Scavenger receptor class B, type I (SR-BI) is the major route for the delivery of high density lipoprotein cholesterol to the steroidogenic pathway in cultured mouse adrenocortical cells

The class B, type I scavenger receptor, SR-BI, binds high density lipoprotein (HDL) and mediates the selective uptake of HDL cholesteryl ester (CE) by cultured transfected cells. The high levels of SR-BI expression in steroidogenic cells in vivo and its regulation by tropic hormones provides support for the hypothesis that SR-BI is a physiologically relevant HDL receptor that supplies substrate cholesterol for steroid hormone synthesis. This hypothesis was tested by determining the ability of antibody directed against murine (m) SR-BI to inhibit the selective uptake of HDL CE in Y1-BS1 adrenocortical cells. Anti-mSR-BI IgG inhibited HDL CE-selective uptake by 70% and cell association of HDL particles by 50% in a dose-dependent manner. The secretion of [3H]steroids derived from HDL containing [3H]CE was inhibited by 78% by anti-mSR-BI IgG. These results establish mSR-BI as the major route for the selective uptake of HDL CE and the delivery of HDL cholesterol to the steroidogenic pathway in cultured mouse adrenal cells.

Expression of scavenger receptor class B type 1 (SR-BI) promotes microvillar channel formation and selective cholesteryl ester transport in a heterologous reconstituted system

In the “selective” cholesteryl ester (CE) uptake process, surface-associated lipoproteins [high density lipoprotein (HDL) and low density lipoprotein] are trapped in the space formed between closely apposed surface microvilli (microvillar channels) in hormone-stimulated steroidogenic cells. This is the same location where an HDL receptor (SR-BI) is found. In the current study, we sought to understand the relationship between SR-BI and selective CE uptake in a heterologous insect cell system. Sf9 (Spodoptera frugiperda) cells overexpressing recombinant SR-BI were examined for (i) SR-BI protein by Western blot analysis and light or electron immunomicroscopy, and (ii) selective lipoprotein CE uptake by the use of radiolabeled or fluorescent (BODIPY-CE)-labeled HDL. Noninfected or infected control Sf9 cells do not express SR-BI, show microvillar channels, or internalize CEs. An unexpected finding was the induction of a complex channel system in Sf9 cells expressing SR-BI. SR-BI-expressing cells showed many cell surface double-membraned channels, immunogold SR-BI, apolipoprotein (HDL) labeling of the channels, and high levels of selective HDL-CE uptake. Thus, double-membraned channels can be induced by expression of recombinant SR-BI in a heterologous system, and these specialized structures facilitate both the binding of HDL and selective HDL-CE uptake.

Role for the class A macrophage scavenger receptor in the phagocytosis of apoptotic thymocytes in vitro.

Numerous immature thymocytes undergo apoptosis and are rapidly engulfed by phagocytic thymic macrophages. The macrophage surface receptors involved in apoptotic thymocyte recognition are unknown. We have examined the role of the class A macrophage scavenger receptor (SR-A) in the engulfment of apoptotic thymocytes. Uptake of steroid-treated apoptotic thymocytes by thymic and inflammatory-elicited SR-A positive macrophages is partially inhibited by an anti-SR-A mAb and more completely by a range of scavenger receptor ligands. Thymic macrophages from mice with targeted disruption of the SR-A gene show a 50% reduction in phagocytosis of apoptotic thymocytes in vitro. These data suggest that SR-A may play a role in the clearance of dying cells in the thymus.

Involvement of specific macrophage-lineage cells surrounding arterioles in barrier and scavenger function in brain cortex.

The transport of solutes between blood and brain is regulated by a specific barrier. Capillary endothelial cells of brain are known to mediate barrier function and facilitate transport. Here we report that specific cells surrounding arterioles, known as Mato's fluorescent granular perithelial (FGP) cells or perivascular microglial cells, contribute to the barrier function. Immunohistochemical and in situ hybridization studies indicate that, in normal brain cortex, type I and type II macrophage scavenger receptors are expressed only in FGP/perivascular microglial cells, and surface markers of macrophage lineage are also detected on them. These cells mediate the uptake of macromolecules, including modified low density lipoprotein, horseradish peroxidase, and ferritin injected either into the blood or into the cerebral ventricles. Accumulation of scavenged materials with aging or after the administration of a high-fat diet results in the formation of honeycomb-like foam cells and the narrowing of the lumen of arterioles in the brain cortex. These results indicate involvement of FGP/perivascular microglial cells in the barrier and scavenger functions in the central nervous system.

beta-Amyloid toxicity in organotypic hippocampal cultures: protection by EUK-8, a synthetic catalytic free radical scavenger.

