the defence against infections, pathologic activation of the system contributes to disease. Here, authors show that their recently developed monoclonal antibody against complement factor 2, empasiprubart, inhibits the classical and lectin pathways in a clinical trial, and its crystal structure provides basis for its inhibitory properties, such as Ca²⁺ binding.

Heydemann et al. investigate alveolar regeneration mechanisms after SARS-CoV-2 infection in the hamster model, offering insight into the pathomechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC).

Beck et al. develop a model where striosomes create a flexible “decision-space” that adapts to environmental context and internal state. It explains how we make choices and why decision-making varies between people, and in neuropsychiatric disorders.

John et al. show that upon classical activation, macrophages undergo nitric oxide-driven reprogramming of nucleotide metabolism, which affects immune functions and responses.

The A3 adenosine receptor is a promising drug target for cancer, inflammation, and glaucoma. Here, authors determine atomic structures of the human A3 receptor, identifying a previously hidden binding pocket that will aid in the development of more effective A3 receptor-targeted medicines.

Immunization via the respiratory route is predicted to increase the effectiveness of SARS-CoV-2 vaccines. Here, Kaiser et al. describe a murine pneumonia virus vectored vaccine expressing spike protein, and show that intranasal immunization of male rhesus macaques provides good mucosal and systemic immunogenicity and efficacy.

A large brain imaging study of over 2000 people worldwide shows that fear conditioning engages brain regions linked to emotion and attention, with differences in individuals with anxiety or depression and strong influences from task design.

Our annual survey highlights startups tackling intractable viruses with new vaccine design, engineering a reliable source of platelets, universalizing cell therapies, improving cancer screening, developing RNA-editing platforms and targeting protein–RNA interactions. Michael Eisenstein, Ken Garber, Caroline Seydel and Laura DeFrancesco report.

Here the authors show that CD4⁺ effector T cells prevent or reverse CD8⁺ T cell dysfunction by licensing Kupffer cells to trigger IL-27 production, defining a liver-specific immune circuit and a potential target for chronic HBV therapeutics.

mRNA-based therapies require efficient and selective delivery systems to advance clinical applications and overcome challenges posed by current formulations. Here, authors developed Discrete Immolative Guanidinium Transporters (DIGITs), chemically defined carriers that enable pHresponsive mRNA release with organ and reticulocyte selectivity, minimal toxicity, and scalable synthesis.

The authors developed a neuromorphic chip with on-chip learning and support for diverse memory devices. It bridges brain-inspired computing and emerging tech, enabling efficient, flexible testing and advancing next-gen neuromorphic architectures.

The antibacterial agent colistin displays synergistic activity with azoles and echinocandins against various pathogenic fungi. Here, the authors show that the mechanisms involve disruption of cell membrane permeability and calcium homeostasis.

Radiotherapy induces expression of the EGFR ligand amphiregulin, which promotes metastasis growth at remote sites in mouse models and human patients by shifting myeloid cells towards an immunosuppressive state.

MORC2, a chromatin remodeler involved in epigenetic silencing and DNA repair, is linked to cancer and neurological disorders when dysregulated. Here, the authors show that MORC2 binds DNA at multiple sites, clamps onto it, and induces compaction, a process regulated by its phosphorylation.

Primary angle-closure glaucoma is a leading cause of blindness. Here, the authors identify rare deleterious variants in UBOX5 as risk factors and implicate BIP ubiquitination as a potential disease mechanism.

Pneumococcal carriage is a useful outcome to evaluate pneumococcal conjugate vaccine (PCV) introduction. Here the authors conducted cross-sectional carriage surveys before (2015) and after 13-valent PCV introduction (2017 and 2022) in Mongolia to determine vaccine impact.

Ryan et al. report a highly conserved mechanism by which arginine induces changes in hypervirulent Klebsiella pneumoniae bacterial cell surface capsule. K. pneumoniae arginine sensing is critical for full virulence potential.

This large meta-analysis of 11 GWAS identified 7 genetic loci associated with strabismus, esotropia and exotropia. Mendelian randomisation provided genetic evidence of the causal link between maternal smoking to increased strabismus risk in offspring.

Sand fly vector control strategies are limited. Here, Cecilio et al. use the bacteria Delftia tsuruhatensis TC1 to reduce the ability of sand flies to become infected with Leishmania parasites and effectively transmit them to mammalian hosts.

Nature Biotechnology’s annual survey highlights university startups that are, among other things, rethinking how to deliver gene-editing therapy and tackling various metabolic conditions, immune disorders and cancer with microbiome treatments or immunotherapy. Michael Eisenstein, Ken Garber, Esther Landhuis, Caroline Seydel and Laura DeFrancesco report.

The regulation of the E2F pathway remains incompletely established. Here the authors find that the O-GlcNAcylated FOXK1 associates with the deubiquitinase BAP1 to upregulate transcription of E2F target genes and promote cancer progression.

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.

Integration of snATAC-seq and snRNA-seq data from brains of individuals with major depressive disorder identifies chromatin accessibility alterations and functional enrichment of risk variants in deep-layer excitatory neurons. Gray matter microglia in these individuals show decreased accessibility at sites bound by regulators of immune homeostasis.

Using large cohorts from published clinical trials involving more than 8,000 patients with multiple sclerosis, a probabilistic machine learning model reconstructs the transition probabilities from data-derived diseases statuses, showing patterns that suggest how progression to severe stages occur and potential inversion of the process.

Therapeutic interventions for motor axon regeneration following peripheral nerve injury are currently unavailable. Here authors show local administration of a non-muscle myosin II inhibitor at the injury site increases motor and sensory function recovery in vivo.

This study highlights sex differences in major depressive disorder using resting-state functional magnetic resonance imaging. Findings suggest hormonal fluctuations influence onset, emphasizing the need for larger investigations to identify sex-specific biomarkers and improve personalized treatment strategies.

The authors report data from the emergency department AURORA study to characterize resilience in more detail than the absence of psychopathology after trauma.

Tuberculosis is a major global health threat. Here, the authors develop a single-cell drug discovery approach and identify a compound that tunes bacterial phenotypic variation. This enhances the activity of anti-tubercular drugs against the pathogen.

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.

Loss-of-function mutations in Myosin Binding Protein C3, MYBPC3, are the most common genetic cause of hypertrophic cardiomyopathy. Here, the authors present an AAV9-based gene therapy system with an optimized expression cassette with minimal promoter and cis-regulatory elements that can ameliorate cardiac functions and prolong survival in a murine MYBPC3-deficient model.