ABSTRACT
Transmissible cancers are malignant cell lineages that spread clonally between individuals. Several such cancers, termed bivalve transmissible neoplasia (BTN), induce leukemia-like disease in marine bivalves. This is the case of BTN lineages affecting the common cockle, Cerastoderma edule, which inhabits the Atlantic coasts of Europe and northwest Africa. To investigate the evolution of cockle BTN, we collected 6,854 cockles, diagnosed 390 BTN tumors, generated a reference genome and assessed genomic variation across 61 tumors. Our analyses confirmed the existence of two BTN lineages with hemocytic origins. Mitochondrial variation revealed mitochondrial capture and host co-infection events. Mutational analyses identified lineage-specific signatures, one of which likely reflects DNA alkylation. Cytogenetic and copy number analyses uncovered pervasive genomic instability, with whole-genome duplication, oncogene amplification and alkylation-repair suppression as likely drivers. Satellite DNA distributions suggested ancient clonal origins. Our study illuminates long-term cancer evolution under the sea and reveals tolerance of extreme instability in neoplastic genomes.
Subject(s)
Bivalvia , Cardiidae , Leukemia , Neoplasms , Animals , Humans , Cardiidae/genetics , Clonal EvolutionABSTRACT
Climate change is expected to increase the number of days with meteorological conditions conducive to uncontrollable wildfires. Thus, it is necessary to strengthen the capacity of wildfire-prone regions to minimize the adverse impacts of these wildfires by creating resilient landscapes. In this paper we develop a participatory multi-criteria evaluation to identify and map landscape values and prioritize areas according to these values in the Montseny Biophere Reserve (Catalonia, NE Spain). Then, we draft a wildfire management strategy to protect the areas that have been prioritized through selected fuel reduction sectors that would reduce wildfire intensity. Finally, we emphasize the added value of a participatory multi-criteria evaluation in the adaptation to and management of expected megafires. We find that the integration of landscape values through participatory multi-criteria evaluation has the potential to alter wildfire management strategies by adding fuel reduction sectors and changing their implementation order. However, the implementation of the planned fuel reduction treatments faces socioeconomic and institutional barriers that call for a deeper engagement with transdisciplinary project design and transformative science.
Subject(s)
Wildfires , Acclimatization , Climate Change , SpainABSTRACT
Most cancers are characterized by the somatic acquisition of genomic rearrangements during tumour evolution that eventually drive the oncogenesis. Here, using multiplatform sequencing technologies, we identify and characterize a remarkable mutational mechanism in human hepatocellular carcinoma caused by Hepatitis B virus, by which DNA molecules from the virus are inserted into the tumour genome causing dramatic changes in its configuration, including non-homologous chromosomal fusions, dicentric chromosomes and megabase-size telomeric deletions. This aberrant mutational mechanism, present in at least 8% of all HCC tumours, can provide the driver rearrangements that a cancer clone requires to survive and grow, including loss of relevant tumour suppressor genes. Most of these events are clonal and occur early during liver cancer evolution. Real-time timing estimation reveals some HBV-mediated rearrangements occur as early as two decades before cancer diagnosis. Overall, these data underscore the importance of characterising liver cancer genomes for patterns of HBV integration.
Subject(s)
Carcinoma, Hepatocellular/genetics , DNA, Viral , Genome, Human , Hepatitis B virus/genetics , Liver Neoplasms/genetics , Carcinoma, Hepatocellular/virology , Gene Expression Regulation, Neoplastic , Humans , Virus Integration , Whole Genome SequencingABSTRACT
Increasing evidence-synthesized in this paper-shows that economic growth contributes to biodiversity loss via greater resource consumption and higher emissions. Nonetheless, a review of international biodiversity and sustainability policies shows that the majority advocate economic growth. Since improvements in resource use efficiency have so far not allowed for absolute global reductions in resource use and pollution, we question the support for economic growth in these policies, where inadequate attention is paid to the question of how growth can be decoupled from biodiversity loss. Drawing on the literature about alternatives to economic growth, we explore this contradiction and suggest ways forward to halt global biodiversity decline. These include policy proposals to move beyond the growth paradigm while enhancing overall prosperity, which can be implemented by combining top-down and bottom-up governance across scales. Finally, we call the attention of researchers and policy makers to two immediate steps: acknowledge the conflict between economic growth and biodiversity conservation in future policies; and explore socioeconomic trajectories beyond economic growth in the next generation of biodiversity scenarios.
ABSTRACT
Drug-decorated nanoparticles (DDNPs) have important medical applications. The current work combined Perturbation Theory with Machine Learning and Information Fusion (PTMLIF). Thus, PTMLIF models were proposed to predict the probability of nanoparticle-compound/drug complexes having antimalarial activity (against Plasmodium). The aim is to save experimental resources and time by using a virtual screening for DDNPs. The raw data was obtained by the fusion of experimental data for nanoparticles with compound chemical assays from the ChEMBL database. The inputs for the eight Machine Learning classifiers were transformed features of drugs/compounds and nanoparticles as perturbations of molecular descriptors in specific experimental conditions (experiment-centered features). The resulting dataset contains 107 input features and 249,992 examples. The best classification model was provided by Random Forest, with 27 selected features of drugs/compounds and nanoparticles in all experimental conditions considered. The high performance of the model was demonstrated by the mean Area Under the Receiver Operating Characteristics (AUC) in a test subset with a value of 0.9921 ± 0.000244 (10-fold cross-validation). The results demonstrated the power of information fusion of the experimental-centered features of drugs/compounds and nanoparticles for the prediction of nanoparticle-compound antimalarial activity. The scripts and dataset for this project are available in the open GitHub repository.
ABSTRACT
Participatory planning networks made of government agencies, stakeholders, citizens and scientists are receiving attention as a potential pathway to build resilient landscapes in the face of increased wildfire impacts due to suppression policies and land-use and climate changes. A key challenge for these networks lies in incorporating local knowledge and social values about landscape into operational wildfire management strategies. As large wildfires overcome the suppression capacity of the fire departments, such strategies entail difficult decisions about intervention priorities among different regions, values and socioeconomic interests. Therefore there is increasing interest in developing tools that facilitate decision-making during emergencies. In this paper we present a method to democratize wildfire strategies by incorporating social values about landscape in both suppression and prevention planning. We do so by reporting and critically reflecting on the experience from a pilot participatory process conducted in a region of Catalonia (Spain). There, we built a network of researchers, practitioners and citizens across spatial and governance scales. We combined knowledge on expected wildfires, landscape co-valuation by relevant actors, and citizen participation sessions to design a wildfire strategy that minimized the loss of social values. Drawing on insights from political ecology and transformation science, we discuss what the attempt to democratize wildfire strategies entails in terms of power relationships and potential for social-ecological transformation. Based on our experience, we suggest a trade-off between current wildfire risk levels and democratic management in the fire-prone regions of many western countries. In turn, the political negotiation about the landscape effects of wildfire expert knowledge is shown as a potential transformation pathway towards lower risk landscapes that can re-define agency over landscape and foster community re-learning on fire. We conclude that democratizing wildfire strategies ultimately entails co-shaping the landscapes and societies of the future.