Suchergebnisse

El presente texto analiza en su totalidad y contexto el juicio de residencia incoado al virrey Melchor de Navarra. Tal enfoque analítico constata cómo la lista de cargos y sucesivas sentencias no constituyen un fiel reflejo de su gestión, ni de las supuestas faltas que pudo cometer. Es más, manifiesta una pugna latente con el juez residenciador, junto a la movilización de todo tipo de recursos para decantar a su favor un proceso inicialmente adverso, bien por cauces legales, bien por otros que traspasaron la legalidad o lo moralmente aceptado. De este modo, los resultados obtenidos permiten esbozar una lectura más amplia, compleja y sutil del propio procedimiento, al mismo tiempo que del accionar y de las potenciales prácticas ilícitas de este vicesoberano rebatiendo formulaciones hasta ahora sostenidas.

Links, Friendships and Avisos in Golden Age Castile: an approximation to the newsletter between Jerónimo de Barrionuevo and Lorenzo Francés de Urrutigoyti.This text explores the importance of social action and interpersonal links in 17th century information systems by focusing specifically on the vertebrate between Jerónimo de Bar-rionuevo and Lorenzo Francés de Urrutigoyti. To this end is used an analytical approach limitated to social practices and dynamics focused on the Avisos elaborated by Barrionue-vo, which has hardly been contemplated and even less systematically executed by histori-ography. In this way, are inquired the nature, dynamics and practices of a structure theo-retically circumscribed to these two actors articulated between Madrid and Sigüenza, but which actually encompassed a conglomerate of individuals settled in multiple places, who intervened and, to a large extent, enabled, hindered or are benefited in one way or another from the generated news. A process, without forgetting, framed in an era of informative maelstrom and development of a public sphere where the power of information was a crucial instrument in political and social praxis ; El presente texto explora la importancia de la acción social y los vínculos interpersonales en los sistemas informativos del siglo XVII centrándose, específicamente, en el mantenido entre Jerónimo de Barrionuevo y Lorenzo Francés de Urrutigoyti. Para ello, se recurre a un enfoque analítico focalizado a las prácticas y dinámicas sociales plasmado en los Avisoselaborados por el propio Barrionuevo, el cual apenas ha sido contemplado y menos aún ejecutado sistemáticamente por la historiografía. De este modo, se indaga en la natura-leza, dinámicas y prácticas de un sistema informativo teóricamente circunscrito a estos dos actores desarrollado entre Madrid y Sigüenza, pero que en realidad englobaba a un conglomerado de individuos afincados en múltiples lugares, quienes intervinieron y, en buena medida, posibilitaron, obstaculizaron o se beneficiaron de una ...

El presente estudio se ha realizado en el marco del Proyecto de Investigación de I+D Dinámicas de corrupción en España y América en los siglos XVII y XVIII: prácticas y mecanismos de control (HAR2017-86463-P), financiado por el MINECO. ; El presente texto explora la importancia de la acción social y los vínculos interpersonales en los sistemas informativos del siglo XVII centrándose, específicamente, en el mantenido entre Jerónimo de Barrionuevo y Lorenzo Francés de Urrutigoyti. Para ello, se recurre a un enfoque analítico focalizado a las prácticas y dinámicas sociales plasmado en los Avisos elaborados por el propio Barrionuevo, el cual apenas ha sido contemplado y menos aún ejecutado sistemáticamente por la historiografía. De este modo, se indaga en la naturaleza, dinámicas y prácticas de un sistema informativo teóricamente circunscrito a estos dos actores desarrollado entre Madrid y Sigüenza, pero que en realidad englobaba a un conglomerado de individuos afincados en múltiples lugares, quienes intervinieron y, en buena medida, posibilitaron, obstaculizaron o se beneficiaron de una forma u otra del caudal noticioso generado. Un proceso, sin olvidar, enmarcado en una época de vorágine informativa y desarrollo de una esfera pública donde el poder de la información era un instrumento crucial en la praxis política y social. ; This text explores the importance of social action and interpersonal links in 17th century information systems by focusing specifically on the vertebrate between Jerónimo de Barrionuevo and Lorenzo Francés de Urrutigoyti. To this end is used an analytical approach limitated to social practices and dynamics focused on the Avisos elaborated by Barrionuevo, which has hardly been contemplated and even less systematically executed by historiography. In this way, are inquired the nature, dynamics and practices of a structure theoretically circumscribed to these two actors articulated between Madrid and Sigüenza, but which actually encompassed a conglomerate of individuals settled in multiple places, who intervened and, to a large extent, enabled, hindered or are benefited in one way or another from the generated news. A process, without forgetting, framed in an era of informative maelstrom and development of a public sphere where the power of information was a crucial instrument in political and social praxis.

