La financiación y la inversión inmobiliaria : repercusiones en el urbanismo y la arquitectura

El presente trabajo de tesis doctoral tiene por finalidad demostrar que las decisiones de financiación y de inversión inmobiliaria en España influyen de manera determinante en la configuración del proceso urbanístico y arquitectónico. Este planteamiento inicial obliga a formular las siguientes cuestiones: - En una primera fase, la situación en España del sector inmobiliario y su relación con el sector financiero en el contexto de la actual crisis financiera, iniciada en el año 2008. - Los métodos de análisis y selección de inversiones y su aplicación a los proyectos de inversión en función de la naturaleza de los activos inmobiliarios. - La valoración inmobiliaria para determinadas entidades financieras. - Características de la gestión financiera empresarial y de las empresas inmobiliarias. - El origen de fondos para financiar el proceso urbanístico y arquitectónico mediante las instituciones de inversión colectiva inmobiliaria y el mercado inmobiliario. - La regulación actual en España, a nivel estatal, del suelo como materia prima del sector inmobiliario. - La edificación residencial y el mercado inmobiliario en el actual contexto económico. - La posibilidad de crear en España un mercado de derivados basado en activos inmobiliarios. - Cómo repercute la actividad económica, a través de la inversión y la financiación, en los activos inmobiliarios, en el urbanismo y la arquitectura. Las cuestiones precedentes se resuelven de forma sistemática y metodológica en esta tesis doctoral estructurada en tres grandes bloques (inversión, financiación y repercusiones en el urbanismo y la arquitectura), obteniendo una serie de respuestas reflejadas en el desarrollo del presente trabajo que se sintetizan en las siguientes líneas: - La actual crisis financiera iniciada en el año 2008 ha provocado en España el colapso del sector inmobiliario y una nueva concepción en la naturaleza de los activos inmobiliarios. El sector inmobiliario trae causa del sector financiero, en especial del crédito bancario. - Dependencia y vinculación del sector inmobiliario español de la política monetaria europea: la incorporación de España a la moneda única transforma por completo el sector inmobiliario español. - Los métodos de análisis y selección de inversiones se conforman como instrumentos relevantes que nos permiten jerarquizar nuestros proyectos. No obstante, presentan una serie de limitaciones y dificultades de aplicación práctica, por lo que no deben considerarse como herramientas que nos aporten una única solución irrefutable. - La valoración de activos inmobiliarios se constituye en un pilar básico que fundamenta la correcta aplicación de los fondos. - La inversión en activos inmobiliarios puede realizarse de forma directa o indirecta. En este último supuesto, con una influencia relevante de las innovaciones financieras surgidas en los últimos años. - Las instituciones de inversión colectiva y el mercado hipotecario constituyen instituciones fundamentales capaces de captar importantes cantidades de fondos que impulsan y financian el proceso urbanístico y arquitectónico. - El complejo y cambiante sistema jurídico español en materia de suelo, dificulta la implementación de los procesos urbanísticos y arquitectónicos. - Tras la crisis financiera de 2008, los activos inmobiliarios tienen un comportamiento similar a otros activos en cuanto a subidas y bajadas de precios. En el actual sistema económico, la especulación forma parte inherente a la naturaleza de los activos inmobiliarios. - Desde una perspectiva teórica, existe la posibilidad de crear un mercado de derivados que tenga como subyacente activos de naturaleza inmobiliaria. - Sin actividad económica, el proceso urbanístico y arquitectónico carecerá finalmente de sentido y tenderá a desaparecer. No obstante, son las innovaciones tecnológicas, a nivel de producto y proceso, las principales causantes del impulso de la actividad económica. - A pesar de lo expresado en los documentos urbanísticos internacionales, la transformación del urbanismo y la arquitectura dependen principalmente de la actividad económica y la tecnología. En un segundo nivel, la inversión y la financiación condicionan y definen el urbanismo y la arquitectura, incluso a nivel de proyecto si se pretende su materialización. En base al desarrollo previo, el objetivo fundamental