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Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

Multiple samples collected at autopsy from women with homologous recombination-deficient high-grade serous ovarian cancer highlight substantial inter- and intratumoral heterogeneity. A plethora of resistance mechanisms were identified within and between patients.

Quantitative multimodal 3D reconstruction of human pancreatic tissue at single-cell resolution reveals a high burden of multifocal, genetically heterogeneous pancreatic intraepithelial neoplasias in the normal adult pancreas.

Tuberous sclerosis complex (TSC) is a multiorgan disease that can lead to hyperactive mTORC1 due to deficient TSC1 or TSC2 protein function. Here, the authors find that despite high mTORC1 activity, TFEB localizes to the nucleus and drives lysosomal gene expression via a non-canonical Rag-dependent mechanism.

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.

Climate change will decrease Arctic Sea ice and increase light, but effects on polar ecosystems remain unclear. Here, the authors predict that warming waters and prey loss will threaten cold-water fish species and severely reduce their habitat by 2060.

Isotopic labelling and multi-omics experiments conducted in Biosphere 2 show how dry conditions reprogramme microbial metabolism.

Analyzing data of the Mexican Biobank project, a new study finds regional differences in clinically relevant genetic frequencies and presents MexVar, a publicly accessible resource designed to support ancestry-informed genetic testing.

Gene fusions are observed in many cancers but their link to tumour fitness is largely unknown. Here, transcriptomic analysis combined with pharmacological and CRISPR-Cas9 screening of cancer cell lines was used to evaluate the functional linkage between fusions and tumour fitness.

A multi-omic analysis of pancreatic cancer identifies spatially resolved, heterogeneous cell populations including transitional cell types. Analysis of primary samples identifies treatment-related changes in cross-talk between tumor and stromal cells.

Genome-wide CRISPRi screens for modulators of androgen receptor (AR) protein levels using live-cell quantitative endogenous AR fluorescence reporters identify PTGES3 as a new regulator of AR stability and function in prostate cancer.

Using a survey of over 4,000 devout Shia pilgrims across Iran and Iraq, Knox and collaborators evaluate theories about the nature of sectarian animosity and find similarities to ethno-nationalism but not transnational or religious movements.

Modern land management often assumes that past human activity shaped iconic landscapes. This study finds that climate, rather than indigenous activity, controlled fire severity in New England, with open landscapes developing after deforestation for European agriculture.

Analysis of the genomes, exomes and transcriptomes of 1,699 childhood cancers identifies 142 driver genes.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Joana Carlevaro-Fita, Andrés Lanzós et al. present the Cancer LncRNA Census (CLC), a manually curated dataset of 122 long noncoding RNAs (lncRNAs) with experimentally-validated functions in cancer based on data from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. CLC lncRNAs have unique gene features, and a number display evidence for cancer-driving functions that are conserved from humans to mice.

Non-pharmaceutical interventions for COVID-19 also reduced circulation of endemic viruses which may have led to immune waning. Here, the authors use multiplex serology data from King County, Washington, US to characterise age-specific changes in antibody levels to a range of endemic viruses during the COVID-19 pandemic.

Lung cancer etiology has largely been studied in homogenous populations of European descent. Here, targeted sequencing in African American lung adenocarcinomas finds significantly higher prevalence of PTPRTand JAK2 mutations, validated independently by whole exome sequencing, highlighting potentially clinically actionable mutations in this population.

Elizabeth Perlman and colleagues use genome-wide sequencing, RNA expression, DNA copy number and methylation analyses to characterize the genomic landscape of Wilms tumors. Their integrated analyses implicate two major classes of genetic changes in Wilms tumors that preserve the progenitor state and/or interrupt normal kidney development.

Tuberous sclerosis complex (TSC) is a rare genetic condition causing tumours with differentiation abnormalities; however the molecular mechanisms causing these defects are unclear. Here the authors show that Notch cooperates with Rheb to block cell differentiation forming a regulatory loop that could underlie TSC tumorigenesis.

Hypoimmune gene editing in human pluripotent stem cells (hPSCs) provides a promising platform for cellular therapies. Here, the authors report that CRISPR mediated deletion of ICAM-1 in hPSC-derived grafts reduces immune cell adhesion, dampens T cell activation, and protects against immune rejection.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

Wood density is an important plant trait. Data from 1.1 million forest inventory plots and 10,703 tree species show a latitudinal gradient in wood density, with temperature and soil moisture explaining variation at the global scale and disturbance also having a role at the local level.

Here, the authors present genome-wide aDNA from 138 Early Bronze Age individuals from Lower Austria. Their findings point to a patrilocal society with non-strict female exogamic practices and long-distance genetic connections across Central Europe.

Mosquitoes use olfactory cues to locate their host. Here, Riabinina et al. use genetic labelling of olfactory receptor neurons in the malaria vector Anopheles gambiaeto show that these neurons project to the antennal lobe, a known insect olfactory centre, and the subesophageal zone, a region previously linked to gustatory processing.

Association analysis identifies 65 new breast cancer risk loci, predicts target genes for known risk loci and demonstrates a strong overlap with somatic driver genes in breast tumours.

Extracellular matrix (ECM) remodeling is a hallmark of fibrosis thought to be driven by mesenchymal cells. Here, the authors discover that YAP-TEAD/LOX axis is activated in distal lung epithelial cells, which contributes to ECM remodeling in pre-clinical models of pulmonary fibrosis.