Quienes transitamos la inconmensurable tarea de la enseñanza del derecho, conocemos la pasión por transmitir esa gran disciplina, asimismo existen colegas que se encuentran desanimados por no lograr el objetivo máximo del docente, que es captar la atención del alumno, pero dicha tarea se torna compleja, aunque no por ello menos grata, cuando el desafío se da en facultades, donde el derecho no es la principal disciplina a aprehender, o cuando forma parte de las denominadas materias no troncales; en nuestro caso al enseñar Derecho en una Facultad de Ciencias Económicas, convivimos desde hace varios años en la incertidumbre que los cambios en la economía traen aparejados, cambios en la forma de realizar negocios, desembarco de formas contractuales aún no legisladas y que pueden adolecer de falta de seguridad jurídica, o casos donde lo legal colisiona con lo económico, además de integrar planteles docentes con quienes enseñan disciplinas llamadas dinámicas, y quienes mal consideran al Derecho, como una disciplina estática y poco permeable a los cambios. Sin lugar a dudas la última década trajo consigo un sinnúmero de reformas legislativas y adecuaciones a institutos que si bien en la práctica ya eran conocidos y utilizados, aún no estaban incorporados al marco legislativo vigente. ; Facultad de Ciencias Jurídicas y Sociales

Presentación Dossier

This is an Open Access article distributed under the terms of the Creative Commons Attribution License. ; [Background]: Activation of microglia, the primary component of the innate immune response in the brain, is a hallmark of neuroinflammation in neurodegenerative disorders, including Alzheimer's disease (AD) and other pathological conditions such as stroke or CNS infection. In response to a variety of insults, microglial cells produce high levels of inflammatory cytokines that are often involved in neuronal injury, and play an important role in the recognition, engulfment, and clearance of apoptotic cells and/or invading microbes. Secreted phospholipase A2-IIA (sPLA2-IIA), an enzyme that interacts with cells involved in the systemic immune/inflammatory response, has been found up-regulated in the cerebrospinal fluid and brain of AD patients. However, despite several approaches, its functions in mediating CNS inflammation remain unknown. In the present study, the role of sPLA2-IIA was examined by investigating its direct effects on microglial cells. [Methods]: Primary and immortalized microglial cells were stimulated by sPLA2-IIA in order to characterize the cytokine-like actions of the phospholipase. The hallmarks of activated microglia analyzed include: mitogenic response, phagocytic capabilities and induction of inflammatory mediators. In addition, we studied several of the potential molecular mechanisms involved in those events. [Results]: The direct exposure of microglial cells to sPLA2-IIA stimulated, in a time- and dose-dependent manner, their phagocytic and proliferative capabilities. sPLA2-IIA also triggered the synthesis of the inflammatory proteins COX-2 and TNFα. In addition, EGFR phosphorylation and shedding of the membrane-anchored heparin-binding EGF-like growth factor (pro-HB-EGF) ectodomain, as well as a rapid activation/phosphorylation of the classical survival proteins ERK, P70S6K and rS6 were induced upon sPLA2-IIA treatment. We further demonstrated that the presence of an EGFR inhibitor (AG1478), a matrix metalloproteinase inhibitor (GM6001), an ADAM inhibitor (TAPI-1), and a HB-EGF neutralizing antibody abrogated the phenotype of activated microglia induced by the sPLA2-IIA. [Conclusion]: These results support the hypothesis that sPLA2-IIA may act as a potent modulator of microglial functions through its ability to induce EGFR transactivation and HB-EGF release. Accordingly, pharmacological modulation of EGFR might be a useful tool for treating neuroinflammatory diseases characterized by sPLA2-IIA accumulation. ; This work was supported by grants SAF2009-08407 from the Spanish Ministry of Science and Innovation, and CSI11A08 from the Government of Castilla y León. Claudia Cordova was funded by the FPI Program from the Government of Castilla y León (co-funded by FSE). ; Peer Reviewed