de esta tesis doctoral ha sido demostrar que las decisiones de financiación y de inversión tienen una importancia capital y determinan la configuración de los activos inmobiliario, del urbanismo y la arquitectura, por lo que deben ser tenidas en cuenta no sólo en su materialización sino incluso en la propia concepción del proceso creativo. ABSTRACT The present dissertation aims to show that real estate financing and investment decisions in Spain play a predominant role in structuring urban development and architectural solutions. The issues addressed to support that contention include: - As a preliminary study, the situation of the real estate industry in Spain and its relationship to the financial sector in the context of the 2008 financial crisis. - The methods used to analyse and select investments and their application to investment projects, by type of real estate asset. - Appraisal of certain financial institutions’ real estate asset holdings. - Characteristics of financial institution and real estate company corporate management. - Sourcing funds for financing urban development and architecture through real estate investment trusts and the real estate market. - Present nation-wide regulations on landed property in Spain as a raw material for the real estate industry. - Residential building construction and the real estate market in the present economic context. - The possibility of creating a real estate asset-based derivatives market in Spain - The impact of economic activity, through investment and financing, on real estate assets, urban development and architecture. The aforementioned issues are addressed systematically and methodically in this dissertation, which is divided into three major units: investment, financing, and impact on urban development and architecture. The conclusions drawn are summarised below. - The financial crisis that began in 2008 has induced the collapse of the Spanish real estate industry and spawned a new perception of the nature of real estate assets. The real estate industry is dependent upon the financial sector, in particular on bank loans. - The Spanish real estate industry also depends on and is related to European monetary policy: Spain’s adherence to the single currency ushered in a thorough overhaul of its real estate industry. - Investment analysis and selection methods constitute highly suitable tools for project evaluation and ranking. Nonetheless, inasmuch as their practical implementation is subject to a series of limitations and difficulties, they should not be thought able to deliver a single irrefutable solution. - Real estate asset appraisal is a mainstay to the rightful application of funds. - Real estate asset investments can be made directly or indirectly. The latter approach is heavily influenced by the financial innovations forthcoming in recent years. - Investment trusts and the mortgage market are key institutions able to raise substantial funding, thereby driving and financing urban development and architecture. - Spain’s complex and changing legal provisions on land management are an obstacle to urban development and architecture. - Since the 2008 crisis, real estate assets have behaved much like other assets in terms of rising and falling prices. In the present economic context, speculation is indivisible from real estate assets. - Theoretically speaking, a derivatives market with real estate holdings as the underlying assets lies within the realm of possibility. - In the absence of economic activity, urban development and architecture are senseless pursuits and tend to disappear. Technological innovation in products and processes are the main drivers of economic activity. - Despite the opinion expressed in international papers on the subject, the transformation of urban development and architecture depend primarily on economic activity and technology. In a second dimension, investment and financing condition and define urban development and architecture, even at the design level for projects aspiring to actual construction. Pursuant to the foregoing, the primary aim of this dissertation is to show that financial and investment decisions are of cardinal importance and determine the structure of real estate assets, urban development and architecture. They must consequently be borne in mind not only in connection with implementation, but also with conceptual design and the creative process itself. I

