El Prado, de territorio a escenario : la construcción del espacio en un lugar tangible y su significado

"Si el hombre es el cuidador de las palabras y sólo de ellas emerge el sentido de las cosas, la arquitectura tiene un cometido preciso: hacer de las condiciones ya dadas de cada lugar palabras que signifiquen las cualidades de la existencia, y que desvelen la riqueza y contenidos que en ellas se contienen potencialmente" Ignasi Solá Morales. Lugar: permanencia o producción, 1992. Esta tesis surge tanto del afán por comprender la identidad de uno de los espacios más representativos de mi ciudad, asumido familiarmente pero que plantea muchas dudas respecto a su caracterización, como de la preocupación personal respecto a la aparente hegemonía del modelo urbano de la "ciudad genérica", crudamente expuesto por Rem Koolhaas a finales del siglo XX, que pone en crisis la ciudad histórica. El territorio, espacio físico concreto, y la memoria asociada a este, obliterados, son considerados como punto de partida para confrontarlos con la proclamación del nuevo modelo de "ciudad genérica", de raíz eminentemente económica y tecnológica. La realidad tangible de un espacio, aparentemente forjado en base a los valores denostados por el nuevo modelo propuesto, se estudia desde las premisas opuestas. La idea del no-lugar, teorizado por Marc Augé y tomado como modelo por Koolhaas, supone éste emancipado tanto de las preexistencias históricas como de su ubicación física concreta, planteando un tipo de espacio de representación al margen del territorio y la memoria. Sin pretender adoptar una postura resistente u opuesta, sino antitética y complementaria, se toman aquí las premisas de Koolhaas para contrastarlas con una porción del territorio a medio camino entre la arquitectura y la ciudad, a fin de desarrollar una reflexión que sirva de complemento y contrapeso al paradigma espacial que la “ciudad genérica” implica y cuya inmediatez y supuesta anomia parecen anular cualquier intención interpretativa al neutralizar los centros históricos y proclamar el agotamiento de la historia. El planteamiento de una teoría dicotómica frente al espacio y las teorías arquitectónicas asociadas a este ya fue formulado por Colin Rowe y Fred Koetter a finales de los años setenta del siglo pasado. Se plantea aquí la idea de una “ciudad tangible” como opuesta a la idea de la "ciudad genérica" enunciada por Koolhaas. Tomando el territorio y la memoria como referencia principal en un lugar concreto y huyendo de la premisa de la inmediatez del instante y el "presente perpetuo" proclamado por Koolhaas, del que según él seríamos prisioneros, se establece una distancia respecto al objeto de análisis que desarrolla el estudio en la dirección opuesta al supuesto origen del mismo, planteando la posibilidad de reactivar una reflexión en torno al territorio y la memoria en el seno del proceso global de habitación para poner de manifiesto determinados mecanismos de configuración de un espacio de representación al margen de la urgencia del presente, reactivando la memoria y su relación con el territorio como punto de partida. Desde de la reconstrucción hipotética del territorio, partiendo de la propia presencia física del mismo, su orografía, la paleo-biología, las analogías etológicas, los restos arqueológicos, la antropología o la historia, se reivindica la reflexión arquitectónica como disciplina diversa y privilegiada en cuanto al análisis espacial, tratando de discernir el proceso mediante el cual el Prado pasó de territorio a escenario. La organización cronológica del estudio y la incorporación de muy diversas fuentes, en su mayoría directas, pretende poner de manifiesto la condición transitiva del espacio de representación y contrastar el pasado remoto del lugar y su construcción con el momento actual, inevitablemente encarnado por el punto de vista desde el cual se desarrolla la tesis. El Prado parece albergar, agazapado en su nombre, la raíz de un origen remoto y olvidado. Si como enunciaba Ignasi Solá-Morales la función de la arquitectura es hacer aflorar los significados inherentes al lugar, esta tesis se plantea como una recuperación de la idea del vínculo entre el territorio y la memoria como fuente fundamental en la definición de un espacio de representación específico. El escrutinio del pasado constituye un acto eminentemente contemporáneo, pues el punto de vista y la distancia, inevitablemente condicionados por el presente, determinan la mirada. El culto contemporáneo a la inmediatez y la proclamación de la superación de los procesos históricos han relegado el pasado, en cierto grado, a depósito de restos o referente a superar, obviando su ineluctable condición de origen o momento anterior condicionante. Partiendo de la reconstrucción del lugar sobre el cual se halla el Prado ubicado y reconsiderando, según las premisas desarrolladas