6 research outputs found
El diagnóstico psicopedagógico para la inclusión socioeducativa de los escolares con necesidades educativas especiales
El presente artículo expone los resultados obtenidos como parte del trabajo desarrollado en una de las tareas del proyecto de investigación “La Pedagogía Especial como sustento para la inclusión socioeducativa de los escolares con necesidades educativas especiales (NEE)”, dirigida a la elaboración de acciones didáctico metodológicas para la realización del diagnóstico psicopedagógico como sustento de la inclusión socioeducativa de los escolares con NEE. Desde una perspectiva cualitativa, considerando como grupos de enfoque a los docentes de instituciones de los diferentes niveles educativos de la ciudad de Santa Clara, provincia Villa Clara, Cuba, quienes participaron en un curso de entrenamiento impartido en el contexto del referido proyecto de investigación, se logró la elaboración, a partir del criterio colectivo, de acciones relativas a la preparación teórica y determinación de aspectos e indicadores que guíen el proceso de diagnóstico; recopilación de datos empíricos acerca del alumno y sus entornos; elaboración de la caracterización psicopedagógica del alumno; la construcción de la estrategia dirigida a favorecer la inclusión socioeducativa de cada alumno y las relativas al seguimiento y retroalimentación del proceso de diagnóstico psicopedagógico
Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer
Aberrant transcriptional activity of androgen receptor (AR) is one of the dominant mechanisms for developing of castration-resistant prostate cancer (CRPC). Analyzing AR-transcriptional complex related to CRPC is therefore important towards understanding the mechanism of therapy-resistance. While studying its mechanism, we observed that a transmembrane protein called neuropilin-2 (NRP2) plays a contributory role in forming a novel AR-transcriptional complex containing nuclear pore proteins. Using immunogold electron microscopy, high-resolution confocal microscopy, chromatin immunoprecipitation, proteomics, and other biochemical techniques, we delineated the molecular mechanism of how a specific splice variant of NRP2 becomes sumoylated upon ligand stimulation and translocates to the inner nuclear membrane. This splice variant of NRP2 then stabilizes the complex between AR and nuclear pore proteins to promote CRPC specific gene expression. Both full-length and splice variants of AR have been identified in this specific transcriptional complex. In vitro cell line-based assays indicated that depletion of NRP2 not only destabilizes the AR-nuclear pore protein interaction but also inhibits the transcriptional activities of AR. Using an in vivo bone metastasis model, we showed that the inhibition of NRP2 led to the sensitization of CRPC cells toward established anti-AR therapies such as enzalutamide. Overall, our finding emphasize the importance of combinatorial inhibition of NRP2 and AR as an effective therapeutic strategy against treatment refractory prostate cancer
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Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer
Aberrant transcriptional activity of androgen receptor (AR) is one of the dominant mechanisms for developing of castration-resistant prostate cancer (CRPC). Analyzing AR-transcriptional complex related to CRPC is therefore important towards understanding the mechanism of therapy resistance. While studying its mechanism, we observed that a transmembrane protein called neuropilin-2 (NRP2) plays a contributory role in forming a novel AR-transcriptional complex containing nuclear pore proteins. Using immunogold electron microscopy, high-resolution confocal microscopy, chromatin immunoprecipitation, proteomics, and other biochemical techniques, we delineated the molecular mechanism of how a specific splice variant of NRP2 becomes sumoylated upon ligand stimulation and translocates to the inner nuclear membrane. This splice variant of NRP2 then stabilizes the complex between AR and nuclear pore proteins to promote CRPC specific gene expression. Both full-length and splice variants of AR have been identified in this specific transcriptional complex. In vitro cell line-based assays indicated that depletion of NRP2 not only destabilizes the AR-nuclear pore protein interaction but also inhibits the transcriptional activities of AR. Using an in vivo bone metastasis model, we showed that the inhibition of NRP2 led to the sensitization of CRPC cells toward established anti-AR therapies such as enzalutamide. Overall, our finding emphasize the importance of combinatorial inhibition of NRP2 and AR as an effective therapeutic strategy against treatment refractory prostate cancer