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This study presents a BRET biosensor that measures how anticancer drugs cooperatively engage PRMT5 complexes in cells, revealing how cellular metabolites such as SAM and MTA enhance drug action and enable precision therapies for MTAP-deleted tumors.

Baretić and Missoury et al. identify vertebrate proteins FAM118B and FAM118A as sirtuins similar to bacterial antiphage enzymes and show that FAM118A/B processing of NAD involves head-to-tail filament formation and a partnership between the two paralogs.

The dynamic behavior of supported metal nanoparticles under reaction conditions plays a crucial role in determining their catalytic performance. Here, time-resolved XRD, PDF, and modulation techniques provide direct evidence of hydrogen-induced breathing and detachment of Pt nanoparticles from an alumina support, uncovering reversible, size-dependent dynamics in both gas and liquid phases.

Making rewarding choices can require either generalization or individuation. Here, the authors show that across contexts, people adapt the specificity with which they represent and, increasingly across development, remember their experiences.

Analysis of data from multiple instruments reveals a giant exoplanet in orbit around the 0.2-solar-mass star TOI-6894. The existence of this exoplanetary system challenges assumptions about planet formation and it is an excellent target for atmospheric characterization.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Here authors identify GluN2D-containing NMDA receptors on interneurons as a specific target for rapid antidepressant action. Blocking GluN2D restores stress-impaired plasticity and mimics the effects of ketamine with fewer side effects.

Ginhoux, Dutertre and colleagues provide a comprehensive analysis of dendritic cell subsets and states across human tumoral and juxtatumoral tissues.

Temporal integration throughout the human auditory cortex is predominantly locked to absolute time and does not vary with the duration of speech structures such as phonemes or words.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

The three-dimensional structure of all cloud complexes in the solar neighbourhood is revealed, showing a narrow and coherent 2.7-kpc arrangement of dense gas, in disagreement with the Gould Belt model.

Large-scale genome-wide analyses identify hundreds of genetic loci associated with hypothyroidism and thyroid hormone levels, demonstrating the potential of using polygenic risk scores to predict disease onset and progression.

NextBrain is an open source, probabilistic atlas of the entire human brain, assembled using artificial-intelligence-enabled registration and segmentation methods to reconstruct the multimodal serial histology of five human half brains, and which can be used to automatically segment brain MRI scans into 333 regions.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

In this study, the authors assess the global response to the toxic aldehyde glyoxal (GO) in Pseudomonas aeruginosa, suggesting that GO controls quorum sensing during infection through a mechanism involving a novel protein, ArqI.

Chromatin “breathing” at DNA lesions is controlled by different waves of histone ADP-ribosylation.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Materials which simultaneously exhibit superconductivity and topologically non-trivial electronic band structure possess potential applications in quantum computing but have yet to be found. Here, the authors find superconductivity in MoTe₂, a material predicted to be topologically non-trivial.

The synthesis of well-defined heterostructure interfaces can be leveraged to design advanced catalysts. Now a catalyst consisting of carbon-supported Janus particles with crystalline Ru and amorphous CrO_x sides is shown to achieve high performance for both alkaline hydrogen oxidation and evolution reactions due to the synergy between both sides.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Polymethacrylate derivatives are widely used in industry but precise incorporation of degradable thioester bonds in polymethacrylates to achieve degradability remains challenging. Here the authors show that a thionolactone can be inserted into poly(methyl methacrylate) using an auxiliary third comonomer.

The authors report nickel-porphyrins derivatives of chlorophyll in ~1 Gyr-old multicellular eukaryotes, preserved in low-grade metamorphic rocks. This brand new approach permits to identify early phototrophic organisms through the geological record.

Rift Valley fever is a zoonotic haemorrhagic fever with complex transmission dynamics influenced by environmental variables and animal movements. Here, the authors develop a metapopulation model incorporating these factors and use it to identify the main drivers of transmission in the Comoros archipelago.

