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VCP/p97 is identified as a co-factor to the fusion oncoprotein ASPSCR1::TFE3. They co-localize on chromatin, co-dependent for enhancer looping and transcriptional regulation in alveolar soft part sarcomas and Xp11- rearranged renal cell carcinomas.

Autoreactivity to myeloperoxidase (MPO) causes autoimmune vasculitis and severe glomerulonephritis. Here, Ooi et al. show that a Staphylococcus aureus plasmid encodes a peptide that is homologous to an immunodominant MPO epitope and induces anti-MPO autoimmunity and glomerulonephritis in mice.

Influenza B viruses are linked to significant morbidity and mortality, and yet their immunobiology is comparatively poorly understood. Here Menon et al identify influenza B virus-specific CD8⁺ T cell epitopes and characterise these in adults, children and the elderly.

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).

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.

SedaDNA can facilitate reconstruction of past species distributions. Here, the authors generate metagenomes from 156 stratigraphically-sampled sediments and use them to reconstruct the history of 10 Adélie penguin colonies, including penguin diet and diversity, spanning 6000 years.

De novo designed interleukin-4 mimetics were engineered that induce biased signaling activation and exhibit high thermal stability. These mimetics offer insight into cytokine signaling and can be directly incorporated into 3D-printed biomaterials

CD1 proteins present lipid antigens to T cells via the T cell receptor. Here the authors describe T cell reactivity to human membrane lipid moieties and provide structural data to define a molecular mechanism of promiscuous recognition of self-derived phospholipids.

Marine heatwaves can have severe impact on corals populations. This study demonstrates that selective breeding could quickly enhance coral tolerance to short-term heat stress by up to 1 °C. This has potential to mitigate some impacts of climate change, however urgent climate action is still needed.

Shiga toxigenic Escherichia coli can cause gastrointestinal disease in humans, with potentially life-threatening consequences. This paper elucidates the mechanism of the bacteria-induced host cell death; a protein crucially involved in endoplasmic reticulum function is specifically targeted and inactivated by the toxin's protease subunit.

The light-driven power stroke of a unidirectional molecular motor is studied using ultrafast fluorescence spectroscopy. The evolution on the excited-state energy surface is observed on the 100 fs timescale and is accompanied by damped coherent molecular motion. The implications of these observations for the operation of the molecular motors are discussed.

It is easy to imagine that carbon nanotubes deform under strain, but the microscopic mechanism of deformation is difficult to relate to the large-scale one. Through aberration-corrected transmission microscopy the atomic displacement under bending is now mapped out, revealing unexpected details.

CD4⁺ T cells recognising shared susceptibility epitope (SE) encoded HLA-DRB1 presenting citrullinated self-peptides are implicated in rheumatoid arthritis. Here the authors characterise the T cell receptor repertoire and structure during recognition of different citrullinated self-epitopes in HLA-DR4 transgenic mice and ACPA + RA patients.

Puddu et al. investigate the role of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) as biomarkers for early-stage colorectal cancer (CRC) detection in cell-free DNA (cfDNA). 6-base genome sequencing, using both 5mC and 5hmC biomarkers, increases the detection of stage I CRC.

Cell free DNA fragmentation is a promising biomarker for disease, but its epigenetic regulation is incompletely understood. Here, the authors investigated the effects of DNA methylation in the production of cfDNA fragmentation, and corelate these changes with gene expression in human cancer.

Disturbances in the gut microbiota of male mice manifest as fitness defects in their offspring by affecting plancenta function, revealing a paternal gut–germline axis.

Apolipoprotein A-I (apoA-I) is the scaffold protein that is essential for the assembly and function of HDL particles. A structural model for monomeric, lipid-free apoA-I, based on previous and new data, is now presented.

KIR2DL2 and KIR2DL3 are two inhibitory members of the killer-cell immunoglobulin-like receptors (KIR) family that share a common HLA-I preference in binding HLA from the C1 group. However, it is still unclear to what extent binding and function is equivalent between KIR2DL2 and 2DL3. Here, the authors present the crystal structures of KIR2DL2 and 2DL3 in complex with HLA-C*07:02 and observe differences in HLA-C recognition between KIR2DL2 and 2DL3, which correlates with differences in HLA-C binding preference as they show with mutagenesis and binding studies.

