172 research outputs found

    A support system for solving problems of two-triangle congruence using "backward chaining"

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    We developed a system called DELTA that supports the students’ use of backward chaining (BC) to prove the congruence of two triangles. DELTA is designed as an interactive learning environment and supports the use of BC by providing hints and a function to automatically check the proofs inputted by the students. DELTA also has coloring, mark- ing, and highlighting functions to support students’ attempts to prove the congruence of two triangles. We evaluated the efficacy of DELTA with 36 students in the second grade of a junior high school in Japan. We found that (1) the mean number of problems, which the experimental group (EG) completely solved, was statistically higher than that of the control group on the post-test; (2) the EG effectively used the BC strategy to solve problems; and (3) the students’ attempt to use both the forward chaining strategy and the BC strategy led to solving the problems completely

    Importin Alpha Subtypes Determine Differential Transcription Factor Localization in Embryonic Stem Cells Maintenance

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    SummaryWe recently demonstrated that the expression of the importin α subtype is switched from α2 to α1 during neural differentiation in mouse embryonic stem cells (ESCs) and that this switching has a major impact on cell differentiation. In this study, we report a cell-fate determination mechanism in which importin α2 negatively regulates the nuclear import of certain transcription factors to maintain ESC properties. The nuclear import of Oct6 and Brn2 was inhibited via the formation of a transport-incompetent complex of the cargo bound to a nuclear localization signal binding site in importin α2. Unless this dominant-negative effect was downregulated upon ESC differentiation, inappropriate cell death was induced. We propose that although certain transcription factors are necessary for differentiation in ESCs, these factors are retained in the cytoplasm by importin α2, thereby preventing transcription factor activity in the nucleus until the cells undergo differentiation

    Regulation of the unfolded protein response via S-nitrosylation of sensors of endoplasmic reticulum stress

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    Protein S-nitrosylation modulates important cellular processes, including neurotransmission, vasodilation, proliferation, and apoptosis in various cell types. We have previously reported that protein disulfide isomerase (PDI) is S-nitrosylated in brains of patients with sporadic neurodegenerative diseases. This modification inhibits PDI enzymatic activity and consequently leads to the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) lumen. Here, we describe S-nitrosylation of additional ER pathways that affect the unfolded protein response (UPR) in cell-based models of Parkinson's disease (PD). We demonstrate that nitric oxide (NO) can S-nitrosylate the ER stress sensors IRE1α and PERK. While S-nitrosylation of IRE1α inhibited its ribonuclease activity, S-nitrosylation of PERK activated its kinase activity and downstream phosphorylation/inactivation or eIF2α. Site-directed mutagenesis of IRE1α(Cys931) prevented S-nitrosylation and inhibition of its ribonuclease activity, indicating that Cys931 is the predominant site of S-nitrosylation. Importantly, cells overexpressing mutant IRE1α(C931S) were resistant to NO-induced damage. Our findings show that nitrosative stress leads to dysfunctional ER stress signaling, thus contributing to neuronal cell death

    PcdhÎČ deficiency affects hippocampal CA1 ensemble activity and contextual fear discrimination

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    Clustered protocadherins (Pcdhs), a large group of adhesion molecules, are important for axonal projections and dendritic spread, but little is known about how they influence neuronal activity. The PcdhÎČ cluster is strongly expressed in the hippocampus, and in vivo Ca2+ imaging in PcdhÎČ-deficient mice revealed altered activity of neuronal ensembles but not of individual cells in this region in freely moving animals. Specifically, PcdhÎČ deficiency increased the number of large-size neuronal ensembles and the proportion of cells shared between ensembles. Furthermore, PcdhÎČ-deficient mice exhibited reduced repetitive neuronal population activity during exploration of a novel context and were less able to discriminate contexts in a contextual fear conditioning paradigm. These results suggest that one function of PcdhÎČs is to modulate neural ensemble activity in the hippocampus to promote context discrimination

    Size-selective encapsulation property of unimolecular reverse micelle consisting of hyperbranched D-glucan core and L-leucine ethyl ether shell

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    金æČąć€§ć­Šç†ć·„ç ”ç©¶ćŸŸè‡Ș然シă‚čăƒ†ăƒ ć­Šçł»The synthesis of a unimolecular reverse micelle (3) consisting of hyper-branched D-glucan as the core and L-leucine ethyl ester as the shell was accomplished through the carbamation reaction of the hyperbranched D-glucan (1) with the N-carbonyl L-leucine ethyl ester (2) in pyridine at 100 °C. The polymer 3 was soluble in a large variety of organic solvents, such as methanol, acetone, chloroform, and ethyl acetate, and insoluble in water, which remarkably differed from the solubility of 1. The solubilities of 3 were also changed by the substitution degrees of the L-leucine moiety. The encapsulation ability of 3 toward water-soluble dyes has been investigated. These results indicated that 3 was a unimolecular reverse micelle with an encapsulation ability toward hydrophilic dye molecules. In addition, 3 showed an molecular size-selective encapsulation ability. Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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