The currently spreading resistance of the malaria parasite Plasmodium falciparum to artemisinin‐based combination therapies makes an urgent need for new efficient drugs. Aiming to kill ...artemisinin‐resistant Plasmodium, a series of novel hybrid drugs named Atokels were synthesized and characterized. Atokels are based on an 8‐amino‐ or 8‐hydroxyquinoline entity covalently bound to a 1,4‐naphthoquinone through a polyamine linker. These drugs have been designed to target the parasite mitochondrion by their naphthoquinone moiety reminiscent of the antimalarial drug atovaquone, and to trigger a damaging oxidative stress due to their ability to chelate metal ions in order to generate redox active complexes in situ. The most effective Atokel drug shown a promising antimalarial activity (IC50=622 nm on an artemisinin‐resistant P. falciparum strain) and no cytotoxicity at 50 μm indicating a specific antiplasmodial mode of action.
Novel Atokel molecules were designed as putative antimalarial drugs combining, in a single molecule, the naphthoquinone residue of atovaquone, an antimalarial drug targeting the parasite mitochondrion, and a copper chelator expected to induce, in presence of biologically available copper ions, a lethal oxidative stress.
Losses of honey bees have been repeatedly reported from many places worldwide. The widespread use of synthetic pesticides has led to concerns regarding their environmental fate and their effects on ...pollinators. Based on a standardised review, we report the use of a wide variety of honey bee matrices and sampling methods in the scientific papers studying pesticide exposure. Matrices such as beeswax and beebread were very little analysed despite their capacities for long-term pesticide storage. Moreover, bioavailability and transfer between in-hive matrices were poorly understood and explored. Many pesticides were studied but interactions between molecules or with other stressors were lacking. Sampling methods, targeted matrices and units of measure should have been, to some extent, standardised between publications to ease comparison and cross checking. Data on honey bee exposure to pesticides would have also benefit from the use of commercial formulations in experiments instead of active ingredients, with a special assessment of co-formulants (quantitative exposure and effects). Finally, the air matrix within the colony must be explored in order to complete current knowledge on honey bee pesticide exposure.
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•PEO and PRISMA standardised methods used for bibliographic analysis.•264 articles analysed to formulated recommendations for scientific experimentations.•Sampling methods, matrices and units should be better described and harmonized to some extent.•Beeswax and beebread should be more studied.•Interactions between stresses and bioavailability of pesticides should be further investigated.
Current global change substantially threatens pollinators, which directly impacts the pollination services underpinning the stability, structure and functioning of ecosystems. Amongst these threats, ...many synergistic drivers, such as habitat destruction and fragmentation, increasing use of agrochemicals, decreasing resource diversity, as well as climate change, are known to affect wild and managed bees. Therefore, reliable indicators for pollinator sensitivity to such threats are needed. Biological traits, such as phenotype (e.g. shape, size and asymmetry) and storage reserves (e.g. fat body size), are important pollinator traits linked to reproductive success, immunity, resilience and foraging efficiency and, therefore, could serve as valuable markers of bee health and pollination service potential.
This data paper contains an extensive dataset of wing morphology and fat body content for the European honeybee (
Apis mellifera
) and the buff-tailed bumblebee (
Bombus terrestris
) sampled at 128 sites across eight European countries in landscape gradients dominated by two major bee-pollinated crops (apple and oilseed rape), before and after focal crop bloom and potential pesticide exposure. The dataset also includes environmental metrics of each sampling site, namely landscape structure and pesticide use. The data offer the opportunity to test whether variation in the phenotype and fat bodies of bees is structured by environmental factors and drivers of global change. Overall, the dataset provides valuable information to identify which environmental threats predominantly contribute to the modification of these traits.
