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Positioned at the crossroads of TNF, IL-1 and Toll-like receptor signalling cascades and cytokine-driven chromatin remodelling, TAK1 is emerging as a new therapeutic target in rheumatoid arthritis.

In land plants, the Ia and IIIb basic helix–loop–helix (Ia-IIIb bHLH) module regulates stomatal development. This study shows that a Ia-IIIb bHLH heterodimer, MpSETA-MpICE2, regulates seta formation in Marchantia and suggests a common mechanism underlying stomata and setae formation.

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.

Interferon stimulated gene 15 (ISG15) is a ubiquitin-like protein with critical roles in the innate immune response. Here, the authors present a Cryo-EM structure of ISG15 in complex with its E1 and E2 enzymes, providing insights into the specificity determinants of this pathway.

Targeting a non-natural micropeptide ‘killswitch’ to several biomolecular condensates altered condensate compositions and revealed condensate functions in human cells

The 3D structure of the human nutrient-sensing complex GATOR2 is resolved using cryo-electron microscopy.

FFAR1 receptor is highly expressed in beta cells and its activation has been suggested as therapy against type-2 diabetes. Here, Tunaru et al. show that 20-hydroxyeicosatetraenoic acid, produced within the islets upon glucose stimulation, acts in an autocrine manner to stimulate insulin secretion via FFAR1 activation.

An RNA-binding protein on leukemia cells provides an effective target in mouse models.

Multinucleated giant cells characterize granuloma formation in mycobacterial infections. Here the authors identify monocyte precursors with distinct immunological and metabolic properties as a source of the granuloma multinucleated giant cell compartment.

Meiotic cells deliberately break their DNA to allow chromosomes to swap genetic material. Here, authors reveal genetically separable pathways controlling the seeding and growth of chromosome-bound protein condensates responsible for DNA breaks.

Sheikh et al. show that deficiency in the lysine acetyltransferase MOF causes aberrant accumulation of fatty acids in neural cells, which in turn triggers inflammation in nearby pericytes, resulting in brain haemorrhaging.

Titin is considered an integrator of muscle cell proteins but direct evidence is limited. Here, titin is inactivated in adult mouse muscles, which causes sarcomere disassembly, protein mis-expression and force impairment, recapitulating key alterations in critical illness myopathy patient muscles.

The authors show that immunosuppression is highly conserved in the bacterial order Xanthomonadales. This feature, which preceded their specialization as host-adapted pathogens, probably contributes to their prominence as core members of the plant microbiota.

Ribosome biogenesis is tightly coordinated with cell-cycle progression. By characterizing the SUMO isopeptidases SENP3/SENP5, Doenig et al. identify a long-sought p53-independent impaired ribosome checkpoint that converges on downregulation of CDK6.

Mono-ADP-ribosylation is a recently discovered post-translational modification whose function remains unclear. Verheugd et al. show that the mono-ADP-ribosyltransferase ARTD10 inhibits NF-κB activation by preventing the poly-ubiquitination of NEMO, suggesting a functional link between these two modifications.

The software platform MaxDIA streamlines analysis of data-independent acquisition proteomics.

Using a sample of more than 1 million individuals, Hatoum et al. identify genomic loci associated with general and substance-specific addiction risk.

BATF3 is a member of the AP-1 transcription factor family. Kastenmüller and colleagues show that BATF3 is needed to promote memory CD8⁺ T cell responses. Activated CD8⁺ T cells transiently upregulate BATF3, which in turn suppresses expression of proapoptotic BIM to promote cell survival.

The antiferromagnet CoNb₃S₆ with chiral crystal lattice has near-zero magnetization, but exhibits a large thermoelectric Nernst effect in zero magnetic field, attributed to topological nodal planes in its electronic structure and magnetic spin-space group symmetries in the ordered state.

Exhaustion is the functional deterioration of T cells following chronic stimulation. Here, Wu et al. show that mitochondrial dysfunction drives T cell exhaustion by inhibiting HIF-1α degradation and transcriptional metabolic reprogramming.

