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There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Immunotherapy has yet to demonstrate efficacy for patients with glioblastoma. Here, the authors employ human single-cell RNA-seq, spatial transcriptomics, and a preclinical mouse model to show that glioblastoma cell-derived synaptogenic factor Thrombospondin-1 promotes neuronal circuit remodeling and regional immunosuppression, highlighting a potential therapeutic target.

Examination of archaeological pottery residues and modern genes suggest that environmental conditions, subsistence economics and pathogen exposure may explain selection for lactase persistence better than prehistoric consumption of milk.

While experiments in younger trees support increased production under higher CO₂, it is unclear whether more mature trees can respond similarly. Here, the authors show increased production of biomass in a 180-year-old Quercus robur L. woodland under 7 years of free-air CO₂ enrichment (FACE).

By bearing firsthand witness to how the climate crisis is affecting life and livelihoods, their fieldwork directly informs policy to protect vulnerable sites.

The transcription factor FOXO1 has a key role in human T cell memory, and manipulating FOXO1 expression could provide a way to enhance CAR T cell therapies by increasing CAR T cell persistence and antitumour activity.

Charlie Clutterbuck, Alan Dalton and Andy Solandt, of the British Society for Social Responsibility in Science, consider what action needs to be taken to identify and regulate industrial health hazards.

A history of disease mapping shows that despite technological developments, little has changed in 500 years, finds Andy Tatem.

The diversity hotspots hypothesis attributes the overall increase in global diversity during the Late Mesozoic and Cenozoic eras to the development of diversity hotspots under prolonged conditions of Earth system stability and maximum continental fragmentation.

Here the authors present improved intramolecular sensors for β-arrestin2 and 1, which enable assessment of conformational changes of both isoforms in living cells. These reveal that the same GPCR induces differential conformational rearrangements that determine the functional diversity between the two β-arrestins.

The Great Oxidation Event represents a tipping point in Earth’s O₂ mass balance—when more O₂ was being produced than destroyed—that forever changed the habitability of worldwide oceans.

A reconstruction of atmospheric CO₂ concentration from boron isotopes recorded in planktonic foraminifera examines climate–carbon interactions over the past tens of millions of years and confirms a strong linkage between climate and atmospheric CO₂.

Brain microvascular dysfunction occurs in Alzheimer’s disease and other taupathies. Here the authors show that soluble pathogenic tau accumulates in brain microvascular endothelial cells of P301S(PS19) mice modeling tauopathy, and that it contributes to vascular deficits in these mice.

It is important to understand why some individuals in endemic regions acquire natural immunity against malaria while others remain susceptible. Here authors show that during episodes of Plasmodium falciparum malaria, circumsporozoite-specific cytolytic memory CD4⁺ T cells are clonally expanded in patients, and those with clinical immunity demonstrate reduction in the chemotactic and inhibitory receptor expression in ZEB2⁺ memory CD4⁺ T cells.

Using lipid residues absorbed in potsherds, the ages of pottery from various archaeological sites are determined and validated using sites for which the dates are well known from other methods.

Genetic susceptibility loci for oropharyngeal cancer have been reported but these studies have not always examined human papillomavirus (HPV) status. Here, the authors perform genome-wide analysis taking into account HPV16 serology status and report two independent loci in the HLA region, suggesting the protective role of HLA variants against HPV infection.

Limb regeneration requires a blastema with progenitor cells, immune cells, and an overlying wound epidermis, but molecular identities of these populations are unclear. Here, the authors use single-cell RNA-sequencing to identify transcriptionally distinct cell populations in adult axolotl limb blastemas.

The entry receptor for SARS-CoV-2, ACE2, translocates to the nucleus following infection with this virus. Here, the authors demonstrate that a peptide targeting the ACE2 nuclear localization signal promotes its methylation and abrogates viral replication of SARS-CoV-2 in Syrian hamsters.

Pericytes play an essential role in blood brain barrier (BBB) integrity. Here, the authors generate pericyte-like cells (PCs) from human pluripotent stem cells (hPSCs) which display functional properties and also promote BBB recovery in a mouse model of cerebral artery occlusion.

In this Perspective, members of the Aging Biomarker Consortium outline the X-Age Project, an Aging Biomarker Consortium plan for building standardized aging clocks in China. The authors discuss the project roadmap and its aims of decoding aging heterogeneity, detecting accelerated aging early and evaluating geroprotective interventions.

A statistical framework quantifies single-cell batch variation and recovers meaningful biological signals.

