The project described here was aimed at developing and evaluating a novel curriculum with corresponding instructional materials for middle school students on an introduction to Newtonian mechanics, ...based on physics education research findings. A case study showed that teachers who attended a half-day workshop on the curriculum subsequently enacted these materials in their classrooms appropriately and saw improved student performance. Thus, the project suggests that with only a relatively short amount of training time teachers are able to utilize such materials and consequently to improve teaching and learning in physics classes. We therefore regard it as a promising approach for professional development programs.
Nach wie vor zählt die Mechanik zu den schwierigsten Inhaltsbereichen der Schulphysik. Auch Lehrkräfte berichteten von Lernschwierigkeiten und erwarteten gute Unterrichtskonzepte von der ...Physikdidaktik. Im Rahmen eines Design-Based Research Ansatzes wurde die Lernwirksamkeit einer zweidimensional-dynamischen Sachstruktur für den Mechanikunterricht in der siebten Jahrgangsstufe in einer großen quasi-experimentellen Feldstudie untersucht. Dabei konnte nachgewiesen werden, dass Schülerinnen und Schüler durch Unterricht nach dieser Sachstruktur einen deutlich höheren Lernerfolg erreichen als durch Unterricht nach einer traditionellen Sachstruktur. Dies führte zu Wirksamkeitserfahrungen der Lehrerinnen und Lehrer, was eine breite Implementation der Sachstruktur möglich machte.
Nach wie vor zählt die Mechanik zu den schwierigsten Inhaltsbereichen der Schulphysik. Auch Lehrkräfte berichteten von Lernschwierigkeiten und erwarteten gute Unterrichtskonzepte von der ...Physikdidaktik. Im Rahmen eines Design-Based Research Ansatzes wurde die Lernwirksamkeit einer zweidimensional-dynamischen Sachstruktur für den Mechanikunterricht in der siebten Jahrgangsstufe in einer großen quasi-experimentellen Feldstudie untersucht. Dabei konnte nachgewiesen werden, dass Schülerinnen und Schüler durch Unterricht nach dieser Sachstruktur einen deutlich höheren Lernerfolg erreichen als durch Unterricht nach einer traditionellen Sachstruktur. Dies führte zu Wirksamkeitserfahrungen der Lehrerinnen und Lehrer, was eine breite Implementation der Sachstruktur möglich machte.
It has been shown repeatedly, that Newtonian mechanics is still to be found among the most difficult topics taught at school and the outcome of the usual instruction is fragmentary. Many teachers see physics education research groups in charge of devising good concepts to enhance students' understanding. Following a Design-Based Research approach, a quasi-experimental field study focusing on the learning outcomes of a content structure for the introduction to this field in grade 7 via two-dimensional dynamics has been undertaken. We found significant improvement of students' understanding compared to classes given according to the traditional content structure. This allowed teachers to experience an unknown effectiveness of their lessons and contributed to the implementation of the material.
A mevalonate-independent pathway of isoprenoid biosynthesis present in Plasmodium falciparum was shown to represent an effective target for chemotherapy of malaria. This pathway includes ...1-deoxy-D-xylulose 5-phosphate (DOXP) as a key metabolite. The presence of two genes encoding the enzymes DOXP synthase and DOXP reductoisomerase suggests that isoprenoid biosynthesis in P. falciparum depends on the DOXP pathway. This pathway is probably located in the apicoplast. The recombinant P. falciparum DOXP reductoisomerase was inhibited by fosmidomycin and its derivative, FR-900098. Both drugs suppressed the in vitro growth of multidrug-resistant P. falciparum strains. After therapy with these drugs, mice infected with the rodent malaria parasite P. vinckei were cured.
Significance Protein–protein interactions mediated by proline-rich motifs are involved in regulation of many important signaling cascades. Protein domains specialized in recognition of these motifs ...expose a flat and relatively rigid binding site that preferentially interacts with sequences adopting a left-handed polyproline helix II. Here, we present a toolkit of new chemical entities that enables rational construction of selective small-molecule inhibitors for these protein domains. As proof of principle, we developed a selective, cell-permeable inhibitor of Drosophila enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) homology 1 (EVH1) domains of the Ena/VASP protein family. Invasive breast-cancer cells treated with our EVH1 inhibitor showed strongly reduced cell invasion.
Small-molecule competitors of protein–protein interactions are urgently needed for functional analysis of large-scale genomics and proteomics data. Particularly abundant, yet so far undruggable, targets include domains specialized in recognizing proline-rich segments, including Src-homology 3 (SH3), WW, GYF, and Drosophila enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) homology 1 (EVH1) domains. Here, we present a modular strategy to obtain an extendable toolkit of chemical fragments (ProMs) designed to replace pairs of conserved prolines in recognition motifs. As proof-of-principle, we developed a small, selective, peptidomimetic inhibitor of Ena/VASP EVH1 domain interactions. Highly invasive MDA MB 231 breast-cancer cells treated with this ligand showed displacement of VASP from focal adhesions, as well as from the front of lamellipodia, and strongly reduced cell invasion. General applicability of our strategy is illustrated by the design of an ErbB4-derived ligand containing two ProM-1 fragments, targeting the yes-associated protein 1 (YAP1)-WW domain with a fivefold higher affinity.
Among mammalian lipoxygenases the 15-lipoxygenase-1 is somewhat special because of its capability of oxygenating complex lipid-protein assemblies (biomembranes, lipoproteins) and previous ...investigations have implicated calcium in enzyme/membrane interaction. We investigated the mechanism of calcium-dependent membrane association and obtained the following results. (i) Membrane binding of 15-lipoxygenase-1 involves electrostatic forces as well as hydrophobic interactions of solvent-exposed apolar amino acids (Tyr(15), Phe(70), Leu(71), Trp(181), and Leu(195)) with the hydrophobic core of membrane phospholipids. These sequence determinants of membrane association are clustered at the membrane contact plane of the enzyme that also involves the entrance to the substrate binding pocket. Site-directed mutagenesis of these determinants to negatively charged residues strongly impaired membrane binding. (ii) Calcium at micromolar concentrations (5-50 microM) is required for efficient membrane binding. For direct 15-lipoxygenase/calcium interaction a dissociation constant of 2-5 x 10(-4) m was determined (low affinity binding) and we failed to detect high affinity calcium-binding sites at the enzyme. Reversible low affinity calcium binding induces subtle structural alterations of the enzyme, which did not impact catalytic activity. (iii) Increasing calcium concentrations failed to reverse impairment of membrane binding induced by mutagenesis of the sequence determinants indicating the priority of hydrophobic interactions. Taken together these data suggest that 15-lipoxygenase-1 associates to biomembranes primarily via hydrophobic interactions between surface-exposed apolar amino acid side chains and membrane lipids. Calcium supports membrane binding probably by forming salt bridges between the negatively charged head groups of membrane phospholipids and acidic surface amino acids of the membrane contact plane and this interaction might contribute to overcome repulsive forces.
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