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The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

Cytosolic ScURA uncouples de novo pyrimidine synthesis from mitochondrial electron transport, and rescues pyrimidine production and cell proliferation under pharmacological or genetic mETC disruption.

The relationship between physical activity and mortality has not clearly emerged from lifestyle intervention trials. In this post hoc trial analysis, the authors show that a three-year physical activity-based counseling intervention in people with type 2 diabetes was associated with a ~ 50% reduction in long-term mortality.

Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.

Langstein-Skora, Schmid, Huth et al. propose that intrinsically disordered region functionality can be driven by the interplay between linear binding motifs and contextual chemical characteristics such as charge and hydrophobicity.

Tests of the predictions of the renormalization group in biological experiments have not yet been decisive. Now, a study on the collective dynamics of insect swarms provides a long-sought match between experiment and theory.

The authors optimize an in vitro human epiblast model, which they utilize to show that early TGFβ family inhibition prevents epithelial identity, whereas it is dispensable after epithelium formation. These phenomena are conserved in mice.

This study associates p53 loss and brain metastasis in breast cancer. Mechanistically, p53-null tumors recruit astrocytes that provide substrates for enhanced fatty acid synthesis via upregulated SCD1 expression, representing a targetable axis in the disease.

HIV-1 integrase forms an RNA-binding module on the luminal side of the mature capsid lattice.

Genetic mapping in mice identified Homer1a as a key modifier of attention. Developmental downregulation in the prefrontal cortex enhances inhibitory tone, neural signal to noise and adult attentional performance, revealing a new control mechanism and target.

Strongly enhanced optical nonlinearities and an ultrafast transition from coherent to incoherent polariton excitations are demonstrated by coupling an atomically thin WS₂ layer to a plasmonic nanostructure using ultrafast multidimensional spectroscopy.

Inhibition of the histone methyltransferase NSD2 and the androgen receptor in preclinical models can reverse lineage plasticity to suppress tumour growth and promote cell death in multiple subtypes of castration-resistant prostate cancer.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

Luppi et al. identify transcriptomic and connectomic controllers of information integration and its breakdown induced by anaesthesia in humans, macaques, marmosets and mice.

The authors uncover a direct, BAI1-dependent, role for C1q in the control of neural stem cell proliferation and quiescence via MDM2–p53 and p32, a complement cascade-independent mechanism of C1q action that has implications for central nervous system health and disease.

Juno radio occultations precisely redefine Jupiter’s shape, measuring a polar diameter of 66,842 km and an equatorial diameter of 71,488 km, both smaller than long-used values, bringing models of the planet’s interior into better agreement with observations.

The authors show that plasma AT(N) biomarkers can distinguish Alzheimer’s disease and frontotemporal lobar degeneration in diverse Latin American populations. Using machine learning and integrating neuroimaging, significant diagnostic accuracy was achieved, enhancing clinical assessments of these conditions in Latin America.

Prenatal Zika virus (ZIKV) exposure can lead to a spectrum of developmental issues, but the mechanisms remain unclear. Here the authors show that prenatal ZIKV exposure in macaques disrupts neurodevelopment, causing prolonged maternal attachment and visual deficits at 3 months that normalize by 12 months, independent of sensory function.

The stability of interactions across trophic levels is crucial for ecosystem resilience but remains poorly understood. This study shows that loss of tree diversity destabilizes specialist herbivores, offering new insights into the mechanisms of pest outbreaks.

Evolutionarily related ‘proto-point’ centromeres providing resolution to the evolutionary origins of point centromeres are identified in yeast, and comparison shows they evolved in an ancestor with retrotransposon-rich centromeres and that long-terminal-repeat retrotransposons are the genetic substrate.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

In plants, the MMC represents the precursor of the female germline. Here, the authors show that SPL/NZZ, together with ovule-identity MADS-domain transcription factors, controls MMC differentiation by acting on an auxin-dependent downstream network.

Transcription factor osr2 is identified as a specific marker and regulator of mural lymphatic endothelial cell (muLEC) differentiation and maintenance, and muLECs and border-associated macrophages share functional analogies but are not homologous, providing an example of convergent evolution.

Spinal cord organoids from SMA patients reveal widespread neurodevelopmental defects. Single-cell and functional analyses show global dysregulation, which can be rescued by SMN-increasing therapy, stressing the importance of timely intervention.

