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The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Humans alter the daily timing of animal activity, potentially reshaping predator–prey interactions. This meta-analysis reveals that larger species tend to “lose” under human disturbance, with large predators overlapping less with their prey, and large prey overlapping more with their predators.

Across a global dataset of over 11,000 naturalized alien plant species, the authors find that species are likely to naturalize both in regions with climates and floras similar to those in their native ranges, and in regions with a lower diversity or stronger human impact than in their native range.

How landscapes are arranged affects soil pathogenic fungi worldwide. The authors reveal the global pattern and pronounced scale-dependency of landscape complexity and land-cover quantity on soil pathogenic fungal diversity.

Sears and colleagues found that ongoing replication stress pathways and T cell clonal responses differentiate liver and lung recurrence and are associated with different clinical outcomes in the context of pancreatic ductal adenocarcinoma.

Compiling data on floral introductions and European colonial history of regions worldwide, the authors find that compositional similarity of floras is higher than expected among regions once occupied by the same empire and similarity increases with the length of time the region was occupied by that empire.

A NutNet experiment in 57 grasslands across six continents shows that when herbivores are excluded from grasslands with a long coevolutionary history of grazing plant diversity is reduced, while in grasslands without a long grazing history the evolutionary history of the plant species regulates the response of plant diversity.

Humans have altered plant biogeography by introducing species from one region to another, but an analysis of how naturalized plant species affect the uniqueness of regional floras around the world was missing. This study presents an analysis using data from native and naturalized alien floras in 658 regions, finding strong taxonomic and phylogenetic floristic homogenization overall.

Antibiotic therapy can lead to pathogen clearance, but also to alterations in the gut microbiota and systemic immune responses. Here, the authors analyze data from patients with tuberculosis and healthy subjects to show that pathogen clearance and gut microbiota alterations are independently associated with antibiotic-induced changes of the inflammatory response of active tuberculosis.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Secretory IgA plays vital roles interfacing between the host immune system and the resident microbiota at the mucosal surface. Here the authors explore the effect of dietary protein on the production of secretory IgA, driven by the production of extracellular vesicles by the intestinal microbiota.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Yakut communities, with Trans-Baikal admixture during the Mongol expansion, preserved genomic diversity and oral microbiomes despite the Russian conquest, which introduced cereals, pathogens and Christianity, whereas marital practices preserved low consanguinity except in one late case of traditional shamanism.

Neoadjuvant therapies with dual anti-HER2 blockade have proven effective in HER2⁺ breast cancer treatment. Here, the authors develop a score that integrates antigen receptor repertoire features and clinical parameters to predict prognosis after anti-HER2 neoadjuvant treatments.

Understanding the emergence, evolution, and transmission of antibiotic resistance genes (ARGs) is essential to combat antimicrobial resistance. Here, Munk et al. analyse ARGs in hundreds of sewage samples from 101 countries and describe regional patterns, diverse genetic environments of common ARGs, and ARG-specific transmission patterns.

This study used the case of summer 2018 in London to show that rooftop photovoltaics could have reduced heat-related mortality by 12% while cool roofs could have reduced it by 32%. In addition, rooftop photovoltaics generate up to 20 TWh of electricity.

Eutrophication has been shown to weaken diversity-stability relationships in grasslands, but it is unclear whether the effect depends on scale. Analysing a globally distributed network of grassland sites, the authors show a positive role of beta diversity and spatial asynchrony as drivers of stability but find that nitrogen enrichment weakens the diversity-stability relationships at different spatial scales.

Human-driven movements and extinctions of species have made plant communities across biomes more homogenous. Here the authors quantify plant vascular species and phylogenetic homogenization across the globe, finding that non-native species naturalisations have been a major driver.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A prospective analysis of gut microbiome signatures in patients treated with neoadjuvant immunocheckpoint blockade for high risk resectable metastatic melanoma identifies new links between microbiota signatures, dietary intake and systemic inflammation in shaping the response and toxicity to immunotherapy.

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.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Patients with partial recombination-activating gene (RAG) deficiency (pRD) present variable late-onset autoimmune clinical phenotypes. Walter and colleagues identified a restricted primary B cell antigen receptor repertoire enriched for autoreactivity and clonal persistence in pRD. They described dysregulated B cell maturation with expansion of T-bet⁺ B cells revealing how RAG impacts stringency of tolerance and B cell fate in the periphery.

Combination of immune checkpoint inhibitors with chemoradiation is now standard of care for patients with locally advanced cervical cancer (LACC). Here, the authors report the results of a phase I trial of neoadjuvant vs concurrent atezolizumab (anti-PD-L1) with chemoradiation for LACC.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

As anyone who has ever spent any time in California can attest, much public attention is being focused on the great earthquake-prediction debate. Unfortunately, this attention focuses on deterministic predictions on the day-to-week timescale. But as some of the participants in this debate have pointed out^1,2 current efforts to identify reliable short-term precursors to large earthquakes have been largely unsuccessful, suggesting that earthquakes are such a complicated process that reliable (and observable) precursors might not exist. That is not to say that earthquakes do not have some 'preparatory phase', but rather that this phase might be not be consistently observable by geophysicists on the surface. But does this mean that all efforts to determine the size, timing and locations of future earthquakes are fruitless? Or are we being misled by human scales of time and distance?

Analysing >1,700 inventory plots from the Amazon Tree Diversity Network, the authors show that the majority of Amazon tree species can occupy floodplains and that patterns of species turnover are closely linked to regional flood patterns.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Dietary protein influences metabolic health and ageing. Here Solon-Biet et al. show that, rather than having a direct toxic effect, dietary branched-chain amino acids (BCAAs) appear to induce hyperphagia, owing to an imbalance between BCAAs and other amino acids, which reduces lifespan as a consequence of obesity.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

The dietary factors causing varying intergenerational responses are not fully identified. Here, the authors show that the relative proportion of protein, fats, and carbohydrates in paternal diets before conception differentially influences the phenotype of the next-generation offspring on energy metabolism and behaviour.

This study combines ethnobotanical and epidemiological data to understand how social networks of seed exchange influence the genetic structure of the African cassava mosaic virus in Gabon. Results reveal contrasted patterns of viral diversity in patrilineal and matrilineal communities, consistent with cultural differences in modes of seed exchange.

CRISPR activation (CRISPRa) can target select genes and, rather than being used to delete them, can be used to activate their expression. Chen and colleagues use a CRISPRa-based approach to drive the expression of multiple endogenous genes in tumors and presentation of the antigens encoded, thus enhancing antitumor immune responses.

This modelling study integrates comprehensive regional plant inventories, environmental conditions and palaeogeographical reconstructions to assess the relative roles of environmental filtering and dispersal barriers in shaping global seed plant diversity, demonstrating that environmental filtering has a persistent effect on species distribution patterns across evolutionary timescales.