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Lake fisheries are vulnerable to environmental changes. Here, Kao et al. develop a Bayesian networks model to analyze time-series data from 31 major fisheries lake across five continents, showing that fish catches can respond either positively or negatively to climate and land-use changes.

Activated B cells and T cells accumulate within joints of patients with rheumatoid arthritis. Here, the authors use single-cell transcriptome and repertoire profiling to identify clonally expanded synovial B cells and T cells and define their phenotypes and predicted cell-cell interactions.

Using two-photon (2P) optogenetics and computational modeling, the authors find that neither space-based nor feature-based rules are sufficient to describe cell–cell interactions within the primary visual cortex (V1). Instead, models must include interactions between these cardinal axes.

Rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin.

A study finds that a protease called granzyme K can activate the entire complement cascade, explaining how it can drive destructive inflammation in inflammatory diseases such as rheumatoid arthritis.

S-isotope and Hg geochemistry across the terrestrial Permian–Triassic mass extinction (252 Ma) provides evidence of repeated volcanic eruptions over ~300 kyr that drove acidification and poisoning of a palaeo-lacustrine ecosystem in northwest China.

MYC amplification is an independent prognostic factor for the most aggressive subgroup (Group 3) of pediatric medulloblastoma (G3 MB). Here, the authors highlight the role of the RNA-binding protein, Musashi-1 (MSI1) in G3 MB and identify MSI1-bound targets sharing MYC associated pathways.

Timothy Chan and colleagues report exome and genome sequencing of 60 adenoid cystic carcinoma (ACC) tumor-normal pairs. They identify multiple pathways recurrently disrupted in ACC and provide evidence that KDM6A and PIK3CA are functionally relevant candidate ACC driver genes.

Michael Talkowski and colleagues analyze balanced chromosomal abnormalities in 273 individuals by whole-genome sequencing. Their findings suggest that sequence-level resolution improves prediction of clinical outcomes for balanced rearrangements and provides insight into pathogenic mechanisms such as altered gene regulation due to changes in chromosome topology.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

SCENT is a nonparametric method that models association between chromatin accessibility and gene expression in single-cell multimodal datasets, enabling construction of cell-type-specific enhancer–gene maps to aid mapping of candidate causal variants and genes for common diseases.

In modern football games, data-driven analysis serves as a key driver in determining tactics. Wang, Veličković, Hennes et al. develop a geometric deep learning algorithm, named TacticAI, to solve high-dimensional learning tasks over corner kicks and suggest tactics favoured over existing ones 90% of the time.

DNA from ancient wolves spanning 100,000 years sheds light on wolves’ evolutionary history and the genomic origin of dogs.

Intra-specific variations may contribute to heterogeneous responses to climate change across a species’ range. Here, the authors investigate the phenology of two bird species across their breeding ranges, and find that their sensitivity to temperature is uncoupled from exposure to climate change.

The influence of mRNA splicing on colon cancer development and progression is unclear. In this study, the authors demonstrate that the SRSF1 splicing factor is essential to sustain the stem cell phenotype of WNT-activated colorectal cancers.

Phosphorus (P) limitation is pervasive in tropical forests. Here the authors analyse the dependence of photosynthesis on leaf N and P in tropical forests, and show that incorporating leaf P constraints in a terrestrial biosphere model enhances its predictive power.

The molecular mechanisms that regulate senescence are incompletely understood. Here the authors couple high-throughput mapping of disease-associated functional SNPs (fSNPs) with proteomics analysis of fSNP-binding proteins to identify the transcription factor CUX1 as an activator of p16 expression and a regulator of senescence.

Ian Alexander and colleagues characterize a liver-specific enhancer–promoter element that is found in the genome of wild-type adeno-associated virus type 2 (AAV2), from which gene transfer vectors have been derived. They suggest that these sequences could provide a possible link between AAV integration events in the liver and gene dysregulation and pathogenesis.

Species interaction data, a field experiment and modelling of plant–insect communities show that landscapes with more habitat types support more even species, more complementary interactions, are more consistently robust to species loss, and confer greater pollination function.

Tumour-microenvironment interactions, pivotal in cancer progression, are challenging to replicate in vitro. Here, the authors use single-cell RNA-seq to analyse these interactions in colorectal cancer within organoid models, and aim to emulate and understand these crucial interactions by introducing specific microenvironmental components.

Crossover numbers and positions are tightly controlled but the mechanism involved is still obscure. Here, the authors, using quantitative super-resolution cytogenetics and mathematical modelling, show that diffusion mediated coarsening of HEI10, an E3-ligase domain containing protein, may explain meiotic crossover positioning in Arabidopsis.

The molecular classification of endometroid ovarian carcinomas (EnOC) has not been established, preventing the development of stratified therapeutic approaches. Here the authors characterise the molecular landscape of EnOC by whole exome sequencing, identifying clinically distinct disease subtypes.

Liquid biopsies allow the non-invasive detection of somatic mutations from tumours. Here, the authors develop and test MSK-ACCESS, an NGS-based clinical assay for identifying low frequency mutations in 129 genes and describe how it benefits patients in the clinic.

The prostate cancer tumour microenvironment in the context of treatment remains to be explored. Here, single-cell RNA-sequencing and spatial transcriptomics analysis of samples at multiple treatment points from 120 patients suggests that club-like cells may contribute to treatment resistance.