por la moderna historiografía, fundamentalmente desarrolladas por la Escuela francesa de los Annales, la cotidianeidad y lo anónimo como fuente de la que dimanan muchos de los actuales significados de nuestros espacios de representación, tomando como punto de partida un lugar remoto y olvidado, se estudia como se fue consolidando el Prado hasta devenir un lugar insigne de referencia asociado a los poderes fácticos y el espacio áulico de la capital de las Españas en el siglo XVII. El proceso mediante el cual el Prado pasó de territorio a escenario implica la recuperación de la memoria de un espacio agropecuario anónimo y el análisis de cómo, poco a poco, se fue depositando sobre el mismo el acervo de los diversos pobladores de la región que con sus particularidades culturales y sociales fueron condicionando, en mayor o menor grado, un lugar cuyo origen se extiende retrospectivamente hasta hace más de dos mil años, cuando se considera que pudo darse la primera habitación a partir de la cual, de manera ininterrumpida, el Prado ha venido siendo parte de lo que devino, más tarde, Madrid. La llegada de nuevos agentes, vinculados con estructuras de poder y territoriales que trascendían la inmediatez del territorio sobre el que se comenzó a erigir dicho lugar, sirven para repasar los diferentes depósitos ideológicos y culturales que han ido conformando el mismo, reivindicando la diversidad y lo heterogéneo del espacio de representación frente a la idea homogeneizadora que el modelo genérico implica. La constitución del Prado como un espacio de referencia asociado al paganismo arcaico a partir de la praxis espacial cotidiana, su relación con las estructuras defensivas de Al-Andalus y la atalaya Omeya, la apropiación del los primitivos santuarios por parte la iglesia, su relación con un determinado tipo de espiritualidad y las órdenes religiosas más poderosas de la época, la preferencia de Carlos V por Madrid y sus vínculos con la cultura europea del momento, o la definitiva metamorfosis del lugar a partir del siglo XVI y el advenimiento de un nuevo paganismo emblemático y estetizado, culminan con el advenimiento de lo económico como representación del poder en el seno de la corte y la erección del Palacio del Buen Retiro como manifestación tangible de la definitiva exaltación del Prado a espacio de representación áulico. Decía T.S. Elliot que la pugna por el espacio de la memoria constituye el principal rasgo del clasicismo, y el Prado, ciertamente, participa de ese carácter al que está profundamente asociado en la conciencia espacial de los madrileños como lugar de referencia. Acaso la obliteración del territorio y la memoria, propuestas en la “ciudad genérica” también tengan algo que ver con ello. ABSTRACT "If man is the caretaker of words and only they provide the sense of things, the architecture has a precise mission: to make out from the given conditions of each place words that mean the qualities of existence, and which unveil the wealth and content they potentially contain " Ignasi Solá Morales. Place: permanence or production, 1992. This thesis arises from both the desire to understand the identity of one of the most representative spaces of my city, assumed in a familiar way but that raises many doubts about its characterization, and from a personal concern about the apparent hegemony of the urban model of the "generic city " so crudely exposed by Rem Koolhaas in the late twentieth century that puts a strain on the historic city. The obliteration of the territory, specific physical space, and its associated memory, are considered as a starting point to confront them with the proclamation of the new model of "generic city" raised from eminently economic and technological roots. The tangible reality of a space, apparently forged based on the values reviled by the proposed new model, is studied from opposite premises. The idea of non-place, theorized by Marc Augé and modeled by Koolhaas, implies the emancipation from both historical preexistences and physical location, posing a type of space representation outside the territory and memory. Without wishing to establish a confrontational or opposite position, but an antithetical and complementary stance, the premises of Koolhaas are here taken to contrast them with a portion of territory halfway between architecture and the city, to develop a study that will complement and counterbalance the spatial paradigm that the "generic city" means and whose alleged immediacy and anomie appear to nullify any interpretative intention by neutralizing the historic centers and proclaiming the exhaustion of history. The approach of a dichotomous theory versus space and architectural theories associated with this were already formulated by Colin Rowe and Fred Koetter during the late seventies of last century. The idea of a "tangible city" as opposed to the