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The authors used long-read sequencing to reveal novel isoforms and differential transcript use in a transgenic model of tau pathology. Similar patterns were found in the human cortex, supporting a role for alternative splicing in Alzheimer’s disease.

Context-dependent, responsive synthetic promoters are crucial for a wide range of applications, yet currently available options are limited. Here, authors develop a library of thousands of candidate promoters based on binding motifs of hundreds transcription factors for use in mammalian cells.

An observational study reports the joint effects of polygenic risk scores and radiation treatment exposure with a subsequent increased risk of multiple solid cancers in two large cohorts of survivors of childhood cancer.

As presented at the 2025 World Conference on Lung Cancer, in a multiarm phase 2 trial, perioperative immunotherapy was safe and feasible in patients with resectable diffuse pleural mesothelioma, with exploratory data suggesting that ctDNA kinetics could be informative of tumor regression and post-treatment survival.

Designed novel protein nanoparticle technology integrates antibody targeting and responds to changes in environmental conditions to release protected molecular cargoes, opening new applications for precision medicine.

HTLV-1 type-C causes more severe disease than type-A, but the underlying reason is unclear. Here the authors show in a macaque model how type-C orf-I affects lung pathogenesis and the immune response to HTLV-1, providing a model to test viral targets for disease prevention.

Karcher et al. use data from the Adolescent Brain Cognitive Development Study to explore how changes in cognition and brain structure influence the relationship between risk factors and persistent distressing psychotic-like experiences in children aged 9–13 years.

FtsN promotes the inward synthesis of septal peptidoglycan (sPG) through the FtsWI complex during bacterial cell division. Here, Lyu et al. apply single-molecule microscopy on E. coli to show that FtsN proteins (I) move processively at a speed similar to that of FtsWI molecules. (II) can be divided into two populations based on their speeds, and (III) their movement is driven exclusively by peptidoglycan synthesis

Using different genetic mice models, Sung et al. show that VEGF-C/VEGFR3 signaling is required for sinusoidal vascular growth in the fetal liver and bone marrow. CDH5 (VE-cadherin) negatively regulates VEGF-C/VEGFR3 signaling and sinusoidal and lymphatic growth. Loss of CDH5 enables growth of sinusoidal and lymphatic vessels in the absence of VEGFR3 signaling through VEGF-C/VEGFR2 signaling.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

UBE3A gene dysregulation is associated with neurodevelopmental disorders, but predicting the function of UBE3A variants remains difficult. The authors use a high-throughput assay to categorize variants by functional activity, and show that UBE3A hyperactivity increases the risk of neurodevelopmental disease.

Animals are more likely to react to rapid rather than slow temperature change. Here, the authors identify a brain circuit in Drosophila that selectively responds to rapid thermal change, priming behavior for escape.

Laboratory simulation experiments with isomer selective photoionization detection techniques reveal that octasulfur (S₈) and sulfanes can be easily formed in low temperature H₂S interstellar ice analogues exposed to ionizing radiation, suggesting a critical link between sulfur chemistry on ice coated nanoparticles in molecular clouds and the inventory of sulfur compounds in our Solar System.

Fluorescent protein reporters based on GFP exist, but have intrinsic disadvantages. Here the authors incorporate pH, Ca²⁺ and protein–protein interaction sensing modalities into de novo designed mini-fluorescence-activating proteins (mFAPs), with increased photostability and smaller size, which bind a range of DFHBI chromophore variants.

The precise mechanism by which seizures disrupt neural coding remains unclear. Here, the authors show that discharges arising from the seizure source travel macroscopic distances, where they go on to influence spiking sequences at the microscopic scale.

Cantu Gutierrez et al. identify the common and unique transcriptional regulatory networks in the endothelium of six different organs throughout development, and further show that these same transcriptional regulators can reprogram endothelial function in vitro.

Between saccades, our eyes undergo random movements called fixational drift, but what drives this motion has remained elusive. In this paper, the authors demonstrate that a central neural circuit within the oculomotor system drives fixational drift.

Phylogenetic analysis of trait heritability (PATH) applies phylogenetic correlations to single-cell lineage tracing data, quantifying cell state plasticity and transition probabilities. PATH offers insights into cell state heritability and transition dynamics in cancers.

By integrating large-scale genomic and proteomic data in cerebrospinal fluid and plasma, the authors identify 49 proteins linked to MRI markers of cerebral small vessel disease, highlighting extracellular matrix and immune pathways, with biomarker and therapeutic potential.

Craniofacial malformations have been linked to congenital heart defects, as in 22q11.2 deletion syndrome, but the mechanisms linking these lineages remain unknown. Here they show that zebrafish nxk2.7 is expressed in cardiopharyngeal progenitors and has roles in craniofacial development that cannot be compensated for by nkx2.5.