The exact molecular mechanisms driving FUS-mediated toxicity remain unclear. Here, the authors demonstrate that muscleblind (Mbl) is a novel modifier of FUS-associated ALS, with knockdown of endogenous Mbl suppressing neuromuscular junction defects and motor dysfunctions associated with FUS expression in Drosophila, as well as restoring reduced SMN protein levels in mammalian neuronal and human iPSC-derived motor neurons.

Differential cross-reactivity to haemagglutinin of various influenza B viruses shows lineage-specific susceptibility that varies between birth cohorts and was determined by early exposure to specific strains.

Energy consumption and compute density are challenges for computing systems. Here researchers show an optical computing architecture using micrometre-scale VCSEL transmitter arrays enabling 7 fJ energy per operation and a potential compute density of 6 tera-operations mm⁻² s⁻¹.

Aromatase inhibitors are an effective treatment for ER+ breast cancer, but response is variable. Here, the authors undertake molecular analyse of response from the POETIC trial and identify several factors associated with response.

The authors report a mechanistic basis for intestinal polyp formation in patients with hereditary mixed polyposis syndrome that involves the aberrant epithelial expression of morphogens and leads to the formation of ectopic intestinal crypts by progenitor cells outside the stem cell niche, a mechanism that seems to also be involved in human ectopic serrated polyps.

Cities may host surprisingly diverse and functionally distinct biological communities. This global analysis on 5302 vertebrate and invertebrate species finds evidence of 4 trait syndromes in urban animal assemblages, modulated by spatial and geographic factors.

Exercise improves metabolic health and physical condition, particularly important for health in aged individuals. Here, the authors identify that Sestrins, proteins induced by exercise, are key mediators of the metabolic adaptation to exercise and increase endurance through the AKT and PGC1a axes.

Evolutionarily conserved gene modules mediate neurodegenerative dementia in a variety of mouse models and in postmortem brain tissue from patients.

Obesity promotes tumor growth yet simultaneously increases susceptibility to PD-1-targeted cancer immunotherapy.

There are large uncertainties in wind-wave climate projections that need to be resolved to allow adaptation planning. A multi-method ensemble of global wave climate projections shows robust changes in wave height, period and direction that put 50% of the global coast at risk.

Adenomyoepithelioma is a rare tumor of the breast with an unknown genetic basis. Here the authors perform a genomic analysis of adenomyoepitheliomas revealing that their repertoire of somatic mutations vary according to the estrogen receptor (ER) status, and that ER-negative tumors harbor recurrent mutations in HRAS and PI3K pathway genes.

Single-cell transcriptomics of more than 20,000 cells from two functionally distinct areas of the mouse neocortex identifies 133 transcriptomic types, and provides a foundation for understanding the diversity of cortical cell types.

Hyperactivation of Akt promotes tumorigenesis. Here, the authors show that SAV1, a member of Hippo signalling, interacts with Akt to suppress Akt activity and MERTK-mediated Akt phosphorylation relieves this suppression to facilitate Akt oncogenic activity in clear cell renal carcinomas.

Peter Scacheri and colleagues report that the activity of enhancer elements in metastatic osteosarcoma is distinct from that in primary tumors and plays a functional role in metastatic progression of osteosarcoma.

Boyle et al. show that ROCK upregulates PERK signalling in epithelia of breast cancer, thereby enhancing recruitment and function of cancer-associated fibroblasts through CRELD2 to promote tumourigenesis.

The advent of single-cell RNA sequencing has revealed significant transcriptional heterogeneity in cancer, but its relationship to genomic heterogeneity remains unclear. Focusing on acute myeloid leukemia samples, the authors describe a general approach for linking mutation-containing cells to their transcriptional phenotypes using single-cell RNA sequencing data.

There are currently no approved treatments for Crimean-Congo Hemorrhagic Fever Virus (CCHFV) infection. In this study, the authors structurally characterize the epitope targeted by protective non-neutralizing mouse and human antibodies and provide insights into their broad range potential against various CCHFV strains.

Wnt secretion is facilitated by retrograde trafficking of the Wnt receptor Wntless. Korswagen and colleagues now show that endosome-to-Golgi trafficking of Wntless depends on an alternative retromer pathway that contains SNX3 in place of the canonical retromer sorting nexins.

Plasma proteins are a potential diagnostic tool to detect multiple diseases, including cancer. Here, the authors leverage multi-omics data to identify 1,463 proteins associated with 19 common cancers in UK Biobank participants. Reviewer Recognition:

By 2050 > 23% of the global population aged 69 + will live in climates with acute heat exposure– the 95th percentile of the distribution of maximum daily temperatures–greater than the critical threshold of 37.5C, compared with 14% in 2020, an increase of 177–246 million older adults exposed to dangerous acute heat.

This paper finds that the winter sea-ice over the Barents-Kara Seas has exhibited strengthened interannual variations in recent decades likely due to increased amplitudes of the El Niño-Southern Oscillation in a warming climate.

APLAID is a rare autoinflammatory disorder driven by mutations in PLCG2. Here the authors provide a new mouse model using the human APLAID p.Ser707Tyr mutation. The mouse recapitulates clinical features of APLAID that can be prevented by anti-G-CSF. Individuals with APLAID were also shown to have high circulating levels of G-CSF suggesting this might be a suitable target for the clinic.

Single-cell transcriptome profiling of mouse embryos and newborn pups is combined with previously published data to construct a tree of cell-type relationships tracing development from zygote to birth.