Johannes Krause et al. synthesized seagrass carbon stock data from 2700+ soil cores to find that they vary by plant functional group and coastal setting, indicating where conservation efforts would most effectively avoid emissions from seagrass loss

The formation of protein aggregates is a hallmark of Parkinson’s disease, with small oligomeric species implicated as a major source of toxicity. In this work, Xu et al. determine their mechanism of formation and role in aggregation.

Perro and colleagues develop a CD3⁺ T cell engager co-targeting BCMA and CD38 to improve immunotherapy for multiple myeloma, demonstrate cytotoxicity in patient-derived samples and murine models and develop a quantitative systems pharmacology model.

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.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

Bipolar disorder (BD) is a severe mood disorder, which has been shown to have a large genetic component. Here the authors identify two previously unreported BD risk loci and provide further insights into the biological mechanisms underlying BD development.

Shallow moonquakes detected at four Apollo landing sites between 1969 and 1977 occurred during maximum stress and in close proximity to young faults, suggesting that the Moon is tectonically active, according to reanalyses of the seismic data and tidal force modelling.

A new Burden of Proof meta-analytic method that accounts for between-study heterogeneity and corrects for bias between different study designs is used to interpret the strength of evidence between different pairs of risk factors and health outcomes.

Observations of a 3-million-year-old pre-main-sequence star with a misaligned disk reveal a giant orbiting planet; the system is ideal for studying the early formation and migration of planets.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

Targeting conserved secondary structure of RNA viruses offers the potential for a customizable therapeutic approach to viral variants.

Disentangling the various pathways by which climate change may drive community shifts in real-world ecosystems is challenging. Here the authors apply a trend attribution approach to a large dataset from the MASTIF database to assess the contribution of direct and indirect effects of climate on tree fecundity in North America, finding that the latter dominate trends by affecting tree growth and size and thereby fecundity.

Antibody Mediated Prevention (AMP) trials showed that the broadly neutralizing antibody VRC01 could prevent some HIV-1 acquisitions. Here the authors use VRC01 levels and the sensitivity of each acquired HIV virus to predict viral loads in the AMP studies and show that VRC01 influenced viral loads, though potency was lower in vivo than expected.

We reconstruct the spatial distribution and timing of wetland loss through conversion to seven human land uses between 1700 and 2020, elucidating the magnitude and land-use drivers of global wetland losses to improve assessments of wetland loss impacts.

Linkages between neighbouring ecosystems are rarely considered when seeking to predict ecological responses to climate change. However, the finding that the impact of climate change on seagrass beds is mediated by the response of neighbouring coral reef habitats highlights the need for a broader-scale view of climate change impacts on ecosystems.

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.

Dual cyclin A/B RxL inhibitors selectively kill small cell lung cancer cells and other cancer cells with high E2F activity.

Heterogeneous chemical processes are vital for many applications, but the crucial interfaces involved are difficult to probe experimentally with elemental and chemical-state specificity. Here, the authors present a photoelectron spectroscopy-based method for studying such interfaces with sub-nanometre accuracy and under realistic pressure conditions

Defects in materials can be used to detect magnetic fields at the nanoscale. Here the authors show that a carbon-related defect in hexagonal boron nitride acts as a robust nanoscale sensor capable of vectorial magnetic field detection.

The local layer alignment in a wide range of trilayer graphene structures has been extracted by interferometric four-dimensional scanning transmission electron microscopy, uncovering the complex picture of lattice reconstruction in twisted trilayers.

This study tracked the initial self-assembly, oligomerization and structural conversion of α-synuclein inside neurons. Early seeding events occur on mitochondrial membranes, where oligomerization induces mitochondrial dysfunction and neuronal loss.

Arterial thrombosis is a leading cause of death and disability with no clinical bioassay for prediction. Here, the authors develop an assay that monitors the multi-dimensional attributes of thrombi forming in its physiologically mimicking rheological condition to predict arterial thrombotic risks

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.