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PARM is a deep-learning model trained on data from massively parallel reporter assays to help predict promoter activity in different human cell types, design synthetic promoters and identify key features of regulatory promoter grammar.

Rapid immune activation requires tight control of mRNA stability in CD8⁺ T cells. Here, the authors show that a compositive RNA motif – m⁶A sites positioned next to AU-rich elements - marks mRNAs for rapid decay during activation, revealing a coordinated mechanism that shapes T-cell immunity.

Jellyfish see light in a similar way that vertebrates smell odours. Here, Michiel van Wyk and Sonja Kleinlogel show how jellyfish has adapted this slow signal detection pathway to support sophisticated vision, and use a similar method to restore vision in blind mice.

CAR-T cell efficacy is often limited by the inability to maintain a memory T cell program. Here, the authors show that intrinsic CXCR4 expression enhances CAR-T cell persistence and memory differentiation in acute myeloid leukemia.

Proximity biotinylation is a powerful tool to profile interactomes, but it requires genetic engineering of the target protein. Here, the authors develop a proximity biotinylation enzyme that can be directed to the target using antibodies, enabling interactome profiling of endogenous proteins or PTMs.

Organic additives frequently shape crystallisation in natural and industrial settings, yet their precise influence on nucleation remains poorly understood. Here, Baken et al. investigate how additives affect the crystallization of the industrially relevant minerals portlandite and gypsum. Using controlled titration coupled with in situ synchrotron monitoring, the team demonstrates that both minerals form via intermediate steps: portlandite gradually becomes more ordered as it develops, while gypsum switches abruptly from a disordered to an ordered state. The study reveals that additives influence these pathways prior to nucleation by altering the nature of prenucleation clusters. How strongly an additive interacts with these clusters depends on its chemical state, which is controlled by the pH conditions specific to each mineral. These findings offer a starting point for creating an industrial “toolbox” to help select more effective additives, and they advance our understanding of biomineralisation processes.

Ozren Bogdanović, Ryan Lister, José Luis Gómez-Skarmeta, Michiel Vermeulen and colleagues report widespread DNA demethylation at developmental enhancers during the phylotypic period in zebrafish, Xenopus and mouse embryos. Their findings suggest a conserved role for Tet proteins and active DNA demethylation in the regulation of phylotypic enhancers.

Affinity purification-mass spectrometry (AP-MS) can identify endogenous protein interactions but the need for high amounts of input material still limits its applicability. Here, the authors present a microfluidic-based AP-MS workflow that can capture protein interactions from 50─100-fold less input material than conventional approaches.

Arthropod vectors induce physiological and immunological changes during ectoparasitic feeding, and Langerhans cells are key immune sentinels in the epidermal barrier. Here, the authors show that tick feeding reprograms Langerhans cells to promote tolerance and weaken T cell responses during pathogen transmission.

A group of plant receptor-like kinases (LysM-RLKs) with high affinity for short-chain chitooligosaccharides and lipo-chitooligosaccharides (LCOs), play a complementary role in arbuscular mycorrhiza establishment with a sister group of LysM-RLKs specifically recognising LCOs.

Small cell lung cancer cells are dependent on the structural, but not enzymatic, function of PRC2. Combined enzymatic inhibition of PRC2 and G9a/GLP induces oxidative stress, leading to selective death of neuroendocrine SCLC cells.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Muconic acid is an important bio-based chemical; however its applications are limited by the lack of efficient methods to access its trans,trans-isomer. Here the authors address this problem with a catalyst based on single Ru atoms dispersed on zeolite BEA that is capable of unlocking hydride chemistries.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Perception and appreciation of food flavour depends on many factors, posing a challenge for effective prediction. Here, the authors combine extensive chemical and sensory analyses of 250 commercial Belgian beers to train machine learning models that enable flavour and consumer appreciation prediction.

Carrier multiplication processes, where photons are converted into multiple charge carriers, promise higher efficiencies for solar cells based on quantum dots and nanorods. Here, the authors demonstrate carrier multiplication in PbS nanosheets, extending this effect to two-dimensional materials.

Current high-throughput single-cell transcriptomic methods are incompatible with paraformaldehyde, a common cell fixation technique. Here the authors present FD-seq, a method for droplet-based RNA sequencing of paraformaldehyde-fixed, stained and sorted single cells.

Heart failure is a leading cause of morbidity and mortality, and ERBB4 signaling has been proposed as a potential therapeutic target. Here they identify small molecule ERBB4 agonists capable of decreasing cardiomyocyte damage and fibrosis in models of cardiovascular disease.

A multidimensional proteomics analysis of the interactions between around 2,000 nuclear proteins and over 80 modified dinucleosomes representing promoter, enhancer and heterochromatin states provides insights into how chromatin states are decoded by chromatin readers.

Two side-by-side papers report that H3K27me3 deposited by polycomb repressive complex 2 represents an epigenetic barrier that restricts naive human pluripotent cell differentiation into alternative lineages including trophoblasts.