Navigating the academic-practitioner divide in intelligence studies / Rubén Arcos, Nicole K. Drumhiller, Mark Phythian -- Being on the outside looking in : reflections of a former practitioner turned academic / David Omand -- Neither knuckle-draggers nor carpetbaggers : proposing the Periclean ideal for intelligence educators / Nicholas Dujmović -- Intelligence, science and the ignorance hypothesis / David R. Mandel -- Intelligence and the US Army War College : the academic-practitioner relationship in professional military education / Genevieve Lester, James G. Breckenridge, and Thomas Spahr -- Assessing the quality of strategic intelligence products : cooperation and competition between scholars and practitioners / José-Miguel Palacios -- Lessons learned for the private sector intelligence analyst / Michael J. Ard -- Understanding and countering hybrid threats through a comprehensive and multinational approach : the role of intelligence / Rasmus Hindren and Hanna Smith -- Building ecosystems of intelligence education : "the good, the bad, and the ugly" / Irena Chiru and Adrian-Liviu Ivan -- The academic-practitioner relationship in France : from strangers to partners / Damien Van Puyvelde -- Playing to our strengths : combining academic rigour and practitioner experience in delivering intelligence education in Australia / Troy Whitford and Charles Vandepeer -- The academic/practitioner divide in intelligence : a Latin American perspective / Andrés de Castro García and Carolina Sancho Hirane -- Teaching ethical intelligence in a world that doesn't think it needs it / Jan Goldman -- Bridging the divide / Rubén Arcos, Nicole K. Drumhiller, Mark Phythian.

Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating diseases that develop as a result of deregulated immune responses causing glial activation and destruction of CNS tissues. Oleanolic acid and erythrodiol are natural triterpenes that display strong anti-inflammatory and immunomodulatory activities. Oleanolic acid beneficially influences the course of established EAE. We now extend our previous observations to erythrodiol and address the efficacy of both compounds to protect against EAE, given under different regimens. ; The utility of both triterpenes in disease prevention was evaluated at a clinical and molecular level: in vivo through their prophylactic administration to myelin oligodendrocyte protein-immunized C57BL/6 mice, and in vitro through their addition to stimulated-BV2 microglial cells. ; These triterpenes protected against EAE by restricting infiltration of inflammatory cells into the CNS and by preventing blood–brain barrier disruption. Triterpene-pretreated EAE-mice exhibited less leptin secretion, and switched cytokine production towards a Th2/regulatory profile, with lower levels of Th1 and Th17 cytokines and higher expression of Th2 cytokines in both serum and spinal cord. Triterpenes also affected the humoral response causing auto-antibody production inhibition. In vitro, triterpenes inhibited ERK and rS6 phosphorylation and reduced the proliferative response, phagocytic properties and synthesis of proinflammatory mediators induced by the addition of inflammatory stimuli to microglia. ; Both triterpenes restricted the development of the characteristic features of EAE. We envision these natural products as novel helpful tools for intervention in autoimmune and neurodegenerative diseases including MS. ; This work was supported by grants SAF2009-08407 from the Spanish Ministry of Science and Innovation, and CSI11A08 from the Autonomous Government of Castilla y León. ; Peer reviewed

