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Analysis of human Robertsonian chromosomes originating from 13, 14 and 21 reveal that they result from breaks at the SST1 macrosatellite DNA array and recombination between homologous sequences surrounding SST1.

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.

iExoKras^G12D are engineered exosomes for the delivery of siRNA targeting KRAS^G12D. Here the authors describe the results of a phase I trial of iExoKrasG12D in patients with metastatic pancreatic cancer, reporting safety and clinical activity, as well as immunological correlates informing on tumor immune microenvironment reprograming and future combination with immune checkpoint inhibitors.’

Heart failure can be caused by cardiac fibroblasts replacing myocytes. Here, the authors use functional genomic data from fibroblasts, genetic signals enriched in people with heart disease, and gene perturbation analyses to link disease-associated regulatory elements to protein-coding genes.

An approach combining bioorthogonal chemistry with genetically encoded fluorogen-activating proteins enables subcellular imaging of phospholipids and glycans, as well as the visualization of lipid transport between organelles and lipid asymmetry across membrane leaflets.

Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

The activity of the membrane-bound enzyme pMMO depends on copper but the location of the copper centers is still under debate. Here, the authors reconstitute pMMO in nanodiscs and use native top-down MS to localize its copper centers, providing insights into which sites are essential for activity.

Brain-wide recordings in mice reveal that prior expectations are distributed through recurrent loops across all levels of cortical and subcortical processing.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

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.

AI copilots are integrated into brain–computer interfaces, enabling a paralysed participant to achieve improved control of computer cursors and robotic arms. This shared autonomy approach offers a promising path to increase BCI performance and clinical viability.

Intratumoral hypoxia promotes cancer progression. Here, authors show that hypoxia upregulates RNA Polymerase I activity and ribosome biogenesis in breast cancer cells and targeting RNA Polymerase I with BMH-21 reduces tumor growth and metastasis in murine models.

Cannabis use has been reported to impair sperm quality but less is known about whether cannabis affects female fertility. Here the authors report that cannabis use and THC levels associate with oocyte maturation rate and reduced number of euploid embryos in a retrospective case-control study of patients undergoing IVF treatment, while in vitro data suggests THC impairs chromosome segregation.

Using historical aerial photographs and new bed topography data, accelerating changes on Kennicott and Root Glaciers, Alaska since 1938 are documented. These observations inform projections showing 38–63% mass loss by 2100, depending on future climate.

Whether and how prefrontal astrocyte Ca²⁺ signaling modulates different neuronal populations in aiding or inhibiting anxiety-like behavior remains not fully understood. Here authors show that prefrontal astrocytes encode anxiogenic cues and modulate excitatory and inhibitory neurons differently. Silencing prefrontal astrocytes heightens anxiety-like behavior and induces proteomic changes in astrocytes and neurons.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

Liver regeneration often fails during chronic liver disease. Here, the authors conduct multiomic profiling of human livers to demonstrate that RNA splicing is dysregulated in alcohol-associated liver disease, interfering with liver regeneration.

This study reports the development and preclinical evaluation of a humanized citrullinated histone H3 (CitH3) monoclonal antibody that mitigates inflammation, restores macrophage function, and protects against sepsis-induced pulmonary injury.

Cells use clathrin-mediated endocytosis to internalize biomolecular cargo. The authors demonstrate that the Epsin1 protein ensures uptake of ubiquitylated cargo through ubiquitin-dependent regulation of the stability of endocytic protein networks.

A large-scale mouse study reveals that while existing epigenomic data detect many developmental enhancers, a substantial fraction is missed - highlighting the need for expanded resources to fully annotate enhancers genome-wide.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

Sedimentary rocks record planetary environmental history convolved with the internal dynamics of depositional landscapes. Ganti et al.show that the advection length of settling sediment sets bounds on internal landscape dynamics, providing a new tool to unravel sedimentary archives.

Intradermal microneedles for the co-delivery of mRNA and near-infrared fluorescent microparticles are used in combination with deep learning-based image analysis for the simultaneous administration of therapeutics and registry of patient information records into the skin.

The human plasma proteome spans over 10 orders of magnitude, but current quantification methods cover only 3-4 orders. Here, authors propose a tuning approach for proximity-based assays, enabling simultaneous quantification of four analytes across a wide concentration range (low fM to mid-nM).

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.