Soneto [Manuscrito]

Alcance y contenido: Ms. poético dedicado a Luis XIII y al Cardenal Richelieu

La Institución Libre de Enseñanza y la arquitectura española de la Edad de Plata (1876-1936)

La tesis doctoral «La Institución Libre de Enseñanza y la arquitectura española de la Edad de Plata (1876-1936)» analiza las relaciones propiciadas por la ILE y la corriente cultural del institucionismo ―identificada desde los primeros años 70 del pasado siglo por el historiador Manuel Tuñón de Lara como crucial en la configuración de la cultura española contemporánea―, con la arquitectura de su tiempo en el marco histórico de la Restauración alfonsina y de la Segunda República. Lo hace desde los cuatro temas que configuran los grandes apartados en los que se estructura y articula el trabajo de investigación. El primero, el de la arquitectura de la escuela, a través del análisis de los escritos sobre la materia de los pedagogos Francisco Giner de los Ríos y Manuel Bartolomé Cossío y su papel en la materialización del edificio escolar. El segundo, el de la geografía madrileña de la ILE a través de un recorrido por las arquitecturas que acogieron su proyecto modernizador, confiado a la moral de la ciencia, a través de los centro por ella impulsados desde la Junta para Ampliación de Estudios e Investigaciones Científicas (JAE), como fueron la Residencia de Estudiantes y su grupo femenino de la Residencia de Señoritas, el Instituto Nacional de Física y Química, el Instituto-Escuela, el Centro de Estudios Históricos o el Instituto Cajal. El tercero, la renovación de la cultura arquitectónica española promovida a través de la política de pensiones de la JAE en el extranjero, de las actividades de extensión universitaria desarrolladas por la Residencia de Estudiantes en el ámbito de la arquitectura o por personas identificadas con su ideario. Y el cuarto, a través de la nueva valoración patrimonial de los monumentos arquitectónicos y de los paisajes españoles alentada por la práctica pedagógica del excursionismo y por los escritos de Francisco Giner de los Ríos y Manuel Bartolomé Cossío, que culmina con la promulgación de la Ley del Tesoro Artístico Nacional de 1933. El trabajo plantea una historia coral, donde tienen cabida arquitectos, pedagogos, políticos, historiadores del arte, críticos de arte y arquitectura de cuatro generaciones distintas: desde Ricardo Velázquez Bosco, coetáneo de Francisco Giner de los Ríos, a Arturo Sáenz de la Calzada, colegial de la Residencia de Estudiantes durante los años treinta y activo miembro de la Federación Universitaria Escolar, pasando por Carlos Velasco, Antonio Flórez Urdapilleta, Pablo Gutiérrez Moreno, Bernardo Giner de los Ríos, Leopoldo Torres Balbás, Carlos Arniches Moltó, Martín Domínguez Esteban, Fernando García Mercadal o Matilde Ucelay, en el caso de los arquitectos; Francisco Giner de los Ríos, Manuel Bartolomé Cossío, José Castillejo o Alberto Jiménez Fraud, entre los pedagogos; Segismundo Moret, Álvaro de Figueroa, Fernando de los Ríos o Marcelino Domingo, entre los políticos; Manuel Gómez-Moreno, Ricardo de Orueta o Emilio Camps Cazorla, entre los historiadores del arte; Javier de Winthuysen como jardinero o José Moreno Villa a través de su papel como crítico de arquitectura a favor del arte nuevo. Para ello, se ha partido del análisis y la interpretación de las arquitecturas de matriz institucionista a través de fuentes muy diversas, entre ellas un nutrido corpus de imágenes como complemento iconográfico fundamental en la articulación del discurso narrativo, que ha permitido situar a los temas analizados y sus protagonistas en su contexto histórico y disciplinar. Todo ello ha puesto de manifiesto el papel asumido por la Institución Libre de Enseñanza como un laboratorio de ideas y proyectos clave en la configuración de la cultura arquitectónica española del primer tercio del siglo XX. ABSTRACT The doctoral thesis «La Institución Libre de Enseñanza y la arquitectura española de la Edad de Plata (1876-1936)» analyzes the relationships fostered by the ILE and the cultural current «institucionismo» ―identified from the early '70s by the historian Manuel Tuñón de Lara as cardinal in shaping the contemporánea Spanish culture―, with the architecture of his time in the historical context of the Restoration and the Second Republic periods. This is done from the four themes that make up the major sections in which the research is structured and articulated. The first, the architecture of the school building, through the analysis of the writings on the subject of pedagogues Francisco Giner and Manuel Bartolomé Cossío and its role in the materialization of the school building. The second, the geography of the ILE in Madrid through a tour of the architectures that supported its modernizing project, entrusted to the moral of science, through the centers promoted by the Junta para Ampliación de Estudios e Investigaciones Científicas (JAE), as the Residencia de Estudiantes and its girls group Residencia de Señoritas, Instituto Nacional de Física y Química, Instituto-Escuela, Centro de Estudios Históricos or Instituto Cajal. The third, the renewal of the Spanish architectural culture promoted through JAE pension abroad, the university extension activities developed by the Residencia de Estudiantes in the field of architecture or people identified with its ideology. And the fourth, through new equity valuation of architectural monuments and the Spanish landscapes encouraged by the pedagogical practice of excursionism and by the writings of Francisco Giner de los Ríos and Manuel Bartolomé Cossío, culminating in the enactment of the Ley del Tesoro Artístico Nacional in 1933. The work raises a choral history, where have place architects, educators, politicians, art historians, art and architecture critics of four distinct generations: from Ricardo Velázquez Bosco, a contemporary of Francisco Giner, Arturo Sáenz de la Calzada, schoolboy student residence during the thirties and active member of the Federación Universitaria Escolar, through Carlos Velasco, Antonio Flórez Urdapilleta, Pablo Gutiérrez Moreno, Bernardo Giner, Leopoldo Torres Balbás, Carlos Arniches Moltó, Martín Domínguez Esteban, Fernando García Mercadal or Matilde Ucelay, in the case of architects; Francisco Giner, Manuel Bartolomé Cossío, José Castillejo and Alberto Jiménez Fraud, among teachers; Segismundo Moret, Álvaro de Figueroa, Fernando de los Ríos and Marcelino Domingo, among politicians; Manuel Gómez-Moreno, Ricardo de Orueta or Emilio Camps Cazorla, including art historians; Javier de Winthuysen as gardener and José Moreno Villa through his role as architecture critic for the new art. To do this, the origin point has been the analysis and interpretation of the «institucionista» architectures through a variety of sources, including a large corpus of iconographic images as a fundamental complement to the articulation of the narrative, which has allowed place the issues discussed and its protagonists in their historical context and discipline. This has highlighted the role played by the Institución Libre de Enseñanza as a laboratory of ideas and projects and key in shaping the Spanish architectural culture of the early twentieth century.