Glioblastoma, the most aggressive type of primary brain tumour, shows worse prognosis linked to diabetes or obesity persistence. These pathologies are chronic inflammatory conditions characterized by altered profiles of inflammatory mediators, including leptin and secreted phospholipase A2-IIA (sPLA2-IIA). Both proteins, in turn, display diverse pro-cancer properties in different cell types, including astrocytes. Herein, to understand the underlying relationship between obesity and brain tumors, we investigated the effect of leptin, alone or in combination with sPLA2-IIA on astrocytoma cell functions. sPLA2-IIA induced up-regulation of leptin receptors in 1321N1 human astrocytoma cells. Leptin, as well as sPLA2-IIA, increased growth and migration in these cells, through activation/phosphorylation of key proteins of survival cascades. Leptin, at concentrations with minimal or no activating effects on astrocytoma cells, enhanced growth and migration promoted by low doses of sPLA2-IIA. sPLA2-IIA alone induced a transient phosphorylation pattern in the Src/ERK/Akt/mTOR/p70S6K/rS6 pathway through EGFR transactivation, and co-addition of leptin resulted in a sustained phosphorylation of these signaling regulators. Mechanistically, EGFR transactivation and tyrosine- and serine/threonine-protein phosphatases revealed a key role in this leptin-sPLA2-IIA cross-talk. This cooperative partnership between both proteins was also found in primary astrocytes. These findings thus indicate that the adipokine leptin, by increasing the susceptibility of cells to inflammatory mediators, could contribute to worsen the prognosis of tumoral and neurodegenerative processes, being a potential mediator of some obesity-related medical complications. ; This work was supported by the FPI Program from the Autonomous Government of Castilla y Leon (to RM and CC) co-funded by FSE, and by the Spanish Ministry of Science and Innovation (grant SAF2009-08407 and SAF2016-81063). ; Peer Reviewed

10 páginas, 5 figuras. ; We have investigated mechanisms that contribute to reinforce the relationship between inflammation and cancer. Secreted phospholipase A2 group IIA (sPLA2-IIA) is a molecule relevant in inflammatory events and has been proposed as a marker for some of these. Previously, we reported the mitogenic properties of this sPLA2 in the human astrocytoma cell line 1321N1. Here, we go deeper into the mechanisms that link this inflammatory protein with proliferation in one of the most aggressive types of tumors. We found that phosphorylation of the extracellular regulated kinase (ERK) was preceded by the activation of the small GTPase Ras, and both failed to be activated by inhibiting protein kinase C (PKC). Fractionation and immunofluorescence studies revealed translocation of PKC alpha, delta, and epsilon to the membrane fraction upon stimulation with sPLA2-IIA. Immunoprecipitation analysis showed that sPLA2-IIA induces phosphorylation of the epidermal growth factor receptor (EGFR) through a PKC-dependent pathway. We found that phosphorylation of this receptor contributed to Ras and ERK activation and that inhibition of ERK, PKC, and EGFR blocked the mitogenic response induced by sPLA2-IIA. This study showed that sPLA2-IIA is able to bring into play EGFR to trigger its signaling and that PKC leads the distribution of resources. Interestingly, we found that this is not a cell-specific response, because sPLA2-IIA was also able to transactivate EGFR in MCF7 human breast cancer cells. Therefore, this mechanism could contribute to worsen the prognosis of a tumor in an inflammatory microenvironment. We also present more links of the tumor chain possibly susceptible to targeting. ; This work was supported by the Ramón y Cajal Program (to M.H.), F.P.I. Program from the Autonomous Government of Castilla y León. (to R.M.), both cofunded by F.S.E and by the ISCIII, Red de Centros RECAVA, C03/01 (to P.M.H. and M.D.G.C.), and by grants SAF2005-01242 and SAF2009-08407 from the Spanish Ministry of Science and Innovation, and CSI11A08 from the Autonomous Government of Castilla y León. ; Peer reviewed