Superconducting qubits operate at microwave frequencies, but it is much more efficient to transmit information optically. Now, a superconducting qubit has been controlled with an optical signal by using a microwave–optical quantum transducer.

A miniature spectrometer has been developed that employs light scattering in a photonic chip with a random structure. It generates wavelength-dependent speckle patterns, which are detected and analysed to recover the spectrum of the input signal. It has a resolution of 0.75 nm in the 1,500 nm wavelength region.

Direct wavefront sensing with laser ‘guide stars’ is used in astronomy and microscopy to correct for optical aberrations. Wang et al.use near-infrared guide stars to extend this approach to the highly scattering mouse brain, allowing high-resolution fluorescence imaging at 700μm depth.

Models of brain organisation can overlook the role of the autonomic nervous system in cognitive processes. Here the authors show a link between the ascending arousal system and both low dimensional neural dynamics and internal shifts in conscious awareness.

In contrast to genetic circuits, here the authors develop protein biocircuits based on proteases. They show these activity-based circuits can execute Boolean logic for programmable drug delivery and perform fuzzy logic to solve a mathematical oracle problem, Learning Parity with Noise.

Kucharska, Ivanochko and Hailemariam and colleagues solved cryo-EM structures of Pfs48/45, needed for Plasmodium falciparum development, with potent antibodies. The work revealed conformational epitopes, with implications for design of therapies against malaria.

Looped trajectories of photons in a three-slit interference experiment could modify the resulting intensity pattern, but they are experimentally hard to observe. Here the authors exploit surface plasmon excitations to increase their probability, measuring their contribution and confirming Born’s rule.

Mice maintain the memory of previous associations between head direction neurons and allocentric cues and this influences the internal head direction representation.

JWST and Keck II spectral observations of Saturn’s moon Titan reveal methyl (CH₃) as well as non-local thermodynamic equilibrium emission bands of CO and CO₂. Imaging shows clouds in Titan’s northern hemisphere at several epochs, with some appearing to evolve in altitude.

A cell-sorting method leveraging leucine zippers allows for the generation of T cells displaying multiple chimaeric antigen receptors as well as receptors converting inhibitory signals into stimulatory signals.

It remains poorly understood how the onset of Alzheimer’s disease affects spatial cognition. Here, the authors report that spatial coding in grid cells deteriorates over time in a mouse model of Alzheimer’s disease during the early stages of pathology while place cell and head direction coding remain intact.

Seismic reflection imaging beneath the northeastern Yellowstone caldera reveals a sharp boundary at about 3.8 km depth, which is inferred to result from a mixture of supercritical fluid and magma filling the pore space.

Development of a biosensor for GPCR trafficking to the lysosome combined with a genome-wide CRISPR screen identified DNAJC13 as a critical regulator of agonist-induced trafficking of the δ-opioid receptor to the lysosome.

Multiferroic BiFeO₃ is promising for applications where electric and magnetic fields need to be coupled, for example, in magnetic data storage. Here, combining theory and experiment the authors provide a microscopic insight into the switching of magnetization by electric fields in BiFeO₃.

Ubiquitination of the CMG helicase triggers replisome disassembly, ensuring genome integrity. Here, the authors show that the deubiquitinase USP37 preserves replisomes during S and G2 phase by binding and deubiquitinating CMG. USP37 is vital in cells expressing oncoproteins which dysregulate DNA replication.

Optimized SORT LNPs enable precise and long-lasting base editing in dual organs in a disease mouse model.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

An exome-wide association study for fetal and maternal rare deleterious variants affecting the normal variation in birth weight identifies nine genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.

New data on brain-wide circuits centred around two interconnected hypothalamic neuron populations provide significant mechanistic insights into the emergence of social need during social isolation and the satiation of social need during social reunion.

Tonic and burst-like locus coeruleus firing distinctly tune brain topology toward associative and sensory regions, recruiting both astrocytic and neuronal inhibitory activity.

Enhanced light–molecule interactions in high-finesse fibre-based Fabry–Pérot microcavities are used to detect and profile individual unlabelled solution-phase biomolecules, leading to potential applications in the life and chemical sciences.

Here the authors describe a biophysical layer-5 pyramidal neuronal model linking microscale spiking to macroscale complex dynamics, that predicts distinct burst dynamics and information processing across unconscious, dreaming, and awake states.