Current rates of habitat and biodiversity loss, and the threat they pose to ecological and economic productivity, would be considered a global emergency even if they were not occurring during a period of rapid anthropogenic climate change. Diversity at all levels of biological organization, both within and among species, and across genomes and communities, is critical for the resilience of the world's ecosystems in the face of such change. However, it remains an urgent scientific challenge to understand how biodiversity underpins these ecological outputs, how patterns of biodiversity are being affected by current threats, and how and where such biodiversity contributes most directly to human economies, well-being and social justice. In addition, even with such scientific understanding, there is a pressing need for societies to incorporate biodiversity protection into their economies and governance, and to stop subsidizing the loss of humanity's future prosperity for short-term private benefit. We highlight key issues and ways forward in these areas, inspired by the research and career of Dame Georgina Mace FRS, and by our discussions during the Royal Society meeting of June 2023. This article is part of the discussion meeting issue 'Bending the curve towards nature recovery: building on Georgina Mace's legacy for a biodiverse future'.

Decomposition of plant litter is a key ecological process in streams, whose contribution to the global carbon cycle is large relative to their extent on Earth. We examined the mechanisms underlying the temperature sensitivity (TS) of instream decomposition and forecast effects of climate warming on this process. Comparing data from 41 globally distributed sites, we assessed the TS of microbial and total decomposition using litter of nine plant species combined in six mixtures. Microbial decomposition conformed to the metabolic theory of ecology and its TS was consistently higher than that of total decomposition, which was higher than found previously. Litter quality influenced the difference between microbial and total decomposition, with total decomposition of more recalcitrant litter being more sensitive to temperature. Our projections suggest that (i) warming will enhance the microbial contribution to decomposition, increasing CO2 outgassing and intensifying the warming trend, especially in colder regions; and (ii) riparian species composition will have a major influence on this process.

This manuscript describes the collation of available water quality data from the freshwater reaches of surface streams within the Great Barrier Reef catchment area, northeastern Australia. This compilation represents one of the most comprehensive online datasets for historical tropical and subtropical freshwater quality around the world. We document the criteria for selection of the data and associated publications as well as the processes of data cleaning used to produce a qualitative assessment of the datasets. The final compilation includes 41 individual datasets that collectively report 466 sites and contain over 26,000 discrete water quality sample records totaling more than 350,000 unique water quality results. Finally, we outline the nuances of the data that end users need to take into account when combining them for spatial and temporal analyses. The dataset ensures that these valuable water quality data collected over the past four decades are preserved for the next generations of researchers, practitioners, management agencies and policy makers.

The population structure of the malaria parasite Plasmodium falciparum can reveal underlying demographic and adaptive evolutionary processes. Here, we analyse population structure in 4,376 P. falciparum genomes from 21 countries across Africa. We identified a strongly differentiated cluster of parasites, comprising ∼1.2% of samples analysed, geographically distributed over 13 countries across the continent. Members of this cluster, named AF1, carry a genetic background consisting of a large number of highly differentiated variants, rarely observed outside this cluster, at a multitude of genomic loci distributed across most chromosomes. At these loci, the AF1 haplotypes appear to have common ancestry, irrespective of the sampling location; outside the shared loci, however, AF1 members are genetically similar to their sympatric parasites. AF1 parasites sharing up to 23 genomic co-inherited regions were found in all major regions of Africa, at locations over 7,000 km apart. We coined the term cryptotype to describe a complex common background which is geographically widespread, but concealed by genomic regions of local origin. Most AF1 differentiated variants are functionally related, comprising structural variations and single nucleotide polymorphisms in components of the MSP1 complex and several other genes involved in interactions with red blood cells, including invasion and erythrocyte antigen export. We propose that AF1 parasites have adapted to some as yet unidentified evolutionary niche, by acquiring a complex compendium of interacting variants that rarely circulate separately in Africa. As the cryptotype spread across the continent, it appears to have been maintained mostly intact in spite of recombination events, suggesting a selective advantage. It is possible that other cryptotypes circulate in Africa, and new analysis methods may be needed to identify them.### Competing Interest StatementThe authors have declared no competing interest.

