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Lee et al. use an aggregation-prone CLN4 mutant that causes lysosomal damage in neurons and show that in non-neurons, the ubiquitin ligase CHIP prevents CLN4-dependent lysotoxicity via microautophagy.

Here, the authors introduce carbon-to-carbon metal migration as a platform for dynamic association and show how such migrations, in combination with the incorporation of a simple hydrocarbon, can be harnessed to achieve autonomous directional translational motion of a metal centre along the length of a polyaromatic thread.

Determining dynamics of Fe–CO bond breaking in heme proteins is essential to understand the interplay between protein function and dynamics. Here, the authors report the first experimental proof for the two-step CO photodissociation, involving the previously unknown slower ~15 ps process.

Exon Junction Complexes influence many aspects of mRNA fate. Here, the authors show that the disassembly factor PYM1 primarily acts in translation-independent EJC removal, with resistant EJCs accumulating at non-canonical sites and impacting mRNA stability in a gene architecture dependent manner.

Aggregates of misfolded proteins are sequestered in the aggresome via dynein transport in an aggregate size-dependent manner. Here, authors find episodic transport kinetics mediated by aggresome-dynein adapters are central to this size-filter effect.

The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

A highly potent and selective small-molecule catalytic inhibitor of the protein lysine methyltransferase NSD2 shows therapeutic efficacy in preclinical models of KRAS-driven pancreatic cancer and lung cancer.

An integrated structural biology approach combining NMR, cryo-EM, X-ray crystallography and molecular dynamics simulations is implemented to characterise the conformational dynamics and interactions of the eukaryotic RNA exosome complex.

CRISPR-Cas9-based screens have allowed the study of gene-drug interactions. Here, the authors develop CRISPR-Cas9 knock-out, activation and repression screens in human gastric 3D organoids, also integrating single-cell CRISPR screens, to identify genes involved in the response to cisplatin in gastric cancer.

The discovery that DNA methylation of different CpG sites can serve as digital barcodes of clonal identity led to the development of EPI-Clone, an algorithm that enables single-cell lineage tracing through cellular differentiation at scale.

Neural networks unlock the ability to predict and manipulate noisy light propagation in nonlinear fibres, advancing control strategies for photonic technologies and paving the way for tailored shaping of incoherent optical signals.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

An analog optical computer that combines analog electronics, three-dimensional optics, and an iterative architecture accelerates artificial intelligence inference and combinatorial optimization in a single platform, paving a promising path for faster and sustainable computing.

Pan-cistrome of the maize leaf under well-watered and drought conditions profiled by haplotype-specific MOA-seq highlights the relevance of transcription factor binding QTLs for understanding phenotypic diversity in maize.

The Perseverance rover detected polycyclic aromatic hydrocarbons preserved within sulfates in the fan and floor of Jezero crater on Mars, offering new insights into past habitability and the preservation of organic matter on Mars.

A superconducting quantum computer is used to realize an out-of-equilibrium topologically ordered state, which hosts anyonic excitations.

Antibody–bottlebrush conjugates expand the options for drug cargos compared to antibody–drug conjugates.

External Control Arm methods for clinical trials were developed to compare the efficacy of a treatment to a control group that is built with data from external sources. Here, the authors present FedECA, a privacy-enhancing method for analyzing treatment effects across institutions, streamlining multi-centric trial design and thereby accelerating drug development while minimizing patient data exposure.

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

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Cooperative paramagnetism refers to a strongly correlated state without long range magnetic order that occurs in frustrated magnetic systems between the Neel temperature and Curie-Weiss temperature. Here, using resonant elastic magnetic and inelastic x-ray scattering, Terilli et al find a spectrally sharp gapped magnetic excitations that persists above the Neel temperature in Y₂Ir₂O₇, implying a cooperative paramagnetic phase.

The enterococcal cytolysin is a two-component toxin that is responsible for a fatal form of alcoholic hepatitis. Here, authors used knowledge of the toxin’s biosynthesis to develop small molecule inhibitors of toxin production.

Through fieldwork and innovative research, he transformed how scientists and the public perceive the prehistoric world.

Determining how replication forks move across the human genome is critical for the effective use of agents that target replication stress. Here, the authors present DNAscent, an AI supported assay for DNA replication stress in human cells using Nanopore sequencing data.

