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Its location in the tracing of the Portuguese Way to Santiago de Compostela, its documented historical development and its constructive characteristics turn the Castellum Sancti Pelagii de Luto into a singular stronghold in the panorama of the military history of the medieval Galicia. This singularity leads us to offering the present bibliographical and documentary synthesis. ; Su localización en el trazado del Camino Portugués a Santiago de Compostela, su documentado devenir histórico y sus características constructivas convierten al Castellum Sancti Pelagii de Luto en una fortificación singular en el panorama de la historia militar de la Galicia medieval. Tal singularidad nos lleva a ofrecer la presente síntesis bibliográfico- documental.

20 páginas, 2 ortofotos. ; [ES] Su localización en el trazado del Camino Portugués a Santiago de Compostela, su documentado devenir histórico y sus características constructivas convierten al Castellum Sancti Pelagii de Luto en una fortificación singular en el panorama de la historia militar de la Galicia medieval. Tal singularidad nos lleva a ofrecer la presente síntesis bibliográfico- documental. ; [EN] Its location in the tracing of the Portuguese Way to Santiago de Compostela, its documented historical development and its constructive characteristics turn the Castellum Sancti Pelagii de Luto into a singular stronghold in the panorama of the military history of the medieval Galicia. This singularity leads us to offering the present bibliographical and documentary synthesis. ; Este artículo se ha realizado dentro del Proyecto de Investigación Dicionario Histórico dos Camiños de Santiago en Galicia. Plan Gallego de I+D+i. Clave: PGIDIT07PXID606078PR. ; Peer reviewed

Colaboración de Antonio Calderón-Rehecho y Alberto Raya Rienda ; Segunda edición 2021. Primera edición 2017, primera reimpresión 2018 ; Este trabajo recopila las tesis doctorales presentadas en la Facultad de Derecho de la Universidad Central de Madrid entre los años 1847, año en que se crea en la universidad española la tesis moderna, y 1914, ampliando esta segunda edición con los registros de los graduandos que alcanzaron el grado de doctor en esta misma facultad en el periodo inmediatamente anterior, 1845 a 1847, y en el que todavía no se exigía la presentación de una tesis doctoral; por ello el número total de registros en esta edición se amplía a 3.092, frente a los 3.073 de la edición anterior. El catálogo está ordenado cronológicamente, lo que facilitará al investigador secuenciar la evolución de una parte importante de la producción científica jurídica del país, y las tendencias de investigación de la Facultad en el periodo estudiado. Al catálogo le acompaña una amplia introducción en la que se estudia la legislación del doctorado en la España liberal y la metodología seguida en la confección del catálogo. Se cierra con varios apéndices que complementan el estudio: cuadro del profesorado de los curso de doctorado (por curso y onomástico), tabla con los planes de estudios vigentes a lo largo de los casi setenta años que abarca el trabajo, gráfica de las tesis presentadas por año. El índice final de graduandos facilita la consulta inmediata del catálogo. ; This work compiles the doctoral theses presented at the Faculty of Law of the Central University of Madrid between 1847, the year in which the modern thesis was created in the Spanish university, and 1914, expanding this second edition with the records of the graduates who achieved the degree of doctor in this same faculty in the immediately preceding period, 1845 to 1847, and in which the presentation of a doctoral thesis was not yet required; therefore, the total number of records in this edition is increased to 3,092, compared to the 3,073 of the previous edition. The catalogue is arranged chronologically, which makes it easier for the researcher to sequence the evolution of an important part of the country's legal scientific production, and the research trends of the Faculty in the period studied. The catalogue is accompanied by an extensive introduction which studies the legislation governing doctorates in liberal Spain and the methodology followed in compiling the catalogue. It closes with several appendices that complement the study: a table of the teaching staff of the doctoral courses (by course and onomastic), a table of the syllabuses in force over the almost seventy years covered by the work, and a graph of the theses presented by year. The final index of graduates facilitates immediate consultation of the catalogue. ; Esta investigación se ha realizado en el marco del proyecto "La memoria del jurista español: génesis y desarrollo de las disciplinas jurídicas" (ref. DER2014-55035-C2-2-P), financiado por el Ministerio de Economía, Industria y Competitividad (España).