Plasmodium vivax elimination is challenged by dormant liver stages (hypnozoites) that can reactivate months after initial infection resulting in relapses. Relapsing infections confound antimalarial clinical efficacy trials due to the inability to distinguish between recurrences arising from blood-stage treatment failure (recrudescence), reinfection or relapse. Genetic relatedness of paired parasite isolates, measured by identity-by-descent (IBD), can provide important information on whether individuals have had single or multiple mosquito inoculations, thus informing on recurrence origin. We developed a high-throughput amplicon sequencing assay comprising 93 multi-SNP (microhaplotype) markers to determine IBD between P. vivax clinical isolates. The assay was evaluated in 745 global infections, including 128 infection pairs from a randomized controlled trial (RCT) (ClinicalTrials.gov NCT01680406). Simulations demonstrate low error in pairwise IBD estimation at the panel (RMSE < 0.12) and IBD-based networks illustrate strong clustering by geography. IBD analysis in the RCT demonstrates a lower frequency of suspected relapses or recrudescence in patients treated with primaquine compared to those without primaquine; the impact is greater when paired with chloroquine than with artemether-lumefantrine. Our results demonstrate the potential to derive new information on P. vivax treatment and transmission using IBD generated by amplicon sequencing data that can be further improved with time-to-event models.

Motivation: Freshwater ecosystems have been heavily impacted by land-use changes, but data syntheses on these impacts are still limited. Here, we compiled a global database encompassing 241 studies with species abundance data (from multiple biological groups and geographic locations) across sites with different land-use categories. This compilation will be useful for addressing questions regarding land-use change and its impact on freshwater biodiversity. Main Types of Variables Contained: The database includes metadata of each study, sites location, sample methods, sample time, land-use category and abundance of each taxon. Spatial Location and Grain: The database contains data from across the globe, with 85% of the sites having well-defined geographical coordinates. Major Taxa and Level of Measurement: The database covers all major freshwater biological groups including algae, macrophytes, zooplankton, macroinvertebrates, fish and amphibians.

Background Genetic surveillance of Plasmodium falciparum (Pf) is an important tool for tracking antimalarial resistant strains, informing decision-making by National Malaria Control Programmes (NMCPs). Here, we present an analysis of 5,754 samples collected by the GenRe-Mekong project, in collaboration with NMCPs in the Greater Mekong Subregion (GMS), powered by new user-friendly visualization tools developed to translate genomic data into accessible actionable information. Methods Samples collected from patients presenting at public health facilities between 2017 and 2022 were genotyped using the SpotMalaria platform. Output data included genotypes for markers of antimalarial resistance, and genetic barcodes for analysis of relatedness. We developed the grcMalaria R package, which allows users to specify sample selection criteria, and produce geographical maps of prevalence, diversity and relatedness. It also identifies circulating parasite clusters, characterizing their drug resistance profile and mapping their spread. Results Since 2020, a rapid reduction in Pf incidence was observed, alongside a decline of the KEL1/PLA1 lineage resistant to dihydroartemisinin-piperaquine (DHA-PPQ), previously dominant in the eastern GMS. The frequency of plasmepsin2/3 amplifications, associated with piperaquine resistance, dropped from 62% in 2017-2019 to 2% in the first half of 2022. This coincided with a switch in frontline therapy, away from DHA-PPQ, in Cambodia, Thailand, and Vietnam. Artemisinin resistance levels remained high, with a regional prevalence of 89% in 2022. No evidence of emerging mefloquine resistance was found. Conclusion Routine genetic surveillance of Pf can reveal changes in parasite populations in response to public health interventions, especially when its results are translated into intuitive graphical visualizations, providing actionable information for NMCPs. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Bill & Melinda Gates Foundation and by The Global Fund to Fight AIDS, Tuberculosis and Malaria. This research was funded in part by the Wellcome Trust. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approvals were obtained both from ethics committees in the country of collection, and from the Oxford Tropical Research Ethics Committee (OxTREC) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon request and will be made publicly available at upon publication in a peer reviewed journal.

