Revisiting the Plasmodium falciparum druggable genome using predicted structures and data mining.

The identification of novel drug targets for the purpose of designing small molecule inhibitors is key component to modern drug discovery. In malaria parasites, discoveries of antimalarial targets have primarily occurred retroactively by investigating the mode of action of compounds found through phenotypic screens. Although this method has yielded many promising candidates, it is time- and resource-consuming and misses targets not captured by existing antimalarial compound libraries and phenotypic assay conditions.

2,8-Disubstituted-1,5-naphthyridines as Dual Inhibitors of Phosphatidylinositol-4-kinase and Hemozoin Formation with Efficacy.

Structure-activity relationship studies of 2,8-disubstituted-1,5-naphthyridines, previously reported as potent inhibitors of () phosphatidylinositol-4-kinase β (PI4K), identified 1,5-naphthyridines with basic groups at 8-position, which retained PI4K inhibitory activity but switched primary mode of action to the host hemoglobin degradation pathway through inhibition of hemozoin formation. These compounds showed minimal off-target inhibitory activity against the human phosphoinositide kinases and MINK1 and MAP4K kinases, which were associated with the teratogenicity and testicular toxicity observed in rats for the PI4K inhibitor clinical candidate MMV390048. A representative compound from the series retained activity against field isolates and lab-raised drug-resistant strains of .

Synthetic and biological surfactant effects on freshwater biofilm community composition and metabolic activity.

Surfactants are used to control microbial biofilms in industrial and medical settings. Their known toxicity on aquatic biota, and their longevity in the environment, has encouraged research on biodegradable alternatives such as rhamnolipids. While previous research has investigated the effects of biological surfactants on single species biofilms, there remains a lack of information regarding the effects of synthetic and biological surfactants in freshwater ecosystems.

Severe glycerol intoxication mimicking toxic alcohol ingestion following large volume consumption of vanilla essence.

Introduction: Patients with ethanol dependence may consume vanilla extract for the high alcohol content.

Case Presentation: A 42-year-old male with ethanol dependence who developed status epilepticus, severe anion gap metabolic acidosis and a hyperosmolar non-ketotic coma after ingestion of 600 mL vanilla essence. He was found to have an osmolar gap of 151 with a marked pseudohypertriglyceridaemia of 96.

Effects of intermittent flow on biofilms are driven by stream characteristics rather than history of intermittency.

Intermittent streams are found all over the world, however most studies focus on intermittency in hot, arid climates. As flow intermittency is expected to increase with climate change, it is important to understand how stream biofilms in temperate regions respond to these changing conditions. In this study, 20 different streams from around Austria were sampled under flowing and non-flowing conditions to evaluate the effect of intermittency on temperate stream biofilms.