Continuous oral chloroquine as a novel route for Plasmodium prophylaxis and cure in experimental murine models

<p>Abstract</p> <p>Background</p> <p>Chloroquine (CQ) is utilized as both cure and prophylaxis to <it>Plasmodium </it>infection. In animal studies, CQ administration to experimental animals is via intraperitoneal (i.p.) injection of a single dose that varies from daily to several times per week. Such daily administration can be distressing to the animals and provoke aggressive behaviors that may affect the immune responses of the animal and interfere with data read-outs.</p> <p>Findings</p> <p>We describe a novel, viable and efficacious prophylactic and curative administration route whereby chloroquine is continuously supplied in the drinking water to experimental animals. The prophylactic effect is robust and the curative effect against patent blood stage infection comparable to the traditional route of i.p. administration. Continuous drinking water administration may decrease animal stress responses and thus improve the reliability of experimental data.</p

Glutathione deficiency down-regulates hepatic lipogenesis in rats

<p>Abstract</p> <p>Background</p> <p>Oxidative stress is supposed to increase lipid accumulation by stimulation of hepatic lipogenesis at transcriptional level. This study was performed to investigate the role of glutathione in the regulation of this process. For that purpose, male rats were treated with buthionine sulfoximine (BSO), a specific inhibitor of γ-glutamylcysteine synthetase, for 7 days and compared with untreated control rats.</p> <p>Results</p> <p>BSO treatment caused a significant reduction of total glutathione in liver (-70%), which was attributable to diminished levels of reduced glutathione (GSH, -71%). Glutathione-deficient rats had lower triglyceride concentrations in their livers than the control rats (-23%), whereas the circulating triglycerides and the cholesterol concentrations in plasma and liver were not different between the two groups of rats. Livers of glutathione-deficient rats had lower mRNA abundance of sterol regulatory element-binding protein (SREBP)-1c (-47%), Spot (S)14 (-29%) and diacylglycerol acyltransferase 2 (DGAT-2, -27%) and a lower enzyme activity of fatty acid synthase (FAS, -26%) than livers of the control rats. Glutathione-deficient rats had also a lower hepatic activity of the redox-sensitive protein-tyrosine phosphatase (PTP)1B, and a higher concentration of irreversible oxidized PTP1B than control rats. No differences were observed in protein expression of total PTP1B and the mature mRNA encoding active XBP1s, a key regulator of unfolded protein and ER stress response.</p> <p>Conclusion</p> <p>This study shows that glutathione deficiency lowers hepatic triglyceride concentrations via influencing lipogenesis. The reduced activity of PTP1B and the higher concentration of irreversible oxidized PTP1B could be, at least in part, responsible for this effect.</p

A crucial role for the C‐terminal domain of exported protein 1 during the mosquito and hepatic stages of the Plasmodium bergheilife cycle

© 2019 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Intracellular Plasmodium parasites develop inside a parasitophorous vacuole (PV), a specialised compartment enclosed by a membrane (PVM) that contains proteins of both host and parasite origin. Although exported protein 1 (EXP1) is one of the earliest described parasitic PVM proteins, its function throughout the Plasmodium life cycle remains insufficiently understood. Here, we show that whereas the N-terminus of Plasmodium berghei EXP1 (PbEXP1) is essential for parasite survival in the blood, parasites lacking PbEXP1's entire C-terminal (CT) domain replicate normally in the blood but cause less severe pathology than their wild-type counterparts. Moreover, truncation of PbEXP1's CT domain not only impairs parasite development in the mosquito but also abrogates PbEXP1 localization to the PVM of intrahepatic parasites, severely limiting their replication and preventing their egress into the blood. Our findings highlight the importance of EXP1 during the Plasmodium life cycle and identify this protein as a promising target for antiplasmodial intervention.This study was sup- ported by German Research Foundation (Deutsche Forschungsgemeinschaft ‐ DFG) Grants SPP 1580 (to A.‐K. M.) and SFB1129 (to A.‐K. M.); Fundação para a Ciência e Tecnologia, Portugal (FCT‐PT) Grants UID/BIM/50005/2019 (Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado) and 02/SAICT/2017 (to M. P.). M. S.‐V. was supported by an FCT‐PT Grant PD/BD/105838/2014. D. F. was supported by FEEI and FCT‐MEC. M. P. was supported by FCT‐PT Investigador FCT 2013 and CEEC 2018 fellowship. A.‐K. M. was a recipient of a Maternity Leave Stipend by the German Center for Infection Research (DZIF, Heidelberg Site)info:eu-repo/semantics/publishedVersio

The ecological origins of snakes as revealed by skull evolution

The ecological origin of snakes remains amongst the most controversial topics in evolution, with three competing hypotheses: fossorial; marine; or terrestrial. Here we use a geometric morphometric approach integrating ecological, phylogenetic, paleontological, and developmental data for building models of skull shape and size evolution and developmental rate changes in squamates. Our large-scale data reveal that whereas the most recent common ancestor of crown snakes had a small skull with a shape undeniably adapted for fossoriality, all snakes plus their sister group derive from a surface-terrestrial form with non-fossorial behavior, thus redirecting the debate toward an underexplored evolutionary scenario. Our comprehensive heterochrony analyses further indicate that snakes later evolved novel craniofacial specializations through global acceleration of skull development. These results highlight the importance of the interplay between natural selection and developmental processes in snake origin and diversification, leading first to invasion of a new habitat and then to subsequent ecological radiations.Peer reviewe

Chasing Lions: Co-Designing Human-Drone Interaction in Sub-Saharan Africa

Drones are an exciting technology that is quickly being adopted in the global consumer market. Africa has become a center of deployment with the first drone airport established in Rwanda and drones currently being used for applications such as medical deliveries, agriculture, and wildlife monitoring. Despite this increasing presence of drones, there is a lack of research on stakeholders' perspectives from this region. We ran a human-drone interaction user study (N=15) with experts from several sub-Saharan countries using a co-design methodology. Participants described novel applications and identified important design aspects for the integration of drones in this context. Our results highlight the potential of drones to address real world problems, the need for them to be culturally situated, and the importance of considering the social aspects of their interaction with humans. This research highlights the need for diverse perspectives in the human-drone interaction design process.Comment: To be published in the ACM conference on Designing Interactive Systems (DIS '20