Papers by miguel franco vidal
arXiv (Cornell University), Aug 20, 2004
2007 Inaugural IEEE-IES Digital EcoSystems and Technologies Conference, 2007
ABSTRACT Not Available
The strongest evidence for the existence of an important control in the flanking region of the gl... more The strongest evidence for the existence of an important control in the flanking region of the globin gene domain was provided by the analysis of human γβ-thalassaemias.1,2 Patients with heterozygous Dutch γβ-thalassaemia have a deletion that removes 100 kb of DNA, leaving the β-globin gene and the promoter and enhancer regions intact. However, it abolishes expression of the deleted chromosome and leaves the gene in an inactive chromatin configuration.3–5 The wild-type allele on the other chromosome is expressed at normal levels, indicating that there is no shortage of trans-acting factors. This suggests a cis effect on β-globin gene transcription, which could be caused by a loss of positive acting elements or by the juxtaposition of the intact β-globin gene and sequences that remain in an inactive chromatin configuration in erythroid cells. The first indication that positive acting sites may be involved in activation of the β-globin domain came with the observation of erythroid specific DNasel hypersensitive sites that map 6–18 kb upstream from the e-globin gene (Fig. 1).6–8
Epigenetics and human health, 2014
The Polycomb group (PcG) products are a set of evolutionary conserved proteins that form chromati... more The Polycomb group (PcG) products are a set of evolutionary conserved proteins that form chromatin regulator complexes that control expression of developmentally relevant genes. PcG activity is essential not only to maintain the developmental potential of pluripotent cells from which specialized cell types arise, but also to ensure the directionality of the differentiation process. In the adult, these PcG functions are essential for normal cell homeostasis and their deregulation is often associated with cell transformation events. PcG-dependent transcriptional control involves posttranslational modifications of histones, decreased DNA accessibility, and other mechanisms. While the stability of Polycomb-determined chromatin landscapes is rather stable in differentiated cells, in pluripotent cells it is characteristically dynamic in order to accommodate the execution of developmental genetic programs. Best known as repressors of gene expression, recent evidence points at roles during gene activation. Besides gene expression control, PcG products also participate in other essential functions such as DNA damage response, indicating that these proteins are involved in a wide spectrum of cellular and organismal functions in need of detailed characterization.
The EMBO Journal, 1990
A 21.5 kb DNA fragment carrying the entire chicken lysozyme gene locus was introduced into the ge... more A 21.5 kb DNA fragment carrying the entire chicken lysozyme gene locus was introduced into the germ line of mice. The fragment contains the transcribed region plus 11.5 kb 5'-flanking and 5.5 kb 3'-flanking sequences including all known cis-regulatory elements and the 5' and 3' attachment elements (A-elements) which define the borders of the DNase I sensitive chromatin domain. All sequences which adopt a DNase I hypersensitive chromatin conformation in vivo are present on the construct. Seven founder mice were analysed. All of these expressed chicken lysozyme RNA at high levels specifically in macrophages, as is the case in the donor species. Expression levels are dependent on the copy number of integrated genes indicating that a complete gene locus, as defined by its chromatin structure, functions as an independent regulatory unit when introduced into a heterologous genome.
Traditionally, neoclassical economics has been the guiding framework in the development of legisl... more Traditionally, neoclassical economics has been the guiding framework in the development of legislative and regulatory rules in the telecommunication markets. The regulatory perspective has long assumed a static environment. However, telecommunication markets have evolved into extremely dynamic, innovative and technology-driven markets. At the same time, economic theory has moved well beyond simple, static concepts of neoclassical analysis. Inter alia, Schumpeterian Economics, Institutional Economics and modern Industrial Organization provide a broader framework more suitable to analyze modern telecom markets. Drawing on an extended theoretical baseline and on major industry trends, we propose a more comprehensive framework for telecom regulation – the new regulatory pentagon – based on the cornerstones competition, investment and innovation, convergence and platformization, macroeconomics and growth and, lastly, commitment and credibility.
The New biologist, 1990
In contrast to the mouse immunoglobulin heavy chain and kappa light chain genes, very little is k... more In contrast to the mouse immunoglobulin heavy chain and kappa light chain genes, very little is known about the regulation of expression of the immunoglobulin lambda light chain locus. To identify elements responsible for lambda gene regulation we mapped DNaseI hypersensitive sites associated with a functionally rearranged lambda 1 gene in nuclei from the myeloma cell line J558L. Tissue-specific hypersensitive sites were identified 2.3 to 2.5 kb upstream of the CAP site of both the lambda 1 gene and the unrearranged variable (V) lambda 2 gene segments. DNA sequences flanking the lambda 1 gene were isolated and tested for their influence on expression of the lambda 1 gene after transfection into myeloma cells and after injection into fertilized mouse eggs. Two enhancer elements were identified downstream of the lambda 1 gene. A proximal element (located 4 to 10 kb 3' of the gene) enhanced expression of a lambda 1 gene in stable myeloma cell transfectants but had no effect on the ...
