Background:Glucose regulated protein 78 (GRP78) functions as a sensor of endoplasmic reticulum (ER) stress. The aim of this study was to test the hypothesis that molecules that bind to GRP78 induce the unfolded protein response (UPR) and enhance cell death in combination with ER stress inducers.Methods:Differential scanning calorimetry (DSC), measurement of cell death by flow cytometry and the induction of ER stress markers using western blotting.Results:Epigallocatechin gallate (EGCG), a flavonoid component of Green Tea Camellia sinensis, and honokiol (HNK), a Magnolia grandiflora derivative, bind to unfolded conformations of the GRP78 ATPase domain. Epigallocatechin gallate and HNK induced death in six neuroectodermal tumour cell lines tested. Levels of death to HNK were twice that for EGCG; half-maximal effective doses were similar but EGCG sensitivity varied more widely between cell types. Honokiol induced ER stress and UPR as predicted from its ability to interact with GRP78, but EGCG was less effective. With respect to cell death, HNK had synergistic effects on melanoma and glioblastoma cells with the ER stress inducers fenretinide or bortezomib, but only additive (fenretinide) or inhibitory (bortezomib) effects on neuroblastoma cells.Conclusion:Honokiol induces apoptosis due to ER stress from an interaction with GRP78. The data are consistent with DSC results that suggest that HNK binds to GRP78 more effectively than EGCG. Therefore, HNK may warrant development as an antitumour drug.

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An agent-based approach to integrating computing in secondary-school science courses.

Background: In this paper, we investigate the relationship between theory and design in the context of creating digital games to support children's development of scientific expertise. Synthesis: Theoretically, we consider two frameworks: Knowledge in Pieces (or KiP) and Science as Practice (or SaP). While KiP is a theory about the structure of human knowledge, SaP is a theoretical perspective about the development of scientific expertise that emphasizes the deeply intertwined nature of conceptual development and the development of epistemic and representational practices. We then synthesize research on modeling and games from our research group and others to create a composite argument and theoretical framing for the importance of disciplinary integration in the design of digital games for science learning. Conclusions: We show how shifting from KiP to SaP as the underlying theoretical anchor in our designs results in shifting from focusing on conceptual integration to focusing on disciplinary integration. We first present our initial framing and design around conceptual integration. We then trace the evolution and rationale for disciplinary integration across our development and research on four game platforms. Finally, we discuss the implications and generalizability of disciplinary integration across the design of digital games for science learning.

Research suggests that translanguaging can be transformative for teaching and learning by making students' diverse linguistic resources a meaningful part of classroom discourse. Building on this study, researchers have explored how translanguaging practices can support learning in STEM (science, technology, engineering, and mathematics), primarily in the context of bilingual classrooms. However, in the United States, most students learn in English‐dominant classrooms. In response, researchers and educators have begun to explore strategies for inviting and leveraging translanguaging in English‐dominant classrooms, primarily focusing on literacy learning. Less is known about supporting translanguaging in English‐dominant STEM classrooms, particularly with monolingual teachers. In an English‐dominant sixth‐grade STEM classroom engaging in a 9‐week ecology unit, we explored how scientific modeling could not only provide a context for inviting translanguaging, but how it could also provide a setting where modeling and translanguaging could be experienced as analogous meaning‐making practices. Our findings demonstrate that translanguaging has the potential to support new kinds of learning in English‐dominant STEM classrooms, not only about STEM content and practices but also about what counts as legitimate and valuable participation in these spaces.

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The parasite ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and host endothelial receptors represent potential targets for antiadhesive therapy for cytoadherence. In the present study, the major host receptor CD36 was targeted in vitro and in vivo with a recombinant peptide, PpMC-179, corresponding to the minimal CD36-binding domain from the cysteine-rich interdomain region 1 (CIDR1) within the MCvar1