Since the Covid-19 epidemic, it has been clear that the availability of small and affordable drugs that are able to efficiently control viral infections in humans is still a challenge in medicinal ...chemistry. The synthesis and biological activities of a series of hybrid molecules that combine an emodin moiety and other structural moieties expected to act as possible synergistic pharmacophores in a single molecule were studied. Emodin has been reported to block the entry of the SARS-CoV-2 virus into human cells and might also inhibit cytokine production, resulting in the reduction of pulmonary injury induced by SARS-CoV-2. The pharmacophore associated with emodin was either a polyamine residue (emodin-PA series), a choice driven by the fact that a natural alkyl PA like spermine and spermidine play regulatory roles in immune cell functions, or a diphenylmethylpiperazine derivative of the norchlorcyclizine series (emoxyzine series). In fact, diphenylmethylpiperazine antagonists of the H1 histamine receptor display activity against several viruses by multiple interrelated mechanisms. In the emoxyzine series, the most potent drug against SARS-CoV-2 was (
R
)-emoxyzine-2, with an EC
50
value = 1.9 μM, which is in the same range as that of the reference drug remdesivir. However, the selectivity index was rather low, indicating that the dissociation of antiviral potency and cytotoxicity remains a challenge. In addition, since emodin was also reported to be a relatively high-affinity inhibitor of the virulence regulator FIKK kinase from the malaria parasite
Plasmodium vivax
, the antimalarial activity of the synthesized hybrid compounds has been evaluated. However, these molecules cannot efficiently compete with the currently used antimalarial drugs.
A series of hybrid emodin-polyamine or emodin-norchlorcyclizine molecules have been synthesized and evaluated as potential antiviral and antimalarial agents. (
R
)-Emoxyzine-2 was as potent as remdesivir in inhibiting SARS-CoV-2 replication.
Since the Covid-19 epidemic, it has been clear that the availability of small and affordable drugs that are able to efficiently control viral infections in humans is still a challenge in medicinal ...chemistry. The synthesis and biological activities of a series of hybrid molecules that combine an emodin moiety and other structural moieties expected to act as possible synergistic pharmacophores in a single molecule were studied. Emodin has been reported to block the entry of the SARS-CoV-2 virus into human cells and might also inhibit cytokine production, resulting in the reduction of pulmonary injury induced by SARS-CoV-2. The pharmacophore associated with emodin was either a polyamine residue (emodin-PA series), a choice driven by the fact that a natural alkyl PA like spermine and spermidine play regulatory roles in immune cell functions, or a diphenylmethylpiperazine derivative of the norchlorcyclizine series (emoxyzine series). In fact, diphenylmethylpiperazine antagonists of the H1 histamine receptor display activity against several viruses by multiple interrelated mechanisms. In the emoxyzine series, the most potent drug against SARS-CoV-2 was ( R )-emoxyzine-2, with an EC 50 value = 1.9 μM, which is in the same range as that of the reference drug remdesivir. However, the selectivity index was rather low, indicating that the dissociation of antiviral potency and cytotoxicity remains a challenge. In addition, since emodin was also reported to be a relatively high-affinity inhibitor of the virulence regulator FIKK kinase from the malaria parasite Plasmodium vivax , the antimalarial activity of the synthesized hybrid compounds has been evaluated. However, these molecules cannot efficiently compete with the currently used antimalarial drugs.
