The main objective of this work is to present and analyze the educational project of Darío Salas (1881-1941), the most important Chilean educator of the first half of the twentieth century. The first ...part is a brief biography. The second is a synthesis of his main work: The national problem, of 1917, in which he proposes a comprehensive educational reform and a "Law of Mandatory Primary Instruction." In the third part, the main comments of education historians on it are presented. Fourth, elements are presented for a new interpretation, complementary to the previous ones, on his teaching and research career, and on the validity of his social and educational thinking. The last section refers to the theoretical and political assumptions contained in his work, which allow us to deepen the analysis of the meaning of his thinking and his career.
El objetivo principal de este trabajo fue presentar y analizar el proyecto educativo de Darío Salas (1881-1941), el más importante educador chileno de la primera mitad del siglo veinte. La primera parte es una breve biografía. La segunda es una síntesis de su obra principal: El problema nacional, de 1917, en la que propone una amplia reforma educativa y una “Ley de Instrucción Primaria Obligatoria”. En la tercera parte se exponen los principales comentarios de historiadores de la educación sobre ella. En cuarto lugar, se presentan elementos para una nueva interpretación, complementaria a las anteriores, sobre su trayectoria docente e investigativa, y sobre la vigencia de su pensamiento social y educativo. La última sección se refiere a los supuestos teóricos y políticos que contiene su obra, los cuales permiten profundizar en el análisis del sentido de su pensamiento y su trayectoria.
El objetivo principal de este trabajo fue presentar y analizar el proyecto educativo de Darío Salas (1881-1941), el más importante educador chileno de la primera mitad del siglo veinte. La primera ...parte es una breve biografía. La segunda es una síntesis de su obra principal: El problema nacional, de 1917, en la que propone una amplia reforma educativa y una "Ley de Instrucción Primaria Obligatoria". En la tercera parte se exponen los principales comentarios de historiadores de la educación sobre ella. En cuarto lugar, se presentan elementos para una nueva interpretación, complementaria a las anteriores, sobre su trayectoria docente e investigativa, y sobre la vigencia de su pensamiento social y educativo. La última sección se refiere a los supuestos teóricos y políticos que contiene su obra, los cuales permiten profundizar en el análisis del sentido de su pensamiento y su trayectoria.
Posttranscriptional mechanisms are increasingly recognized as important contributors to the formation of hyperexcitable networks in epilepsy. Messenger RNA (mRNA) polyadenylation is a key regulatory ...mechanism governing protein expression by enhancing mRNA stability and translation. Previous studies have shown large-scale changes in mRNA polyadenylation in the hippocampus of mice during epilepsy development. The cytoplasmic polyadenylation element-binding protein CPEB4 was found to drive epilepsy-induced poly(A) tail changes, and mice lacking CPEB4 develop a more severe seizure and epilepsy phenotype. The mechanisms controlling CPEB4 function and the downstream pathways that influence the recurrence of spontaneous seizures in epilepsy remain poorly understood.
Status epilepticus was induced in wild-type and CPEB4-deficient male mice via an intra-amygdala microinjection of kainic acid. CLOCK binding to the CPEB4 promoter was analyzed via chromatin immunoprecipitation assay and melatonin levels via high-performance liquid chromatography in plasma.
Here, we show increased binding of CLOCK to recognition sites in the CPEB4 promoter region during status epilepticus in mice and increased Cpeb4 mRNA levels in N2A cells overexpressing CLOCK. Bioinformatic analysis of CPEB4-dependent genes undergoing changes in their poly(A) tail during epilepsy found that genes involved in the regulation of circadian rhythms are particularly enriched. Clock transcripts displayed a longer poly(A) tail length in the hippocampus of mice post-status epilepticus and during epilepsy. Moreover, CLOCK expression was increased in the hippocampus in mice post-status epilepticus and during epilepsy, and in resected hippocampus and cortex of patients with drug-resistant temporal lobe epilepsy. Furthermore, CPEB4 is required for CLOCK expression after status epilepticus, with lower levels in CPEB4-deficient compared to wild-type mice. Last, CPEB4-deficient mice showed altered circadian function, including altered melatonin blood levels and altered clustering of spontaneous seizures during the day.
Our results reveal a new positive transcriptional-translational feedback loop involving CPEB4 and CLOCK, which may contribute to the regulation of the sleep-wake cycle during epilepsy.
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