[Background]: Triterpene alcohols and acids are multifunctional compounds widely distributed throughout the plant kingdom that exhibit a variety of beneficial health properties, being synthetic analogs of oleanolic acid under clinical evaluation as anti-tumoral therapeutic agents. However, the antineoplastic activity of two natural occuring triterpenoid alcohols extracted from olive oil, erythrodiol (an intermediate from oleanolic acid), and its isomer, uvaol, has barely been reported, particularly on brain cancer cells. Astrocytomas are among the most common and aggressive type of primary malignant tumors in the neurological system lacking effective treatments, and in this study, we addressed the effect of these two triterpenic diols on the human 1321N1 astrocytoma cell line. ; [Principal Findings]: Erythrodiol and uvaol effectively affected cell proliferation, as well as cell cycle phases and induced 1321N1 cell death. Both triterpenes successfully modulated the apoptotic response, promoting nuclear condensation and fragmentation. They caused retraction and rounding of cultured cells, which lost adherence from their supports, while F-actin and vimentin filaments disappeared as an organized cytoplasmic network. At molecular level, changes in the expression of surface proteins associated with adhesion or death processes were also observed. Moreover, triterpene exposure resulted in the production of reactive oxygen species (ROS) with loss of mitochondrial transmembrane potential, and correlated with the activation of c-Jun N-terminal kinases (JNK). The presence of catalase reversed the triterpenic diols-induced mitochondrial depolarization, JNK activation, and apoptotic death, indicating the critical role of ROS in the action of these compounds. ; [Conclusions]: Overall, we provide a significant insight into the anticarcinogenic action of erythrodiol and uvaol that may have a potential in prevention and treatment of brain tumors and other cancers. ; This study has been funded by a grants SAF2005-01242, SAF2008-00245 and AGL2008-022845 from MICINN, and CSI11A08 from the Government of Castilla y Leon. MH is under the Ramon y Cajal Program (Co-funded by F.S.E.). E.I., R.M. and J.C-T. are supported by a fellowship from the Spanish Ministerio de Educación y Ciencia. ; Peer reviewed

Human group IIA secreted phospholipase A2 (sPLA2-IIA) has been characterized in numerous inflammatory and neoplastic conditions. sPLA2-IIA can either promote or inhibit cell growth depending on the cellular type and the specific injury. We have previously demonstrated that exogenous sPLA2-IIA, by engagement to a membrane structure, induces proliferation and activation of mitogen-activated protein kinases cascade in human astrocytoma cells. In this study, we used human astrocytoma 1321N1 cells to investigate the key molecules mediating sPLA2-IIA-induced cell proliferation. We found that sPLA2-IIA promoted reactive oxygen species (ROS) accumulation, which was abrogated in the presence of allopurinol and DPI, but not by rotenone, discarding mitochondria as a ROS source. In addition, sPLA2-IIA triggered Ras and Raf-1 activation, with kinetics that paralleled ERK phosphorylation, and co-immunoprecipitation assays indicated an association between Ras, Raf-1 and ERK. Additionally, Akt, p70 ribosomal protein S6 kinase, and S6 ribosomal protein were also phosphorylated upon sPLA2-IIA treatment, effect that was abrogated by N-acetylcysteine or LY294002 treatment indicating that ROS and phosphatidylinositol 3 kinase are upstream signaling regulators. As the inhibitors N-acetylcysteine, PD98059, LY294002 or rapamycin blocked sPLA 2-IIA-induced proliferation without activation of the apoptotic program, we suggest that inhibition of these intracellular signal transduction elements may represent a mechanism of growth arrest. Our results reveal new potential targets for therapeutic intervention in neuroinflammatory disorders and brain cancer in particular. © 2009 International Society for Neurochemistry. ; This work was supported by the Ramón y Cajal Program (to M. H.), F. P. I. Program from the Government of Castilla y Leon. (to R. M.) both co-funded by F. S. E, Grants SAF2005-01242 and SAF2008-00245 from the Ministry of Science and Technology, and Grant CSI11A08 from the Government of Castilla y León. ; Peer Reviewed