Reports of honey bee population decline has spurred many national efforts to understand the extent of the problem and to identify causative or associated factors. However, our collective ...understanding of the factors has been hampered by a lack of joined up trans-national effort. Moreover, the impacts of beekeeper knowledge and beekeeping management practices have often been overlooked, despite honey bees being a managed pollinator. Here, we established a standardised active monitoring network for 5 798 apiaries over two consecutive years to quantify honey bee colony mortality across 17 European countries. Our data demonstrate that overwinter losses ranged between 2% and 32%, and that high summer losses were likely to follow high winter losses. Multivariate Poisson regression models revealed that hobbyist beekeepers with small apiaries and little experience in beekeeping had double the winter mortality rate when compared to professional beekeepers. Furthermore, honey bees kept by professional beekeepers never showed signs of disease, unlike apiaries from hobbyist beekeepers that had symptoms of bacterial infection and heavy Varroa infestation. Our data highlight beekeeper background and apicultural practices as major drivers of honey bee colony losses. The benefits of conducting trans-national monitoring schemes and improving beekeeper training are discussed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bees play an essential role in plant pollination and their decline is a threat to crop yields and biodiversity sustainability. The causes of their decline have not yet been fully identified, despite ...the numerous studies that have been carried out, especially on Apis mellifera. This meta-analysis was conducted to identify gaps in the current research and new potential directions for research. The aim of this analysis of 293 international scientific papers was to achieve an inventory of the studied populations, the stressors and the methods used to study their impact on Apis mellifera. It also aimed to investigate the stressors with the greatest impact on bees and explore whether the evidence for an impact varies according to the type of study or the scale of study. According to this analysis, it is important to identify the populations and the critical developmental stages most at risk, and to determine the differences in stress sensibility between subspecies. This meta-analysis also showed that studies on climate change or habitat fragmentation were lacking. Moreover, it highlighted that technical difficulties in the field and the buffer effect of the colony represent methodological and biological barriers that are still difficult to overcome. Mathematical modeling or radio frequency identification (RFID) chips represent promising ways to overcome current methodological difficulties.
Sustainable agriculture requires balancing crop yields with the effects of pesticides on non-target organisms, such as bees and other crop pollinators. Field studies demonstrated that agricultural ...use of neonicotinoid insecticides can negatively affect wild bee species
, leading to restrictions on these compounds
. However, besides neonicotinoids, field-based evidence of the effects of landscape pesticide exposure on wild bees is lacking. Bees encounter many pesticides in agricultural landscapes
and the effects of this landscape exposure on colony growth and development of any bee species remains unknown. Here we show that the many pesticides found in bumble bee-collected pollen are associated with reduced colony performance during crop bloom, especially in simplified landscapes with intensive agricultural practices. Our results from 316 Bombus terrestris colonies at 106 agricultural sites across eight European countries confirm that the regulatory system fails to sufficiently prevent pesticide-related impacts on non-target organisms, even for a eusocial pollinator species in which colony size may buffer against such impacts
. These findings support the need for postapproval monitoring of both pesticide exposure and effects to confirm that the regulatory process is sufficiently protective in limiting the collateral environmental damage of agricultural pesticide use.
Declines in insect pollinators have been linked to a range of causative factors such as disease, loss of habitats, the quality and availability of food, and exposure to pesticides. Here, we analysed ...an extensive dataset generated from pesticide screening of foraging insects, pollen-nectar stores/beebread, pollen and ingested nectar across three species of bees collected at 128 European sites set in two types of crop. In this paper, we aimed to (i) derive a new index to summarise key aspects of complex pesticide exposure data and (ii) understand the links between pesticide exposures depicted by the different matrices, bee species and apple orchards versus oilseed rape crops. We found that summary indices were highly correlated with the number of pesticides detected in the related matrix but not with which pesticides were present. Matrices collected from apple orchards generally contained a higher number of pesticides (7.6 pesticides per site) than matrices from sites collected from oilseed rape crops (3.5 pesticides), with fungicides being highly represented in apple crops. A greater number of pesticides were found in pollen-nectar stores/beebread and pollen matrices compared with nectar and bee body matrices. Our results show that for a complete assessment of pollinator pesticide exposure, it is necessary to consider several different exposure routes and multiple species of bees across different agricultural systems.
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•We use new indices to summarise big datasets on pesticide exposure of three species of bees•Novel indices are calculated using Item Response Theory (IRT) models•The indices are linked to the number of pesticides rather than the active ingredients•Matrices collected from apple orchards are exposed to a higher number of pesticides compared to oilseed rape crop sites•Pollen related matrices contained more pesticides than were found in nectar and on the bees themselves
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