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RAS-driven cancers depend on SHOC2–PP1C. Here, the authors reveal that KRAS forms a low-affinity SHOC2–PP1C complex with fewer contacts than MRAS and show that dual inhibition of KRAS- and MRAS-dependent assemblies strengthens SHOC2 suppression and may overcome resistance.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

The role of the complement system (CS) - part of the immune system - in pancreatic ductal adenocarcinoma (PDAC) remains underexplored. Here, the authors evaluate the association of genetic variants in CS-related genes with PDAC risk, and explore their potential role in prognosis and immune infiltration.

Tripathi et al. identify a noncanonical RAS•GTP activity that increases XPO1-dependent export of nuclear proteins into the cytoplasm. This depends on a RAS–RanGAP1 complex, and this export function contributes to RAS oncogenic activity.

Multidrug resistance of the opportunistic pathogen Stenotrophomonas maltophilia is an increasing problem. Here, analyzing strains from 22 countries, the authors show that the S. maltophilia complex is divided into 23 monophyletic lineages and find evidence for intra-hospital transmission.

This study uncovers a U-shaped trajectory in gray matter volume during pregnancy and postpartum, linked to hormonal changes. Brain recovery postpartum correlates with maternal attachment, highlighting the interplay between neuroplasticity, hormones, and maternal well-being.

The molecular mechanisms underlying drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML) remain to be explored. Here, the use of bulk and single cell multi-omics and ex vivo drug profiling for 21 rrAML patients reveals mechanisms of resistance to the Bcl-2 inhibitor venetoclax and treatment vulnerabilities.

HistoPlexer, a deep learning model, generates multiplexed protein expression maps from H&E images, capturing tumour–immune cell interactions. It outperforms baselines, enhances immune subtyping and survival prediction and offers a cost-effective tool for precision oncology.

The role of mutations within long noncoding RNAs (lncRNAs) exons on tumour cell fitness remains to be explored. Here, the authors investigate the landscape of driver lncRNAs in primary and metastatic samples and validate the functional significance of single nucleotide variants in the NEAT1 oncogene in vitro and in vivo.

In the Tumor Profiler proof-of-concept observational study, a multiomics approach for profiling tumors from patients with melanoma was feasible, returning data within 4 weeks and informing treatment recommendations in 75% of cases.

Managing power exhaust in fusion reactors is a key challenge, especially in compact designs for cost-effective commercial energy. This study shows how alternative divertor configurations improve exhaust control, enhance stability, absorb transients and enable independent plasma regulation.

Spatial boundaries influence hippocampal neural coding, but if abstract boundaries do the same is unclear. This study finds knowledge retrieval within changing abstract boundary-defined contexts is supported by flexible hippocampal representations.

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.

There is lack of therapies targeting the PAX3-FOXO1 fusion oncogene in fusion-positive rhabdomyosarcoma (FP-RMS). Here, the authors identify and characterise an inhibitor with highest inhibition of histone lysine demethylase 3B that suppresses PAX3-FOXO1 activity in FP-RMS.

An extreme Einstein ring ~10,000 times as bright as the Milky Way in the infrared is studied with VLT/ERIS and ALMA, and the authors find that the lensed galaxy is a starburst with a fast-rotating disk, rather than being driven by a major merger.

Plasma turbulence is the main driver to deteriorate the performance of fusion power plants. This work presents an unprecedented comparison of plasma turbulence between experiment and simulation, proving that the gyrokinetic model GENE reached a high level of maturity to predict core turbulence.

Motile and non-motile cilia have distinct functions and protein complexes associated with them. Here, the authors show the conserved protein CFAP20 is important for both motile and non-motile cilia and is distinct from other ciliopathy-associated domains or macromolecular complexes.

Confining plasma and managing disruptions in tokamak devices is a challenge. Here the authors demonstrate a method predicting and possibly preventing disruptions and macroscopic instabilities in tokamak plasma using data from JET.

