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It remains unclear whether rRNA modifications can be naturally altered in response to antibiotics in bacteria. Here, the authors analyzed direct RNA nanopore sequencing data with an analytical pipeline Nanoconsensus, to investigate whether bacterial rRNA modifications are modulated upon exposure to various antibiotics.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

RNA-binding proteins play key roles in post-transcriptional gene regulation. Here, Hemm et al. developed RAPDOR, a widely applicable tool based on Jensen-Shannon Distance and the analysis of similarities that identified 165 potential RNA-binding proteins from GradR analysis in a cyanobacterium.

Increasing mitochondrial oxidative capacity and energy expenditure holds therapeutic potential for obesity and metabolic disorders. Here, the authors identify MTCH2 as a mitochondrial regulator of fatty acid oxidation via interaction with CPT1.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

EXO1 performs multiple roles in DNA replication and DNA damage repair (DDR), but its role in DDR-deficient cancers remains unclear. Here, the authors find EXO1 loss as synthetic lethal with many DDR genes involved in various cancers, including genes from Fanconi Anaemia pathway, BRCA1-A complex, and spliceosome factor ZRSR2; such interactions represent potential clinical targets.

The regulatory landscape controlling Hoxd gene expression in tetrapod digit development was probably co-opted from a pre-existing cloacal regulatory mechanism, as evidenced by the effects of genetic deletion experiments in zebrafish fin, cloaca and mouse urogenital development.

Head and neck cancer patients could greatly benefit from personalised treatment, but a lack of large public datasets hampers this potential. Here, the authors present HANCOCK, a multimodal dataset that integrates demographical, clinical, and histopathological data for 763 head and neck cancer patients that empowers machine learning models for clinical outcome prediction.

Creative experiences such as dance, music, drawing, and strategy video games might preserve brain health. The authors show that regular practice or short training in these activities is linked to brains that look younger and work more efficiently.

Brain contractile pericytes control capillary blood flow to match neuronal demands. Here, the authors show that pericytes express ATP-releasing pannexin1 channels and establish their role in the regulation of capillary diameter and memory function in mice.

Ecological effects, such as disturbances, have a spatial dimension, but what influences their spatial propagation is not fully understood. Here, the authors find generalist and widespread species are key to propagating effects spatially, mediated by landscape characteristics and species provenance.

Single-cell RNA-seq facilitates the study of transcriptome diversity in individual cells. Here, authors introduce a tool for isoform quantification at the single-cell level using 3’ scRNA-seq data, contributing to the study of post-transcriptional gene regulation in individual cells.

Resistance to anti-EGFR therapy is a clinical issue for patients with advanced head and neck cancers. Here, the authors show that therapy-resistant cancer cells enhance fatty acid metabolism, which can be therapeutically targeted by inhibiting peroxisome proliferator-activated receptor alpha (PPARα).

Gene editing of hematopoietic stem and progenitor cells offers promise as a curative treatment for chronic granulomatous disease (CGD). Here, the authors develop a D10A Cas9n based gene editing strategy to treat CGD with no detectable off-target activity or chromosomal translocations.

The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

Overexpression of c-MYC regulates tumor metabolism in pancreatic ductal adenocarcinoma (PDAC). Here the authors identify ELOVL6, a fatty acid elongase regulated by c-MYC, as a potential therapeutic target of PDAC.

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.

Using two wavelengths to activate different photoreactions in a resin system has attracted attention in the scientific community. Here, the authors use wavelength orthogonal photochemistry to spatially control the curing kinetics of a thiol-ene photopolymerization reaction.

In the era of global foodborne pathogens’ genomic surveillance, this study shows that large-scale inter-laboratory comparisons are needed and feasible, opening good perspectives for efficient and cooperative One Health outbreak investigations.

Enhanced polyamine depletion in neuroblastoma models decreases translation of mRNA codons with adenosine in the third position, reprogramming the tumour proteome away from cell cycle progression and towards differentiation.

Dinoflagellates and cyanobacteria produce saxitoxin (STX) congeners that block voltage-gated sodium channels. Here authors show how amphibians may sequester STX congeners using a ‘lock and key’ mode, expanding the understanding of toxic sponge action.

A geological climate archive documents the effects of ocean warming on Antarctic marine ice-sheets. Large sediment fluxes from the interior of West Antarctica precede the onset of sustained retreat to a smaller footprint for the ice-sheet.

Demystifying the spawning strategies of fish can help us understand their evolutionary drivers and better inform fisheries management. This study reveals the spawning strategies of pelagic fish, showing that the benefits of co-located spawning across time and space outweigh the potential drawbacks.

Oral vaccines against Vibrio cholera have been critical for cholera management, but the production of more efficacious and cost-effective approaches is still needed. Here the authors deliver a bivalent V_HH construct that binds to cholera toxin and show protection in a murine cholera model.

Here the authors introduce a CRISPR-based, dual-fluorescent reporter system in mice, which enables rapid in vivo testing of the effects of human non-coding variants linked to disease, implicating rare and common enhancer variants in autism.