Ganguli et al. show that CDKN2A loss in Barrett’s esophagus prevents esophageal adenocarcinoma initiation by counterselecting subsequent TP53 loss and report context-dependent effects of 9p21 gene co-deletions on disease progression.

Bacterial genome evolution is shaped by epistasis, which can constrain or promote specific evolutionary paths. The authors review how integrating the effects of epistatic interactions into population-scale analyses can improve genotype–phenotype mapping and provide a deeper understanding of the complex traits that shape the microbial world.

Despite often being poorly immunogenic, some subsets of patients with hormone receptor-positive, HER2-negative (HR + /HER2-) breast cancer benefit from immunotherapy. Here, the authors present a randomised pilot clinical trial comparing a neoadjuvant run-in of either nab-paclitaxel or pembrolizumab (anti-PD-1) monotherapy, followed by the combination, in patients with stage II-III HR + /HER2- breast cancer.

In Acute Myeloid Leukemia a population of quiescent leukemic stem cells (LSCs) evade chemotherapy and initiate relapse, but what makes them grow again is unknown. Here, the authors show (i) that LSCs hijack ectopic signaling pathways to kick-start their growth and (ii) that growth can be blocked with repurposed drugs in t(8;21) AML sub-type.

A bile acid-bound structure of toxin TcdB revealed the mechanism of inhibition and guided the design of a synthetic bile acid that alleviated Clostridioides difficile infection in mice.

Analysis of exomes and transcriptomes from 100 African American patients with acute myeloid leukemia identifies ancestry-related variation in mutation profiles and survival. Refined risk classification suggests clinical relevance of these ancestry-associated differences.

This study shows that adherent cells maintain membrane tension gradients even without moving. Using a fluorescent probe, the authors reveal that actin and adhesion forces shape these gradients, providing a new view of cell mechanics.

Whole-genome sequencing is used to analyse the landscape of somatic mutation in intestinal crypts from 16 mammalian species, revealing that rates of somatic mutation inversely scale with the lifespan of the animal across species.

Engineering human microglia with a Down-syndrome-linked myeloid gene variant resists tau-induced dysfunction and protects neurons in chimeric brains, offering proof of concept for transformative microglial replacement therapies in Alzheimer’s disease.

As proof of principle, an analysis using a suite of human-aligned immunocompetent mouse models of hepatocellular carcinoma identifies a promising therapeutic candidate, cladribine, which acts in a highly effective subtype-specific manner in combination with standard-of-care therapy.

Kidney transplantation usually relies on hypothermia to safely preserve the graft. Here, the authors show that keeping kidneys at 37°C, using a machine to supply them with blood, oxygen, and nutrition, is feasible for up to 24 hours, and may be useful for testing and treating them pre-transplant.

Charles Mullighan, Stephen Hunger, Jinghui Zhang and colleagues report a genomic analysis of 264 pediatric and young adult T-lineage acute lymphoblastic leukemia (T-ALL) samples. They identify 106 candidate driver genes, 53 of which have not been described previously in pediatric T-ALL, as well as associations between mutations and disease stage or subtype.

The molecular basis for differences in immune response to SARS-CoV-2 in children and adults is still unclear. Here, the authors show that antibodies are of high binding and functional quality in children with mild or asymptomatic infection, but antibody response is delayed as compared to adults.

PPM1D is a known mediator of p53 signalling, and has been linked to treatment resistance in glioma. In this work, the authors utilise genomics, proteomics, and mouse models to determine the role of PPM1D in the development of diffuse midline glioma.

Targeted genetic dissection of tissues can be used to identify cell populations and lineages. Here the authors develop 4-hydroxytamoxifen liposomes for the localized induction of CreER^T2.

Npm1 promotes tumor formation via attenuating the integrated stress response and p53 activation in mouse WNT-driven intestinal and liver tumorigenesis.

CUT and HOX are conserved DNA binding elements prevalent in human transcription factors. Here, the authors use an integrative approach to study the mechanism of CUT-HOX cross-talk towards DNA binding by the prostate cancer target ONECUT2.

A single-cell study integrating data from lung tissues from patients with fatal COVID-19 from Malawi, the United States and Europe identifies shared and distinct immune and inflammatory mechanisms of response.

Our current understanding of neurofibromatosis type 1 (NF1) is based on patients ascertained through phenotype-first approaches, which estimate a low prevalence at 1 in 3,000. Here, the authors leverage a genotype-first approach in multiple large patient cohorts to demonstrate an unexpectedly high prevalence (1 in 1,286) of NF1 pathogenic variants with distinct disease associations.

A genomic and transcriptomic analysis identifies molecular features associated with long-term survival in ovarian cancer. Exceptional survival was heterogeneous across the cohort, suggesting that it is likely the function of multiple cell-intrinsic and microenvironmental factors working in combination.

Accurate estimates of tropical forest carbon stocks are needed for policies to reduce emissions from loss of forests. By looking at a central area in the Congo Basin, Kearsleyet al.find that inconsistencies in height–diameter relationships across Central Africa cause overestimations between regions.

A meta-analysis synthesizes the range of effects of megafauna on ecosystems, finding that megafauna significantly increase ecosystem heterogeneity and impact a wide range of ecosystem properties by altering soil nutrient availability, promoting open vegetation structure and reducing the abundance of smaller animals.