El I+D en la universidad española (y II)

En el presente artículo, segundo y último de la serie, se presentan las vías no oficiales de la investigación en la Universidad. Se dan algunas de las formas de trabajar de los grupos universitarios y se concluye con una breve estad��stica de datos de colaboraciones entre empresas y la Universidad.

Decisio S. Rotae Romanae coram Rmo. D. Pirouano decano, in causa Valentina Praeeminentiarum, Lucae II Martij 1641, ad instantiam Syndici Ciuitatis Valentiae [Texto impreso]

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D. Luis Moya, Arquitecto: Dos edificios inéditos de los años 50. Casa en Pedro Valdivia, 8 (1956-57); Nuevo Pabellón para el Colegio del Pilar en la calle Castelló, nº 56 (1959). Madrid

D. Luis Moya, Arquitecto: Dos edificios inéditos de los años 50. Casa en Pedro Valdivia, 8 (1956-57); Nuevo Pabellón para el Colegio del Pilar en la calle Castelló, nº 56 (1959). Madrid

[Oficio de la reina Germana de Foix dirigido a Pedro Cedrán, escribano de ración y del Consejo, por el que le manda le sean entregados a Martin Cabrero, su caballerizo mayor, todos los albaranes y cuenta de la quitación ordinaria de los últimos 9 meses, desde el 1 de mayo de 1516 hasta el 31 de enero de 1517 [Manuscrito]

Firma autógrafa de Germana de Foix

A “REVOLTA” DE JEÚ E A ESTELA DE D��: Um Estudo Em 2 Reis 10,28-36

A pesquisa tem por objetivo trabalhar o evento da Revolta de Jeú, em conjunto com a Estela de D��, tendo como ponto de partida para tal, a exegese da perícope de 2 Reis 10-28,36. A história Deuteronomista apresenta o ato da Revolta de Jeú como sendo um feito demasiadamente importante, na restauração do culto a Javé em Israel, a partir de um contexto onde o culto a outras divindades, em Israel Norte, estava em pleno curso. No entanto, a partir da análise conjunta da Estela de D��, que tem como provável autor o rei Hazael de Damasco, somos desafiados a ler esta história pelas entrelinhas não contempladas pelo texto, que apontam para uma participação ativa de Hazael, nos desfechos referentes a Revolta de Jeú, como sendo o responsável direto que proporcionou a subida de Jeú ao trono em Israel, clarificando desta forma este importante período na história Bíblica. Para tal análise, observar-se-á três distintos tópicos, ligados diretamente ao tema proposto: (1) A Revolta de Jeú e a Redação Deuteronomista, a partir do estudo exegético da perícope de 2 Reis 10,28-36, onde estão descritas informações pontuais sobre período em que Jeú reinou em Israel; (2) Jeú e a Estela de D��, a partir da apresentação e análise do conteúdo da Estela de D��, tratando diretamente dos desdobramentos da guerra em Ramote de Gileade, de onde se d�� o ponto de partida à Revolta de Jeú; e por fim (3) O Império da Síria, onde a partir da continuidade da análise do conteúdo da Estela de D��, demonstraremos a significância deste reino, além de apontamentos diretamente ligados ao reinado de Hazael, personagem mui relevante no evento da Revolta de Jeú.

Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation

Antigen presentation by major histocompatibility complex (MHC) class II molecules requires the participation of different proteases in the endocytic route to degrade endocytosed antigens as well as the MHC class II-associated invariant chain (Ii). Thus far, only the cysteine protease cathepsin (Cat) S appears essential for complete destruction of Ii. The enzymes involved in degradation of the antigens themselves remain to be identified. Degradation of antigens in vitro and experiments using protease inhibitors have suggested that Cat B and Cat D, two major aspartyl and cysteine proteases, respectively, are involved in antigen degradation. We have analyzed the antigen-presenting properties of cells derived from mice deficient in either Cat B or Cat D. Although the absence of these proteases provoked a modest shift in the efficiency of presentation of some antigenic determinants, the overall capacity of Cat B−/− or Cat D���/− antigen-presenting cells was unaffected. Degradation of Ii proceeded normally in Cat B−/− splenocytes, as it did in Cat D���/− cells. We conclude that neither Cat B nor Cat D are essential for MHC class II-mediated antigen presentation.