McGeachan et al. observe oligomeric tau in synapses from individuals with progressive supranuclear palsy and provide evidence that tau pathology may spread through the brain via synapses.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

Future robots require compact sensing architectures capable of discerning multiple stimuli. Here, Baines et al., present a multi-modal deformation and temperature sensor which, exploiting the light-to-state mapping, discerns combined stimuli of bending, stretching, compression, and temperature.

Individuals with long COVID show marked biological changes in cortisol and immune factors relative to convalescent populations.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

This study reports that herbivory-induced volatiles can trigger plant–soil feedbacks that boost performance and yields of cereals in the field.

Here, the authors describe scDEEP-mC, an improved single-cell whole-genome bisulfite sequencing method for complex libraries and deep genomic coverage, and show advanced analyses of allele-specific methylation, replication dynamics, and X-inactivation.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

A purpose-built implantable system based on biomimetic epidural electrical stimulation of the spinal cord reduces the severity of hypotensive complications in people with spinal cord injury and improves quality of life.

A new study considers how disruption to energy systems is experienced and takes on meaning. On the basis of workshop data, the study finds that public views of heat decarbonization in the United Kingdom are shaped by relationships to family, cultural expectations, housing and financial position.

DNA from tumour cells can be detected in the blood of cancer patients. Here, the authors show that cell free DNA fragmentation patterns can identify lung cancer patients and when this information is further interrogated it can be used to predict lung cancer histological subtype.

Gram-negative bacteria assemble biofilms from amyloid fibres, which translocate across the outer membrane as unfolded amyloid precursors through a secretion system. Here, the authors characterise the structural details of the amyloid transporter FapF in Pseudomonas.

Type 2 inflammation drives the formation of pathologic mucus in patients with asthma. Here, authors reveal a role for intelectin-1 in IL-13-induced mucus properties, and that an ITLN1 eQTL is associated with protection from the formation of mucus plugs in T2-high asthma.

The authors analyse hundreds of animal and human footprints spanning at least 8,000 years at Formby on the Irish Sea coast of Britain. In the absence of conventional faunal records, the footprints document long-term changes in large mammal diversity and human activity during the Holocene.

Large language models are being considered to simulate responses from participants of different backgrounds in computational social science experiments. Here it is shown that this practice can misportray and flatten demographic groups in distinctively harmful ways.

The molecular architecture of peptidoglycan in the bacterial cell wall remains unclear. Here, Turner et al. use atomic force microscopy to image individual glycan strands in peptidoglycan at an unprecedented detail, revealing novel features of its molecular organisation.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Examination of immunological changes in transgender individuals undergoing gender-affirming testosterone treatment reveals sex hormone-regulated pathways in humans and explains sex-divergent responses in cisgender individuals.

T cell receptors are generally thought to contact antigens presented in an end to end configuration. Here the authors show a geometrically alternate sideways mode of recognition of the antigen-presenting molecule CD1a by a γδ T cell receptor.

A hyper-stable de novo protein mimic of interleukin-2 computationally designed to not interact with a regulatory T-cell specific receptor subunit has improved therapeutic activity in mouse models of melanoma and colon cancer.

Scientific progress relies on integrating and building on existing knowledge. Here, the authors propose improving cumulative science by developing data-driven ontologies, and they apply this approach to understanding the construct of self-regulation.

Phipps et al. report a cohesin-dependent double-strand break (DSB) DNA end-tethering mechanism that requires Exo1 and SMC5/6 in budding yeast. They show that cohesin oligomerization promotes DSB end-tethering and repair, safeguarding genomic integrity.

In this work, the authors demonstrate a 2D memristor with high switching speeds of 120 ps and study its dynamic response with 3 ns short voltage pulses using statistical analysis, simulation, and modeling.

Isolating and studying haematopoietic stem cells in young and aged mice demonstrates evolutionary processes related to blood production and provides a framework for interpreting future work using laboratory mice to study stem cell ageing.

In November 2023, the Division of Aging Biology of the National Institute on Aging held a workshop to discuss the long-term effects of pregnancy on aging. A synthesis of these discussions and a set of considerations are presented in this Meeting Report.

It is unclear why flying insects congregate around artificial light sources. Here, the authors use high-speed videography and motion-capture, finding that insects fly perpendicular to light sources due to a disruption of the dorsal light response.