Representación que Francisco Peyro, proto-albeytar [sic] del Reino manda al Rey Don Carlos solicitando le sean reconocidos sus derechos de Albeytería [sic] y resolución real confirmando dichos derechos [Texto impreso]

Hay un ejemplar encuadernado con: Pragmatica que su Magestad ha mandado promulgar revalidando los anteriores en qu ese prohibe el uso de armas blancas cortas y las de fuego ... (XVIII/4280).

Triplex forming oligonucleotide targeted to 3′UTR downregulates the expression of the bcl-2 proto-oncogene in HeLa cells

The bcl-2 proto-oncogene is overexpressed in a variety of human cancers and plays an important role in programmed cell death. Recent reports implied that the 3′-untranslated region (3′UTR) functions effectively in the regulation of gene expression. Here, we attempt to assay the ability of triplex forming oligonucleotides (TFOs) to inhibit expression of a target gene in vivo and to examine the potential of the 3′UTR of the bcl-2 proto-oncogene in the regulation of bcl-2 gene expression. To do this, we have developed a novel cellular system that involves transfection of a Doxycyclin inducible expression plasmid containing the bcl-2 ORF and the 3′UTR together with a TFO targeted to the 3′UTR of the bcl-2 proto-oncogene. Phosphorothioate-modified TFO targeted to the 3′UTR of the bcl-2 gene significantly downregulated the expression of the bcl-2 gene in HeLa cells as demonstrated by western blotting. Our results indicate that blocking the functions of the 3′UTR using the TFO can downregulate the expression of the targeted gene, and suggest that triplex strategy is a promising approach for oligonucleotide-based gene therapy. In addition, triplex-based sequence targeting may provide a useful tool for studying the regulation of gene expression.

Triplex targeting of human PDGF-B (c-sis, proto-oncogene) promoter specifically inhibits factors binding and PDGF-B transcription

Human c-sis/PDGF-B proto-oncogene has been shown to be overexpressed in a large percentage of human tumor cells establishing a growth-promoting, autocrine growth circuit. Triplex forming oligonucleotides (TFOs) can recognize and bind sequences in duplex DNA, and have received considerable attention because of their potential for targeting specific genomic sites. The c-sis/PDGF-B promoter contains a unique homopurine/homopyrimidine sequence (SIS proximal element, SPE), which is crucial for binding nuclear factors that provoke transcription. In order to develop specific transcriptional inhibitors of the human c-sis/PDGF-B proto-oncogene, 20 potential TFOs targeting part or all of the SPE were screened by gel mobility analysis. DNase I footprinting shows that the TFOs we designed can form a sequence-specific triplex with the target. Protein binding assays demonstrate that triplex formation inhibits nuclear factors binding the c-sis/PDGF-B promoter. Both transient and stable transfection experiments demonstrate that the transcriptional activity of the promoter is considerably inhibited by the TFOs. We propose that TFOs represent a therapeutic potential to specifically diminish the expression of c-sis/PDGF-B proto-oncogene in various pathologic settings where constitutive expression of this gene has been observed.

E2F-dependent transcription of the raf proto-oncogene during Drosophila development

D-raf, a Drosophila homolog of the raf proto-oncogene, has diverse functions throughout development and is transcribed in a wide range of tissues, with high levels of expression in the ovary and in association with rapid proliferation. The expression pattern resembles those of S phase genes, which are regulated by E2F transcription factors. In the 5′-flanking region of D-raf, four sequences (E2F sites 1–4) similar to the E2F recognition sequence were found, one of them (E2F site 3) being recognized efficiently by Drosophila E2F (dE2F) in vitro. Transient luciferase expression assays confirmed activation of the D-raf gene promoter by dE2F/dDP. Expression of Draf–lacZ was greatly reduced in embryos homozygous for the dE2F mutation. These results suggest that dE2F is likely to be an important regulator of D-raf transcription.

Axotomized neonatal motoneurons overexpressing the bcl2 proto-oncogene retain functional electrophysiological properties.

Bcl2 overexpression prevents axotomy-induced neuronal death of neonatal facial motoneurons, as defined by morphological criteria. However, the functional properties of these surviving lesioned transgenic neurons are unknown. Using transgenic mice overexpressing the protein Bcl2, we have investigated the bioelectrical properties of transgenic facial motoneurons from 7 to 20 days after neonatal unilateral axotomy using brain-stem slices and whole cell patch-clamp recording. Nonaxotomized facial motoneurons from wild-type and transgenic mice had similar properties; they had an input resistance of 38 +/- 6 M omega and fired repetitively after injection of positive current pulses. When cells were voltage-clamped at or near their resting membrane potential, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartic acid (NMDA), or vasopressin generated sustained inward currents. In transgenic axotomized mice, facial motoneurons could be found located ipsilaterally to the lesion; they had an input resistance of 150 +/- 30 M omega, indicating that they were smaller in size, fired repetitively, and were also responsive to AMPA, NMDA, and vasopressin. Morphological measurements achieved 1 week after the lesion have shown that application of brain-derived neurotrophic factor prevented the reduction in size of axotomized transgenic motoneurons. These data indicate that Bcl2 not only prevents morphological apoptotic death of axotomized neonatal transgenic motoneurons but also permits motoneurons to conserve functional electrophysiological properties.

Myc and Max: molecular evolution of a family of proto-oncogene products and their dimerization partner.

