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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.

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.

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.

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

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.

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.

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.

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.

This Analysis estimates the health benefits and economic value of enhancing social determinants of mental health in Brisbane South, Australia, home to 1.2 million people. Crosland et al. analyze the impact of a 5% improvement in social cohesion, childhood difficulties, substance misuse, unemployment, underemployment, homelessness and staying engaged with education over 11 years.

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.

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.

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.

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.

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.

Analysis of soil microbial communities from five cities on three continents finds that urbanization is linked to the convergence of archaeal and fungal communities, and loss of ectomycorrhizal fungal diversity and abundance.

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.

A dynamic optimization approach using plant species data from 458 forest ecoregions suggests a strategy for when and where to conserve forests globally over the next 50 years to maximize the conservation of plant biodiversity.

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:

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.

Sarcoidosis is a heterogenous disorder often treated with glucocorticoids. Here the authors show, in an open label, non-randomized, single arm clinical trial involving 10 patients, that treatment with tofacitinib, a Janus kinase inhibitor, is associated with improved clinical symptoms and reduced activity of Th1 cytokines such as IFN-γ and IL-12.

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.

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.

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.

The ratio of predator-to-prey biomass is a key element in food webs. Here, the authors report a unified analysis of predator-prey biomass scaling in complex food webs, finding general patterns of sub-linear scaling across ecosystems and levels of organization.

People often change their preferences to conform with others. Using a longitudinal design, the authors show that such conformity decreases over the course of adolescence and that this reduction in conformity is accompanied by a decreasing degree of uncertainty about what to like.

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.

A new high-resolution record for the Antarctic Zone shows persistent anti-phasing of high interglacial ocean productivity and high glacial dust deposition, suggesting a close inter-hemispheric coupling of cryosphere, ocean and atmosphere.

Predicting species responses to climate change may be complicated by the influence of other factors. Here, the authors report that warming is linked to terrestrial and freshwater community shifts towards warm-adapted species overall, but body size, thermal niche breadth, species richness and baseline temperature modulate the trends.

Cardiomyocytes of heart ventricles consist of subpopulations of trabecular and compact subtypes. Here the authors describe the generation of structurally, metabolically and functionally mature compact ventricular cardiomyocytes as well as mature atrial cardiomyocytes from human pluripotent stem cells.

Agnihotri and colleagues show that loss of the MAT2A enzyme of the methionine cycle induces a global depletion of H3K36me3 and extends survival in glioma models, representing a potential therapeutic vulnerability.

Trends in boreal summer large scale circulation have been a key factor in the moistening of the Arctic over recent decades, according to analyses of Earth system model simulations.

Monoclonal antibodies show great promise in treating Covid-19 patients. Here, Maisonnasse, Aldon and colleagues report pre-clinical results for COVA1-18 and demonstrate that it reduces viral infectivity in three animal models with over 95% efficacy in macaques upper respiratory tract.

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.

A high-resolution local palaeoclimatic archive is correlated to the early Holocene human behavioural record at the British Mesolithic site of Star Carr. Despite environmental stresses at this time, intensive human activity persisted over centuries, suggesting resilience to climate change.

Microbial rhodopsins are major contributors to global light harvesting on Earth, but their role in carbon fixation is unclear. Here, the authors construct an artificial photosynthesis system by combining rhodopsin with an extracellular electron uptake mechanism for photoelectrosynthetic CO₂ fixation in Ralstonia eutropha.

Power et al. catalogue the microbial biodiversity and physicochemistry of around 1000 hotsprings across New Zealand, providing insights into the ecological conditions that drive community assembly in these ecosystems.

Effective solutions for food systems transformation must be designed in a participatory way. This study illustrates the application of an integrated assessment framework to explore stakeholder-driven scenarios towards climate-smart nutrition security in Malawi, South Africa, Tanzania and Zambia.

Anthropogenic eutrophication is a driver of plant community shifts in many grassland ecosystems. Here, the authors use data from a globally distributed experiment to assess how nutrient addition affects multiple facets of grassland ecological stability and their correlations.

The genomic and epigenomic landscape during metastasis in osteosarcoma remains to be investigated. Here, functional and pharmacological studies identify the dynamic epigenomic changes and gene vulnerabilities during the formation of osteosarcoma tumours in the lung microenvironment.

Adenosine is an immunosuppressive metabolite known to limit anti-tumor immune responses. Here the authors report the characterization of an adenosine A2A receptor (A2AR) eGFP reporter mouse, providing immunological insights into the biology of A2AR expression in the context of anti-tumor immunity.

Goel and colleagues show that CDK4/6 inhibition induces global chromatin changes mediated by AP-1 factors, which mediate key biological and clinical effects in breast cancer.

Analysis of 1,988 cases of B-cell acute lymphoblastic leukemia characterizes 23 subtypes defined by genomic features and shows that two of the subtypes have frequent PAX5 alterations.

Which vapors are responsible for new particle formation in the Arctic is largely unknown. Here, the authors show that the formation of new particles at the central Arctic Ocean is mainly driven by iodic acid and that particles smaller than 30 nm in diameter can activate as cloud condensation nuclei.

Transferrin receptor 2 (Trf2) is known to regulate iron homeostasis through its action in the liver. Here the authors report a previously unrecognised role of Trf2 in regulating bone homeostasis mediated by modulation of BMP signalling specifically on osteoblasts.

The MYST acetyltransferase HBO1 is a critical regulator in maintaining leukaemia stem cells, and a small-molecule inhibitor of HBO1 is developed that shows efficacy against a range of acute myeloid leukaemia cells.

Renal angiomyolipomas (AML) contain a mix of clonal tumour cells. Here, through reverse tumour engineering experiments, mouse genetics and analyses of human AML tumours, the authors provide evidence that these mesenchymal tumours originate from renal proximal tubule epithelial cells.

The combination of tumor barcoding with CRISPR-mediated targeting of tumor suppressors allows quantitative analysis of tumor-suppressor function during tumor growth in vivo.