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Drug resistance remains a major challenge in cancer treatment. Here, the authors identify Connexin43 as target that enhances BRAF/MEKi efficacy by interfering with DNA repair pathways, overcoming drug resistance. They develop an mRNA therapy that improves efficacy and sensitizes resistant cells.

Du and Haith show that behaviour can become habitual in two different ways, involving response initiation and response preparation.

Green hydrogen production via water electrolysis requires a low-cost solution to provide efficient catalysts. Here, the authors report an industrially scalable method for synthesizing NiFe layered double hydroxide at room temperature and atmospheric pressure, enhancing alkaline electrolysis.

Interactions with the extracellular matrix (ECM) control tumor proliferation, invasion and metastasis. Here, authors provide spatial information on ECM organization and how it influences tumor cell invasive and metastasis properties through induction of cytoskeletal and transcriptional memory.

Whole-genome sequences and field experiments focusing on the global invasive forage crop, Trifolium repens, show high levels of genetic variation across continents and parallel signatures of selection in five haploblocks.

Allelic losses occurring in cancer cells have been suggested as potential targets for therapy. Here, the authors show how recurring loss of heterozygosity of a drug metabolic gene in colorectal cancers can be exploited using a low molecular weight compound.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Horses have lived in Iberia since the Ice Age. Using ancient genomes to study their history, Lira Garrido et al. reveal a local wild lineage lasting until Late Iron Age, and highlight the far-reaching influence of Iberian bloodlines across Europe and north Africa during the Iron Age and beyond.

Fatty liver disease exacerbates atherosclerosis, but the underlying mechanisms remain unclear. Here, the authors show that D-dopachrome tautomerase (D-DT/MIF-2) acts as an atypical chemokine, promoting both atherosclerosis and hepatic lipid accumulation.

Neural computations are envisioned as arising from either distinct function subpopulations or distributed collective dynamics. Dubreuil and Valente et al. examined recurrent neural networks trained on various cognitive tasks and found that a mixed-selective yet non-random subpopulation structure enabled flexible responding through gain-modulated latent dynamics.

Deterministic generation of photonic multi-partite entangled states has previously been achieved for specific states using ad-hoc devices. Here, the authors present a single superconducting circuit device to deterministically generate a variety of states, namely W, GHZ, and cluster states.

Tumour endothelial cell macropinocytosis is the dominant mechanism for nanoparticle entry into the tumour. Enhanced nanoparticle tumour accumulation may be due to upregulated macropinocytosis membrane ruffling compared with most healthy tissues.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Microbial communities, exposed to early Earth-like conditions in a modern microbialite reef, change cyclically due to seasonal environmental variations, implying evolved metabolic processes in microbialites over time, based on multiple chemical, physical, and biological analyses.

Previous studies have explored the integration of episodic memory into reinforcement learning and control. Inspired by hippocampal memory, Freire et al. develop a model that improves learning speed and stability by storing experiences as sequences, demonstrating resilience and efficiency under memory constraints.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

KSHV modifies paraspeckles during its lytic replication cycle. They enhance virus replication by functioning as hubs for viral RNA processing and their modification is implicated in virus-mediated genomic instability.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Fluorogenic RNA aptamers such as Mango are powerful tools for RNA imaging. An ultrabright RNA-activated fluorophore with improved photophysical performance has now been developed using a structure-informed, fragment-based screening approach. This system was studied using high-resolution crystallography and applied to image RNA in cells.

To reveal cellular mechanisms of cognitive decline after stroke the authors established an experimental paradigm in mice monitoring individual nerve cells involved in spatial memory in health and disease allowing to identify functional biomarkers.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

Ziwen Liu et al. report Cytoland, an approach to train robust models to virtually stain landmark organelles of cells and address the generalization gap of current models. The training pipeline, models and datasets are shared under open-source permissive licences.

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

Circadian disruption can promote tumour formation. Now it is shown that the loss of circadian synchronization can drive this effect by disrupting the coupling between the circadian rhythm and the cell cycle within individual cells.