Crosstalk between the p53 and Hippo pathway has been reported in different physiological contexts. Here, the authors show that p53 DNA contact mutations upregulate TEAD/YAP transcription indirectly and transform cells via hyperactivation of RhoA/ROCK/actomyosin signaling.

Exsolved Nickel nanoparticles enhance the performance in energy conversion devices. Here, we report a nanoengineered vertically aligned nanostructure (VAN) that provides faster and more selective paths for Ni diffusion compared to traditional films.

Edge-localized plasma modes in a tokamak can damage its innermost wall. Simulations now show that fast ions can modify the spatio-temporal structure of these modes. These effects need to be considered in the optimization of control techniques.

In this study, the authors employ metagenomics to explore the impact of environmental pollution on the human gut microbiome using samples from a cohort living in a very polluted area in Southern Italy, showing that pollutants degradation genes are more abundant in subjects with higher blood levels of those specific xenobiotics.

The high-resolution crystal structure of the SHOC2–MRAS–PP1C complex provides insights into the complex assembly, RAF dephosphorylation, MRAS selectivity versus canonical RAS isoforms, and the impact of Noonan syndrome mutations on complex formation.

When seen in ultraviolet light, Venus has contrast features that arise from the non-uniform distribution of unknown absorbers within the sulphuric acid clouds. This paper reports multi-wavelength imaging that reveals that the dark low latitudes are dominated by convective mixing that brings the ultraviolet absorbers up from depth. The bright and uniform mid-latitude clouds reside in the 'cold collar', which suppresses vertical mixing. In low and middle latitudes, the visible cloud top is located at a constant altitude of 72 ± 1 km in both the ultraviolet dark and bright regions, indicating that the brightness variations result from compositional differences caused by the colder environment.

Molecular networking connects molecules based on their fragment ion mass spectra (MS²), but may leave adduct species from the same molecular family separate. To address this issue, the authors develop a networking approach that fuses MS¹- and MS²-based networks and integrate it into the GNPS environment.

Photo-induced phase transitions triggered by an ultrafast excitation cannot be described within the quasi-equilibrium framework. Here, using time-resolved experimental probes, the authors report a transient charge-density-wave order in TbTe₃ and describe it using a model with a non-equilibrium transition temperature.

Long-read single-cell RNA sequencing is capable of detecting isoform-level gene expression and genomic alterations such as mutations and gene fusions, thereby providing cell-specific genotype-phenotype information. Here, the authors use long-read scRNA-seq on metastatic ovarian cancer samples and detect cell-type specific isoforms and gene fusions that may otherwise be misclassified in short-read data.

The suppression of edge-localized modes in tokamak plasmas is crucial to prevent them from damaging the walls of the chamber. Now experiments confirm the role that magnetic islands play in suppressing these detrimental modes.

Giancotti and colleagues report that the Rnd1 Rho GTPase suppresses the epithelial–mesenchymal transition and mammary tumorigenesis by inhibiting Ras-MAPK signalling through a Plexin B1–Rap1–p120 Ras-GAP signalling axis.

Photo-excitation in strongly correlated materials is usually modelled as an increase of electronic energy that is then transferred to other degrees of freedom. Contrarily, Novelli et al.show that in a charge-transfer insulator, sub-gap excitation forms electrons that are suddenly dressed by the boson field.

Ultrafast control of materials draws interest. Here, the authors extend X-ray powder diffraction to the femtosecond timescale to follow the photo-induced semiconductor to metal transition in titanium pentaoxide, observing a phase front that moves at the speed of sound and proposing a little explored mechanism.

Coagulation factor VIII deficiency in hemophilia A disrupts clotting and prolongs bleeding. Here, the authors show that vagus nerve stimulation bypasses this defect and improves hemostasis in hemophilia A mice through a mechanism requiring acetylcholine-secreting ChAT⁺ T lymphocytes in spleen and α7nAChR on circulating platelets.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.