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.

Analyses of ancient human DNA show that cultural and political transformations in Central Europe during the second half of the first millennium ce were associated with movements of Slavic populations into Germany, Poland and Croatia.

Virus-host competition drives evolution of diverse antiviral defences in bacteria and antidefense systems in their viruses (phages). Here, Silas et al. use a functional screen of phage accessory genes to show how bacterial cell-surface sugars can be major determinants of phage host-range, and how some phage proteins injected into bacterial cells inhibit host immunity.

Rare earth mineralisation at Maoniuping formed when its carrying carbonatite brine-melt reacted with surrounding siliceous rocks, forming an antiskarn. The melt lost its fluxing alkali elements, which led to deposition of coarse grained bastnäsite.

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.

Wildfire risk in California’s WUI is rising. Analysis of past events shows home hardening and defensible space can reduce structure loss by up to 52%, but coordinated, community-scale action is essential to maximize impact.

This study shows that aboveground plant diversity is only weakly related to belowground mycorrhizal fungal diversity, although these relationships can be stronger at regional scales. Therefore, conservation efforts centered only on plant diversity may overlook critical fungal diversity hotspots.

The exact role of ATP in the function of Hsp90, an essential molecular chaperone, is unclear since ATP binding but not hydrolysis is essential for viability. Here, the authors propose that ATP plays a structural role by reversibly stabilizing the closed conformation of Hsp90

A modelling study based on satellite observations, machine learning and a chemical transport model quantifies the global and regional exposure to particulate-matter pollution and the human health impacts related to the 2023 Canadian wildfires.

The authors introduce the Neurolipid Atlas, a dynamic resource for the community to gain insight into lipid alterations in neurodegenerative disease, and they leverage the platform to show how cholesterol alterations in astrocytes can dysregulate neuroinflammatory pathways in Alzheimer disease.

Spatial relationships between clustered proteins within synapses shape neurotransmission. Here, NMDA receptors are shown to align with only a subset of presynaptic release sites, suggesting a structural mechanism controls NMDAR-mediated synaptic transmission.

Phenotype variation is higher in mutants than wild types. Examining a range of mutant severities, this study unexpectedly found that variation decreases in severe conditions. A quadratic trend best fits the relationship between severity and variation.

Hippocampal neurons adapt to experience through changes in gene expression and chromatin accessibility. Here, authors show that novel environment exposure induces region- and cell-type specific transcriptional changes coordinated by FOS/AP-1.

Selective chemical upcycling of polyolefin mixtures remains challenging due to the structural similarity of their backbones. Now it has been shown that a single-site nickel catalyst can preferentially and efficiently cleave branched C–C bonds, enabling the hydrogenolytic separation of isotactic polypropylene from mixtures containing both isotactic polypropylene and polyethylene.

The emissions of leading fossil-fuel and cement producers have been systematically linked to particular heatwaves. Three scientists discuss the methodology behind the result and its potential impact on climate-liability court cases.

Although exporting hydrogen can raise domestic power costs, applying temporal matching with renewables can cut them by 31%, reduce emissions and steer welfare among exporters and consumers, offering a fairer approach to the global hydrogen trade.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

The nucleoporin RanBP2 functions in cellular transport, mitosis and SUMO conjugation. Here, the authors determine cryo-EM structures of RanBP2 complexed with SUMO1-RanGAP1, Ubc9, Crm1, Ran and use cell and biochemical assays to probe its functions.

CRAF is one of three RAF-family kinases and is mutated in cancer and RASopathies. Jang et al. report structural and mechanistic studies of CRAF/MEK1/14-3-3 complexes that explain distinct features of CRAF regulation.

Imaging of a Devonian jawless fish reveals advanced features previously thought to be exclusive to jawed vertebrates, challenging the idea that jaws were the primary driver for the evolution of derived traits in the vertebrate body plan.

Single-cell multi-omics in Drosophila testis reveals enhancer-driven gene regulatory networks and shows how Wnt signaling and key transcription factors orchestrate stem cell maintenance and lineage progression during early spermatogenesis.

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.

Single-cell transcriptomic analysis of mouse hypothalamus and behavioural experiments show that specific hypothalamic networks regulate conflicting feeding versus parenting behaviours of female mice.