Informes de la Construcción, 1997
aproximación a las propiedades tensión-deformación del material. Se ha adoptado un método de cálc... more aproximación a las propiedades tensión-deformación del material. Se ha adoptado un método de cálculo por diferencias finitas en el dominio del tiempo, con un modelo de masas concentradas en los nodos. SlMlvlARY Influence in the dynamics of an articulated structure of sweep wooden, of the approximation to the material tensiondeformation properties.A time-domain calculation method by finite differences has been used with a model of lumped masses in the nodes. En ambos casos se analiza el movimiento de la estructura, debido a la fuerza dinámica, a partir del equilibrio y
Vierteljahrshefte zur Wirtschaftsforschung, 2012
Der Telekommunikationsmarkt hat sich zu einem äußerst dynamischen, innovationsund technologiegetr... more Der Telekommunikationsmarkt hat sich zu einem äußerst dynamischen, innovationsund technologiegetriebenen Markt entwickelt. Die Lebenszyklen der Telekommunikationstechnik sind heute vergleichsweise kurz, die Technik entwickelt sich zunehmend in Sprüngen weiter. Der Ende der 90er Jahre eingeführte Regulierungsrahmen zielte auf Privatisierung, Marktöffnung und Schaffung von Wettbewerb ab und löste das alte Monopolregime ab. Mit rapide zunehmendem Bandbreitenbedarf, der Konvergenz verschiedener digitaler Kommunikationstechnologien und der zunehmenden wirtschaftlichen Bedeutung des Internets stellt sich die Frage, wie sich die Telekommunikationsmärkte in der Zukunft entwickeln werden und welche Rolle die Regulierung in diesem Prozess spielen sollte. Stark wachsende Datenverkehre, neue Dienste und Plattformen stellen hohe Anforderungen an den Ausbau der Breitbandinfrastruktur. Das regulatorische Umfeld muss diesem dynamischen Charakter des Wettbewerbs in technologie-und innovationsgetriebenen Märkten mit ausreichender Flexibilität Rechnung tragen. Digitale Plattformen, die die typischen Kennzeichen zweiseitiger Märkte aufweisen, prägen die moderne Internetökonomie. Konvergenz erfordert, dass das Marktverständnis erweitert und die gesamte digitale Wertschöpfungskette umfassen sollte. In einem schwierigen wirtschaftlichen Umfeld müssen Anreize für Investitionen geschaffen werden, die den Ausbau der Breitbandinfrastruktur vorantreiben. summary: Telecommunication markets have evolved into extremely dynamic, innovative and technologydriven markets. Modern telecommunications technologies and products are characterized by short life cycles, as the advancement of these technologies continues in leaps and bounds. The regulatory framework introduced at the end of the 1990s aimed at privatization as well as the creation of open markets and competition
Nucleic Acids Research, 1993
We have carried out a structural and functional analysis on the human NF-L (H-NF-L) gene. It cont... more We have carried out a structural and functional analysis on the human NF-L (H-NF-L) gene. It contains a methylation-free island, spanning the 5' flanking sequences and the first exon and a number of neuronalspecific DNase I hypersensitive sites have been identified in the upstream region as well as within the body of the gene. Analysis in cell lines and transgenic mice using a combination of these sites has revealed the presence of a conserved element(s) between-300bp and-190bp which is required for neuronalspecific expression.
Molecular Cell, 2013
Reversible cellular quiescence is critical for developmental processes in metazoan organisms and ... more Reversible cellular quiescence is critical for developmental processes in metazoan organisms and is characterized by a reduction in cell size and transcriptional activity. We show that the Aurora B kinase and the polycomb protein Ring1B have essential roles in regulating transcriptionally active genes in quiescent lymphocytes. Ring1B and Aurora B bind to a wide range of active promoters in resting B and T cells. Conditional knockout of either protein results in reduced transcription and binding of RNA Pol II to promoter regions and decreased cell viability. Aurora B phosphorylates histone H3S28 at active promoters in resting B cells as well as inhibiting Ring1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes. Our results identify a mechanism for regulating transcription in quiescent cells that has implications for epigenetic regulation of the choice between proliferation and quiescence.