Reciprocal interactions between β1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: A different perspective in epithelial biology

Anchorage and growth factor independence are cardinal features of the transformed phenotype. Although it is logical that the two pathways must be coregulated in normal tissues to maintain homeostasis, this has not been demonstrated directly. We showed previously that down-modulation of β1-integrin signaling reverted the malignant behavior of a human breast tumor cell line (T4–2) derived from phenotypically normal cells (HMT-3522) and led to growth arrest in a three-dimensional (3D) basement membrane assay in which the cells formed tissue-like acini (14). Here, we show that there is a bidirectional cross-modulation of β1-integrin and epidermal growth factor receptor (EGFR) signaling via the mitogen-activated protein kinase (MAPK) pathway. The reciprocal modulation does not occur in monolayer (2D) cultures. Antibody-mediated inhibition of either of these receptors in the tumor cells, or inhibition of MAPK kinase, induced a concomitant down-regulation of both receptors, followed by growth-arrest and restoration of normal breast tissue morphogenesis. Cross-modulation and tissue morphogenesis were associated with attenuation of EGF-induced transient MAPK activation. To specifically test EGFR and β1-integrin interdependency, EGFR was overexpressed in nonmalignant cells, leading to disruption of morphogenesis and a compensatory up-regulation of β1-integrin expression, again only in 3D. Our results indicate that when breast cells are spatially organized as a result of contact with basement membrane, the signaling pathways become coupled and bidirectional. They further explain why breast cells fail to differentiate in monolayer cultures in which these events are mostly uncoupled. Moreover, in a subset of tumor cells in which these pathways are misregulated but functional, the cells could be “normalized” by manipulating either pathway.

Defects in embryonic hindbrain development and fetal resorption resulting from vitamin A deficiency in the rat are prevented by feeding pharmacological levels of all-trans-retinoic acid

Vitamin A is required for reproduction and normal embryonic development. We have determined that all-trans-retinoic acid (atRA) can support development of the mammalian embryo to parturition in vitamin A-deficient (VAD) rats. At embryonic day (E) 0.5, VAD dams were fed purified diets containing either 12 μg of atRA per g of diet (230 μg per rat per day) or 250 μg of atRA per g of diet (4.5 mg per rat per day) or were fed the purified diet supplemented with a source of retinol (100 units of retinyl palmitate per day). An additional group was fed both 250 μg of atRA per g of diet in combination with retinyl palmitate. Embryonic survival to E12.5 was similar for all groups. However, embryonic development in the group fed 12 μg of atRA per g of diet was grossly abnormal. The most notable defects were in the region of the hindbrain, which included a loss of posterior cranial nerves (IX, X, XI, and XII) and postotic pharyngeal arches as well as the presence of ectopic otic vesicles and a swollen anterior cardinal vein. All embryonic abnormalities at E12.5 were prevented by feeding pharmacological amounts of atRA (250 μg/g diet) or by supplementation with retinyl palmitate. Embryos from VAD dams receiving 12 μg of atRA per g of diet were resorbed by E18.5, whereas those in the group fed 250 μg of atRA per g of diet survived to parturition but died shortly thereafter. Equivalent results were obtained by using commercial grade atRA or atRA that had been purified to eliminate any potential contamination by neutral retinoids, such as retinol. Thus, 250 μg of atRA per g of diet fed to VAD dams (≈4.5 mg per rat per day) can prevent the death of embryos at midgestation and prevents the early embryonic abnormalities that arise when VAD dams are fed insufficient amounts of atRA.

