Loss-of-function mutations in the Wnt inhibitor secreted frizzled receptor protein 4 (SFRP4) cause Pyle’s disease (OMIM 265900), a rare skeletal disorder characterized by wide metaphyses, significant thinning of cortical bone, and fragility fractures. In mice, we have shown that the cortical thinning seen in the absence ofSfrp4is associated with decreased periosteal and endosteal bone formation and increased endocortical resorption. While the increase in Rankl/Opg in cortical bone of mice lackingSfrp4suggests an osteoblast-dependent effect on endocortical osteoclast (OC) activity, whether Sfrp4 can cell-autonomously affect OCs is not known. We found thatSfrp4is expressed during bone marrow macrophage OC differentiation and that Sfrp4 significantly suppresses the ability of early and late OC precursors to respond to Rankl-induced OC differentiation.Sfrp4deletion in OCs resulted in activation of canonical Wnt/β-catenin and noncanonical Wnt/Ror2/Jnk signaling cascades. However, while inhibition of canonical Wnt/β-catenin signaling did not alter the effect ofSfrp4on OCgenesis, blocking the noncanonical Wnt/Ror2/Jnk cascade markedly suppressed its regulation of OC differentiation in vitro. Importantly, we report that deletion ofRor2exclusively in OCs (CtskCreRor2fl/fl) inSfrp4null mice significantly reversed the increased number of endosteal OCs seen in these mice and reduced their cortical thinning. Altogether, these data show autocrine and paracrine effects of Sfrp4 in regulating OCgenesis and demonstrate that the increase in endosteal OCs seen inSfrp4−/−mice is a consequence of noncanonical Wnt/Ror2/Jnk signaling activation in OCs overriding the negative effect that activation of canonical Wnt/β-catenin signaling has on OCgenesis.
El presente trabajo tiene como propósito reflexionar sobre las tendencias pedagógicas para el desarrollo de competencias científicas en el contexto del proceso de enseñanza-aprendizaje de las ciencias naturales, en aras de propiciar proyectos integradores y clases creativas, como contribución a propuestas innovadoras que posibiliten enfoques pedagógicos con nuevos escenarios y ambientes de aprendizajes renovados y creativos de las ciencias naturales. El ensayo es el resultado de un estudio de revisión bibliográfica, sustentado en la hermenéutica. Entre los hallazgos más significativos se encuentra que para alcanzar las competencias científicas en los educandos es fundamental que el docente propicie escenarios y ambientes de aprendizaje significativo a través de medios pedagógicos para dinamizar los procesos académicos centrados en la integralidad del conocimiento y la producción de sólidos saberes; de esta manera se asegura la calidad del proceso de enseñanza-aprendizaje de las ciencias naturales.
USA Today and The London Free Press offer two examples of the increasing rationalization of the North American newspaper industry. From a Weberian perspective, both are more formally rational at the organizational level than conventional newspapers. In addition, they also provide readers with a news product which is more instrumentally rational. Such a news product gives the reader a greater role in creating a sense of meaning out of the day's news. However, the move towards a more reader-centred news product diminishes the reporter's ability to provide subtextual commentary on the issues, people or events being covered. Furthermore, highly rationalized news formats contribute to the perception that newspapers can provide an impartial treatment of the subjects addressed in their pages. Résumé: USA Today et The London Free Press sont deux exemples de rationalisation dans l'industrie journalistique en Amérique du Nord. En effet, considérés d'un point de vue weberien, ils ont plus de rationalité formelle que les journaux traditionnels. Ils ont en outre plus de rationalité instrumentale que ceux-ci. Des produits journalistiques comme USA Today et The London Free Press permettent au lecteur de jouer un plus grand rôle dans la création du sens. Cependant, le développement de reportages centrés sur le lecteur entrave les journalistes qui voudraient commenter l'actualité plus à fond. De plus, les journaux dont la présentation de l'information est très rationalisée peuvent donner au public la fausse impression que leurs reportages sont impartiaux.
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