Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

The synthesis of a GSK 2(nd) generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I) and gold(I) catalysts in this reaction was established by working with chiral phosphoramidites or with chiral BINAP. The best reaction conditions were used for the total synthesis of the hepatitis C virus inhibitor by a four step procedure affording this product in 99% ee and in 63% overall yield. The origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial.

[Reseña] F. Petrarca, De viris illustribus, I, II, IV (eds. S. Ferrone, C. Malta, P. de Capua), Firenze, Le Lettere, 2006-2007

[ES] Un real decreto de 1904, emitido con motivo de la celebración del VI Centenario del nacimiento de Petrarca (1304-1374), creó la Commissione per l’Edizione Nazionale delle Opere di Francesco Petrarca. Después de un siglo en el que los estudios petrarquescos han experimentado un florecimiento espectacular, con varias revistas y colecciones dedicadas exclusivamente a Petrarca y con una deslumbrante nómina de especialistas, han visto la luz siete de los veinte volúmenes previstos inicialmente.

Mechanisms Responsible for the Trophic Effect of Beta-Adrenoceptors on the I-to Current Density in Type 1 Diabetic Rat Cardiomyocytes

Background/Aims: In diabetic ventricular myocytes, transient outward potassium current (I-to) amplitude is severely reduced because of the impaired catecholamine release that characterizes diabetic autonomic neuropathy. Sympathetic nervous system exhibits a trophic effect on I-to since incubation of myocytes with noradrenaline restores current amplitude via beta-adrenoceptor (beta AR) stimulation. Here, we investigate the intracellular signalling pathway though which incubation of diabetic cardiomyocytes with the beta AR agonist isoproterenol recovers I-to amplitude to normal values. Methods: Experiments were performed in ventricular myocytes isolated from streptozotocin-diabetic rats. I-to current was recorded by using the patch-clamp technique. Kv4 channel expression was determined by immunofluorescence. Protein-protein interaction was determined by coimmunoprecipitation. Results: Stimulation of beta AR activates first a G alpha s protein, adenylyl cyclase and Protein Kinase A. PKA-phosphorylated receptor then switches to the G alpha i protein. This leads to the activation of the beta AR-Kinase-1 and further receptor phosphorylation and arrestin dependent internalization. The internalized receptor-arrestin complex recruits and activates cSrc and the MAPK cascade, where Ras, c-Raf1 and finally ERK1/2 mediate the increase in Kv4.2 and Kv4.3 protein abundance in the plasma membrane. Conclusion: beta(2)AR stimulation activates a G alpha s and G alpha i protein dependent pathway where the ERK1/2 modulates the Ito current amplitude and the density of the Kv4.2 and Kv4.2 channels in the plasma membrane upon sympathetic stimulation in diabetic heart.

Diagnosis of invasive candidiasis by enzyme-linked immunosorbent assay using the N-terminal fragment of Candida albicans hyphal wall protein I

Background: The diagnosis of invasive candidiasis is difficult because there are no specific clinical manifestations of the disease and colonization and infection are difficult to distinguish. In the last decade, much effort has been made to develop reliable tests for rapid diagnosis of invasive candidiasis, but none of them have found widespread clinical use. Results: Antibodies against a recombinant N-terminal fragment of the Candida albicans germ tube-specific antigen hyphal wall protein 1 (Hwp1) generated in Escherichia coli were detected by both immunoblotting and ELISA tests in a group of 36 hematological or Intensive Care Unit patients with invasive candidiasis and in a group of 45 control patients at high risk for the mycosis who did not have clinical or microbiological data to document invasive candidiasis. Results were compared with an immunofluorescence test to detect antibodies to C. albicans germ tubes (CAGT). The sensitivity, specificity, positive and negative predictive values of a diagnostic test based on the detection of antibodies against the N-terminal fragment of Hwp1 by immunoblotting were 27.8 %, 95.6 %, 83.3 % and 62.3 %, respectively. Detection of antibodies to the N-terminal fragment of Hwp1 by ELISA increased the sensitivity (88.9 %) and the negative predictive value (90.2 %) but slightly decreased the specificity (82.6 %) and positive predictive values (80 %). The kinetics of antibody response to the N-terminal fragment of Hwp1 by ELISA was very similar to that observed by detecting antibodies to CAGT. Conclusion: An ELISA test to detect antibodies against a recombinant N-terminal fragment of the C. albicans germ tube cell wall antigen Hwp1 allows the diagnosis of invasive candidiasis with similar results to those obtained by detecting antibodies to CAGT but without the need of treating the sera to adsorb the antibodies against the cell wall surface of the blastospore.

El genio de un solo ojo, I: en la mitología griega, Polifemo

En este trabajo se estudia la figura de Polifemo, el hijo de Poseidón y la ninfa Toosa, como ejemplo de las sucesivas reinterpretaciones que la mitología griega hacía de temas populares que resultaban de su interés: se analizan e interpretan los episodios de su historia y las características del personaje en la primitiva versión homérica y sus sucesivas reelaboraciones, de época clásica (Eurípides) y de época postclásica en obras griegas (Filóxeno de Citera, Teócrito y Mosco) y latinas (Virgilio y Ovidio).

lnscripciones romanas de Segovia. I: inscripciones inéditas

[ES] Se dan a conocer en este trabajo catorce nuevas inscripciones romanas de Segovia y su provincia. Nueve de ellas han aparecido en Segovia (ocho funerarias y una votiva), dos en Coca (ambas funerarias), dos en Duratón (no conociéndose su naturaleza por estar bastante fracturadas) y una en Sepúlveda (parece honorífica, a pesar de estar muy fracturada). En lo referente a su contenido hay dos unidades organizativas indígenas, en ambos casos expresadas por medio de genitivos de plural y halladas en la muralla de Segovia ("Cantabr(e)cum" en la inscripción n.º 2 y "Moveq(um)" en la inscripción n.º 4), referencia a un "contub(ernalis)" en la n.º 6 y la posibilidad de la existencia de un "collegium", si completamos como "fratribus" la cuarta línea de la inscripción n.º 14.