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Using inbred medaka strains, the authors mapped 59 genetic loci linked to heart rate. Gene editing validated conserved genes affecting heart rate and morphology, highlighting the power of isogenic strains in uncovering mechanisms of cardiac traits and disease.

Using data from the CoVPN 3008 study, the authors show that the neutralizing antibody correlate of risk holds in people living with HIV. However, the nAb correlate was weaker and shorter-lived in a vaccine-immunity versus hybrid-immunity population.

Cryptococcal meningitis is a common infection in patients with compromised CD4 T cell function. Using a CD4 T cell activation tracking mouse the authors show the localisation and activation of CD4 T cells in the brain after cryptococcus infection and how these cells interact with MHCII expressing microglia which may increase pathologic brain inflammation.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

Natural disasters induce power outages with unequal impacts on poverty and non-poverty counties in China. Climate change will further exacerbate this disparity.

CAR-T cells engineered with αPD-L1–IL-12 fusion proteins show antitumour activity in mouse models of prostate and ovarian cancer.

Different types of SETBP1 variants cause variable developmental syndromes with only partial clinical and functional overlaps. Here, the authors report that SETBP1 variants outside the degron region impair DNA-binding, transcription, and neuronal differentiation capacity and morphologies.

Viruses such as coxsackievirus B (CVB) have been associated with type I diabetes (T1D) and islet destruction. Here the authors show that Yes-associated protein (YAP) is upregulated in the whole pancreas in T1D and at-risk autoantibody (AAb + ) organ donors and that YAP over-expression enhances CVB replication, islet inflammation and β-cell apoptosis and suggest exocrine-islet-immune interactions as targeted interventions for T1D.

A complementary analysis of DESI DR2 distance measurements along with supernova and CMB data shows consistent, moderate evidence that dark energy changes over time rather than behaving as a simple cosmological constant.

Over 20 species of geographically and phylogenetically diverse bird species produce convergent whining vocalizations towards their respective brood parasites. Model presentation and playback experiments across multiple continents suggest that these learned calls provoke an innate response even among allopatric species.

By carefully dispersing small amounts of Ir into the RuO₂ lattice, a Ru₆IrOₓ catalyst reduces Ir usage by 80% while still running stably for over 1,500 h at 2 A cm⁻² in both laboratory- and industrial-scale proton-exchange membrane water electrolysers.

Shigella sonnei is divided into five lineages and most infections are caused by Lineage 3. Here, the authors investigate factors contributing to the epidemiological success of Lineage 3 through comparative genomics and virulence analyses in a zebrafish infection model.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Neuroinflammation following intracortical microelectrode implantation impairs long-term brain-machine interface performance. Here, the authors developed a nanoparticle-based therapy that improves local hemostasis and delivers dexamethasone, reducing inflammation.

Here the authors develop a genetic priority score to predict side effects by integrating multiple lines of genetic evidence. By applying this score, they provide evidence of known side effects and suggest ones with no clinical trial evidence.

In a prospective study enrolling 1,222 patients from 22 emergency departments, a device using a machine-learning-based signature of blood mRNAs demonstrated clinically acceptable performance to diagnose bacterial and viral infections and to predict the all-cause need for critical care interventions within 7 days, with benchmark to established biomarkers and risk scores.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

The authors identify defective viral particles, in people with non-suppressible HIV-1, that can replicate through superinfection and interfere with the wild-type virus. However, they show no evidence of these preventing disease progression in the individuals studied.

LARGE1 glycosyltransferase synthesizes matriglycan (xylose-glucuronate)_n on dystroglycan, and short matriglycan can cause neuromuscular disorders. Authors show that LARGE1 processively polymerizes matriglycan of defined length on prodystroglycan.

This prespecified updated survival and exploratory subgroup efficacy analysis of the phase 3 DESTINY-Breast04 trial shows that trastuzumab deruxtecan treatment in patients with HER2-low metastatic breast cancer leads to continuous survival benefit irrespective of estrogen receptor or hormone receptor status.

Researchers induced ploidy reduction in human oocytes generated by somatic cell nuclear transfer, enabling fertilization and embryo development with integrated somatic and sperm chromosomes, highlighting a proof-of-concept for in vitro gametogenesis.

Natural and sexual selection can be in opposition favouring different trait sizes, but disentangling these processes empirically is difficult. Here Okada et al. show that predation on males shifts the balance of selection in experimentally evolving beetle populations, disfavoring a sexually-selected male trait but increasing female fitness.

A proteotoxic stress response specific to exhausted T cells, governed by AKT signaling and accompanied by increased protein translation, represents a mechanistic vulnerability and a new therapeutic target to improve cancer immunotherapies.

Scoliosis is a common yet poorly understood pediatric disorder. Using zebrafish disease models, Pumputis et al. identify pervasive cell stress responses as causing spine deformity and present possibilities for new therapies and diagnostic tools.