Vaccinia locomotion in host cells: Evidence for the universal involvement of actin-based motility sequences ABM-1 and ABM-2

Vaccinia uses actin-based motility for virion movement in host cells, but the specific protein components have yet to be defined. A cardinal feature of Listeria and Shigella actin-based motility is the involvement of vasodilator-stimulated phosphoprotein (VASP). This essential adapter recognizes and binds to actin-based motility 1 (ABM-1) consensus sequences [(D/E)FPPPPX(D/E), X = P or T] contained in Listeria ActA and in the p90 host-cell vinculin fragment generated by Shigella infection. VASP, in turn, provides the ABM-2 sequences [XPPPPP, X = G, P, L, S, A] for binding profilin, an actin-regulatory protein that stimulates actin filament assembly. Immunolocalization using rabbit anti-VASP antibody revealed that VASP concentrates behind motile virions in HeLa cells. Profilin was also present in these actin-rich rocket tails, and microinjection of 10 μM (intracellular) ABM-2 peptide (GPPPPP)3 blocked vaccinia actin-based motility. Vinculin did not colocalize with VASP on motile virions and remained in focal adhesion contacts; however, another ABM-1-containing host protein, zyxin, was concentrated at the rear of motile virions. We also examined time-dependent changes in the location of these cytoskeletal proteins during vaccinia infection. VASP and zyxin were redistributed dramatically several hours before the formation of actin rocket tails, concentrating in the viral factories of the perinuclear cytoplasm. Our findings underscore the universal involvement of ABM-1 and ABM-2 docking sites in actin-based motility of Listeria, Shigella, and now vaccinia.

Measuring the thickness of the human cerebral cortex from magnetic resonance images

Accurate and automated methods for measuring the thickness of human cerebral cortex could provide powerful tools for diagnosing and studying a variety of neurodegenerative and psychiatric disorders. Manual methods for estimating cortical thickness from neuroimaging data are labor intensive, requiring several days of effort by a trained anatomist. Furthermore, the highly folded nature of the cortex is problematic for manual techniques, frequently resulting in measurement errors in regions in which the cortical surface is not perpendicular to any of the cardinal axes. As a consequence, it has been impractical to obtain accurate thickness estimates for the entire cortex in individual subjects, or group statistics for patient or control populations. Here, we present an automated method for accurately measuring the thickness of the cerebral cortex across the entire brain and for generating cross-subject statistics in a coordinate system based on cortical anatomy. The intersubject standard deviation of the thickness measures is shown to be less than 0.5 mm, implying the ability to detect focal atrophy in small populations or even individual subjects. The reliability and accuracy of this new method are assessed by within-subject test–retest studies, as well as by comparison of cross-subject regional thickness measures with published values.

A synaptic basis for memory storage in the cerebral cortex

A cardinal feature of neurons in the cerebral cortex is stimulus selectivity, and experience-dependent shifts in selectivity are a common correlate of memory formation. We have used a theoretical “learning rule,” devised to account for experience-dependent shifts in neuronal selectivity, to guide experiments on the elementary mechanisms of synaptic plasticity in hippocampus and neocortex. These experiments reveal that many synapses in hippocampus and neocortex are bidirectionally modifiable, that the modifications persist long enough to contribute to long-term memory storage, and that key variables governing the sign of synaptic plasticity are the amount of NMDA receptor activation and the recent history of cortical activity.

Irreversibility of cellular aging and neoplastic transformation: a clonal analysis.