SUMARIO: I. Semblanza.-II. Publicaciones de José D. Prat García—1. Monografías-2. Conferencias y discursos.-3. Artículos y ensayos.-4. Correspondencia y documentación política.-5. Prólogos, traducciones y comentarios.-III Debates parlamentarios-IV. Publicaciones sobre José D. Prat García - Fuentes consultadas.

SUMARIO: Introducción. 1.- Felipe II y su familia. 2.- La política de Felipe II. 3.- El momento cultural. Índice de autores y obras anónima

Abstract The transcriptional repressor DREAM (downstream regulatory element antagonist modulator) is a multifunctional neuronal calcium sensor (NCS) that controls Ca2+ and protein homeostasis through gene regulation and protein-protein interactions. Downregulation of DREAM is part of an endogenous neuroprotective mechanism that improves ATF6 (activating transcription factor 6) processing, neuronal survival in the striatum, and motor coordination in R6/2 mice, a model of Huntington's disease (HD). Whether modulation of DREAM activity can also ameliorate cognition deficits in HD mice has not been studied. Moreover, it is not known whether DREAM downregulation in HD is unique, or also occurs for other NCS family members. Using the novel object recognition test, we show that chronic administration of the DREAM-binding molecule repaglinide, or induced DREAM haplodeficiency delays onset of cognitive impairment in R6/1 mice, another HD model. The mechanism involves a notable rise in the levels of transcriptionally active ATF6 protein in the hippocampus after repaglinide administration. In addition, we show that reduction in DREAM protein in the hippocampus of HD patients was not accompanied by downregulation of other NCS family members. Our results indicate that DREAM inhibition markedly improves ATF6 processing in the hippocampus and that it might contribute to a delay in memory decline in HD mice. The mechanism of neuroprotection through DREAM silencing in HD does not apply to other NCS family members. ; This work was funded by the Instituto de Salud Carlos III/CIBERNED (to JRN, BM and AR), the Madrid regional government/Neurodegmodels (to JRN), and SAF2014–53412-R and SAF2017–89554-R (AEI-FEDER, EU) (to JRN).

DREAM, a neuronal calcium sensor protein, has multiple cellular roles including the regulation of Ca2+ and protein homeostasis. We recently showed that reduced DREAM expression or blockade of DREAM activity by repaglinide is neuroprotective in Huntington's disease (HD). Here we used structure-based drug design to guide the identification of IQM-PC330, which was more potent and had longer lasting effects than repaglinide to inhibit DREAM in cellular and in vivo HD models. We disclosed and validated an unexplored ligand binding site, showing Tyr118 and Tyr130 as critical residues for binding and modulation of DREAM activity. IQM-PC330 binding de-repressed c-fos gene expression, silenced the DREAM effect on KV4.3 channel gating and blocked the ATF6/DREAM interaction. Our results validate DREAM as a valuable target and propose more effective molecules for HD treatment ; This work was funded by the Spanish Ministery of Economy, Industry and Competitivity (AEI-FEDER, EU grants): BFU2015-67284-R (to M.G.R., R.H.), SAF2017-89554-R (to J.R.N.), SAF2016-75021-R (to C.V.) and SAF2015-66275-C2-2-R (to M.M.M.); the Instituto de Salud Carlos III CIBERNED and CIBERCV programs (to J.R.N. and to C.V., respectively) and the Madrid regional government/Neurodegmodels (to J.R.N.); CSIC grant PIE201880E109 (to M.G.R., R.H. and M.M.M.) and PIE201820E104 (to C.V.)

Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD ; This work was funded by the Instituto de Salud Carlos III/CIBERNED (to J.R. Naranjo, B. Mellström, and A. Rábano), FISS-RIC RD12/0042/0019 (to C. Valenzuela), Madrid regional government/Neurodegmodels (to J.R. Naranjo), MINECO grants SAF2010-21784 and SAF2014-53412-R (to J.R. Naranjo), SAF2012-32209 (to M. Gutierrez-Rodriguez), SAF2010-14916 and SAF2013-45800-R (to C. Valenzuela), and a grant from the Swedish Research Council (J.Y. Li)