Animal-mediated pollination is a key ecosystem service required to some extent by almost three-quarters of the leading human food crops in global food production. Anthropogenic pressures such as habitat loss and land-use intensification are causing shifts in ecological community composition, potentially resulting in declines in pollination services and impacting crop production. Previous research has often overlooked interspecific differences in pollination contribution, yet such differences mean that biodiversity declines will not necessarily negatively impact pollination. Here, we use a novel species-level ecosystem service contribution matrix along with mixed-effects models to explore how groups of terrestrial species who contribute differently to crop pollination respond globally to land-use type, land-use intensity, and availability of natural habitats in the surrounding landscape. We find that the species whose contribution to crop pollination is higher generally respond less negatively (and in some cases positively) to human disturbance of land, compared to species that contribute less or not at all to pollination. This result may be due to these high-contribution species being less sensitive to anthropogenic land conversions, which has led humans to being more reliant on them for crop pollination. However, it also suggests that there is potential for crop pollination to be resilient in the face of anthropogenic land conversions. With such a high proportion of food crops requiring animal-mediated pollination to some extent, understanding how anthropogenic landscapes impact ecological communities and the consequences for pollination is critical for ensuring food security.

BACKGROUND:Metazoans inherited genes from unicellular ancestors that perform essential biological processes such as cell division, metabolism, and protein translation. Multicellularity requires careful control and coordination of these unicellular genes to maintain tissue integrity and homeostasis. Gene regulatory networks (GRNs) that arose during metazoan evolution are frequently altered in cancer, resulting in over-expression of unicellular genes. We propose that an imbalance in co-expression of unicellular (UC) and multicellular (MC) genes is a driving force in cancer. RESULTS:We combine gene co-expression analysis to infer changes to GRNs in cancer with protein sequence conservation data to distinguish genes with UC and MC origins. Co-expression networks created using RNA sequencing data from 31 tumor types and normal tissue samples are divided into modules enriched for UC genes, MC genes, or mixed UC-MC modules. The greatest differences between tumor and normal tissue co-expression networks occur within mixed UC-MC modules. MC and UC genes not commonly co-expressed in normal tissues form distinct co-expression modules seen only in tumors. The degree of rewiring of genes within mixed UC-MC modules increases with tumor grade and stage. Mixed UC-MC modules are enriched for somatic mutations in cancer genes, particularly amplifications, suggesting an important driver of the rewiring observed in tumors is copy number changes. CONCLUSIONS:Our study shows the greatest changes to gene co-expression patterns during tumor progression occur between genes of MC and UC origins, implicating the breakdown and rewiring of metazoan gene regulatory networks in cancer development and progression.

Background: A shift toward human diets that include more fruit and vegetables, and less meat is a potential pathway to improve public health and reduce food system-related greenhouse gas emissions. Associated changes in land use could include conversion of grazing land into horticulture, which makes more efficient use of land per unit of dietary energy and frees-up land for other uses. Methods: Here we use Great Britain as a case study to estimate potential impacts on biodiversity from converting grazing land to a mixture of horticulture and natural land covers by fitting species distribution models for over 800 species, including pollinating insects and species of conservation priority. Results: Across several land use scenarios that consider the current ratio of domestic fruit and vegetable production to imports, our statistical models suggest a potential for gains to biodiversity, including a tendency for more species to gain habitable area than to lose habitable area. Moreover, the models suggest that climate change impacts on biodiversity could be mitigated to a degree by land use changes associated with dietary shifts. Conclusions: Our analysis demonstrates that options exist for changing agricultural land uses in a way that can generate win-win-win outcomes for biodiversity, adaptation to climate change and public health.

Trees structure the Earth's most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1-6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth's 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world's most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.

The high rates of protein synthesis and processing render multiple myeloma (MM) cells vulnerable to perturbations in protein homeostasis. The induction of proteotoxic stress by targeting protein degradation with proteasome inhibitors (PIs) has revolutionized the treatment of MM. However, resistance to PIs is inevitable and represents an ongoing clinical challenge. Our first-in-human study of the selective inhibitor of RNA polymerase I transcription of ribosomal RNA genes, CX-5461, has demonstrated a potential signal for anti-tumor activity in three of six heavily pre-treated MM patients. Here, we show that CX-5461 has potent anti-myeloma activity in PI-resistant MM preclinical models in vitro and in vivo. In addition to inhibiting ribosome biogenesis, CX-5461 causes topoisomerase II trapping and replication-dependent DNA damage, leading to G2/M cell-cycle arrest and apoptotic cell death. Combining CX-5461 with PI does not further enhance the anti-myeloma activity of CX-5461 in vivo. In contrast, CX-5461 shows synergistic interaction with the histone deacetylase inhibitor panobinostat in both the Vk∗MYC and the 5T33-KaLwRij mouse models of MM by targeting ribosome biogenesis and protein synthesis through distinct mechanisms. Our findings thus provide strong evidence to facilitate the clinical development of targeting the ribosome to treat relapsed and refractory MM.