Using single broadband X-ray pulses from a free-electron laser on a gaseous neon target, coherent, nonlinear four-photon interactions with core–shell electrons is demonstrated, representing a strategy for multidimensional correlation spectroscopy at the atomic scale.

Cells depend on early protein modifications for proper function. Here, the authors show that when Src-family signaling kinases lack their typical myristoylation, an alternative acetylated start is detected by DCAF10, directing them to degradation.

Here the authors show that the dipole-active phonon resonance of semiconducting nanocrystals can be hybridized by a strongly concentrated terahertz vacuum field of a plasmonic nanocavity, thus achieving strong plasmon–phonon coupling even in the absence of direct terahertz illumination.

Tumour-induced dysregulation of cAMP–PKA–CREB1 signalling in skeletal muscle is shown to be a driver of mitochondrial dysfunction, contributing to cancer cachexia in mice.

The MOUNTAINEER phase 2 trial demonstrated the efficacy and safety of tucatinib (HER2-targeted TKI) and trastuzumab (anti-HER2 antibody) in patients with HER2 + , RAS wildtype unresectable or metastatic colorectal cancer that had progressed on chemotherapy, resulting in the approval of the regimen. Here, the authors report the updated analysis of the MOUNTAINEER trial.

Protein-activity-based identification of hypermorphic, hypomorphic, neomorphic effectors and therapeutically relevant mutations uses transcriptomic data to categorize variants of unknown significance into hypermorphic, hypomorphic and neomorphic mutations based on their effects on transcription factor activity and subsequent gene expression.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

A closed-loop in-memory computing accelerator, implemented in a fully integrated chip with on-chip mixed-signal circuits, can be used to solve multiple inverse matrix–vector problems.

This study of magic-angle twisted trilayer graphene moiré superconductors using scanning tunnelling microscopy and spectroscopy identifies two energy gaps that develop from many-body resonance in this highly tunable class of materials.

There has been considerable interest in using magnons for information processing. Such ‘magnonic’ devices will require magnetic patterning analogous to the lithographic patterns of integrated circuits. Here, Levati, Vitali and coauthors present one possible approach to this, demonstrating laser induced changes in the perpendicular magnetic anisotropy of Yttrium Iron Garnet.

HCN4 channels control cardiac pacing. Here, the authors isolated a nanobody (NB5) that binds HCN4 extracellularly in an ortholog- and isoform-specific manner and promotes its activation in sinoatrial node myocytes, leading to an increase in pacemaker rhythm.

In the proof-of-concept phase 2 ROME trial, comprehensive genomic profiling followed by molecular tumor board evaluation and randomization of patients with metastatic solid cancer to receive personalized therapy or standard of care led to a significantly higher objective response rate and longer progression-free survival in patients who received personalized therapy.

Inhibitor-induced kinase degradation is a common event that positions supercharging of endogenous degradation circuits as an alternative to classical proximity-inducing degraders.

Riboswitches are allosteric RNA molecules that change conformation upon ligand binding to regulate downstream genes. Here, the authors use Restricted Boltzmann machines trained on natural sequences to design new riboswitch aptamer domains, and validate their functionality via chemical probing.

Here authors used patient-derived forebrain organoids to reveal how LIS1 mutations cause varying severity in a neurodevelopmental disorder, uncovering links between cytoskeletal defects, protein stress, and potential therapeutic strategies.

Chromosomes interact with the cell environment through their interface. Here, the authors use Atomic Force Microscopy to probe the interface and local micromechanics of the chromatin network of native human mitotic chromosomes.

This study reveals that the ability to maintain a stable body weight predicts longevity in mice. By tracking weight dynamics throughout life, the authors identify genetic loci linked to body weight, energy homeostasis and healthy aging.

Experimental realizations of discrete time crystals have mainly involved 1D models with Ising-like couplings. Here, the authors realize a 2D discrete time crystal with anisotropic Heisenberg coupling on a quantum simulator based on superconducting qubits, uncovering a rich phase diagram.

Hepatocyte organoids derived directly from human tissue enable long-term hepatocyte expansion and can be combined with portal mesenchyme and cholangiocyte organoids to form a donor-specific periportal liver assembloid system.

Observations of a fast X-ray transient reveal that it is a gamma-ray-burst explosion from a very distant galaxy that emits light with the wavelength necessary to drive cosmic reionization, the last major phase change in the history of the Universe.

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.