The myc gene family encodes a group of transcription factors that regulate cell proliferation and differentiation. These genes are widely studied because of their importance as proto-oncogenes. Phylogenetic analyses are described here for 45 Myc protein sequences representing c-, N-, L-, S-, and B-myc genes. A gene duplication early in vertebrate evolution produced the c-myc lineage and another lineage that later gave rise to the N- and L-myc lineages by another gene duplication. Evolutionary divergence in the myc gene family corresponds closely to the known branching order of the major vertebrate groups. The patterns of sequence evolution are described for five separate highly conserved regions, and these analyses show that differential rates of sequence divergence (= mosaic evolution) have occurred among conserved motifs. Further, the closely related dimerization partner protein Max exhibits significantly less sequence variability than Myc. It is suggested that the reduced variability in max stems from natural selection acting to preserve dimerization capability with products of myc and related genes.

PROTO-COL. Aportaciones de una red interuniversitaria para la formación en protocolo y eventos (2010-2015)

Este proyecto de innovación docente denominado “Proto-col: red interuniversitaria de trabajo colaborativo en protocolo y gestión de eventos” se ha desarrollado durante los últimos cinco cursos académicos (2010-2011, 2011-2012, 2012-2013, 2013-2014, 2014-2015) y constituye en la actualidad un grupo de trabajo consolidado, en el que sus miembros han compartido un ejercicio de reflexión sobre las capacidades, habilidades y destrezas en este ámbito, por parte de los estudiantes de los Grados en Publicidad y Relaciones Públicas ofertados por la Universidad de Alicante y la Universitat Jaume I de Castellón. Para ello, durante estos años, se ha trabajado en el diseño de metodología didáctica aplicada a las asignaturas optativas vinculadas al protocolo y la gestión de eventos, y se han realizado diferentes investigaciones exploratorias sobre perfiles profesionales o la presencia de materias vinculadas a la gestión de eventos, el protocolo y las relaciones institucionales en las universidades españolas. Todas estas aportaciones, junto con la participación en cursos de especialización y másteres universitarios, la realización de proyectos académicos, la dirección de TFGs, TFMs y tesis doctorales reflejan el trabajo colaborativo de un grupo de profesores especializados en esta materia y justifica la pertinencia de este proyecto interuniversitario que se ha traducido en diversas contribuciones académicas y experiencias de enseñanza-aprendizaje.

Forms and role of the cluster initiatives in fostering innovation in post-industrial regions: A comparative study of environmental clusters in British West Midlands and Spanish Basque country. ACES Working Paper No. 8, August 2008

The objective of this research is to present cluster initiative approaches in post industrial regions characterized by similar economic history and challenges, with additional emphasis on their role in promoting innovation among regional businesses. The research is based on a comparison study of two environmental industry clusters: Environmental Technology Cluster (ET) from British West Midlands and ACLIMA from Spanish Basque Country. The study analyzes clusters' design and their role in fostering innovation based on environment industry clusters. In both regions environmental industry clusters represent strong potential for further dynamic development with grow opportunities driven by legislation introduced at EU, national or regional levels. The paper compares clusters' heterogeneity, goals and priorities, financing schemes, management structure, types of projects, character of private-public partnerships, challenges, as well as clusters' collaboration at regional/national/international levels. Also focus is given on how the clusters enhance innovation and what types of projects are executed by the regions in this field.

Die proto-konstitutionelle Etablierung der europäischen Innenpolitik, Rückblick und Ausblick auf Bedingungen föderaler Ordnung in Europa = The proto-constitutional establishment of European domestic policy. Review and outlook on conditions of federal order in Europe. ZEI Discussion Paper C225, 2014

ZEI Director Prof. Ludger Kühnhardt recalls the leading ideas of federalism as territorial equivalent for political pluralism. Celebrating the 80th anniversary of Bonn historian and political scientist Prof. Dr. Hans-Peter Schwarz, he reflects on the emerging EU domestic policies in ZEI Discussion Paper C 225.

The Basque Diaspora in Latin America: Euskal Etxeak, Integration, and Tensions. EDAP 1/2016

The establishment of the Basque diaspora in Latin America can be divided in several different periods. First, from the 16th to 18th century, the so-called original diaspora of Basques who were part of the Spanish colonial regime. The second can be traced to the 19th century, consisting of a mixture of impoverished Basque migrants seeking jobs, especially in Uruguay and Argentina, and of refugees fleeing from the Spanish War of Independence and the Carlist wars. The third wave is identified by, but not only through, the considerable amount of refugees from the Spanish Civil War on the 1930's. The fourth wave came during the 1970s, with refugees from the Franco Dictatorship, ETA members and sympathisers. In this paper I will argue that each new wave of migrants brought tension to the diaspora, with the Euskal Etxeak, or ‘Basque houses’, as a focus point. The main idea is to analyse the different tensions and political discussions of this set of diasporic waves in Latin America.

Breve instruccion sobre el modo de conseruar los niños expósitos, aprobada por el real tribunal del proto-medicato ... /

Mode of access: Internet.

Arancel general de los derechos de los oficiales de esta Real Audiencia, de los jueces ordinarios, abogados, y escribanos publicos, y reales de provincia, medidores y tasadores, y de las vistas y examenes del Proto-medicato de este Distrito.

Mode of access: Internet.