CO₂ capture with amines is an important technology for net zero, but is hampered by the high regeneration costs of the amines. Here, the authors develop an effective ZrO_xH_y solid catalyst for this process and demonstrate its applicability in a pilot test in a fixed-bed continuous reactor.

Cold acclimation has been shown to have beneficial metabolic effects, including improved insulin sensitivity in patients with type 2 diabetes. Here the authors show that a mild cold acclimation regiment during which overt shivering was prevented did not result in improved insulin sensitivity in a small group of patients with type 2 diabetes.

Incorporating bioorthogonally-modified amino acids into newly synthesized proteins allows studying the nascent proteome, but current methods often require special conditions or are toxic to cells. Here, the authors develop a method that uses β-ethynylserine to label nascent proteins under standard conditions without harming cells.

Long noncoding RNAs regulate tissue-specific gene expression. Here the authors profile lineage-specific lncRNAs in human dermal lymphatic and blood vascular endothelial cells (LECs and BECs) and show a role of LEC-specific lncRNA, LETR1, in cell proliferation and migration.

The impact of chromatin context on transcription factor binding affinities is quantified.

Mutations in SHANK2 are associated with autism spectrum disorders (ASD). Here, Peter et al. show that selective loss of Shank2in Purkinje cells of the mouse cerebellum leads to deficits in plasticity, motor behaviour, and a social behaviour phenotype similar to that seen in ASD.

In the phase 2 adaptive BELLINI trial, patients with early-stage triple-negative breast cancer received neoadjuvant nivolumab with or without ipilimumab, showing immune activation, clearance of circulating tumor DNA and promising clinical response rates, especially in patients preselected based on high levels of tumor-infiltrating lymphocytes.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

JNJ-9676—a small-molecule inhibitor targeting coronavirus M protein that shows excellent efficacy in Syrian golden hamster models—binds to and stabilizes the M protein dimer in an altered conformational state between its long and short forms, preventing the release of infectious virus.

Satellite observations over the Greenland Ice Sheet reveal a destructive mode of meltwater drainage whereby a subglacial flood induced by the rapid drainage of a subglacial lake burst through the surface, fracturing the ice sheet.

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.

Foot-and-mouth disease vaccine efficacy is reduced when full virion 146S dissociates into pentameric 12S subunit. Here, the authors elucidate the molecular basis of this compromised immunogenicity by comparing antigenicity, humoral immunogenicity and structures of 146S and 12S particles.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Integrating biofuel production with petrorefinery operations offers potential efficiency savings, but is technologically immature. Here, Deneyer et al. use a two-phase catalytic process that converts (hemi)cellulose into light naphtha, utilizing petro-derived solvent streams to deliver a fuel containing 10% bio-derived carbon.

The authors demonstrate a 3-tier mass spectrometry approach, including bottom-up and top-down proteomics, as well as native mass spectrometry to provide a detailed description of proteoforms, protein processing and post-translational modifications present within ribosomes from bacteria, plant, and human.

Patients with different small round cell sarcoma (SRCS) often receive the same treatment regimen but for some SRCS subtypes, response to chemotherapy is poor and targeted treatment options are limited. Here, the authors establish a biobank of paediatric patient-derived SRCS tumoroids and perform drug screening, identifying MCL inhibition as a potential therapeutic strategy in CIC::DUX4 sarcomas.

In a multicenter, open-label, randomized controlled trial, digital consults including digital data sharing, patient e-learning and guideline recommendations to clinicians improved guideline-directed medical therapy over the course of 12 weeks.

ISG15 conjugation is essential to activate the RIG-I-like receptor MDA5 and trigger antiviral responses. SARS-CoV-2 suppresses MDA5 activation by direct PLpro-mediated de-ISGylation to escape innate immunity.

The authors show that dynamics of protein phosphorylation in the vertebrate cell cycle is largely attributable to CDK-mediated regulation of intrinsically disordered proteins that are involved in biomolecular condensate formation.

The authors here investigate information integration in plants using light and nutrient stimuli and identify a novel regulation pathway towards photoreceptor-regulated stem growth.

BANP is identified as the transcription factor that binds the CGCG element in a DNA-methylation-dependent manner, opens chromatin and activates a class of essential CpG-island-regulated genes.

Neugebauer et al. show activation of the usually silenced embryonic factor DUX4 by herpesviruses in vitro and in patients, and demonstrate that depletion of DUX4 by nanobody degraders abrogates viral replication.

Stomata regulate gas exchange and help plants cope with abiotic stress. The authors identify a signalling pathway that coordinates the balance between stomatal opening and closing under high-temperature and/or drought conditions.

Transcription-Coupled Nucleotide Excision Repair (TC-NER) removes transcription-blocking DNA lesions. This study reveals that DDA1 is a crucial player in TC-NER, protecting transcription programs against genotoxic insults.

Multielement Z-tag X-ray fluorescence (MEZ-XRF) offers a new avenue for nondestructive and highly multiplexed tissue imaging and operates from the nanometer to whole-tissue scale, unlocking new biological observations.