Premios que ofrece la Real Sociedad Económica de Amigos del País de Valencia para el día 9 de diciembre de 1806 [Texto impreso]

Tomás de Otero, secretario

1866-1870: Richard Baxter Foster

1st PrincipalIn Office: 1866-1870

O problema do direito civil do imigrante e a queda do gabinete de olinda, 1866

Bibliografia

RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism

We have generated RANK (receptor activator of NF-κB) nullizygous mice to determine the molecular genetic interactions between osteoprotegerin, osteoprotegerin ligand, and RANK during bone resorption and remodeling processes. RANK−/− mice lack osteoclasts and have a profound defect in bone resorption and remodeling and in the development of the cartilaginous growth plates of endochondral bone. The osteopetrosis observed in these mice can be reversed by transplantation of bone marrow from rag1−/− (recombinase activating gene 1) mice, indicating that RANK−/− mice have an intrinsic defect in osteoclast function. Calciotropic hormones and proresorptive cytokines that are known to induce bone resorption in mice and human were administered to RANK−/− mice without inducing hypercalcemia, although tumor necrosis factor α treatment leads to the rare appearance of osteoclast-like cells near the site of injection. Osteoclastogenesis can be initiated in RANK−/− mice by transfer of the RANK cDNA back into hematopoietic precursors, suggesting a means to critically evaluate RANK structural features required for bone resorption. Together these data indicate that RANK is the intrinsic cell surface determinant that mediates osteoprotegerin ligand effects on bone resorption and remodeling as well as the physiological and pathological effects of calciotropic hormones and proresorptive cytokines.

Role of the proteasome and NF-κB in streptococcal cell wall-induced polyarthritis

The transcription factor NF-κB activates a number of genes whose protein products are proinflammatory. In quiescent cells, NF-κB exists in a latent form and is activated via a signal-dependent proteolytic mechanism in which the inhibitory protein IκB is degraded by the ubiquitin–proteasome pathway. Consequently, inhibition of the proteasome suppresses activation of NF-κB. This suppression should therefore decrease transcription of many genes encoding proinflammatory proteins and should ultimately have an anti-inflammatory effect. To this end, a series of peptide boronic acid inhibitors of the proteasome, exemplified herein by PS-341, were developed. The proteasome is the large multimeric protease that catalyzes the final proteolytic step of the ubiquitin–proteasome pathway. PS-341, a potent, competitive inhibitor of the proteasome, readily entered cells and inhibited the activation of NF-κB and the subsequent transcription of genes that are regulated by NF-κB. Significantly, PS-341 displayed similar effects in vivo. Oral administration of PS-341 had anti-inflammatory effects in a model of Streptococcal cell wall-induced polyarthritis and liver inflammation in rats. The attenuation of inflammation in this model was associated with an inhibition of IκBα degradation and NF-κB-dependent gene expression. These experiments clearly demonstrate that the ubiquitin–proteasome pathway and NF-κB play important roles in regulating chronic inflammation and that, as predicted, proteasome inhibition has an anti-inflammatory effect.

Guerras europeas, conflictos civiles, proyectos nacionales. Una interpretación de las restauraciones napolitanas (1799-1866)

La elección de examinar la contrarrevolución a través de sus mayores éxitos, las cuatro restauraciones victoriosas, y su derrota, la restauración fallida, puede enriquecer las perspectivas tradicionales sobre la resistencia y la crisis del Reino de las dos Sicilias. Los conflictos europeos, las guerras civiles, las construcciones estatales y la creación de identidades nacionales modernas son fenómenos que se entrecruzan con la complicada historia del reino napolitano. A través de la perspectiva de las restauraciones, bien dinásticas (1799 y 1815), o bien absolutistas (1821 y 1849), podemos insertar en un esquema interpretativo general la dialéctica entre conflicto interno y crisis internacionales, la interrelación con la formación de las ideas y adscripciones nacionalistas y la comparación con la contrarrevolución en el mundo borbónico. El paradigma del conflicto nos permite también el contraste con el más amplio mundo borbónico, francés y, sobre todo, iberoamericano. De este modo podemos reflexionar tanto sobre el éxito del legitimismo napolitano como sobre los términos de su derrota en 1860 y sobre las razones de su reciente fortuna en el imaginario colectivo italiano.