Land use change is crucial to addressing the existential threats of climate change and biodiversity loss while enhancing food security [M. Zurek et al., Science 376, 1416-1421 (2022)]. The interconnected and spatially varying nature of the impacts of land use change means that these challenges must be addressed simultaneously [H.-O. Pörtner et al., Science 380, eabl4881 (2023)]. However, governments commonly focus on single issues, incentivizing land use change via "Flat-Rate" subsidies offering constant per hectare payments, uptake of which is determined by the economic circumstances of landowners rather than the integrated environmental outcomes that will be delivered [G. Q. Bull et al., Forest Policy Econ. 9, 13-31 (2006)]. Here, we compare Flat-Rate subsidies to two alternatives: "Land Use Scenario" allocation of subsidies through consultation across stakeholders and interested parties; and a "Natural Capital" approach which targets subsidies according to expected ecosystem service response. This comparison is achieved by developing a comprehensive decision support system, integrating new and existing natural, physical, and economic science models to quantify environmental, agricultural, and economic outcomes. Applying this system to the United Kingdom's net zero commitment to increase carbon storage via afforestation, we show that the three approaches result in significantly different outcomes in terms of where planting occurs, their environmental consequences, and economic costs and benefits. The Flat-Rate approach actually increases net carbon emissions while Land Use Scenario allocation yields poor economic outcomes. The Natural Capital targeted approach outperforms both alternatives, providing the highest possible social values while satisfying net zero commitments.

Artemisinin partial resistance (ART-R) in Plasmodium falciparum is one of the most pressing threats to global malaria control. Over the last two decades, ART-R has spread widely across Southeast Asia, compromising public health strategies and hindering elimination efforts. As of 2024, ART-R has now emerged in East Africa, with the potential to dramatically increase human mortality in the region. Mitigating the spread of ART-R requires detailed genomic surveillance of point mutations in the kelch13 gene, the primary determinant of resistance to artemisinin derivatives. Although extensive surveillance data on these markers is available, it is distributed across many literature studies and open databases. In this literature review, we aggregate publicly available spatiotemporal data for 112,933 P. falciparum samples between 1980 - 2023 into a single resource, providing the most comprehensive overview of kelch13 markers to date. By synthesising insights from these samples over a global scale, we outline the history and current status of kelch13 mutations associated with ART-R, with particular reference to their emergence in Southeast Asia and recent emergence in East and Northeast Africa. Concerningly, we find their recent increases in frequency in these areas of Africa are comparable to those observed in Southeast Asia 10-15 years ago. We review several factors that may influence the spread of ART-R going forwards, such as fitness costs, treatment strategies, and local epidemiological dynamics, before articulating possible scenarios on how resistance may spread in Africa in coming years. In summary, this review provides a unified, comprehensive account of how the situation of ART-R has unfolded globally so far, highlighting insights both for researchers in the field and public health bodies which aim to reduce its negative effects. More broadly, we highlight the critical role genomic surveillance has had, and will continue to have in combating the spread of ART-R. ### Competing Interest Statement The authors have declared no competing interest.

MOTIVATION:Monitoring the genomic evolution of Plasmodium falciparum-the most widespread and deadliest of the human-infecting malaria species-is critical for making decisions in response to changes in drug resistance, diagnostic test failures, and vaccine effectiveness. The MalariaGEN data resources are the world's largest whole genome sequencing databases for Plasmodium parasites. The size and complexity of such data is a barrier to many potential end users in both public health and academic research. A user-friendly method for accessing and exploring data on the genetic variation of P. falciparum would greatly enable efforts in studying and controlling malaria. RESULTS:We developed Pf-HaploAtlas, a web application enabling exploratory data analysis of genomic variation without requiring advanced technical expertise. The app provides analysis-ready data catalogues and visualizations of amino acid haplotypes for all 5102 core P. falciparum genes. Pf-HaploAtlas facilitates comprehensive spatial and temporal exploration of genes and variants of interest by using data from 16 203 samples, from 33 countries, and spread between the years 1984 and 2018. The scope of Pf-HaploAtlas will expand with each new MalariaGEN Plasmodium data release. AVAILABILITY AND IMPLEMENTATION:Pf-HaploAtlas is available online for public use at https://apps.malariagen.net/pf-haploatlas, which allows users to download the underlying amino acid haplotype data for further analyses, and its source code is freely available on GitHub under the MIT licence at https://github.com/malariagen/pf-haploatlas.