idea of the "generic city" enunciated by Koolhaas arises here. Taking the territory and memory as the main reference in a particular place and trying to avoid the premise of the immediacy of the moment and the "perpetual present" proclaimed by Koolhaas, of which he pleas we would be prisoners, a distance is established from the object of analysis developing the study in the opposite direction to the alleged origin of it, raising the possibility of reactivating a reflection on the territory and memory within the overall process of inhabiting to reveal certain representational space configuration mechanisms outside the urgency of the present, reviving the memory and its relationship with the territory as a starting point. From the hypothetical reconstruction of the territory, starting from its physical presence, geography, paleo-biology, ethological analogies, archaeological remains, anthropology or history, architecture is claimed as a diverse as privileged discipline for spatial analysis, trying to discern the process by which the Prado moved from territory to stage. The chronological organization of the study and incorporating a variety of sources, most direct, aims to highlight the transitive condition of representational space and contrast the remote past of the place and its construction with the current moment, inevitably played by the view point from which the thesis develops. The Prado seems to harbor, in its name, the root of a remote and forgotten origin. If, as Ignasi Sola-Morales said, the aim of architecture is to bring out the meanings inherent in the site, this thesis is presented as a recovery of the idea of the link between the territory and memory as a key source in defining a specific space of representation. The scrutiny of the past is an eminently contemporary act, for the view and distance inevitably conditioned by the present, determine the way we look. The contemporary cult of immediacy and the proclamation of overcoming historical processes have relegated the past, to some extent, to remains deposit or a reference to overcome, ignoring its ineluctable condition as origin or previous constraint. From rebuilding the site on which the Prado is located and reconsidering everyday life and the anonymous as a source of many arising current meanings of our space of representation, according to the premises developed by modern historiography mainly developed by the French school of Annales, trying to recover the remote and forgotten is attempted, the thesis studies how el Prado was consolidated to become the most significant place of Madrid, deeply associated with the power in the capital of Spain during the XVII century. The process by which the Prado evolved from territory to stage involves the recovery of the memory of an anonymous agricultural space and the analysis of how, little by little, the influence of the various inhabitants of the region with their own and how their cultural and social peculiarities was deposited through time on the common ground and how that determined, to a greater or lesser degree, a place whose origin retrospectively extends over more than two thousand years ago, when we can consider the first inhabiting from which, without interruption, the Prado has come to be part of what became, later, Madrid. The arrival of new players, linked to power structures and territorial issues which transcended the immediacy of the territory on which the place begun to be a characteristic space, serve to review the different ideological and cultural deposits that have shaped the place, claiming diversity and heterogeneous space of representation before the homogenizing idea which the generic model implies. The constitution of the Prado as a benchmark associated with the archaic paganism developed from the ancient everyday spatial praxis, its relationship with the defensive structures of Al-Andalus and the Umayyad watchtower, the appropriation of the early sanctuaries by the roman church, its relationship with a certain type of spirituality and the most powerful religious orders of the time, the preference of Carlos V towards Madrid and its links with the European culture of the moment and the final metamorphosis of the place during the sixteenth century, end at the moment on which the advent of the economic as a representation of power within the court and the erection of the Palacio del Buen Retiro, as a tangible manifestation of the ultimate exaltation of courtly Prado space representation, happened in the mid XVII century. T. S. Elliot said that the struggle for memory space is the main feature of classicism, and the Prado certainly shares part of that character deeply associated in the mental spatial structure of the locals as a landmark. Perhaps the obliteration of territory and memory proposed in the "generic city" might also have something to do with that.

