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Image noise is a common problem in light microscopy, and denoising is a key step in microscopic imaging pipelines. Lequyer et al. propose a self-supervised denoising method and apply it to diverse imaging and analysis pipelines.

Senescence causes age-related diseases and stress-related injury, but it is also physiologically essential during development. Here, Yao et al. show that programmed senescence in mesenchymal cells orchestrates postnatal lung development and that neonatal hyperoxia can induce senescence, particularly in type II, Pdgfra+ mesenchymal and immune cells, during the alveolar stage, resulting in lung injury.

Responses of agriculture and fisheries to climate change are interlinked, yet rarely studied together. Here, the authors analyse more than 3000 households from 5 tropical countries and forecast mid-century climate change impacts, finding that communities with higher fishery dependence and lower socioeconomic status communities face greater losses.

The authors took a multimodal approach to characterize the differential transcriptome and epigenetic landscape between distinct regions of the embryonic mouse forebrain, revealing many unexplored presumptive promoter-enhancer interactions.

Rapid antigen tests and syndromic surveillance for identification of COVID-19 cases are limited by low sensitivity and specificity, respectively. Here, the authors use data from Bangladesh and show that combining the two methods improves diagnostic accuracy in a range of epidemiological scenarios.

Aromatic amino acids in proteins support ligand binding and protein stability. To parse the physiocochemical roles of aromatic interactions, here Galles, Infield and co-authors identify pyrrolysine-based aminoacyl-tRNA synthetases that enable the encoding of fluorinated phenylalanine amino acids.

A six-letter sequencing workflow can simultaneously detect genetic and epigenetic bases.

TOP2 collaborates with the BAF complex genome-wide to form and resolve facultative heterochromatin at transcriptional regulatory elements recognized by pluripotency factors.

The cytokine IL-6 controls the survival, proliferation and effector functions of lymphocytes. Jones and colleagues show that activation of CD4⁺ T cells leads to suppression of STAT1 activation by tyrosine phosphatases and changes the effector characteristics of memory CD4⁺ T cells in response to IL-6.

Pioneer factors are a special class of transcription factor that can associate with compacted chromatin to facilitate the binding of additional transcription factors. This Progress article discusses the importance of pioneer factors in breast cancer and prostate cancer.

This study elucidates how long-range chromatin loops are altered during short- and long-term changes in neural activity, and analyzes the interplay between the 3D genome and the linear epigenome during activity-dependent transcriptional responses.

Genetic diversity in social genes is expected to be shaped by conflict. Here, the authors show that in Dictyostelium discoideum, social genes in fact exhibit diversification patterns consistent with relaxed purifying selection, likely due to their expression only in intermittent social generations.

Many pathogens manipulate ubiquitin-mediated signaling to evade host cell defense. Here, the authors characterize the structure and enzymatic activity of a deubiquitylase domain from the causative pathogen of scrub typhus, providing evidence for a distinct mechanism of ubiquitin chain selectivity.

The lack of effective drug delivery strategies has impaired the therapeutic progress in the treatment of glioblastoma (GBM). Here, the authors engineer synthetic protein nanoparticle based on polymerized human serum albumin equipped with the cell-penetrating peptide iRGD to deliver siRNA against STAT3 and report improved survival in a mouse model of GBM.

ARID1A and other SWI/SNF components are critical for response to estrogen-receptor antagonists in breast cancer. SWI/SNF-specific gene knockouts lead to drug resistance and ARID1A mutations are more frequent in resistant tumors from patients.

Fine-mapping of blood cell traits in the UK Biobank identifies putative causal variants and enrichment of fine-mapped variants in accessible chromatin of hematopoietic progenitor cells. The study provides an analytical framework for single-variant and single-cell analyses of genetic associations.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Deforestation by the ancient Maya led to a destabilization of organic carbon preserved in the underlying soils and reduced the magnitude of the soil carbon sink in this region.

Gastrointestinal stromal tumours can be initiated by gain-of-function mutations of the KIT or PDGFRA oncogenes but also by loss of the metabolic complex succinate dehydrogenase (SDH), which leads to DNA hypermethylation; this study shows that in SDH-deficient tumours, displacement of CTCF insulators by DNA methylation activates oncogene expression, illustrating how epigenetic alterations can drive oncogenic signalling in the absence of kinase mutations.

DoTA-seq leverages a microfluidic droplet system to isolate and lyse diverse microbes and amplify target genetic loci, enabling high-throughput single-cell sequencing of microbial populations.

How mechanosensitive ion channels, such as MscL, are activated by lipids and physical properties of the membrane remains unclear. Here authors use PELDOR/DEER spectroscopy and identify a single site which generated an allosteric structural response in the absence of membrane tension.

An analysis of the fruitENCODE data consisting of multiple transcriptome, accessible chromatin, histone and DNA methylation profiles from 11 fleshy fruits reveals three types of transcriptional feedback circuits controlling fruit ripening.

How traits specific to modern humans have evolved is difficult to study. Here, Gokhman et al. compare measured and reconstructed DNA methylation maps of present-day humans, archaic humans and chimpanzees and find that genes that affect vocal tract and facial anatomy show methylation changes between archaic and modern humans.

Retinoic acid signaling is involved in patterning the embryonic antero-posterior axis, and also regulates hindbrain segmentation in jawed vertebrates. Here they show that retinoic acid signaling plays important roles in hindbrain segmentation in a jawless vertebrate, the lamprey, thus indicating this feature of hindbrain development is conserved in all vertebrates.