By embedding a spatially explicit ecosystem services modelling tool within a policy simulator we examine the insights that natural capital analysis can bring to the design of policies for nature recovery. Our study is illustrated through a case example of policies incentivising the establishment of new natural habitat in England. We find that a policy mirroring the current practice of offering payments per hectare of habitat creation fails to break even, delivering less value in improved flows of ecosystem services than public money spent and only 26% of that which is theoretically achievable. Using optimization methods, we discover that progressively more efficient outcomes are delivered by policies that optimally price activities (34%), quantities of environmental change (55%) and ecosystem service value flows (81%). Further, we show that additionally attaining targets for unmonetized ecosystem services (in our case, biodiversity) demands trade-offs in delivery of monetized services. For some policy instruments it is not even possible to achieve the targets. Finally, we establish that extending policy instruments to offer payments for unmonetized services delivers target-achieving and value-maximizing policy designs. Our findings reveal that policy design is of first-order importance in determining the efficiency and efficacy of programmes pursuing nature recovery. This article is part of the theme issue ‘Bringing nature into decision-making’.

The mopane worm (Gonimbrasia belina) is an edible insect distributed across southern Africa. As a culturally important source of food, the mopane worm provides nutrition, livelihoods and improves wellbeing for rural communities across its range. However, this is strong evidence that insect populations are declining worldwide, and climate change is likely to cause many insect species to shift in their distributions. For these reasons, we aimed to model how the ecosystem service benefits of the mopane worm are likely to change in the coming decades. We modelled the distribution of the mopane worm under two contrasting climate change scenarios (RCPs 4.5 and 8.5). Moreover, given that the mopane worm shows strong interactions with other species, particularly trees, we incorporated biotic interactions in our models using a Bayesian network. Our models project significant contraction across the species’ range, with up to 70% decline in habitat by the 2080s. Botswana and Zimbabwe are predicted to be the most severely impacted countries, with almost all habitat in Botswana and Zimbabwe modelled to be lost by the 2080s. Decline of mopane worm habitat would likely have negative implications for the health of people in rural communities due to loss of an important source of protein as well as household income provided by their harvest. Biogeographic shifts therefore have potential to exacerbate food insecurity, socio-economic inequalities, and gender imbalance (women are the main harvesters), with cascading effects that most negatively impact poor rural communities dependent on natural resources.

Ethiopia has the greatest burden of Plasmodium vivax in Africa, but little is known about the epidemiological landscape of parasites across the country. We analysed the genomic diversity of 137 P. vivax isolates collected nine Ethiopian districts from 2012 to 2016. Signatures of selection were detected by cross-country comparisons with isolates from Thailand ( n = 104) and Indonesia ( n = 111), representing regions with low and high chloroquine resistance respectively. 26% (35/137) of Ethiopian infections were polyclonal, and 48.5% (17/35) of these comprised highly related clones (within-host identity-by-descent > 25%), indicating frequent co-transmission and superinfection. Parasite gene flow between districts could not be explained entirely by geographic distance, with economic and cultural factors hypothesised to have an impact on connectivity. Amplification of the duffy binding protein gene ( pvdbp1 ) was prevalent across all districts (16–75%). Cross-population haplotype homozygosity revealed positive selection in a region proximal to the putative chloroquine resistance transporter gene ( pvcrt-o ). An S25P variant in amino acid transporter 1 ( pvaat1 ), whose homologue has recently been implicated in P. falciparum chloroquine resistance evolution, was prevalent in Ethiopia (96%) but not Thailand or Indonesia (35–53%). The genomic architecture in Ethiopia highlights circulating variants of potential public health concern in an endemic setting with evidence of stable transmission.