An analysis of the impact of logging intensity on biodiversity in tropical forests in Sabah, Malaysia, identifies a threshold of tree biomass removal below which logged forests still have conservation value.

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.

The divisome is a macromolecular machine composed of more than 30 proteins that controls cell wall constriction during bacterial cell division. Here, the authors provide insights into the structure and dynamics of the divisome core complex using a combination of structure prediction, molecular dynamics simulation, single-molecule imaging, and mutagenesis.

Phage-assisted noncontinuous selection of protein binders (PANCS-Binders) allows multiple high-diversity protein libraries to each be screened against a panel of dozens of targets for high-throughput protein binder discovery.

Understanding functional role of different neuronal cell types is challenging. Here the authors associate multi-modal in vitro cell properties with in vivo physiology of mouse visual cortex.

Bone marrow stromal cells (BMSCs) lining sinusoidal blood vessels are mesenchymal cells whose function is critical for the skeleton. Here the authors show that quiescent CXCL12-expressing BMSCs can convert into a skeletal stem cell-like state, and differentiate into cortical bone osteoblasts only in response to injury.

The authors introduce ChronoGauge as a machine learning model which can estimate a plant’s internal circadian time using gene expression. This can be used to compare the circadian clock across different environments and genotypes.

Influenza A viruses pose a continuing pandemic threat to humans. Le Sage, et al. describe a pandemic triage pipeline to evaluate the pandemic risk of emerging viruses and utilize it to characterize two widespread swine influenza A viruses.

The function of TRPA1 channels in the mammalian cochlea is poorly understood. Here, the authors show that TRPA1 channels in supporting cells of the organ of Corti mediate contractile responses that may contribute to temporary shifts in hearing thresholds after noise exposure in mice.

Clonal hematopoiesis of indeterminate potential (CHIP) was found to be associated with a protective effect from Alzheimer’s disease (AD) in large population-based cohorts.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

The authors find the human red nucleus is functionally connected with action and motivated behavior networks, instead of motor-effector networks. They argue the red nucleus implements goal-directed behavior, integrating behavioral valence and action plans.

Using an autonomous underwater vehicle, this study presents an integrated biogeochemical and multiomic analysis of microbial eukaryotes from the North Atlantic Ocean. The work highlights diverse communities that shift through depth zones, with signatures of nutrient biomarkers changing across a coastal-offshore spatial gradient.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

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.

The rapid dissociation of methanetetrol has been suggested as an impediment to its observation, despite the stability of its substituted derivative orthocarbonates. The authors identify methanetetrol as a product of carbon dioxide and water reactions in space-simulation experiments via photoionization mass spectrometry working in tandem with computation quantum chemistry.

This work explored whether people would rather choose to receive empathy from human or AI empathizers. When given the choice, participants sought human empathy, despite rating AI responses as more empathetic and making them feel more heard.

Muscle fibers have diverse properties—for example, slow and fast twitch. Groups of fibers are activated by motoneurons. Marshall et al. found that motoneurons are used flexibly, presumably allowing us to intelligently employ fibers suited to each task.

The authors identify a cluster of ~160 peptidergic neurons in the mouse brainstem whose activity is necessary and sufficient for producing sound and controlling sound volume. These neurons form the final common pathway for vocalization.

European rivers have over a million barriers hindering aquatic species migration and altering freshwater habitats. This study quantifies the spatial extent of upstream fish habitat alteration caused by physical blockage and shows that impoundments have altered 10% or 200,000 km of free-flowing river habitat in Europe.

PIWI-interacting RNAs (piRNAs) are regulatory RNAs that bind to PIWI proteins to control transposons and maintain genome integrity. Here the authors characterized their binding specificity and reveal the 5′ nucleotide bias of the Drosophila Piwi protein, through mutation of its specificity loop.

A pediatric cancer dependency map generated with genome-scale CRISPR–Cas9 loss-of-function screens in 82 pediatric cancer cell lines highlights genetic dependencies across a range of tumor types.

Chromatin undergoes extensive reprogramming during immune cell differentiation. Here Kuo and colleagues uncover an epigenetic mechanism that primes the chromatin to facilitate macrophage development.

Structural analysis of the uridyl transferases TUT4 and TUT7 reveals the use of two functional modules in the switch from monouridylation of pre-let-7, which promotes let-7 expression, to oligouridylation of pre-let-7, which marks it for degradation.

Low frequency brain waves convey information between regions. Here, the authors demonstrate that for patients with major depression, mood becomes more negative as low frequency waves increase intensity  across the prefrontal cortex.

Stabl selects sparse and reliable biomarker candidates from predictive models.