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Breakage of both chromosomal DNA strands creates unique problems for DNA repair. Here, Luthman et al. show that for some broken ends, the two strand breaks are repaired in parallel, while for other ends one strand must be repaired before the other.

Understanding asteroid materials is critical for determining deflection methods for planetary defense. Here the authors show, via experiments performed in High-Radiation to Materials facility at CERN, that iron-rich asteroid materials can absorb more energy without structural failure than standard material parameters would suggest.

TCR-engineered T cells have shown limited efficacy in part due to the absence of co-stimulation leading to limited accumulation in solid tumors. The authors here show engineering the CD8β coreceptor with an intracellular CD28 domain enhances cytokine production, persistence, and tumor control in vivo independent of tumor-associated co-stimulatory ligand encounter.

The emerging field of imaging-by-sequencing aims to perform spatial biological analyses by molecular interactions. Here, authors used previously undiscovered spatial networks within Slide-tags data to reconstruct cell positions and capture biological information comparable to the original method.

Little millet is an orphan crop offering a promising yet underutilized option in the pursuit of food and nutritional security. Here, the authors report its genome assembly, and elucidate its recent tetraploid structure, sub-genome dominance, and the genetic basis for micronutrient content.

In patients with advanced cancer, the development of brain metastasis (BM) often signals a worsening prognosis with limited therapeutic options. Here, the authors assemble a large, open-source neuroimaging dataset of BM and perform spatial and morphological analysis which they use to develop a framework for function-sparing brain radiotherapy design.

Genomic and transcriptomic analysis of samples from patients with multiple myeloma, followed by in vitro validation, indicate mechanisms of antigen escape in response to GPRC5D T cell-engager talquetamab, including biallelic deletions, small nucleotide variants, insertion-deletions and chromatin silencing.

Coupling of ecology and evolution in microbiomes can lead to time-dependent community interactions. Here, the authors introduce Dynamic Covariance Mapping (DCM), an approach to quantify the community matrix and, with high-resolution lineage tracking, show how inter- and intra-species interactions shape the dynamics of mouse gut colonization.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

Cellular target engagement technologies enable quantification of intracellular drug binding, but the simultaneous assessment of drug-associated phenotypes is challenging. Here, the authors develop CeTEAM (cellular target engagement by accumulation of mutant), a platform that can simultaneously evaluate drug-target interactions and phenotypic responses for holistic assessment of drug pharmacology using conditionally stabilized drug biosensors.

Mucosal influenza vaccines promise enhanced protection but lack defined immune correlates of protection. Here, the authors conduct a phase I trial of an intranasal recombinant influenza A/H5 vaccine with a nanoemulsion adjuvant, demonstrating successful mucosal priming and broad cross-clade immune responses, advancing the development of intranasal influenza vaccines.

Kathiriya et al. identify a cardiac progenitor lineage with expression of Tbx5 and anterior heart field-specific expression of Mef2c that bisects the intraventricular septum during development and show that alterations in this lineage lead to congenital heart defects in mice.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

The authors detail human antibodies that neutralize all three serotypes of poliovirus and mimic poliovirus receptor binding, accelerating antiviral development to further efforts to eradicate poliovirus.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Confocal microscopy enables high-resolution, high-plex 3D cyclic immunofluorescence of 30- to 50-µm-thick tissue sections. The approach allows for rich phenotypic assessments of intact cells and intercellular interactions with subcellular resolution.

The early genetic evolution of uveal melanoma (UM) remains poorly understood. Here, the authors perform genetic profiling of 1140 primary UMs, including 131 small early-stage tumours, finding that most genetic driver aberrations have occurred by the time small tumours are biopsied; in addition, the15-gene expression profile discriminant score can predict the transition from low- to high-risk tumours.

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.

Recurring deep ocean oxygen minimum events occur in the Pacific Southern Ocean during the warm climate interval Marine Isotope Stage 11. They are linked with perturbed Antarctic Bottom Water formation caused by West Antarctic Ice Sheet retreat.

The ~500-metre-thick Prudhoe Dome in northwestern Greenland completely deglaciated 7,000 years ago, highlighting the sensitivity of the ice sheet to mid-Holocene warming, according to luminescence and geochemical data from sub-ice sediments and ice cores.

Base editor off-target effects are profiled with high precision in a tailored approach.

Ionizing radiation can cause simultaneous charge noise in multi-qubit superconducting devices. Here, the authors measure space- and time-correlated charge jumps in a four-qubit system in a low-radiation underground facility, achieving operation with minimal correlated events over 22 h at qubit separations beyond 3 mm.

People tend to connect with similar others in different groups, shaping how ideas and diseases spread. The authors introduce a data-validated model that captures homophily across group sizes and show it can raise or lower connectivity and epidemic thresholds, informing better intervention design.

The interactions of CAR-T cells and solid tumors are modeled on a chip.