What role does climate change play in agricultural market uncertainty? An integrated assessment taking into account market-driven adjustments

Recent studies point to climate change being one of the long-term drivers of agricultural market uncertainty. To advance in the understanding of the influence of climate change on future agricultural market developments, we compare a reference scenario for 2030 with alternative simulation scenarios that differ regarding: (1) emission scenarios; (2) climate projections; and (3) the consideration of carbon fertilization effects. For each simulation scenario, the CAPRI model provides global and EU-wide impacts of climate change on agricultural markets. Results show that climate change would considerably affect agrifood markets up to 2030. Nevertheless, market-driven adaptation strategies (production intensification, trade adjustments) would soften the impact of yield shocks on supply and demand. As a result, regional changes in production would be lower than foreseen by other studies focused on supply effects.

Extracellular enveloped vaccinia virus is resistant to complement because of incorporation of host complement control proteins into its envelope

Vaccinia virus (VV) produces two antigenically and structurally distinct infectious virions, intracellular mature virus (IMV) and extracellular enveloped virus (EEV). Here we have investigated the resistance of EEV and IMV to neutralization by complement in the absence of immune antibodies. When EEV is challenged with complement from the same species as the cells used to grow the virus, EEV is resistant to neutralization by complement, whereas IMV is not. EEV resistance was not a result of EEV protein B5R, despite its similarity to proteins of the regulators of complement activation (RCA) family, or to any of the other EEV proteins tested (A34R, A36R, and A56R gene products). EEV was sensitive to complement when the virus was grown in one species and challenged with complement from a different species, suggesting that complement resistance might be mediated by host RCA incorporated into the EEV outer envelope. This hypothesis was confirmed by several observations: (i) immunoblot analysis revealed that cellular membrane proteins CD46, CD55, CD59, CD71, CD81, and major histocompatibility complex class I antigen were detected in purified EEV but not IMV; (ii) immunoelectron microscopy revealed cellular RCA on the surface of EEV retained on the cell surface; and (iii) EEV derived from rat cells expressing the human RCA CD55 or CD55 and CD59 were more resistant to human complement than EEV derived from control rat cells that expressed neither CD55 nor CD59. These data justify further analysis of the roles of these (and possible other) cellular proteins in EEV biology.

Humoral response to herpes simplex virus is complement-dependent

The complement system represents a cascade of serum proteins, which provide a major effector function in innate immunity. Recent studies have revealed that complement links innate and adaptive immunity via complement receptors CD21/CD35 in that it enhances the B cell memory response to noninfectious protein antigens introduced i.v. To examine the importance of complement for immune responses to virus infection in a peripheral tissue, we compared the B cell memory response of mice deficient in complement C3, C4, or CD21/CD35 with wild-type controls. We found that the deficient mice failed to generate a normal memory response, which is characterized by a reduction in IgG antibody and germinal centers. Thus, complement is important not only in the effector function of innate immunity but also in the stimulation of memory B cell responses to viral-infected cell antigens in both blood and peripheral tissues.

Abrogation of the alternative complement pathway by targeted deletion of murine factor B

To investigate the role of complement protein factor B (Bf) and alternative pathway activity in vivo, and to test the hypothesized potential genetic lethal effect of Bf deficiency, the murine Bf gene was interrupted by exchange of exon 3 through exon 7 (including the factor D cleaving site) with the neor gene. Mice heterozygous for the targeted Bf allele were interbred, yielding Bf-deficient offspring after the F1 generation at a frequency suggesting that Bf deficiency alone has no major effect on fertility or fetal development. However, in the context of one or more genes derived from the 129 mouse strain, offspring homozygous for Bf deficiency were generated at less than expected numbers (P = 0.012). Bf-deficient mice showed no gross phenotypic difference from wild-type littermates. Sera from Bf-deficient mice lacked detectable alternative complement pathway activity; purified mouse Bf overcame the deficit. Classical pathway-dependent total hemolytic activity was lower in Bf-deficient than wild-type mice, possibly reflecting loss of the alternative pathway amplification loop. Lymphoid organ structure and IgG1 antibody response to a T-dependent antigen appeared normal in Bf-deficient mice. Sensitivity to lethal endotoxic shock was not significantly altered in Bf-deficient mice. Thus, deficiency of Bf and alternative complement activation pathway led to a less dramatic phenotype than expected. Nevertheless, these mice provide an excellent model for the assessment of the role of Bf and the alternative pathway in host defense and other functions in vivo.

