29 research outputs found

    Combining video games and constructionist design to support deep learning in play

    No full text
    This effort has produced many interesting games though it is unclear if “educational video games” have achieved their promise. Similarly, for many years constructionists have engaged children in learning across a variety of contexts, including game design. While these programs have been successful, their exploratory nature leads to concerns about content coverage. In this symposium we discuss the potential of blending these two design traditions. Constructionist video games infuse traditional game structures with constructionist ideals to create gaming experiences that encourage exploration while ensuring engagement with desired content. This symposium presents the constructionist video games construct and showcases empirical research on the use of such games in both formal and informal contexts

    Structural Basis for Regulated Proteolysis by the α-Secretase ADAM10

    No full text
    International audienceCleavage of membrane-anchored proteins by ADAM (a disintegrin and metalloproteinase) endopeptidases plays a key role in a wide variety of biological signal transduction and protein turnover processes. Among ADAM family members, ADAM10 stands out as particularly important because it is both responsible for regulated proteolysis of Notch receptors and catalyzes the non-amyloidogenic α-secretase cleavage of the Alzheimer’s precursor protein (APP). We present here the X-ray crystal structure of the ADAM10 ectodomain, which, together with biochemical and cellular studies, reveals how access to the enzyme active site is regulated. The enzyme adopts an unanticipated architecture in which the C-terminal cysteine-rich domain partially occludes the enzyme active site, preventing unfettered substrate access. Binding of a modulatory antibody to the cysteine-rich domain liberates the catalytic domain from autoinhibition, enhancing enzymatic activity toward a peptide substrate. Together, these studies reveal a mechanism for regulation of ADAM activity and offer a roadmap for its modulation

    Multiple sulfur isotope signals associated with the late Smithian event and the Smithian/Spathian boundary.

    No full text
    18 pagesInternational audienceThe Early Triassic is generally portrayed as a time of various, high ecological stresses leading to a delayed biotic recovery after the devastating end-Permian mass extinction. This interval is notably characterized by repeated biotic crises (e.g., during the late Smithian), large-scale fluctuations of the global carbon, nitrogen and sulfur cycles as well as harsh marine conditions including a combination of ocean acidification, anoxia, extreme seawater temperatures and shifting productivity. Observations from different paleolatitudes suggest that sulfidic (H2S-rich) conditions may have developed widely during the Early Triassic, possibly reaching up to ultra-shallow environments in some places. However, the existence and the spatio-temporal extent of such redox swings remain poorly constrained. In order to explore Early Triassic paleoceanographic redox changes and their potential influences on the biotic recovery, we analyzed multiple sulfur isotopes (32S, 33S, 34S, and 36S) of sedimentary pyrite and carbonate associated sulfate (ή34SCAS) from the Mineral Mountains section, Utah. Sediments from this section were mainly deposited in shallow waters and span the Smithian and lower Spathian. We report a 68‰ range of variations in ή34Spy associated with Δ33Spy varying from −0.01‰ to +0.12‰, whereas the ή34SCAS varies between +19.5‰ and + 34.8‰. We interpret the observed signal of multiple sulfur isotopes as reflecting the operation of pore-water synsedimentary microbial sulfate reduction in open system with respect to sulfates before the late Smithian, evolving to a closed system, sulfate limited, Rayleigh-type distillation across the Smithian/Spathian boundary (SSB) and immediately after the SSB. We argue that this marked change is driven by the effectiveness of the connection between the sedimentary pore waters and the overlying water column, which is, in this case, controlled by the local sedimentological conditions such as the bioturbation intensity and the sedimentation rate. Therefore, our results suggest that changes in the sulfur cycle before and across the SSB at Mineral Mountains is probably a local consequence of the loss of the mixed sedimentary layer during the late Smithian extinction event, as opposed to reflecting the development of a lethal anoxic ocean at the global scale
    corecore