Noel et al. show aberrant updating of expectations in three distinct mouse models of autism spectrum disorder. Brain-wide neurophysiology data suggest this stems from excess units encoding deviations from prior mean and a lack of sensory prediction errors in frontal areas.

Respiration enhances cerebrospinal fluid flow through mechanical and autonomic pathways. Inhale length and diaphragm motion influence its displacement and net flow, identifying a modifiable, noninvasive mechanism relevant to brain homeostasis.

Kephart et al. use biophysical approaches to probe changes in H5N1 influenza hemagglutinin dynamic behavior resulting from transmission-adaptation mutations. Subtype-specific patterns of activation dynamics are revealed that indicate underlying physical constraints on HA adaptation.

Zeinert et al. provide cryo-EM structures of the E. coli Mg²⁺ importer MgtA: unexpectedly, this P-type ATPase is a dimer with an uncommon transmembrane ion-binding site and knotted N-terminus, which are functionally important features.

Gray wolf hunting and feeding priorities shift throughout the breeding season in accordance with prey availability.

Bacterial resistance to polymyxin antibiotics is conferred by enzymes such as phosphoethanolamine transferases, which add positively charged phosphoethanolamine to lipid A. Here, the authors present the structure of one such enzyme in its liganded form, and propose an enzymatic mechanism that may be generally applicable to other phosphoform transferases.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

The developmental dynamics of distinct cell types across brain regions remain poorly understood. Here authors generate DevAtlas, a high-resolution developmental 3D atlas, mapping region and cell type-specific growth in GABAergic cells and microglia in early postnatal mouse brains.

Two groups of ammonia-oxidizing archaea drive marine nitrification. Stuehrenberg et al. reveal that their distribution reflects substrate use, with one relying on urea and the other on ammonia to maintain nitrification in open-ocean waters.

Optical neuromorphic systems promise significant advantages in terms of bandwidth, power efficiency, and speed. Here, authors demonstrate how networks of spiking photonic crystal nanolasers can be trained to perform Bayesian inference through sampling from multivariate probability distributions.

A combination of high-resolution spatial imaging, spatial proteomics and transcriptional data reveals sparse and heterogeneous bacterial signals in gliomas and brain metastases.

Deletion of functional sequence is predicted to represent a fundamental mechanism of molecular evolution. Here the authors use CRISPR-based perturbations and epigenetic profiling in chimpanzee cells to identify gene regulatory roles for genomic sequence lost in the human lineage.

The mechanisms that impact tumorigenesis during aging are incompletely understood. Here Shuldiner et al. show that in mice, aging represses KRAS-driven lung tumorigenesis and dampens the impact of inactivating many tumor suppressor genes, which may contribute to the deceleration in cancer incidence with extreme age in humans.

Here, the authors present archaeology of the Namorotukunan site in Kenya’s Turkana Basin that demonstrates adaptive shifts in hominin tool-making behaviour spanning 300,000 years and increasing environmental variability. They contextualize these findings with paleoenvironmental proxies, dating, and geological descriptions.

A metagenomic screen identifies retron reverse transcriptases for precise genome-editing applications.

Neural progenitor cell transplantation shows promise for treating spinal cord injury. However, here, the authors show that graft-derived neurons form limited synaptic connections with host spinal motor circuits after injury, constraining functional motor recovery.

Off-target activation of nerve fibers is an ongoing problem in bioelectronic medicines such as vagus nerve stimulation. Here, the authors show that high-frequency stimulation can selectively block nerve fibers in the vagus nerve in swine models.

Simulating gauge theories is a central challenge for quantum computing in theoretical physics. The authors present a quantum algorithm for 2+1D lattice QED that extracts the static potential between charges across Coulomb, confinement and string-breaking regimes, visualizing electric fluxes and demonstrating accurate results from a trapped-ion device.

Engineering qubits with long coherence times requires the ability to distinguish multiple noise sources, which is not possible with typical two-level qubit sensors. Here the authors utilize the multiple level transitions of a superconducting qubit to characterize two common types of external noise.

This work presents a global wind power simulation tool that uses high-resolution data and extensive validation to improve accuracy. It corrects wind speed biases and validates against real-world data, enhancing reliability for wind energy assessments across various scales and regions.

The Janssen effect refers to the saturation of the apparent mass of a column of granular material, due to friction with the boundary of the column. Here, using ferromagnetic beads, Thorens et al. succeed in controlling the apparent mass of the column via an applied magnetic field.

Injection of AAV–shRNA below the pial surface of the spinal cord prevents onset or ameliorates progression in a mouse model of ALS, and achieves widespread delivery to the spinal cord and brain motor centers in adult pigs and non-human primates.

Engineering polymerases to synthesize alternative genetic polymers remains a challenging problem in synthetic biology. Using DNA shuffling and droplet microfluidics, the current study provides a short evolutionary path from a DNA polymerase to one with robust RNA-synthesizing activity.