Genetic mechanisms of blood pressure regulation remain poorly defined. Here, the authors perform a kidney multi-omics study to identify 399 kidney effector genes, 11 miRNAs and 97 proteins for blood pressure and hypertension.

The RNA for ALS- and frontotemporal dementia-associated C9ORF72 gene is exported from nucleus via an unknown mechanism. This study shows that reduction of nuclear export adaptor SRSF1 can alleviate neuronal cell death and nuclear export of C9ORF72 inDrosophilaand patient-derived induced motor neurons.

Speleothem records from caves in Arctic Siberia allow for the reconstruction of multiannual air temperatures during the late Miocene (8.68±0.09 million years ago). These temperatures suggest that Eurasia was mostly permafrost-free during that time.

The International Mouse Phenotyping Consortium (IMPC) aims to identify the function of all protein-coding genes in the mouse genome. Hayday and colleagues leverage 530 knockout lines from the IPMC to develop the 3i Project, which immunophenotypes mice and leads to the identification of new and unexpected gene influences on immune function and on the structural organization of the immune system.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Indigenous territory extent in the Amazon biome can reduce the incidence of fire-related and zoonotic/vector-borne diseases, but only in certain contexts, according to an analysis of disease incidence data from the region.

Illness signals from the gut reactivate and strengthen flavour representations in the amygdala to support learning from delayed postingestive feedback.

The Hedgehog signalling gradient is established by dynamic signalling filopodia (cytonemes). Here, the authors show that EGF signalling may regulate cytoneme dynamics by maintaining basal plasma membrane levels of the Hedgehog co-receptor Ihog in the wing disc epithelium.

Liver macrophages are a major obstacle to extrahepatic drug delivery. This study identifies the receptor–ligand interactions that they use to capture circulating nanoparticles and leverages this understanding to engineer nanoparticles that escape macrophage uptake.

Pompe disease (PD) is a rare disorder that leads to progressive muscle weakness if left untreated. Here, the authors use multispectral optoacoustic tomography (MSOT) to map and quantify the composition of affected muscle tissue to determine disease severity and potentially monitor future therapies.

In cerebral cavernous malformations, mutant cells recruit healthy endothelial cells to form mosaic lesions. Here, the authors show that mutant cells can hijack and reprogram neighboring wildtype cells by mechanically pulling on them.

The understanding of altered lipid metabolism by isocitrate dehydrogenase 1 (IDH1) mutations in gliomas at a compartment-specific level is limited. Here, the authors use Raman spectroscopy to monitor organelle-specific metabolic changes and report that IDH1 mutations induce phospholipid imbalances which lead to ER and Golgi dilation.

A framework is presented to extrapolate the range of behaviors for influenza antibodies. Using this basis set of behaviors, the collective action of multiple antibodies can be teased apart to describe the individual antibodies within.

In gastrointestinal stromal tumours early mutations in known genes are frequently followed by chromosome 14q deletion. Here the authors find mutations resulting in loss of MAX protein expression conserved between primary tumours and metastases in the same patients, suggesting thatMAXmutation is an early event.

Factors limiting CNS remyelination with age are poorly understood. Here the authors show that aged Treg lose capacity to support CNS remyelination in mice, which can be restored in a young environment.

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

GPCR dynamics are critical for signal transmission into the cell. Here, the authors probe receptor plasticity using molecular dynamics simulations, enabling the detection of allosteric sites and drug entry gateways for a broad range of GPCR types.

Neurons receive their input in three dimensions via their dendrites, but how electrical activity in dendrites is organized is unknown. Here, the authors work out the distinct rules that govern activity across this 3D structure in different brain states.

The thymus is essential for T cell maturation and selection, and thymic defects result in severe immune problems. Here the authors identify a thymus cell population that is expandable in vitro, and can repopulate natural thymic matrix to generate tissue that supports mature T cell development in vitro and in vivo.