Search

Here authors show in a human stem cell–derived model, neural cultures from children with MPSIIIA exhibit hyperactive excitatory synapses associated with excitation–inhibition imbalance, altered network dynamics, and broad dysregulation of genes involved in synaptic homeostasis.

mRNA–lipid-nanoparticle vaccines do not require type 1 conventional dendritic (cDC1) cells or the WDFY4-dependent cross-presentation pathway for CD8⁺ T cell priming but, instead, engage both cDC1 and cDC2 cells redundantly.

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.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

In a phase 1 basket trial, the small interfering RNA zodasiran, targeting ANGPTL3, lowered triglycerides in patients with severe hypertriglyceridemia and lowered both triglycerides and low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolemia.

The two species of African elephants are facing severe declines. Here, authors assess their continent-wide genomic diversity, identifying differences in their evolutionary histories and highlighting the formative role of gene flow.

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.

Age-related microbiome changes increase medium-chain fatty acid-producing bacteria, driving GPR84-mediated myeloid inflammation, impaired vagal signalling and hippocampal dysfunction; targeting this gut–brain pathway restores memory in aged mice.

A deep-tissue light source made from mechanoluminescent transducers stimulated by focused ultrasound enables wide imaging of live animal vasculature, and modulation of neuronal activity and behaviour.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

Clostridium perfringens lacking perfringolysin O toxin isolated from preterm infants metabolizes human milk oligosaccharide disialyllacto-N-tetraose to produce metabolites that promote the growth of commensal bifidobacteria, inhibit pathogens and suppress inflammation in an organoid model.

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

Single-nucleus chromatin and RNA sequencing identifies epigenetic chromatin domains that confer vulnerability to paediatric brain tumours such as ependymomas, providing insight into the development of such tumours despite ‘quiet’ genomes.

KRAS G12C inhibitors have improved outcomes but mainly in non-small cell lung cancer and colorectal cancer, despite it being a well-established oncogene in a range of cancer types. Here, the authors present a first-in-human phase I/II clinical trial investigating the next-generation KRAS G12C inhibitor, olomorasib, in KRAS G12C-mutant advanced solid tumors.

The rapid evolution of SARS-CoV-2 challenges antibody therapeutics, but glycan-masked antigens enable isolation of class 3 monoclonal antibodies that potently neutralize diverse Omicron variants and reveal cross-reactive epitopes.

Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

The long-term natural history of long-COVID is not well understood. In this population-based cohort study from Scotland, the authors describe symptom prevalence and health-related quality of life up to 18 months after a positive SARS-CoV-2 test and compare with matched test-negative controls.

ATRX mutations are associated with developmental disorders and cancer, but how they affect gene regulation is unclear. Here, the authors report that ATRX loss can perturb alpha-globin gene expression by promoting G4- and R-loop-associated DNA damage via a G-rich repeat.

Imprinting by influenza viruses can cause a deleterious shift of nearly the entire memory recall response against key, conserved epitopes.

A human spinal cord organoid model can replicate two different types of spinal cord injury and can be used as an in vitro system to evaluate therapeutics and inflammatory reactions to treatments.

Here the authors show that mitochondrial RNA leaks into the cytosol of senescent cells through sublethal apoptosis, driving inflammation. Blocking this pathway improves outcomes in Metabolic Dysfunction-Associated Steatohepatitis.

This multicenter study demonstrates use of dried and capillary blood as a minimally invasive, scalable approach for Alzheimer’s biomarker testing in research, with potential as a widely scalable population-based research approach, especially in resource-limited settings.

Subcellular compartmentalization of the glycolytic enzyme PFKM regulates cell fate and metabolic switch during skeletal muscle differentiation.

Maurice et al. examine how cytokines regulate antigen-independent activation of memory CD8⁺ T cells. They show that IL-4 signaling changes the quality of the bystander T cell response by antagonizing IL-18 sensing and subsequent IFNγ production, but increasing granzyme B expression without changing perforin, thereby limiting bystander-mediated protection.

Saccadic eye movements during free viewing exhibit patterns that reflect a strategy to increase neural responses by matching motor behavior with the statistics of the natural world and with the processing limitations of sensory systems.

Jude et al. present a communication intracortical brain–computer interface typing neuroprosthesis enabling familiar, high-speed, bimanual QWERTY keyboard functionality for people with paralysis through the decoding of attempted finger movements.

On the North Western European Shelf, increased sea-level reduces seabed exposure to ocean waves and currents, while climate change increases storm intensity, leading to more frequent periodic disturbance of the seabed, according to analyses of hydrodynamic, wave, and climate models.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

Ibiza, an island in present-day Spain, was under Islamic rule between the 10^th and 13^th centuries CE. Here, the authors analyse the remains of thirteen individuals from medieval Islamic burials in Ibiza, describing their ancestries and pathogens.

Germline and somatic interactions define actionable genomic patterns driving acquired therapy resistance in breast cancer.

Acute depletion of NIPBL reveals a class of chromatin loops that are independent of NIPBL for their maintenance but not their establishment and that NIPBL is necessary for the expression of lineage-defining genes.

Projected impacts of climate change on malaria burden in Africa by 2050 highlight the urgent need for climate-resilient malaria control strategies and robust emergency response systems to safeguard progress towards malaria eradication.

Prenatal Zika virus (ZIKV) exposure can lead to a spectrum of developmental issues, but the mechanisms remain unclear. Here the authors show that prenatal ZIKV exposure in macaques disrupts neurodevelopment, causing prolonged maternal attachment and visual deficits at 3 months that normalize by 12 months, independent of sensory function.

Humans alter the daily timing of animal activity, potentially reshaping predator–prey interactions. This meta-analysis reveals that larger species tend to “lose” under human disturbance, with large predators overlapping less with their prey, and large prey overlapping more with their predators.

Cells rely on diversification and redundancy of protein chaperones to maintain proteostasis. Here, the authors show that two C. elegans orthologs of a chaperone have distinct roles in stress resistance, aging, and autophagy through an ER-phagy receptor-dependent pathway.

Psilocybin may help treat chronic pain, possibly due to direct analgesic effects. Here, authors tested psilocybin on acute and chronic pain in three mouse models of pain and found minimal effects on sensory, affective, or functional pain measures.

Myeloid-specific mechanotransduction ablation downregulates pro-fibrotic fibroblast transcriptional profiles to reduce scar formation in human cells

The success of allogeneic hematopoietic stem cell transplantation for the treatment of haematological cancers is limited by the morbidity and mortality associated with graft-versus-host disease (GVHD). Here the authors show that the microbial metabolite desaminotyrosine contributes to graft-versus-leukemia responses while protecting against GVHD and promoting mTORC1 and STING-dependent intestinal regeneration.

Thermogenetics enables spatiotemporal control of protein activity using temperature. Now, engineering of a compact, insertable thermoresponsive protein module diversifies the classes of proteins amenable to allosteric thermoregulation.

Activity in a set of parabranchial neurons in the mouse brain is increased during chronic pain, predicts coping behaviour, and can be modulated by circuits activated by survival threats.

Here, the authors analyze the microbiome composition and resistome pre-, during- and post-antibiotic exposure in Malawian adults, and find that commonly used antibiotics, such as ceftriaxone, exert strong off-target effects, both increasing abundance of opportunistic pathogens and the prevalence of a wide number of antibiotic resistance genes.