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Base editing of the pathogenic trinucleotide repeat expansions underlying Huntington’s disease and Friedreich’s ataxia introduces repeat interruptions that reduce somatic expansion in patient cells and mice.

Using visible-light-induced crosslinking, a local stiffening approach is developed for ex vivo mouse and human lung tissue as an early lung injury model, directing epithelial cell mechanosensing, differentiation and nascent protein deposition.

A super-pangenome analysis incorporating 123 newly sequenced bryophyte genomes reveals that bryophytes exhibit a larger number of unique and lineage-specific gene families than vascular plants.

Roy et al. quantify the impact of a high-fat diet across genetically diverse strains of mice, revealing a generally negative effect on lifespan but also a wide variability.

A lung-on-a-chip device containing immune cells and stromal cells mimics the small airways, recapitulating human immune response to severe H1N1 infection.

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 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.

Meng et al. report that lymphoid fate is programmed epigenetically rather than transcriptionally in haematopoietic stem cells and shed light on how epigenetic programming generates platelet differentiation pathways with distinct kinetics.

Synthetic hydrogels and immune organs-on-chip mimicking human immune tissue developed from blood samples allow effective modelling of immune responses and B cell disorders, with implications for the development of improved immunotherapies and vaccines.

The oral drug obeldesivir confers 80% survival when given after lethal Marburg virus exposure in cynomolgus macaques and also delays viral replication and disease onset, suggesting a potential treatment option for an infection with no approved therapies.

Iwakuma and colleagues report that statins, through their action on the mevalonate pathway, lead to the ubiquitin-mediated degradation of misfolded mutant p53 by impairing its interaction with the Hsp40 family member, DNAJA1.

The Omicron variant is partially attenuated, likely because it fails to efficiently infect lung cells. Here, Hoffmann et. al. show that this defect can be lost during Omicron evolution as demonstrated for the subvariant BA.5 that robustly infects lung cells in vitro and in vivo.

Comprehensive genomic profiling of human H3K27M mutant diffuse midline gliomas, combining single-cell RNA sequencing and ATAC sequencing with bulk ChIP sequencing and other data, proposes distinct oligodendrocyte populations as potential cells of origin.

mTORC1 blocks lysosomal nutrient generation. Here, the authors show that mTORC1 inactivation triggers V-ATPase assembly, which rapidly initiates lysosomal acidification and degradation of protein contents throughout the lysosomal population.

Robbins and colleagues show that cigarette smoke-induced endothelial dysfunction enables atherosclerotic plaque macrophages to drive abdominal aortic aneurysm formation in a mouse model of atherosclerosis.

Inhibiting glycogen synthase kinase 3 (GSK3) improves muscle function, metabolism, and bone health in many other diseases. Here, Marcella et al. found that inhibiting glycogen synthase kinase 3, alone or combined with exercise, improves muscle health and function in mouse models of Duchenne muscular dystrophy without negatively affecting insulin sensitivity or bone health.

Engineering of a biosensor allows the authors to map the signaling activity of the phytohormones gibberellins (GAs) and to show that GAs orient cell division at the shoot apex to establish the organization in parallel cell files of plant stems.

Crossing the blood–brain barrier in primates is a major obstacle to gene delivery in the brain. Here an adeno-associated virus variant (AAV.CAP-Mac) is identified and demonstrated for crossing the blood–brain barrier and delivering gene sequences to the brain of different non-human primates species.

Gan et al. identify the GPCR-like protein GPR137B that interacts with Rag GTPases to recruit mTORC1 to lysosomes. They show that GPR137B controls dynamic Rag and mTORC1 activity as well as lysosome morphology.

Sudipto Roy, Carol Wicking, Carsten Bergmann and colleagues report that mutations in DZIP1L cause autosomal recessive polycystic kidney disease (ARPKD). Through studies of mouse and zebrafish models of DZIP1L loss of function, the authors demonstrate that DZIP1L is required for proper function of the periciliary diffusion barrier.

Lolamicin, a novel antibiotic developed from a pyridinepyrazole precursor, exhibits potent activity against a broad range of Gram-negative multidrug-resistant clinical isolates, and good efficacy in mouse models of infection without inducing gut dysbiosis.

Here the authors describe a simple reverse genetics method that relies on overlapping cDNA fragments for generation of positive-strand viruses including SARS-CoV-2 and characterize them in vitro and in vivo.

The few options available for the measurement of in-plane and cross-plane thermal conductivity of covalent organic frameworks films limit their application for lightweight thermal management. Here, the authors measure both, the in-plane and cross-plane thermal conductivity of two dimensional covalent organic frameworks with different pore sizes using laser-based pump-probe techniques.

