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Eryptosis and Malaria: New Experimental Guidelines and Re-Evaluation of the Antimalarial Potential of Eryptosis Inducers.

ABSTRACT: Erythrocytes possess an unusual programmed cell death mechanism termed eryptosis, and several compounds have been previously claimed to induce eryptosis in vitro. Malaria parasites (genus Plasmodium) reside in erythrocytes during the pathogenic part of their life cycle, and the potential of several eryptosis inducers to act as antimalarials has been tested in recent years. However, the eryptosis-inducing capacity of these compounds varies significantly between eryptosis-focused studies and malaria investigations. Here, we investigated the reasons for these discrepancies, we developed a protocol to investigate eryptosis in malaria cultures and we re-evaluated the potential of eryptosis inducers as antimalarials. First, we showed that eryptosis read-out in vitro is dependent on culture conditions. Indeed, conditions that have consistently been used to study eryptosis do not support P. falciparum growth and prime erythrocytes for eryptosis. Next, we defined culture conditions that allow the detection of eryptosis while supporting P. falciparum survival. Finally, we selected six eryptosis-inducers based on their clinical use, molecular target and antimalarial activities, and re-evaluated their eryptosis inducing capacities and their potential as antimalarials. We demonstrate that none of these compounds affect the viability of naïve or P. falciparum-infected erythrocytes in vitro. Nevertheless, three of these compounds impair parasite development, although through a mechanism unrelated to eryptosis and yet to be elucidated. We conclude that careful consideration of experimental set up is key for the accurate assessment of the eryptosis-inducing potential of compounds and their evaluation as potential antimalarials.

SUBMITTER: Boulet C

PROVIDER: S-EPMC7994622 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Sentiment quantification is the task of training, by means of supervised learning, estimators of the relative frequency (also called "prevalence") of sentiment-related classes (such as Positive, Neutral, Negative) in a sample of unlabelled texts. This task is especially important when these texts are tweets, since the final goal of most sentiment classification efforts carried out on Twitter data is actually quantification (and not the classification of individual tweets). It is well-known that solving quantification by means of "classify and count" (i.e., by classifying all unlabelled items by means of a standard classifier and counting the items that have been assigned to a given class) is less than optimal in terms of accuracy, and that more accurate quantification methods exist. Gao and Sebastiani 2016 carried out a systematic comparison of quantification methods on the task of tweet sentiment quantification. In hindsight, we observe that the experimentation carried out in that work was weak, and that the reliability of the conclusions that were drawn from the results is thus questionable. We here re-evaluate those quantification methods (plus a few more modern ones) on exactly the same datasets, this time following a now consolidated and robust experimental protocol (which also involves simulating the presence, in the test data, of class prevalence values very different from those of the training set). This experimental protocol (even without counting the newly added methods) involves a number of experiments 5,775 times larger than that of the original study. Due to the above-mentioned presence, in the test data, of samples characterised by class prevalence values very different from those of the training set, the results of our experiments are dramatically different from those obtained by Gao and Sebastiani, and provide a different, much more solid understanding of the relative strengths and weaknesses of different sentiment quantification methods.

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Eryptosis and Malaria: New Experimental Guidelines and Re-Evaluation of the Antimalarial Potential of Eryptosis Inducers.

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