Construction of a Plasmodium falciparum Rab-interactome identifies CK1 and PKA as Rab-effector kinases in malaria parasites

Background information The pathology causing stages of the human malaria parasite Plasmodium falciparum reside within red blood cells that are devoid of any regulated transport system. The parasite, therefore, is entirely responsible for mediating vesicular transport within itself and in the infected erythrocyte cytoplasm, and it does so in part via its family of 11 Rab GTPases. Putative functions have been ascribed to Plasmodium Rabs due to their homology with Rabs of yeast, particularly with Saccharomyces that has an equivalent number of rab/ypt genes and where analyses of Ypt function is well characterized. Results Rabs are important regulators of vesicular traffic due to their capacity to recruit specific effectors. In order to identify P. falciparum Rab (PfRab) effectors, we first built a Ypt-interactome by exploiting genetic and physical binding data available at the Saccharomyces genome database (SGD). We then constructed a PfRab-interactome using putative parasite Rab-effectors identified by homology to Ypt-effectors. We demonstrate its potential by wet-bench testing three predictions; that casein kinase-1 (PfCK1) is a specific Rab5B interacting protein and that the catalytic subunit of cAMP-dependent protein kinase A (PfPKA-C) is a PfRab5A and PfRab7 effector. Conclusions The establishment of a shared set of physical Ypt/PfRab-effector proteins sheds light on a core set Plasmodium Rab-interactants shared with yeast. The PfRab-interactome should benefit vesicular trafficking studies in malaria parasites. The recruitment of PfCK1 to PfRab5B+ and PfPKA-C to PfRab5A+ and PfRab7+ vesicles, respectively, suggests that PfRab-recruited kinases potentially play a role in early and late endosome function in malaria parasites

Effects of aronia berry (poly)phenols on vascular function and gut microbiota: A double-blind randomized controlled trial in adult men

Background: Aronia melanocarpa is a rich source of (poly)phenols. Previous research has demonstrated that these berries may provide cardiovascular health benefits in high-risk populations. However, very few studies have investigated the effects of daily consumption of dietary achievable amounts of the berries in healthy subjects. Objectives: The aim of this study was to investigate the effects of aronia berries on vascular function and gut microbiota composition in a healthy population. Methods: A double-blind, placebo-controlled, parallel designed study was conducted in 66 healthy men randomly allocated to consume a (poly)phenol-rich extract (116 mg, 75 g berries), a whole fruit powder (12 mg, 10 g berries), or placebo (maltodextrin) for 12 wk. Flow-mediated dilation (FMD), arterial stiffness, blood pressure, heart rate, and serum biochemistry were assessed. Plasma (poly)phenol metabolites were analyzed by LC-MS. Gut microbiota composition was determined via 16S rRNA sequencing in stool samples. Results: Consumption of aronia whole fruit and extract powder for 12 wk led to a significant increase in FMD over control of 0.9% \ub1 0.4% (95% CI: 0.13%, 1.72%) and 1.2% \ub1 0.4% (95% CI: 0.36%, 1.97%), respectively. Acute improvements in FMD were also observed 2 h after consumption of aronia extract on day 1 (1.1% \ub1 0.3%, P = 0.003) and 12 wk later (1.5% \ub1 0.4%, P = 0.0001). Circulating plasma phenolic metabolites increased upon consumption of the aronia treatments. Although no changes were found in gut microbiota diversity, consumption of aronia extract increased the growth of Anaerostipes (+10.6%, P = 0.01), whereas aronia whole fruit showed significant increases in Bacteroides (+193%, P = 0.01). Correlation analysis identified significant associations between changes in FMD, aronia-derived phenolic metabolites, and specific gut microbial genera. Conclusions: In healthy men, consumption of aronia berry (poly)phenols improved endothelial function and modulated gut microbiota composition, indicating that regular aronia consumption has the potential to maintain cardiovascular health in individuals at low risk of cardiovascular disease. This trial was registered at CLINICALTRIALs.gov as NCT03041961