Intratumoral tertiary lymphoid structure (TLS) density has been associated with better prognosis in several cancer types. Here the authors provide a comprehensive characterization of TLSs in patients with high-grade serous ovarian carcinoma.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

The distribution and organisation of matrix molecules in the tumour stroma help shape solid tumour progression. Here they perform temporal proteomic profiling of the matrisome during breast cancer progression and show that collagen XII secreted from CAFs provides a pro-invasive microenvironment.

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined and the pathophysiology unknown. Here, the authors conduct deep phenotyping of a cohort of PI-ME/CFS patients.

Mendelian randomization (MR) identifies causal relationships from observational data but has increased error rates when the genetic variants used as instruments come from a single region, a typical scenario when assessing molecular traits like protein or metabolite levels as risk factors. Here the authors introduce a single-region pleiotropy-robust MR method, validating the method on three ground truth sources, showing its capability to identify disease-causing molecular traits.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

Neural mechanisms underlying state-dependent flexible selection are not fully understood. Here authors show that NPY homologues in Drosophila larva differentially modulate reciprocally connected inhibitory neurons to bias non-feeding decisions, favoring escape-type actions (Head Cast), over protective-type actions (Hunch), in response to a mechanical cue.

Here the authors report asperigimycins, fungal ribosomally synthesized and post-translationally modified peptides with a heptacyclic scaffold. After chemically modifying them for nanomolar anticancer activity, CRISPR screening identifies SLC46A3 as a key transporter for their uptake in cells.

The extensive information capacity of DNA makes it an attractive alternative to traditional data storage. DNA-Aeon is a DNA data storage solution that can correct all error types commonly observed in DNA storage, while encoding data into sequences that meet user-defined constraints such as GC content, homopolymer length, and no undesired motifs.

The authors show that telomere length resetting in embryos, a key determinant of healthy aging, is established by mitochondrial function at conception.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Neuromuscular junctions (NMJs) are denervated in amyotrophic lateral sclerosis (ALS) through unknown mechanisms. Here, the authors show immune cells infiltrating muscle of ALS patients and mouse models, driven by CCL2-CCR2, which can be blocked to protect NMJs.

Prime editing can generate undesired editing outcomes. Here, authors describe a method for reducing both on-target and off-target imprecise editing outcomes of diverse prime editing modalities in different cell types with a combination of small molecules that inhibit both DNA-PK and PolΘ activity.

Mechanisms of transcription of expanded G4C2 repeats in C9ORF72, associated with ALS/FTD, are not fully understood. Here authors use both Drosophila and C9ORF72 iPSC-derived neurons and identify AFF2/FMR2 as a regulator of poly(GR) toxicity by regulating expression of the expanded G4C2 repeats.

The immune response to tumour development is frequently targeted with therapeutics but remains largely unexplored in diagnostics. Here this groups designs an immunodiagnostic platform targeting amino acid residue biomarkers associated with tumour development and distinct from autoimmune and infectious diseases.

Here, the authors provide evidence that SARS-CoV-2 N protein leads to autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inducing DNA damage and proteotoxic stress, eventually causing pneumonia. The small-molecule drug PJ34 or anastrozole alleviates N protein-induced pneumonia.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Cancer cells adapt to changes in metabolism to ensure their survival. Here the authors show that glucose responsive transcription factor ChREBP reprograms liver cancer metabolism in part via enhancing the PI3K/AKT signaling.

This work compares the preclinical lung biodistribution and efficacy profile of inhaled anti-CCN2 (cellular communication network factor 2) Anticalin® protein PRS-220 for the treatment for idiopathic pulmonary fibrosis (IPF) compared to systemic delivery of a CCN2 inhibitor.

Non-coding introns are excised from RNA transcripts of most eukaryotic genes by splicing. Here, Kenny et al. show that LUC7 proteins promote the splicing of different subsets of introns with distinct 5′ splice site sequences, and that these preferences are conserved from plants to human.

The role of metabolism in acute myeloid leukaemia (AML) onset remains to be explored. Here, the authors explore the metabolic landscape of AML cells and the signature of extracellular vesicles (EVs) in peripheral blood and show that circulating EVs regulate leukaemia (stem) cell metabolic reprogramming.

Photoactive transition metal complexes usually feature 4d6 and 5d6 precious metals with charge transfer excited state lifetimes exceeding hundreds of nanoseconds, while complexes with earth abundant 3d6 metals exhibit lifetimes of less than 1–2 ns. Here, the authors report a tetracarbene manganese(I) complex with an excited state lifetime of 190 ns.

Type 2 inflammation drives the formation of pathologic mucus in patients with asthma. Here, authors reveal a role for intelectin-1 in IL-13-induced mucus properties, and that an ITLN1 eQTL is associated with protection from the formation of mucus plugs in T2-high asthma.

Cancers in different populations have been shown to be genetically distinct. Here, the authors sequence breast cancers from Mexican-Hispanic patients and find that these patients have a higher percentage of Akt1 mutations compared to Caucasian and Asian populations, suggesting these are clinically actionable.