B-cell receptor (BCR) signalling in chronic lymphocytic leukaemia (CLL) is found not to be dependent on exogenous antigens; instead, signalling may involve the binding of the BCR heavy-chain complementarity-determining region to self epitopes on the same receptor, a finding that may have important implications for understanding the pathogenesis of CLL and potential therapeutic approaches.

Time-resolved crystallography (TRX) is used for monitoring only small conformational changes of biomacromolecules within the same lattice. Here, the authors report the interplay between synchronous molecular rearrangements and lattice phase transitions in RNA crystals, providing the basis for the investigation of large conformational changes using TRX.

Diagnosis of Barrett’s esophagus depends on pathologist assessment of stained slides. Here, the authors utilise a deep learning approach to prioritize potential cases using diagnostic labels in two datasets, with the aim to improve Barrett’s screening capacity.

The PI3K–PTEN signalling pathway is a central regulator of metabolic homeostasis. Brunner et al. find that cell-intrinsic PI3K signalling allows adipose tissue macrophages to buffer obesity-induced lipotoxicity by promoting lipid uptake and catabolism.

Aligned collagen I is associated with the emergence of leader cells that are responsible for collective invasion. Here, the authors show that Collagen I and Yap signalling are in a feed-forward loop to drive the collective invasion of basal-like tumour cells.

CEP63 is a centrosomal protein that is mutated in the microcephaly disease Seckel syndrome. Here the authors disrupt Cep63 in the mouse and find that neural progenitor cells undergo p53-dependent cell death, and uncover a role for CEP63 in ensuring correct meiotic recombination in male gametes.

A multi-frequency observing campaign of the γ-ray burst GRB 190114C reveals a broadband double-peaked spectral energy distribution, and the teraelectronvolt emission could be attributed to inverse Compton scattering.

A growing number of G protein-coupled receptors (GPCRs) are being identified as sensors for ligands that are energy substrates or metabolic intermediates, and their central role in the coordination of metabolic processes is increasingly being recognized. Offermanns and colleagues summarize the function of these metabolite-sensing GPCRs in physiology and disease, and discuss the emerging pharmacological agents that are being developed to target these GPCRs for the treatment of metabolic disorders.

Atomically dispersed metal catalysts display high atom efficiency for electrocatalytic processes. Here, the authors report that sulfur-doped zeolite-templated carbon stabilizes highly dispersed platinum species, predominantly as single-atom centres, and probe its oxygen reduction selectivity.

FRESH, a multi-lab collaboration, reveals how data quality, analysis pipelines, and researcher expertise influence reproducibility in fNIRS neuroimaging, highlighting key factors driving variability in hypothesis outcomes.

Rama Khokha and colleagues report a new mutagenesis method, called Lentihop, for creating spontaneous, genetically tractable tumors from normal human cells. Through genetic analysis of Lentihop-derived tumors, they find known drivers of sarcomas and identify new candidate tumor suppressor genes, including HDLBP and ADARB2.

Gigaelectronvolt emission from a magnetar giant flare is discovered by the Fermi Gamma-ray Space Telescope, between 19 s and 284 s after the initial detection of a signal in the megaelectronvolt energy band, potentially generated by an ultra-relativistic outflow far from the stellar magnetosphere.

This Review summarizes the history and current concepts of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), including epidemiology, clinical and neuroimaging features and pathophysiology. It also discusses new molecularly targeted therapies for NMOSD that might be also applied to MOGAD in the future.

Understanding strong X-ray induced phenomena is important for applications of X-ray free-electron laser imaging. Here, the authors show time-resolved measurements of X-ray free-electron laser induced electronic decay of CH₂I₂ molecule probed with NIR pulses and identify mechanisms behind different transient states lifetimes.

Biology can help to design materials and approaches for tumour tissue engineering. Biomaterials are a requisite for modelling cancer to rebuild tissue organization, composition and function. This Review discusses bioengineering strategies that recreate the pathophysiology of tumour tissues to address questions in cancer research.

Researchers from Hawaii and an international consortium have produced a draft genome assembly for 'SunUp', the first commercial virus-resistant transgenic fruit tree. Comparison of this plant genome to those of Arabidopsis and others sheds light on evolution of characteristics such as biosynthesis, starch deposition, control of photosynthesis and pathways for creating volatile compounds.