Three members of a novel small gene-family from Arabidopsis thaliana able to complement functionally an Escherichia coli mutant defective in PAPS reductase activity encode proteins with a thioredoxin-like domain and “APS reductase” activity

Three different cDNAs, Prh-19, Prh-26, and Prh-43 [3′-phosphoadenosine-5′-phosphosulfate (PAPS) reductase homolog], have been isolated by complementation of an Escherichia coli cysH mutant, defective in PAPS reductase activity, to prototrophy with an Arabidopsis thaliana cDNA library in the expression vector λYES. Sequence analysis of the cDNAs revealed continuous open reading frames encoding polypeptides of 465, 458, and 453 amino acids, with calculated molecular masses of 51.3, 50.5, and 50.4 kDa, respectively, that have strong homology with fungal, yeast, and bacterial PAPS reductases. However, unlike microbial PAPS reductases, each PRH protein has an N-terminal extension, characteristic of a plastid transit peptide, and a C-terminal extension that has amino acid and deduced three-dimensional homology to thioredoxin proteins. Adenosine 5′-phosphosulfate (APS) was shown to be a much more efficient substrate than PAPS when the activity of the PRH proteins was tested by their ability to convert 35S-labeled substrate to acid-volatile 35S-sulfite. We speculate that the thioredoxin-like domain is involved in catalytic function, and that the PRH proteins may function as novel “APS reductase” enzymes. Southern hybridization analysis showed the presence of a small multigene family in the Arabidopsis genome. RNA blot hybridization with gene-specific probes revealed for each gene the presence of a transcript of ≈1.85 kb in leaves, stems, and roots that increased on sulfate starvation. To our knowledge, this is the first report of the cloning and characterization of plant genes that encode proteins with APS reductase activity and supports the suggestion that APS can be utilized directly, without activation to PAPS, as an intermediary substrate in reductive sulfate assimilation.

Molecular basis for a link between complement and the vascular complications of diabetes

Activated terminal complement proteins C5b to C9 form the membrane attack complex (MAC) pore. Insertion of the MAC into endothelial cell membranes causes the release of growth factors that stimulate tissue growth and proliferation. The complement regulatory membrane protein CD59 restricts MAC formation. Because increased cell proliferation characterizes the major chronic vascular complications of human diabetes and because increased glucose levels in diabetes cause protein glycation and impairment of protein function, we investigated whether glycation could inhibit CD59. Glycation-inactivation of CD59 would cause increased MAC deposition and MAC-stimulated cell proliferation. Here, we report that (i) human CD59 is glycated in vivo, (ii) glycated human CD59 loses its MAC-inhibitory function, and (iii) inactivation of CD59 increases MAC-induced growth factor release from endothelial cells. We demonstrate by site-directed mutagenesis that residues K41 and H44 form a preferential glycation motif in human CD59. The presence of this glycation motif in human CD59, but not in CD59 of other species, may help explain the distinct propensity of humans to develop vascular proliferative complications of diabetes.

Effect of educational leaflets and questions on knowledge of contraception in women taking the combined contraceptive pill: randomised controlled trial

Objective: To assess whether provision of educational leaflets or questions on contraception improves knowledge of contraception in women taking the combined contraceptive pill.

Mortality in people taking selegiline: observational study

Objective: To evaluate mortality among patients with Parkinson’s disease receiving different treatment.

Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice

Adipocyte complement-related protein (30 kDa) (Acrp30), a secreted protein of unknown function, is exclusively expressed in differentiated adipocytes; its mRNA is decreased in obese humans and mice. Here we describe novel pharmacological properties of the protease-generated globular head domain of Acrp30 (gAcrp30). Acute treatment of mice with gAcrp30 significantly decreased the elevated levels of plasma free fatty acids caused either by administration of a high fat test meal or by i.v. injection of Intralipid. This effect of gAcrp30 was caused, at least in part, by an acute increase in fatty acid oxidation by muscle. As a result, daily administration of a very low dose of gAcrp30 to mice consuming a high-fat/sucrose diet caused profound and sustainable weight reduction without affecting food intake. Thus, gAcrp30 is a novel pharmacological compound that controls energy homeostasis and exerts its effect primarily at the peripheral level.