This pilot trial showed that perioperative treatment with the isocitrate dehydrogenase (IDH) inhibitor safusidenib of patients with low-grade IDH-mutant glioma, with craniotomy and lumbar puncture before and after treatment, is feasible and safe and enabled in-depth translational investigation of safusidenib treatment-induced changes in the tumor, including electrophysiological effects.

SARS-CoV-2 rebound is a recurrence of symptoms or return to test positivity after initial recovery. Here, the authors demonstrate an association between SARS-CoV-2 rebound and post-acute COVID conditions using data from Hong Kong.

Temporal interference stimulation is thought to act via low-frequency envelope demodulation. Here, the authors demonstrate that stimulation thresholds in TIS follow the same carrier frequency dependence as direct kHz stimulation, indicating a shared biophysical mechanism.

Infection of mosquito immune cells by dengue and Zika virus enhances the spread of virus infection to mosquito tissues, such as the salivary glands, to promote virus transmission and highlights conserved roles of immune cells in virus dissemination.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

This study uses spatial proteomic and spatial compartment-based whole-transcriptome profiling to develop predictive models for immunotherapy outcomes in non-small cell lung cancer.

Distinguishing glioblastoma and primary central nervous system lymphoma (PCNSL) remains challenging due to their overlapping pathology features. Here, the authors develop a computational tool, PICTURE, for differentiating similar pathological features enabling improved diagnosis of CNS tumours.

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

Phaeocystales are ecologically significant nanoplankton whose evolutionary history and functional diversity remain incompletely characterized. Here, the authors integrate genomic and transcriptomic data to reveal their lineage diversification, metabolic plasticity, and adaptation to polar and temperate regimes.

Urbanization disrupts oak tree microbiomes by reducing beneficial fungi and increasing plant and human pathogens across leaves, roots and soils, with consequences for tree health, urban climate mitigation and potential human exposure to pathogens.

Errors in oocyte division can cause infertility and birth defects. Here, authors combine a genetic strategy with a novel optochemical tool to show that spindle pole-localized F-actin is essential for proper meiotic spindle assembly and chromosome segregation.

Lithium-ion batteries rely on lithium diffusion within particles, traditionally assumed to follow concentration gradients. Here, authors use X-ray microscopy to track lithium movement in single particles, discovering that lithium can move against concentration gradients due to strain effects.

The homeostasis of myelin in the central nervous system is highly regulated, but the underlying mechanisms are unclear. Here, the authors show that the FBXW7 protein has a role in constraining myelin growth in the developing and adult central nervous system, preventing the accumulation of myelin abnormalities. FBXW7 acts in part through targeting the MYRF transcription factor for degradation.

Head motion is an artifact in structural and functional MRI signals, and some traits or groups are more strongly correlated with motion than others. Here the authors describe a method to attribute a motion impact score to specific trait-functional connectivity relationships.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

Li-Fraumeni syndrome is a cancer predisposition disorder caused by TP53 variants, but the way different TP53 variants contribute remains unclear. Here, the authors analyse TP53 mutagenesis datasets and identify five TP53 variant clusters that show associations with specific cancer patterns as well as potential clinical strategies.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

Tilt-corrected bright-field scanning transmission electron microscopy offers enhanced cryogenic electron microscopy contrast and substantial improvement in dose efficiency for thick samples such as bacterial cells and large organelles, while still being able to perform single-particle analysis.

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.

Zhang, Lahry, Cipurko et al. show that the microbial metabolites queuine and preQ₁ modify the same host tRNA. PreQ₁-tRNA reduces cell proliferation, slows tumour growth, decreases the translation of ribosomal proteins and is cleaved by IRE1 on the ER ribosome.

Exercise alters the mitochondrial proteome, but little is known about changes in different fibre types. Here, the authors provide insight into fibre-specific mitochondrial differences before and after training using proteomics in human skeletal muscle.

Enterololin is a narrow-spectrum antibiotic that selectively kills Enterobacteriaceae in vitro and in a mouse model of adherent-invasive Escherichia coli gut infection. AI-guided mechanism-of-action studies identified LolCDE as its molecular target.

Commensal Candida albicans enhances the virulence and dissemination of Salmonella enterica subsp. enterica serovar Typhimurium.

Human transplantation with allogeneic donor organs results in non-matching of MHC and differential presentation of T cell antigens. Here the authors show that in a lung transplanted SARS-CoV-2 infected patient T cell responses generated from the host may not be able to recognise infected cells within the graft and this may contribute to virus persistence.

Chapman, Klaourakis and colleagues reveal that a lymphatic vasculature with poor clearance capacity in perinatal, regeneration-competent mouse hearts is required to retain pro-reparative macrophages and allow cardiac regeneration.

Accurate quantum mechanical benchmarks modeling ligand interactions with protein pockets are key in drug design. Here, such a large dimers dataset is created, analyzed, and probed with many methods