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This study uses single-cell transcriptomics to examine how lung cells respond to targeted damage. The authors employ genetically modified mouse models and cell sorting to enrich for rare, actively dividing cells, revealing cell types/states and alternative differentiation paths.

Chemists can make liquid fuel from biomass — or from coal. Heidi Ledford weighs up the pros and cons.

Neurons in the median preoptic nucleus that express the prostaglandin EP3 receptor produce prolonged hypothermic responses or hyperthermic responses, respectively, following brief activation or inhibition.

Polymers are known to spontaneously produce micro- and nanoplastics but the mechanisms by which environmentally-triggered Å-level random bond breaking events lead to the formation of these relatively large fragments are unclear. Here, the authors show that chain scission accumulates in the amorphous phase of a semicrystalline morphology which leads to mechanical failure and the concurrent release of nanoplastics even under quiescent conditions.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

In most cancers, mutations that lead to oncogene activation and tumor suppressor inactivation synergize to promote tumorigenesis. However, in neuroblastomas, MYCN amplification and ATRX mutations are mutually exclusive and incompatible.

The effects of chromosomal translocations involving the mixed-lineage leukemia (MLL) locus on gene expression regulation remain to be explored. Here, the authors find that MLL oncoproteins support lineage-switching events through dynamic chromatin binding.

In individuals with long-term cardiac symptoms after an initially mild course of COVID-19 illness, magnetic resonance imaging and measurement of cardiac injury biomarkers commonly detected ongoing cardiac inflammation but not structural heart disease.

The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources such as environmental amino acids, providing a potential therapeutic target.

Silent nociceptors remained enigmatic ever since they were first described decades ago. Here, Nees. et al. show that inflammation-induced upregulation of TMEM100 unsilences silent nociceptors, which triggers secondary mechanical pain hypersensitivity.

Smells are detected in the nose by odorant molecules binding to a specific G protein-coupled receptor on the cell surface. Here, authors have determined the atomic structure of a receptor bound to an odorant molecule that showing how the odorant binds and activates the receptor.

Histone methyltransferase, DOTL1 is implicated in the pathogenesis of MLL-rearranged leukemia, however, not much is known of its role in prostate cancer (PCa). Here, the authors report that DOTL1 inhibition suppresses both androgen receptor and MYC pathways in a negative feed forward manner to reduce growth of AR-positive PCa.

A cell-based phenotypic screen led to the discovery of compounds called NVS-STGs, which bind to the N-terminal domain of STING and act as a molecular glue to induce higher-order oligomerization and activation.

An unusual family of bifunctional terpene synthases has been identified in which a prenyltransferase assembles 5-carbon precursors to form C20 geranylgeranyl diphosphate (GGPP), which is then converted into a polycyclic product by a cyclase. Here, the authors report the cryoEM structure of a 495-kD bifunctional terpene synthase, variediene synthase from Emericella variecolor, in which GGPP is not channeled intramolecularly, but can be channeled intermolecularly to a non-native cyclase.

Medulloblastomas (MBs) are highly heterogeneous paediatric brain tumours that remain challenging to treat. Here, the authors integrate proteomics, epigenomics, transcriptomics and post-translational modification analyses to find molecular subgroups and potential therapeutic targets in MB tumours.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

Remdesivir is a nucleoside analog that inhibits the SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and is used as a drug to treat COVID19 patients. Here, the authors provide insights into the mechanism of remdesivir-induced RdRp stalling by determining the cryo-EM structures of SARS-CoV-2 RdRp with bound RNA molecules that contain remdesivir at defined positions and observe that addition of the fourth nucleotide following remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation.

Systemic sclerosis (SSc) is a fibrotic disease affecting multiple organs. Here the authors use patient samples plus mouse studies to show a central role for tenascin C as a TLR4 activator responsible for persistence of fibrosis in the context of SSc and SSc-like disease.

The binding of a DARPin to p53 displaces the human papillomavirus (HPV) E6 protein and stabilizes p53 in HPV-infected cells. This interaction reactivates a p53-dependent transcriptional program, suggesting a potential new therapeutic strategy for treating HPV-induced cancers.

The transcriptional regulation of oligodendrocytes has an essential role in myelin formation and maintenance. Here, the authors identify the transcription factor Tfii-i as a regulator of myelin genes expression in the nervous system and show that its loss enhances myelin thickness and nerve conduction.