Identification of three physically and functionally distinct binding sites for C3b in human complement factor H by deletion mutagenesis.

Human complement factor H controls spontaneous activation of complement in plasma and appears to play a role in distinguishing host cells from activators of the alternative pathway of complement. In both mice and humans, the protein is composed of 20 homologous short consensus repeat (SCR) domains. The size of the protein suggests that portions of the structure outside the known C3b binding site (SCR 1-4) possess a significant biological role. We have expressed the full-length cDNA of factor H in the baculovirus system and have shown the recombinant protein to be fully active. Mutants of this full-length protein have now been prepared, purified, and examined for cofactor activity and binding to C3b and heparin. The results demonstrate (i) that factor H has at least three sites that bind C3b, (ii) that one of these sites is located in SCR domains 1-4, as has been shown by others, (iii) that a second site exists in the domain 6-10 region, (iv) that a third site resides in the SCR 16-20 region, and (v) that two heparin binding sites exist in factor H, one near SCR 13 and another in the SCR 6-10 region. Functional assays demonstrated that only the first C3b site located in SCR 1-4 expresses factor I cofactor activity. Mutant proteins lacking any one of the three C3b binding sites exhibited 6- to 8-fold reductions in affinity for C3b on sheep erythrocytes, indicating that all three sites contribute to the control of complement activation on erythrocytes. The identification of multiple functionally distinct sites on factor H clarifies many of the heretofore unexplainable behaviors of this protein, including the heterogeneous binding of factor H to surface-bound C3b, the effects of trypsin cleavage, and the differential control of complement activation on activators and nonactivators of the alternative pathway of complement.

Multiple forms of complement C3 in trout that differ in binding to complement activators.

In all other species analyzed to date, the functionally active form of complement component C3 exists as the product of a single gene. We have now identified and characterized three functional C3 proteins (C3-1, C3-3, and C3-4) in trout that are the products of at least two distinct C3 genes. All three proteins are composed of an alpha-and a beta-chain and contain a thioester bond in the alpha-chain. However, they differ in their electrophoretic mobility, glycosylation, reactivity with monospecific C3 antibodies, and relative ability to bind to various surfaces (zymosan, Escherichia coli, erythrocytes). A comparison of the partial amino acid sequences of the three proteins showed that the amino acid sequence identity/similarity of C3-3 to C3-4 is 87/91%, while that of C3-3 and C3-4 to C3-1 is 51.5/65.5% and 60/73% respectively. Thus, trout possess multiple forms of functional C3 that represent the products of several distinct genes and differ in their ability to bind covalently to various complement activators.

Amelioration of lupus-like autoimmune disease in NZB/WF1 mice after treatment with a blocking monoclonal antibody specific for complement component C5.

New Zealand black x New Zealand white (NZB/W) F1 mice spontaneously develop an autoimmune syndrome with notable similarities to human systemic lupus erythematosus. Female NZB/WF1 mice produce high titers of antinuclear antibodies and invariably succumb to severe glomerulonephritis by 12 months of age. Although the development of the immune-complex nephritis is accompanied by abundant local and systemic complement activation, the role of proinflammatory complement components in disease progression has not been established. In this study we have examined the contribution of activated terminal complement proteins to the pathogenesis of the lupus-like autoimmune disease. Female NZB/W F1 mice were treated with a monoclonal antibody (mAb) specific for the C5 component of complement that blocks the cleavage of C5 and thus prevents the generation of the potent proinflammatory factors C5a and C5b-9. Continuous therapy with anti-C5 mAb for 6 months resulted in significant amelioration of the course of glomerulonephritis and in markedly increased survival. These findings demonstrate an important role for the terminal complement cascade in the progression of renal disease in NZB/W F1 mice, and suggest that mAb-mediated C5 inhibition may be a useful approach to the therapy of immune-complex glomerulonephritis in humans.