Targeted ablation of the vitamin D receptor: An animal model of vitamin D-dependent rickets type II with alopecia

Vitamin D, the major steroid hormone that controls mineral ion homeostasis, exerts its actions through the vitamin D receptor (VDR). The VDR is expressed in many tissues, including several tissues not thought to play a role in mineral metabolism. Studies in kindreds with VDR mutations (vitamin D-dependent rickets type II, VDDR II) have demonstrated hypocalcemia, hyperparathyroidism, rickets, and osteomalacia. Alopecia, which is not a feature of vitamin D deficiency, is seen in some kindreds. We have generated a mouse model of VDDR II by targeted ablation of the second zinc finger of the VDR DNA-binding domain. Despite known expression of the VDR in fetal life, homozygous mice are phenotypically normal at birth and demonstrate normal survival at least until 6 months. They become hypocalcemic at 21 days of age, at which time their parathyroid hormone (PTH) levels begin to rise. Hyperparathyroidism is accompanied by an increase in the size of the parathyroid gland as well as an increase in PTH mRNA levels. Rickets and osteomalacia are seen by day 35; however, as early as day 15, there is an expansion in the zone of hypertrophic chondrocytes in the growth plate. In contrast to animals made vitamin D deficient by dietary means, and like some patients with VDDR II, these mice develop progressive alopecia from the age of 4 weeks.

Chemical complementation identifies a proton acceptor for redox-active tyrosine D in photosystem II

Through the use of site-directed mutagenesis and chemical rescue, we have identified the proton acceptor for redox-active tyrosine D in photosystem II (PSII). Effects of chemical rescue on the tyrosyl radical were monitored by EPR spectroscopy. We also have acquired the Fourier–transform infrared (FT-IR) spectrum associated with the oxidation of tyrosine D and concomitant protonation of the acceptor. Mutant and isotopically labeled PSII samples are used to assign vibrational lines in the 3,600–3,100 cm−1 region to N-H modes of His-189 in the D2 polypeptide. When His-189 in D2 is changed to a leucine (HL189D2) in PSII, dramatic alterations of both EPR and FT-IR spectra are observed. When imidazole is introduced into HL189D2 samples, results from both EPR and FT-IR spectroscopy argue that imidazole is functionally reconstituted into an accessible pocket and that imidazole acts as a chemical mimic for His-189. Small perturbations of EPR and FT-IR spectra are consistent with access to this pocket in wild-type PSII, as well. Structures of the analogous site in bacterial reaction centers suggest that an accessible pocket, large enough to contain imidazole, is bordered by tyrosine D and His-189 in the D2 polypeptide. These data provide evidence that His-189 in the D2 polypeptide of PSII acts as a proton acceptor for redox-active tyrosine D and that proton transfer to the imidazole ring facilitates the efficient oxidation/reduction of tyrosine D.

Photosystem II single crystals studied by EPR spectroscopy at 94 GHz: The tyrosine radical Y\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{D}^{{\bullet}}}}\end{equation*}\end{document}

Electron paramagnetic resonance (EPR) spectroscopy at 94 GHz is used to study the dark-stable tyrosine radical Y\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{D}^{{\bullet}}}}\end{equation*}\end{document} in single crystals of photosystem II core complexes (cc) isolated from the thermophilic cyanobacterium Synechococcus elongatus. These complexes contain at least 17 subunits, including the water-oxidizing complex (WOC), and 32 chlorophyll a molecules/PS II; they are active in light-induced electron transfer and water oxidation. The crystals belong to the orthorhombic space group P212121, with four PS II dimers per unit cell. High-frequency EPR is used for enhancing the sensitivity of experiments performed on small single crystals as well as for increasing the spectral resolution of the g tensor components and of the different crystal sites. Magnitude and orientation of the g tensor of Y\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{D}^{{\bullet}}}}\end{equation*}\end{document} and related information on several proton hyperfine tensors are deduced from analysis of angular-dependent EPR spectra. The precise orientation of tyrosine Y\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{D}^{{\bullet}}}}\end{equation*}\end{document} in PS II is obtained as a first step in the EPR characterization of paramagnetic species in these single crystals.

Human vitamin D receptor phosphorylation by casein kinase II at Ser-208 potentiates transcriptional activation.

The potential functional significance of human 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] receptor (hVDR) phosphorylation at Ser-208 was evaluated by cotransfecting COS-7 kidney cells with hVDR constructs and the catalytic subunit of human casein kinase 11 (CK-11). Under these conditions, hVDR is intensely phosphorylated in a reaction that depends on both CK-II and the presence of Ser-208. The resulting hyperphosphorylated receptor is unaltered in its kinetics for binding the 1,25(OH)2D3 ligand, its partitioning into the nucleus, and its ability to associate with a vitamin D responsive element. Replacement of Ser-208 with glycine or alanine indicates that phosphorylation of hVDR at Ser-208 is not obligatory for 1,25(OH)2D3 action, but coexpression of wild-type hVDR and CK-11 elicits a dose-dependent enhancement of 1,25(OH)2D3-stimulated transcription of a vitamin D responsive element reporter construct. This enhancement by CK-II is abolished by mutating Ser-208 to glycine or alanine and does not occur with glucocorticoid receptor-mediated transcription. Therefore, phosphorylation of hVDR by CK-11 at Ser-208 specifically modulates its transcriptional capacity, suggesting that this covalent modification alters the conformation of VDR to potentiate its interaction with the machinery for DNA transcription.