Performing a CRISPR–Cas9 screen in aged mice, Sun and colleagues identify clusterin as a driver of myeloid-biased hematopoietic stem cell differentiation in aging, through regulation of mitochondrial function via a Mnf2-OXPHOS-p38-Cebpb regulatory axis.

Zimmermann et al. present OrgaPlexing, an imaging pipeline mapping metabolic organelles and their interactions. They find changes in mitochondria, ER, peroxisome and lipid droplet dynamics that impact macrophage inflammatory lipid mediator synthesis.

Intestinal tuft cell subtypes represent successive stages of differentiation that is driven by crypt-villus signaling gradients. Here, the authors show that applying these gradients to organoids generates mature immune-related chemosensory tuft cells suitable for experimental studies.

Live-cell RNA imaging with high spatial and temporal resolution remains a major challenge. Here the authors design spirocyclic rhodamine probes that enable a fluorescent light-up aptamer system suitable for visualizing RNAs in live or fixed cells with two different super-resolution microscopy modalities SMLM and STED.

The antiviral dsRNA sensor PKR is regulated by PACT. This paper shows how PACT prevents aberrant PKR activation by endogenous dsRNAs like Alu. PACT disrupts PKR’s dsRNA scanning without blocking its binding, resetting its activation threshold to tolerate cellular dsRNA and preserve homeostasis.

Industrial bioethanol production is driven by ecological interactions within the microbial community rather than the interactions within yeast population. Here, the authors identify bacteria affecting ethanol production and reveal temperature as the major driving force for strain-level dynamics.

While the biological roles of ubiquitin chains are well studied, little is known about the functions of SUMO polymers. Here, the authors identify poly-SUMOylation substrates and provide evidence that SUMO polymers regulate the accumulation of CCAN subunits at chromatin and centromeres.

Introduction of structured neutron waves carrying orbital angular momentum (OAM) in small-angle neutron scattering experiments provides novel approaches to the characterisation of material properties. Here the authors demonstrate the retrieval of phase information in far-field intensity profiles by means of an interferometric technique using helical neutron waves.

Tetraspanins play critical roles in various physiological processes, ranging from cell adhesion to virus infection. Here authors report the crystal structure of CD9 and the cryo-electron microscopic structure of CD9 in complex with its single membrane-spanning partner protein, EWI-2.

During speech, neurons in the subthalamic nucleus transiently couple with cortex oscillations. Speech sound errors occur when this coupling is delayed. These findings enhance understanding of information processing in human brain during speech.

Frontal ring-opening metathesis polymerization (FROMP) is a promising energy-efficient approach to fabricate polymeric materials but the characteristic properties of the front are currently controlled primarily by varying the resin composition or the environmental conditions. Here, the authors present an approach to control FROMP of dicyclopentadiene using photochemical methods.

Studies using mouse models of lung adenocarcinoma identify an association between age, iron homeostasis and tumour initiation potential that involves NUPR1 and lipocalin-2.

It remains unclear how cells respond to complex extracellular geometries at the mesoscale. Here, the authors study the organization of bone cells in landscapes with varying curvatures, observing a preference for local concavities, multicellular bridging, and collective stress fiber orientation.

International maritime shipping accounts for an important proportion of global CO₂ emissions, but its role in a world with deep decarbonization has not been thoroughly examined. Through a multi-model comparison, this study reveals the necessity of reducing and stabilizing emissions from this sector in the next few decades.

Structural, pharmacological and computational studies reveal how different classes of positive allosteric modulators bind to distinct allosteric sites and use noncanonical mechanisms to activate the free-fatty acid receptor FFA2.

The pro-tumorigenic effects of vimentin have been attributed to intracellular functions in tumour cells so far. Here, the authors show that tumour endothelial cells can secrete vimentin as a pro-angiogenic factor and that targeting of vimentin can be used as an immunotherapeutic strategy.

Linnerbauer and colleagues find that HB-EGF produced by reactive astrocytes is protective during autoimmune neuroinflammation, but epigenetically suppressed during late stages.

Mutations in profilin 1 (PFN1), which modulates actin dynamics, are associated with ALS. Here the authors show that expression of ALS-PFN1 is sufficient to induce deficits in human microglia-like cells, including impaired phagocytosis and lipid metabolism, and that gain-of-function interactions between ALS-PFN1 and PI3P may underlie these deficits.

The immaturity of iPSC-derived cardiomyocytes limits their use in drug testing. This study provides a systematic evaluation of how culture medium, calcium, nanopatterning and electrostimulation distinctly affect their structural, metabolic, and electrophysiological maturation.