Mechanisms of Development, 2005
The Polycomb and trithorax groups of genes control the maintenance of homeotic gene expression in... more The Polycomb and trithorax groups of genes control the maintenance of homeotic gene expression in a variety of organisms. A putative participant in the regulation of this process is the murine RYBP (Ring and YY1 Binding Protein) gene. Sequence comparison between different species has identified the homologous gene in Drosophila, the dRYBP gene. We have investigated whether dRYBP participates in the mechanisms of silencing of homeotic genes expression. We first studied its expression by RNA in situ hybridisation and detected dRYBP expression ubiquitously and throughout development. Moreover, we generated a polyclonal anti-dRYBP antibody that recognises the dRYBP protein. dRYBP protein is nuclear and expressed maternally and ubiquitously throughout development. To study the transcriptional activity of dRYBP, we generated a fusion protein containing the entire dRYBP protein and the GAL4 DNA binding domain. This fusion protein functions, in vivo, as a transcriptional repressor throughout development. Importantly, this repression is dependent on the function of the Polycomb group genes. Furthermore, using the GAL4/UAS system, we have over expressed dRYBP in the haltere and the wing imaginal discs. In the haltere discs, high levels of dRYBP repress the expression of the homeotic Ultrabithorax gene. This repression is Polycomb dependent. In the wing discs, dRYBP over expression produces a variety of phenotypes suggesting the overall miss regulation of the many putative genes affected by high levels of dRYBP. Taking together, our results indicate that dRYBP is able to interact with PcG proteins to repress transcription suggesting that the dRYBP gene might belong to the Polycomb group of genes in Drosophila.
Journal of Medicinal Chemistry, 2013
(25R)-3β-Hydroxy-5α-spirostan-12-one (hecogenin) and 11α-hydroxypregn-4-ene-3,20-dione (11α-hydro... more (25R)-3β-Hydroxy-5α-spirostan-12-one (hecogenin) and 11α-hydroxypregn-4-ene-3,20-dione (11α-hydroxyprogesterone) were used as starting materials for the synthesis of a series of 11-and 12-substituted derivatives of 5ξ-pregnanolone (3α-hydroxy-5α-pregnan-20one and 3α-hydroxy-5-pregnan-20-one), the principal neurosteroid acting via γ-aminobutyric acid (GABA). These analogues were designed to study the structural requirements of the corresponding GABA A receptor. Their biological activity was measured by in vitro test with [ 3 H]-flunitrazepam as radioligand in which allopregnanolone and its active analogues stimulated the binding to the GABA A receptor. Analysis of the SAR data suggests dependence of the flunitrazepam binding activity on the lipophobic-lipophilic balance of the groups at the C-ring edge, rather than on specific interactions between them and the receptor.
Genes & Development, 1989
Using the dominant control region (DCR) sequences that flank the beta-globin gene locus, we have ... more Using the dominant control region (DCR) sequences that flank the beta-globin gene locus, we have been able to achieve high-level expression of the human alpha-globin gene in transgenic mice. Expression in fetal liver and blood is copy number dependent and at levels comparable to that of the endogenous mouse alpha-globin genes. Transgenic fetuses with high-copy numbers of the transgene suffer severe anemia and die before birth. Using a construct with both the human alpha- and beta-globin genes and the beta-globin DCR, live mice with low-copy numbers were obtained. Both human globin genes are expressed at high levels in adult red cells to give human hemoglobin HbA in amounts equal to or greater than endogenous mouse hemoglobin. Expression of HbA in murine red cells is not accompanied by any increase in mean corpuscular volume (MCV) or mean corpuscular hemoglobin concentration (MCHC). However, these transgenic mice tend to have an increased number of reticulocytes in peripheral blood; ...
... Gestión de la prevención de riesgos laborales en la pequeña y mediana empresa. Información Ge... more ... Gestión de la prevención de riesgos laborales en la pequeña y mediana empresa. Información General. Autores: Manuel Bestratén Bellovi, Miguel Angel Marrón Vidal; Editores: Ministerio de Trabajo y Asuntos Sociales; Año de publicación: 2001; ...
Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, 1990
Arch. Hosp. …, 1997
Fornazzari, Luis; Alvarez, Fernando; Gabrielli, Hernan; Sastre, Alcira; Fustinioni, Osvaldo; Gold... more Fornazzari, Luis; Alvarez, Fernando; Gabrielli, Hernan; Sastre, Alcira; Fustinioni, Osvaldo; Gold, Leonor; Pangre, Norma; Palacios, Manuel; Bruggeman, Laurent; Hernández, Rosa Elena; Villavicencio de Ojeda, Ada; Grau Vidal, Miguel; Flaskamp, Renate; Castañeda, ...
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Papers by miguel franco vidal