Refine
Document Type
- Article (3)
Language
- English (3)
Has Fulltext
- yes (3)
Is part of the Bibliography
- no (3)
Keywords
- Agroecology (1)
- Biota (1)
- Cancer models (1)
- Chemicals of emerging concern (1)
- Epidemiology (1)
- Freshwater ecology (1)
- Genetic engineering (1)
- Leukaemia (1)
- Occurrence (1)
- Risk assessment (1)
Institute
Schistosomiasis is a severe neglected tropical disease caused by trematodes and transmitted by freshwater snails. Snails are known to be highly tolerant to agricultural pesticides. However, little attention has been paid to the ecological consequences of pesticide pollution in areas endemic for schistosomiasis, where people live in close contact with non-sanitized freshwaters. In complementary laboratory and field studies on Kenyan inland areas along Lake Victoria, we show that pesticide pollution is a major driver in increasing the occurrence of host snails and thus the risk of schistosomiasis transmission. In the laboratory, snails showed higher insecticide tolerance to commonly found pesticides than associated invertebrates, in particular to the neonicotinoid Imidacloprid and the organophosphate Diazinon. In the field, we demonstrated at 48 sites that snails were present exclusively in habitats characterized by pesticide pollution and eutrophication. Our analysis revealed that insensitive snails dominated over their less tolerant competitors. The study shows for the first time that in the field, pesticide concentrations considered “safe” in environmental risk assessment have indirect effects on human health. Thus we conclude there is a need for rethinking the environmental risk of low pesticide concentrations and of integrating agricultural mitigation measures in the control of schistosomiasis.
In vivo inducible reverse genetics in patients' tumors to identify individual therapeutic targets
(2021)
High-throughput sequencing describes multiple alterations in individual tumors, but their functional relevance is often unclear. Clinic-close, individualized molecular model systems are required for functional validation and to identify therapeutic targets of high significance for each patient. Here, we establish a Cre-ERT2-loxP (causes recombination, estrogen receptor mutant T2, locus of X-over P1) based inducible RNAi- (ribonucleic acid interference) mediated gene silencing system in patient-derived xenograft (PDX) models of acute leukemias in vivo. Mimicking anti-cancer therapy in patients, gene inhibition is initiated in mice harboring orthotopic tumors. In fluorochrome guided, competitive in vivo trials, silencing of the apoptosis regulator MCL1 (myeloid cell leukemia sequence 1) correlates to pharmacological MCL1 inhibition in patients´ tumors, demonstrating the ability of the method to detect therapeutic vulnerabilities. The technique identifies a major tumor-maintaining potency of the MLL-AF4 (mixed lineage leukemia, ALL1-fused gene from chromosome 4) fusion, restricted to samples carrying the translocation. DUX4 (double homeobox 4) plays an essential role in patients’ leukemias carrying the recently described DUX4-IGH (immunoglobulin heavy chain) translocation, while the downstream mediator DDIT4L (DNA-damage-inducible transcript 4 like) is identified as therapeutic vulnerability. By individualizing functional genomics in established tumors in vivo, our technique decisively complements the value chain of precision oncology. Being broadly applicable to tumors of all kinds, it will considerably reinforce personalizing anti-cancer treatment in the future.
Background: Within the last decades, there has been increasing research on the occurrence of chemicals of emerging concern (CECs) in aquatic ecosystems due to their potential adverse effects on freshwater organisms and risk to human health. However, information on CECs in freshwater environments in sub-Saharan countries is very limited. Here, we investigated the occurrence of CECs in snails and sediments collected from 48 sites within the Lake Victoria South Basin, Kenya, which have been previously investigated for water contamination. Samples were analyzed by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) with a target list of 429 compounds.
Results: In total, 30 compounds have been detected in snails and 78 in sediment samples, compared to 79 previously identified compounds in water. By extending the monitoring of CECs to snails and sediments, we found 68 compounds that were not previously detected in water. These compounds include the anti-cancer drug anastrozole, detected for the first time in the Kenyan environment. Individual compound concentrations were detected up to 480 ng/g wet weight (N-ethyl-o-toluenesulfonamide) in snails and 110 ng/g organic carbon (pirimiphos-methyl) in sediments. Higher contaminant concentrations were found in agricultural sites than in areas not impacted by anthropogenic activities. Crustaceans were the organisms at greatest toxic risk from sediment contamination [toxic unit (TU) up to 0.99] with diazinon and pirimiphos-methyl driving this risk. Acute and chronic risks to algae were driven by diuron (TU up to 0.24), whereas fish were found to be at low-to-no acute risk (TU up to 0.007).
Conclusions: The compound classes present at the highest frequencies in all matrices were pesticides and biocides. This study shows substantial contamination of surface water in rural western Kenya. By filling data gaps on contamination of sediments and aquatic biota, our study reveals that CECs pose a substantial risk to environmental health in Kenya demanding for monitoring and mitigation.