We introduce a scalable, high-resolution, 3D printing technique for the fabrication of shape-specific particles based on roll-to-roll continuous liquid interface production, enabling direct integration within biomedical, analytical and advanced materials applications.

In an interim analysis of a phase 1/2 trial, a heterologous prime boost vaccine comprised of a chimpanzee adenovirus and self-amplifying mRNA that encodes neoantigens derived from common oncogenic driver mutations in combination with immune checkpoint blockade was safe and elicited neoantigen-specific T cell responses in patients with advanced solid tumors.

Predators, including prawns, can suppress schistosomiasis by eating snail hosts. This modelling study finds that two prawn species in sub-Saharan Africa can reduce snail hosts and help control schistosomiasis at densities that maximize profits of associated aquaculture—a potential win–win.

Alonso and colleagues develop immune-stimulating antibody conjugates capable of specific delivery of TLR7/8 agonists to tumors, which induces durable antitumor immunity.

The RIG-I like receptors sense RNA viruses and initiate antiviral immunity. Here the authors screen 375 definite ubiquitin ligases and propose UBR5 promotes RLR transcription by disengaging the TRIM28-imposed brake on the RLR promoters.

Kelly et al. describe two cerebellum–thalamus–mPFC pathways in mice that regulate social and repetitive behavior. PC activation in Rcrus1 and posterior vermis improved social and reduced repetitive behaviors, respectively, in PC-Tsc1 mutant mice.

Understanding the timing and fitness of somatic copy number alterations (SCNAs) in cancer would shed light on cancer progression and evolution. Here, the authors develop Butte, a computational framework to estimate the timing of clonal SCNAs that encompass multiple gains, and apply it on whole-genome sequencing data from 184 samples.

The response of tropical precipitation to variation in sea surface temperature is stronger than in most climate models, with cool and warm ocean regions linked by strong shallow atmospheric circulations.

Despite growing interest in environmental metabolomics, we lack conceptual frameworks for considering how metabolites vary across space and time in ecological systems. Here, the authors apply (species) community assembly concepts to metabolomics data, offering a way forward in understanding the assembly of metabolite assemblages.

Theodorescu and colleagues describe a Molecular Twin approach that integrates multi-omic and computational pathology data from patients with pancreatic ductal adenocarcinoma using artificial intelligence to predict clinical outcomes.

Ubhi et al. describe the contribution of APOBEC family members A3C and A3D in the gemcitabine resistance mechanism in the context of pancreatic cancer, which is mediated by facilitating the restart of treatment-induced stalled replication forks.

Immune infiltration provides critical information for health and disease, yet it is unclear what factors influence infiltration levels. Here, the authors analyze human tissue transcriptomes from the Genotype-Tissue Expression project to find infiltration patterns regulated by age, sex and host genetic information.

The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.

The degree to which the conformation of the human metapneumovirus fusion (F) protein affects immunogenicity has been debated. Here, Hsieh et al. engineer prefusion-stabilized F variants with enhanced thermostability that elicit higher neutralizing antibody titers in mice than postfusion F.

The synovial fluid lubricates joints while also collecting molecular mediators from surrounding tissues. This Review highlights how molecular analyses of the synovial fluid might provide information on the progression of knee osteoarthritis and treatment efficacy, and identify potential therapeutic strategies targeting synovial fluid mediators in knee osteoarthritis.

The ability to target DNA methylation to specific loci is important for both basic and applied research. Here, the authors fuse CG-specific methyltransferase SssI with an artificial zinc finger protein for DNA methylation targeting and show the chromatin features favorable for efficient gain of methylation.

SOX2 amplification and overexpression represents a hallmark of squamous cancers with distinct distribution of chromatin accessible regions depending on cancer type. Here, the authors identify a single enhancer e1 that predominantly drives SOX2 expression in squamous cancer.

Disease-specific gut microbiome signatures have been previously defined for patients with liver cirrhosis or hepatocellular carcinoma (HCC). Here the authors examine the composition of the gut microbiota in cirrhotic patients with non-alcoholic fatty liver disease with or without HCC and evaluate how dysbiosis influences peripheral immune responses.

It remains unclear how rapid antibiotic switching affects the evolution of antibiotic resistance in individual patients. Here, Chung et al. combine short- and long-read sequencing and resistance phenotyping of 420 serial isolates of Pseudomonas aeruginosa collected from the onset of respiratory infection, and show that rare resistance mutations can increase by nearly 40-fold over 5–12 days in response to antibiotic changes, while mutations conferring resistance to antibiotics not administered diminish and even go to extinction.

Extracellular vesicles have been implicated in the transmission of pathogens from the arthropod to the human host. Here the authors show that tick-derived extracellular vesicles play a role in feeding and modulate the outcome of bacterial infection.

The restriction of dietary protein or amino acid intake is well established to extend lifespan in multiple species. Here, the authors show that the endocrine hormone FGF21 is necessary for dietary protein restriction to extend lifespan and improve metabolic health in aged, male mice.

A lead-optimization strategy combining porin permeation properties and biochemical potency leads to development of a new class of antibiotic based on broad inhibition of penicillin-binding proteins from Gram-negative bacteria.

Macropinocytosis is a cellular process for the uptake of extracellular fluid. Here, the authors use lattice light sheet microscopy to examine the spatial dynamics of the plasma membrane, PI3K activity, and structural differences of various macrophage cell types during macropinocytosis.