Oxygen free radicals have been proposed to mediate amyloid peptide (beta-AP)-induced neurotoxicity. To test this hypothesis, we evaluated the effects of EUK-8, a synthetic catalytic superoxide and hydrogen peroxide scavenger, on neuronal injury produced by beta-AP in organotypic hippocampal slice cultures. Cultures of equivalent postnatal day 35 (defined as mature) and 14 (defined as immature) were exposed to various concentrations of beta-AP (1-42 or 1-40) in the absence or presence of 25 microM EUK-8 for up to 72 hours. Neuronal injury was assessed by lactate dehydrogenase release and semiquantitative analysis of propidium iodide uptake at various times after the initiation of beta-AP exposure. Free radical production was inferred from the relative increase in dichlorofluorescein fluorescence, and the degree of lipid peroxidation was determined by assaying thiobarbituric acid-reactive substances. Treatment of mature cultures with beta-AP (50-250 microg/ml) in serum-free conditions resulted in a reproducible pattern of damage, causing a time-dependent increase in neuronal injury accompanied with formation of reactive oxygen species. However, immature cultures were entirely resistant to beta-AP-induced neurotoxicity and also demonstrated no dichlorofluorescein fluorescence or increased lipid peroxidation after beta-AP treatment. Moreover, mature slices exposed to beta-AP in the presence of 25 microM EUK-8 were significantly protected from beta-AP-induced neurotoxicity. EUK-8 also completely blocked beta-AP-induced free radical accumulation and lipid peroxidation. These results not only support a role for oxygen free radicals in beta-AP toxicity but also highlight the therapeutic potential of synthetic radical scavengers in Alzheimer disease.

Scavenger receptor A gene regulatory elements target gene expression to macrophages and to foam cells of atherosclerotic lesions.

Transcription of the macrophage scavenger receptor A gene is markedly upregulated during monocyte to macrophage differentiation. In these studies, we demonstrate that 291 bp of the proximal scavenger receptor promoter, in concert with a 400-bp upstream enhancer element, is sufficient to direct macrophage-specific expression of a human growth hormone reporter in transgenic mice. These regulatory elements, which contain binding sites for PU.1, AP-1, and cooperating ets-domain transcription factors, are also sufficient to mediate regulation of transgene expression during the in vitro differentiation of bone marrow progenitor cells in response to macrophage colony-stimulating factor. Mutation of the PU.1 binding site within the scavenger receptor promoter severely impairs transgene expression, consistent with a crucial role of PU.1 in regulating the expression of the scavenger receptor gene. The ability of the scavenger receptor promoter and enhancer to target gene expression to macrophages in vivo, including foam cells of atherosclerotic lesions, suggests that these regulatory elements will be of general utility in the study of macrophage differentiation and function by permitting specific modifications of macrophage gene expression.

Expression cloning of dSR-CI, a class C macrophage-specific scavenger receptor from Drosophila melanogaster.

Mammalian class A macrophage-specific scavenger receptors (SR-A) exhibit unusually broad binding specificity for a wide variety of polyanionic ligands. The properties of these receptors suggest that they may be involved in atherosclerosis and host defense. We have previously observed a similar receptor activity in Drosophila melanogaster embryonic macrophages and in the Drosophila macrophage-like Schneider L2 cell line. Expression cloning was used to isolate from L2 cells a cDNA that encodes a third class (class C) of scavenger receptor, Drosophila SR-CI (dSR-CI). dSR-CI expression was restricted to macrophages/hemocytes during embryonic development. When expressed in mammalian cells, dSR-CI exhibited high affinity and saturable binding of 125I-labeled acetylated low density lipoprotein and mediated its chloroquine-dependent, presumably lysosomal, degradation. Although the broad polyanionic ligand-binding specificity of dSR-CI was similar to that of SR-A, their predicted protein sequences are not similar. dSR-CI is a 609-residue type I integral membrane protein containing several well-known sequence motifs, including two complement control protein (CCP) domains and somatomedin B, MAM, and mucin-like domains. Macrophage scavenger receptors apparently mediate important, well-conserved functions and may be pattern-recognition receptors that arose early in the evolution of host-defense mechanisms. Genetic and physiologic analysis of dSR-CI function in Drosophila should provide further insights into the roles played by scavenger receptors in host defense and development.

