Purpose: To investigate the role of neutrophil extracellular traps (NETs) and NET-associated proteins in the pathogenesis of oGVHD and whether dismantling of NETs with heparin reduces those changes. Methods: Ocular surface washings from oGVHD patients and healthy subjects were analyzed. Isolated peripheral blood human neutrophils were stimulated to generate NETs and heparinized NETs. We performed in vitro experiments using cell lines (corneal epithelial, conjunctival fibroblast, meibomian gland (MG) epithelial and T cells), and in vivo experiments using murine models, and compared the effects of NETs, heparinized NETs, NET-associated proteins and neutralizing antibodies to NET-associated proteins. Results: Neutrophils, exfoliated epithelial cells, NETs and NET-associated proteins (extracellular DNA, Neutrophil Elastase, Myeloperoxidase, Oncostatin M (OSM), Neutrophil gelatinaseassociated lipocalin (NGAL) and LIGHT/TNFSF14) are present in ocular surface washings (OSW) and mucocellular aggregates (MCA). Eyes with high number of neutrophils in OSW have more severe signs and symptoms of oGVHD. NETs (and OSM) cause epitheliopathy in murine corneas. NETs (and LIGHT/TNFSF14) increase proliferation of T cells. NETs (and NGAL) inhibit proliferation and differentiation of MG epithelial cells. NETs enhance proliferation and myofibroblast transformation of conjunctival fibroblasts. Sub-anticoagulant dose Heparin (100 IU/mL) dismantles NETs and reduces epithelial, fibroblast, T cell and MG cell changes induced by NETs.
In this study, selected Chinese, Japanese and US mathematics textbooks were examined in terms of their ways of conceptualizing and organizing content for the teaching and learning of fraction division. Three Chinese mathematics textbook series, three Japanese textbook series, and four US textbook series were selected and examined to locate the content instruction of fraction division. Textbook organization of fraction division and other content topics were described. Further analyses were then conducted to specify how the content topic of fraction division was conceptualized and introduced. Specific attention was also given to the textbooks' uses of content constructs including examples, representations, and exercise problems in order to show their approaches for the teaching and learning of fraction division. The results provide a glimpse of the metaphors of mathematics teaching and learning that have been employed in Chinese, Japanese, and US textbooks. In particular, the results from the textbook analyses demonstrate how conceptual underpinnings were developed while targeting procedures and operations. Implications of the study are then discussed.
This article presents exploratory research investigating the way teachers integrate music into their regular mathematics lessons as well as the effects of music-mathematics interdisciplinary lessons on elementary school students' mathematical abilities of modeling, strategy and application. Two teachers and two classes of first grade and third grade students (n=46) participated in the present study. The two teachers designed and implemented music activities as an integrated part of their regular mathematics lessons across five weeks. Results demonstrated that both teachers integrated a variety of music activities with different mathematical content. The music-math interdisciplinary lessons had positive effects on multiple mathematical ability areas.
Since the publication of this article, the authors have noticed several errors that in any case do not affect the original conclusions presented. The authors apologize for any inconvenience caused.The gel presented in panel A of Figure 2 suggests a slightly incorrect size for the purified CYC domain of XC_250. Panel E in the same figure incorrectly describes D28 as D41 (see below). The correct figure and legend are shown below. Source data for this figure is now available on the online supplementary information page.The predicted critical amino acid sites of XC_0250 were reported incorrectly in the section 'The cyclase domain of XC_0250 is active in cyclic GMP synthesis', with D28 described as D41. The text should have read:'The two critical metal-ion binding aspartates are conserved (D28 and D71) as well as an alanine (A150) residue that occupies a substrate-specifying position. However, the transition state-stabilizing asparagine and arginine residues are substituted by leucine (L157) and alanine (A161). The importance of both conserved and altered residues (D28, D41, D71, L73, A150, L157, A161) for the enzymatic activity of this domain was examined by assessing the effects of alanine or serine substitutions'.And at a later point in the same section: 'Several of these residues (D28, D71, A150, L157) are conserved in the R. centenum guanylyl cyclase (Supplementary Fig S1).' Consistent with this, the alignment in Supplementary Fig S1 panel A incorrectly shows the position of D28. The correct figure and legend are available below.
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