Prolonged incubation of NIH 3T3 cells under the growth constraint of confluence results in a persistent impairment of proliferation when the cells are subcultured at low density and a greatly increased probability of neoplastic transformation in assays for transformation. These properties, along with the large accumulation of age pigment bodies in the confluent cells, are cardinal cellular characteristics of aging in organisms and validate the system as a model of cellular aging. Two cultures labeled alpha and beta were obtained after prolonged confluence; both were dominated by cells that were both slowed in growth at low population density and enhanced in growth capacity at high density, a marker of neoplastic transformation. An experiment was designed to study the reversibility of these age-related properties by serial subculture at low density of the two uncloned cultures and their progeny clones derived from assuredly single cells. Both uncloned cultures had many transformed cells and a reduced growth rate on subculture. Serial subculture resulted in a gradual increase in growth rates of both populations, but a reversal of transformation only in the alpha population. The clones originating from both populations varied in the degree of growth impairment and neoplastic transformation. None of the alpha clones increased in growth rate on low density passage nor did the transformed clones among them revert to normal growth behavior. The fastest growing beta clone was originally slower than the control clone, but caught up to it after four weekly subcultures. The other beta clones retained their reduced growth rates. Four of the five beta clones, including the fastest grower, were transformed, and none reverted on subculture. We conclude that the apparent reversal of impaired growth and transformation in the uncloned parental alpha population resulted from the selective growth at low density of fast growing nontransformed clones. The reversal of impaired growth in the uncloned parental beta population was also the result of selective growth of fast growing clones, but in this case they were highly transformed so no apparent reversal of transformation occurred. The clonal results indicate that neither the impaired growth nor the neoplastic transformation found in aging cells is reversible. We discuss the possible contribution of epigenetic and genetic processes to these irreversible changes.

Granzyme A is critical for recovery of mice from infection with the natural cytopathic viral pathogen, ectromelia.

Cytolytic lymphocytes are of cardinal importance in the recovery from primary viral infections. Both natural killer cells and cytolytic T cells mediate at least part of their effector function by target cell lysis and DNA fragmentation. Two proteins, perforin and granzyme B, contained within the cytoplasmic granules of these cytolytic effector cells have been shown to be directly involved in these processes. A third protein contained within these granules, granzyme A, has so far not been attributed with any biological relevance. Using mice deficient for granzyme A, we show here that granzyme A plays a crucial role in recovery from the natural mouse pathogen, ectromelia, by mechanisms other than cytolytic activity.

Cellular aging, destabilization, and cancer.

Three major characteristics of aging in animals are a slowdown of cell proliferation, an increase in residual bodies associated with age pigments, and a marked increase in the likelihood of neoplastic transformation. The 28 L subline of the NIH 3T3 line of mouse embryo fibroblasts exhibits all these characteristics when held at confluence for extended periods. The impairment of proliferation is the first behavioral characteristic detected in low density subcultures from the confluent cultures, and it persists through many cell generations of exponential multiplication. There is an equal degree of growth impairment among replicate cultures (lineages) recovered after each of 2 successive rounds of confluence, although heterogeneity appears after the third round. The growth impairment pervades the entire cell population of each lineage. The degree and duration of impairment increase with repeated rounds of confluence. A marked increase of residual bodies characteristic of age pigments occurs in the cytoplasm of all the cells kept under prolonged confluence. Neoplastic transformation first appears as foci of multilayered cells on a monolayered background of nontransformed cells. The transformed cells arise at different times in the lineages and originate from a very small fraction of the population. The transformed cells selectively overgrow the entire population in successive rounds of confluence leading to an increase in saturation density of each lineage at different times. Under cloning conditions, isolated colonies of transformed cells develop more slowly than colonies of nontransformed cells but eventually reach a higher population density. The regularity of persistent growth impairment among the lineages and the appearance of large numbers of residual bodies in all the cells of each population are more characteristic of an epigenetic process than of specific local mutations. although random chromosomal lesions cannot be ruled out. By contrast, the low frequency and stochastic character of neoplastic transformation are consistent with a conventional genetic origin. The advent in long-term confluent NIH 3T3 cultures of three cardinal characteristics of cellular aging in vivo recommends it as a model for aging cells.

Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human beta-amyloid precursor protein.

The beta-amyloid precursor protein (beta-APP), from which the beta-A4 peptide is derived, is considered to be central to the pathogenesis of Alzheimer disease (AD). Transgenic mice expressing the 751-amino acid isoform of human beta-APP (beta-APP751) have been shown to develop early AD-like histopathology with diffuse deposits of beta-A4 and aberrant tau protein expression in the brain, particularly in the hippocampus, cortex, and amygdala. We now report that beta-APP751 transgenic mice exhibit age-dependent deficits in spatial learning in a water-maze task and in spontaneous alternation in a Y maze. These deficits were mild or absent in 6-month-old transgenic mice but were severe in 12-month-old transgenic mice compared to age-matched wild-type control mice. No other behavioral abnormalities were observed. These mice therefore model the progressive learning and memory impairment that is a cardinal feature of AD. These results provide evidence for a relationship between abnormal expression of beta-APP and cognitive impairments.

Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development.

We have recently cloned the human fms-like tyrosine kinase 4 gene FLT4, whose protein product is related to two vascular endothelial growth factor receptors FLT1 and KDR/FLK1. Here the expression of FLT4 has been analyzed by in situ hybridization during mouse embryogenesis and in adult human tissues. The FLT4 mRNA signals first became detectable in the angioblasts of head mesenchyme, the cardinal vein, and extraembryonally in the allantois of 8.5-day postcoitus (p.c.) embryos. In 12.5-day p.c. embryos, the FLT4 signal decorated developing venous and presumptive lymphatic endothelia, but arterial endothelia were negative. During later stages of development, FLT4 mRNA became restricted to vascular plexuses devoid of red cells, representing developing lymphatic vessels. Only the lymphatic endothelia and some high endothelial venules expressed FLT4 mRNA in adult human tissues. Increased expression occurred in lymphatic sinuses in metastatic lymph nodes and in lymphangioma. Our results suggest that FLT4 is a marker for lymphatic vessels and some high endothelial venules in human adult tissues. They also support the theory on the venous origin of lymphatic vessels.

Difference and Hierarchy Revisited by Feminism

Drawing heavily on the work of classicist Page duBois, which eloquently explains the emergence, in ancient Greece, of hierarchy and of what is still understood today as the great chain of being (scala naturae: male, female, slave, barbarian, animal), this paper analyzes the age-old negative conotations of the concept of difference in western culture, considers the reinvention of difference as “positive” by Rosi Braidotti (after Deleuze & Guattari), and reassesses the efforts of several other feminist philosophers (e.g. Luce Irigaray, Judith Butler, Gayatry Spivak, Drucilla Cornell) to counter Lacan on the impossibility of “speaking women” beyond the dominant (male) philosophical discourse. Or, to paraphrase Marie Cardinal, their efforts to find “les mots pour le dire”.

Développement d’un nouveau modèle murin expérimental de sclérodermie

La sclérodermie (SSc) est une maladie rare affectant les personnes génétiquement prédisposées d’une réponse immunitaire défectueuse. Malgré les derniers avancements et développements dans le domaine, l’étiologie et la pathogénèse de la maladie demeurent peu comprises. Par ailleurs, il y a un ralentissement dans la compréhension de cette maladie à cause du manque de modèle animal représentatif de la SSc humaine. Malgré plusieurs lacunes, les souris traitées avec la bléomycine ou portant des modifications génétiques (TSK-1) sont très utilisées dans les études précliniques de la SSc mais elles ne présentent pas toutes les caractéristiques de cette maladie. Pour contribuer à la recherche sur la SSc, la stagiaire postdoctorale Dre Heena Mehta a développé dans le laboratoire du Dre Sarfati en collaboration avec le Dr Senécal, un modèle de souris expérimental induit par l’immunisation de cellules dendritiques (DCs) chargées de peptides de la protéine topoisomérase I (TOPOIA et TOPOIB). Dans le but de caractériser ce modèle murin et d’établir un profil immunitaire, j’ai concentré mes analyses principalement sur les caractéristiques de la SSc telles que la fibrose, l’inflammation, l’hyper-γ-globulinémie polyclonale, la vasculopathie ainsi que de l’expression de cytokines. Brièvement, l’immunisation de souris avec les DCs chargées avec la topoisomérase I (TOPOI) a induit l’inflammation pulmonaire et cutanée, en plus de la fibrose sous forme diffuse (dcSSc). Les souris présentaient également des symptômes de la vasculopathie ainsi que des taux élevés d’anticorps polyclonaux. Les résultats démontraient que les peptides TOPOIA étaient efficaces dans l’induction de la fibrose et de la réponse inflammatoire alors que les peptides TOPOIB étaient surtout impliqués dans la fibrose cutanée. En plus de nos résultats, les observations préliminaires sur le profil de cytokines tissulaires suggéraient que ce modèle pourrait remplacer ou complémenter les autres modèles animaux de SSc.