Avenidas fluviales e inundaciones de los ríos Vinalopó y Segura en época islámica y sus consecuencias en el poblamiento

Son escasas las noticias de época andalusí sobre inundaciones fluviales en el sur de la provincia de Alicante. En la descripción de Elche del Mugrib de Ibn Sa’īd se nos informa indirectamente de una inundación del Vinalopó en el segundo cuarto del s. XIII; como consecuencia, la ciudad musulmana se anegó y bastante población la abandonó. Respecto al vecino río Segura, el geógrafo al-‘Udrī (m. 1085) al describimos el curso del río nos informa que su sistema de riegos es como el del Nilo; este paralelo se debe al uso inteligente que hacían los egipcios y los habitantes de la Vega Baja de las aguas de la inundación fluvial como abono periódico de sus tierras y como elemento para luchar contra los marjales. También se analizan otras noticias sobre la torre de Embergoñes, la cual, situada a la entrada del curso fluvial en Orihuela, consideramos que era un promontorio de señales y de vigilancia de la inundación. Finalmente se recuerda la existencia de acanaladuras en las puertas de la catedral de Orihuela para proteger el interior del templo de las aguas de avenida.

Construcción, reconstrucción y consolidación del desaparecido Grupo Escolar “Francisco Giner de los Ríos” de Alicante (España)

La demolición del Grupo Escolar “Francisco Giner de los Ríos” supuso una pérdida incuestionable para la ciudad de Alicante (España), desapareciendo uno de los más relevantes ejemplos racionalistas, símbolo de modernidad y del desarrollo que en materia de enseñanza significó en la ciudad el “Plan de Construcción de Escuelas y Ordenación Escolar” de 1931. Con el fin de contribuir a subsanar el vacío documental que antecedió su demolición, el presente artículo muestra los resultados del estudio de las fases determinantes de la historia del edificio: proyecto (1933), construcción (1934-1935), reconstrucción y consolidación (1943-1944). Se concluyen las causas que originaron la ruina del inmueble, el alcance y magnitud de los daños y las avanzadas técnicas empleadas en su recuperación, prestando especial interés a las intervenciones de cimentación y consolidación del terreno, pilotajes e inyecciones de cemento, prácticas de relevancia internacional en el periodo de posguerra en España y Segunda Guerra Mundial.

El ars de traducir en Joan Roís de Corella, los límites de la difusión de sus obras y las claves para una Tragèdia de Caldesa políglota

Joan Roís de Corella traduce (obras religiosas) y, lo más importante, crea y traduce para crear. Traduce obras profanas y obras religiosas y, al hacerlo, recibe directamente las tradiciones literarias y culturales de su tiempo y de los clásicos. Destaca, por su extensión, complejidad y ambición, el conjunto de su actividad traductológica en cuanto a obras religiosas que marcaban la espiritualidad de la época. La más extensa y ambiciosa de sus traducciones es la versión catalana de la Vita Christi de Ludolfo de Sajonia, conocido como el Cartoixà y aparecido en cuatro volúmenes en 1495 (el Quart, con dos ediciones, y el Tercero), en 1496 (el Primer) y el 1500 (el Segon), ya póstumamente. En estos volúmenes, tan extensos, Roís de Corella más bien manifiesta tendencia a abreviar, si bien no renuncia a impregnar el texto resultante de las característics propias de su maestría estilística. No opera aquí como otros traductores de su tiempo, que no tenían tanto miramiento y hacían avenir el estilo de la traducción resultante con los gustos de moda en la época e independientemente del original.

En estil de fictes paraules que tenen sentits no fictes: anàlisi de locucions i col·locacions en Joan Roís de Corella en el context del llenguatge literari de la Corona d’Aragó en el segle XV

Aquest article presenta una mostra dels resultats de l’anàlisi detallada de locucions, col·locacions i altres elements fraseològics i d’ordre de mots significatius quant a la caracterització del cabal de llenguatge literari de Joan Roís de Corella. Aquesta anàlisi es fa amb metodologia interdisciplinar de base de lingüistica de corpus i de diacronia lingüistica, i amb el concurs de les tecnologies de la informació i la comunicació (humanitats digitals), que s’apliquen a l’anàlisi de l’aportació lèxica i estilística d’un autor clau com és Roís de Corella a fide calibrar el grau de sintonia i, alhora, d’especificitat del seu llenguatge literari; en quin grau coincideix el seu llenguatge literari amb el d’altres grans clàssics culturals de la Corona d’Aragó, i en què basa, alhora, Roís de Corella la clau de la seua mestria estilística.

L'ús de la llengua valenciana a la Il·lustració: la figura de Carles Ros

L'arribada de la nova dinastia borbònica va suposar a nivell cultural la desaparició oficial del valencià en el llenguatge de l'administració i un retrocés de la llengua en tots els àmbits d'ús. El notari valencià Carles Ros va ser un ferm defensor de la llengua en un context poc favorable, com així ho demostra a les seues obres. Gran part de la seua producció literària, la qual inclou tractats gramaticals i lexicogràfics, vocabularis, obres apologètiques, col·loquis i romanços, està dedicada a defensar i promoure el valencià, així com facilitar-ne el seu coneixement.