Active Transport of Hepatotoxic Pyrrolizidine Alkaloids in HepaRG Cells

1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the beginning of being recognized as a key determinant of PA toxicity. Therefore, this study concentrated on assessing the general mode of action of PA transport in the human hepatoma cell line HepaRG using seven structurally different PAs. Furthermore, several hepatic uptake and efflux transporters were targeted with pharmacological inhibitors to identify their role in the uptake of the PAs retrorsine and senecionine and in the disposition of their N-oxides (PANO). For this purpose, PA and PANO content was measured in the supernatant using LC-MS/MS. Also, PA-mediated cytotoxicity was analyzed after transport inhibition. It was found that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner. This pattern correlates with other experimental endpoints such as cytotoxicity. Pharmacological inhibition of the influx transporters Na⁺/taurocholate co-transporting polypeptide (SLC10A1) and organic cation transporter 1 (SLC22A1) led to a reduced uptake of retrorsine and senecionine into HepaRG cells, emphasizing the relevance of these transporters for PA toxicokinetics.     

The effectiveness of adaptive versus non-adaptive learning with digital educational games

For the training of academic skills, digital educational games with integrated adaptivity are promising. Adaptive games are considered superior to non-adaptive games, because they constantly assess children's performance, and accordingly adapt the difficulty of the tasks corresponding to the children's individual level. However, empirical evidence with regard to the effectivity of adaptive compared to non-adaptive games is limited. A study was conducted with 191 children from the third year of Kinder garten who were enrolled in one of three conditions, that is, playing an adaptive version of the reading game (RG), a non-adaptive version of the RG or training with pen-and-paper exercises. In all three conditions, children trained emergent reading (phonological awareness and letter knowledge) once a week for 30 min over a period of 5 weeks. Children's performance on cognitive (phonological awareness, letter knowledge, reading fluency) and non-cognitive (motivation, self-concept) factors was assessed. Results revealed a significant improvement in phonological awareness and letter knowledge in all conditions. However, no differences between the conditions were observed with respect to children's improvement on phonological awareness and letter knowledge or on their post-test scores for reading fluency. With regard to motivation and self-concept, again, no differences in these non-cognitive factors were observed across conditions.     

A novel fiber-optic pressure sensor operated at 1300-nm wavelength

In this paper, we discuss a particular topology of a fiber-optic pressure transducer, developed recently at the Laboratory of the Photonics Research Center, University of Quebec en Outaouais. The sensor, which is an extension of our previous polarimetric configuration, was designed to operate using typical telecommunications components at the wavelength of 1300 nm. The pressure sensor is temperature compensated in an innovative way and has no polarizer between the LD and the sensor. The absolute accuracy of this sensor can be less than 1% in a wide range of temperatures, and including all types of metrological errors such as hysteresis and unrepeatability.     

Self-stabilizing somersaults

We investigate the open-loop stability of a planar biped robot performing a periodic motion of forward somersaults with alternating single-leg contacts. The robot has a trunk and two actuated telescopic legs with point feet which are coupled to the trunk by actuated hinges. There is compliance and damping in the hip and in the legs. The concept of open-loop control implies that all actuators of the system receive predetermined inputs that are never altered by any feedback interference. Only with the right choice of model parameters and actuator inputs is it possible to create such self-stabilizing motions exploiting the natural stability properties of the system. These unknowns have been determined using special-purpose stability-optimization methods. The resulting motion is not only stable, but also a more efficient form of forward motion than running for the investigated robot.