Dick and colleagues identify human LT-HSC subsets with distinct quiescent states. They link these differences to INKA1-mediated downregulation of the transmembrane protein CD112 and its interaction with the protein deacetylase SIRT1. INKA1 is inversely correlated with the histone H4K16Ac mark, which then distinguishes ‘latent’ CD112^lo LT-HSCs from CD112^hi LT-HSCs that are more readily activated in response to hematopoietic stress.

Present understanding of Plasmodium vivax biology is hampered by its inability to grow in vitro. Here, the authors developed an in vitro culture of its simian counterpart, P. cynomolgi, which shares morphological and phenotypic similarities with P. vivax, initiating a new phase in vivax research.

Proteins contain modular structural and functional units called domains. Here, the authors have developed Merizo, a deep learning method for domain segmentation applicable to experimental structures as well as those generated by AlphaFold2.

Analysis of whole-genome doubling (WGD) by using cancer sequencing data combined with simulations of tumor evolution suggests that there is negative selection against homozygous loss of essential genes before WGD but not after.

The early Eocene was marked by a series of abrupt warming events. Numerical modelling suggests that the events were the result of nonlinear interactions between orbital forcing, ocean circulation and the carbon cycle.

The impact of breakage fusion bridge (BFB) cycles on tumour heterogeneity and clinical outcomes remains poorly understood. Here, the authors develop OM2BFB, an algorithm to detect and reconstruct BFB amplifications using optical genome maps and use it to study BFB events across 2557 primary tumours and cancer cell lines.

How We Feel is a web and mobile-phone application for collecting de-identified self-reported COVID-19-related data. These data are used to map a diverse set of symptomatic, demographic, exposure and behavioural factors relevant to the ongoing pandemic.

Lipid droplets (LDs) and peroxisomes are both generated by budding off the endoplasmic reticulum (ER). Here, the authors show that the yeast protein Pex30 marks ER subdomains where both LD and peroxisome biogenesis occurs, and identify MCTP2 as the putative mammalian Pex30 ortholog.

A comprehensive analysis of omics data from biopsies and blood samples from more than 12,000 cases of heart, lung, liver and kidney transplants provides insights into shared mechanisms of allograft dysfunction across organs.

The nations that are most vulnerable to climate change must drive discussions of modelling, ethics and governance, argue A. Atiq Rahman, Paulo Artaxo, Asfawossen Asrat, Andy Parker and 8 co-signatories.

A spatially resolved transcriptional atlas of the mid-gestational developing human brain has been created using laser-capture microdissection and microarray technology, providing a comprehensive reference resource which also enables new hypotheses about the nature of human brain evolution and the origins of neurodevelopmental disorders.

Emerging variants of SARS-CoV-2 raise concerns about vaccine efficiency. Here, the authors present a post-hoc analysis for the ChAdOx1 nCoV-19 (AZD1222) vaccine trial in Brazil and provide efficacy against symptomatic COVID-19 caused by the Zeta (P.2) and other variants.

Mammalians rely on brown adipocytes to generate heat under cold exposure, this thermogenic function requires dynamic remodeling of the mitochondria. Here the authors identify a protein called FAM210A as a key regulator of cold-induced mitochondrial remodeling in brown adipocytes.

Improvements in European freshwater biodiversity occurred mainly before 2010 but have since plateaued, and communities downstream of dams, urban areas and cropland were less likely to experience recovery.

Vast networks of capillaries feed the brain. Hartmann et al. show that pericyte contractility is critical for maintenance of enduring capillary tone, which sets an optimized rate and distribution of blood flow through brain capillary networks.

Rebecca Fitzgerald and colleagues report whole-genome sequence analyses of 23 paired samples of Barrett's esophagus and esophageal adenocarcinoma. Their analyses of the clonal architecture of these lesions shows that copy number increases and heterogeneity persists during development of esophageal adenocarcinoma.

Analyses of mitochondrial genomes from populations in southern Africa provide evidence of a southern African origin of anatomically modern humans and a sustained occupation of the homeland before the first migrations of people appear to be driven by regional climate shifts.

The mechanism underlying the cellular entry of Zika virus is not fully understood. Here, the authors use a chemically modified virus and time-resolved proteomics to capture interacting host proteins during virus entry and identify NCAM1 as a ZIKV receptor.

A protein platform rapidly develops peptide-focused major histocompatibility complex class I binders with high specificity.

Adenosine-to-inosine editing is a form of RNA modification observed in the human brain transcriptome. Here the authors question the accuracy of utilizing postmortem samples to reflect the RNA biology of living brains. This is due to significant differences in adenosine-to-inosine editing between living and postmortem brain tissues, with most sites exhibiting higher editing levels postmortem.

Inspirational conservation scientist.