In the digital era, tech devices (hardware and software) are increasingly within hand’s reach. Yet, implementing information and communication technologies for educational contexts that have robust and long-lasting effects on student learning outcomes is still a challenge. We propose that any such system must a) be theoretically motivated and designed to tackle specific cognitive skills (e.g., inference making) supporting a given cognitive task (e.g., reading comprehension) and b) must be able to identify and adapt to the user’s profile. In the present study, we implemented a feedback-based adaptive system called A-book (assisted-reading book) and tested it in a sample of 4th, 5th, and 6th graders. To assess our hypotheses, we contrasted three experimental assisted-reading conditions; one that supported meta-cognitive skills and adapted to the user profile (adaptive condition), one that supported meta-cognitive skills but did not adapt to the user profile (training condition) and a control condition. The results provide initial support for our proposal; participants in the adaptive condition improved their accuracy scores on inference making questions over time, outperforming both the training and control groups. There was no evidence, however, of significant improvements on other tested meta-cognitive skills (i.e., text structure knowledge, comprehension monitoring). We discussed the practical implications of using the A-book for the enhancement of meta-cognitive skills in school contexts, as well as its current limitations and future developments that could improve the system.
and Gem/Kir (RGK) sub-family of small GTP-binding protein include e the most potent endogenous inhibitor of High-Voltage Activated (HVA) calcium channels. RGK proteins use several mechanisms to inhibit calcium current (I CA): i) they promote dynamin-dependent endocytocys; ii) the lower the Po of the channel: ii) and they voltage sensor or reduction of charge. All RGK proteins associate directly with Ca 2þ channel b subunits (Cavb), and the binding between CaVa1 / Cavb has been shown to be essential for their inhibitory action for CaV1.2 and Ca V 2.1 and Ca V 2.2. In this study, we investigated inhibition of Ca V 2.3 Ca 2þ channels by RGK proteins. We found that when Xenopus laevis oocytes expressing Cav2.3 channels were injected with purified Gem protein, but not Rem, calcium currents where significantly decreased. This reduction was accompanied by a right shift in the conductance-voltage (GV curve) relationship of the channel. Furthermore, Gem also decreases the number of channels in the plasma membrane, evidenced by a reduction in maximal charge movement after injection of purified protein. The kinetic and voltage dependence of the reduced charge movement was not affected and thus immobilization of a subset of voltage-sensor seems unlikely. Surprisingly both effects are not dependent on the binding between CaVa1 to Cavb since CaV2.3 were expressed alone. Thus unlike than other neuronal calcium channels, Gem inhibit Cav2.3 channels in a CaVb-independent manner and through two synergistic mechanisms: a increase in voltage for activation and a decrease in the number of channels.
Spider toxin SNX-482 is a cysteine-rich peptide that interferes with calcium channel activity by binding to voltage-sensing domains of the CaV2.3 subtype. Two mechanisms dominate the binding process of cysteine-rich peptides.: direct binding from the aqueous phase or through lateral diffusion from the membrane, the so-called reduction in dimensionality mechanism. In this work, via coarse-grained and atomistic molecular dynamics simulations, we have systematically studied the spontaneous partitioning of SNX-482 with membranes of different anionic compositions and explored via diffusional analysis both binding mechanisms. Our simulations revealed a conserved protein patch that inserts in the membrane, a preference for binding towards partially negatively charged membranes, and that electrostatics guides membrane binding by incrementing and aligning the molecular dipole. Finally, diffusivity calculations showed that the toxin diffusion along the membrane plane is an order of magnitude slower than the aqueous phase suggesting that the critical factor in determining the SNX-482-CaV2.3 binding mechanism is the affinity between the membrane and SNX-482.
Spider toxin SNX-482 is a cysteine-rich peptide that interferes with calcium channel activity by binding to voltage-sensing domains of CaV2.3 subtype. Two general binding mechanisms are present in nature: direct binding from the aqueous phase or through lateral diffusion from the membrane, the so-called reduction in dimensionality mechanism. In this work, via coarse-grained and atomistic molecular dynamics simulations, we have systematically studied the spontaneous partitioning of SNX-482 with membranes of different anionic compositions and explored via diffusional analysis both binding mechanisms. Our simulations revealed a conserved protein patch that inserts within the membrane, a preference for binding towards partially negatively charged membranes, and that electrostatics drives membrane binding. Finally, diffusivity calculations showed that the toxin diffusion along the membrane plane is an order of magnitude slower than the aqueous phase suggesting that the critical factor in determin-ing the SNX-482-CaV2.3 binding mechanism is the affinity between the membrane and SNX-482
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.