The identification of prognostic biomarkers can help stratify cancer patients. Here, the authors apply deep RNA sequencing from primary melanomas coupled with long-term clinical outcome data from a prospective multicentre phase III trial, to develop and validate a 121 metastasis-associated gene signature identifying early-stage melanoma patients at higher risk of metastasis and worse survival.

Clinical translation of cell products is impeded by the lack of clinically predictive potency assays. Here, the authors report a microfluidic system to evaluate patient-derived cells used in a clinical trial for osteoarthritis pain, and use the results and patient-matched clinical data to build prediction models, showing improved clinical prediction and higher correlative power with pain scores compared to 2D culture.

The formation of the mitotic checkpoint complex requires an intricate spatial coordination amongst the proteins Bub1, Mad1, Cdc20, and Mad2. Chen et al show that a structural flexibility in Mad1 plays an essential role in achieving this coordination.

Roy et al. describe a generalized method for computationally designing miniproteins selective for a single integrin heterodimer and conformational state. The designed αvβ6 inhibitor remains monomeric and maintains biological activity following aerosolization and shows excellent efficacy in bleomycin induced lung fibrosis.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Postmortem studies indicate reduced synaptic density in schizophrenia. Sellgren et al. show increased synaptic pruning in patient-derived cell models and provide evidence that C4 risk variants increase engulfment, while minocycline decreases it.

Achieving genetic circuits on single DNA molecules could have varied applications. Here, authors observed proteins emerging from single DNA molecules through coupled transcription-translation complexes, and show that nascent proteins lingered on DNA, regulating cascaded reactions on the same DNA and allowing the design of a pulsatile genetic circuit.

Nanopore sequencing enables direct and accurate detection of 5-methylcytosine and 5-hydroxymethylcytosine, providing a simultaneous readout of modification states on both strands of DNA from a single molecule.

Profiling >200,000 live human microglia from 74 donors across neurological diseases reveals 12 subtypes of microglia that were validated in situ. Camptothecin is also identified as a compound reducing disease-enriched microglial subsets.

Ultraviolet exposure on the skin promotes food intake and body weight gain in males, but not females, by increasing ghrelin expression in skin adipocytes.

Irisin is shown to mediate beneficial effects on cognitive function associated with exercise and to improve cognitive function in mouse models of Alzheimer’s disease, probably through its direct action in the brain.

Asthma is associated with mucus overproduction; however, the immunological consequences of excess mucus remain poorly understood. Here the authors show that formation of airway plugs by mucus promotes airway hypersensitivity, while deletion of mucous component Muc5acablates it independently of inflammation.

Histone H3-mutant gliomas are deadly brain tumours and the tumour microenvironment is not fully understood. Here the authors profile the immune microenvironment from human samples and mouse models and implicate myeloid cells in immune suppression and show inhibition of myeloid cells and checkpoint blockade demonstrates therapeutic benefits in mice.

Atherosclerosis is accompanied by an autoimmune response that includes CD4 T cells recognizing epitopes in apolipoprotein B (APOB). Saigusa et al. analyzed the transcriptomes and T cell receptors of APOB-specific CD4 T cells by single-cell RNA sequencing using MHC-II tetramers in women with atherosclerosis, and showed that APOB-specific regulatory T cells switch to a more memory-like phenotype in atherosclerosis.

Understanding how cells discriminate between stimuli is an ongoing challenge. Here, the authors propose a mathematical framework for inferring the mutual information encoded in temporal signaling dynamics and use it to study how information is transmitted over time in response to different stimuli in NFκB, MAPK and p53 signaling pathways.

Zhang et al. report curved adhesions, which are integrin-based adhesions formed in response to membrane curvatures that can be imposed by the overlying extracellular matrix fibre geometry.

The use of oncolytic viruses as a therapy for cancer is limited by mechanisms inhibiting viral replication in the tumor. Here, the authors show that a chemical derivative of itaconate, 4-octyl itaconate, increases oncolytic virus VSVΔ51 efficacy in various cancer models, through decreasing antiviral immunity.

Historical and contemporary data of whitefish radiations from pre-alpine European lakes and reconstruction of changes in whitefish genetic species differentiation through time show that species diversity may have evolved in response to ecological opportunity, and that eutrophication, by diminishing this opportunity, has driven extinctions through speciation reversal and demographic decline.

Hereditary tyrosinemia type 1 (HT1) is an inborn error of metabolism caused by a deficiency in fumarylacetoacetate hydrolase (FAH). Here, the authors show in an animal model that HT1 can be treated via in vivo portal vein administration of a lentiviral vector carrying the human FAH transgene.

Sodium/proton exchangers (NHEs) are critical regulators of pH within the cell and the extracellular microenvironment. Here, the authors show that hypoxia induces mobilization of NHE6 from endosomal compartment to the plasma membrane in a PKC-dependent manner inducing hyper acidification of endosomes and drug resistance.