“Se le dé papel, prensa y letras”. Albert O’Farail y el libro misionero "The Life of the Virgin Marie" (1671-1693)

El proyecto tipográfico del irlandés Albert O’Farail se concibió como un libro misionero destinado a la empresa confesional que la monarquía de España desarrollaba en las Islas Británicas desde comienzos del Seiscientos. Las traducciones de distintos tratados doctrinales y teológicos, representados por su devoción particular a la Virgen María, procuraban acercar la religión a los católicos del Norte a través de mecanismos de proximidad cultural como complemento a la predicación de los ministros espirituales patrocinados por Carlos II. El empeño por dar a las prensas esta miscelánea de obras, financiada por la corona y compuesta por el arte de su propio autor, discurrió en paralelo a la querella abierta por su esposa, María Manuela Laínez, para reivindicar sus derechos nobiliarios al título marquesal de Mayo. Tanto en Madrid como en Roma, la imbricación de ambos negociados determinó su malograda resolución.

La cultura en la traducción teatral: el caso de la versión de "Les Fourberies de Scapin" (1671) por Julio Gómez de la Serna

Las referencias culturales en las obras teatrales representan auténticos retos de traducción, puesto que afectan a la representabilidad del texto teatral y condicionan su recepción. Les Fourberies de Scapin (1671), una de las piezas más conocidas de Molière, contiene una gran cantidad de referencias culturales que afectan su mise en scène. Mediante un análisis comparativo, se ha comprobado que la traducción al español de Julio Gómez de la Serna de los años setenta, con un estilo literario y en ocasiones libre, no consigue trasladar ciertos componentes culturales que resultan empero esenciales para la lectura y representación del texto teatral.

Genomic islands in the pathogenic filamentous fungus Aspergillus fumigatus

We present the genome sequences of a new clinical isolate of the important human pathogen, Aspergillus fumigatus, A1163, and two closely related but rarely pathogenic species, Neosartorya fischeri NRRL181 and Aspergillus clavatus NRRL1. Comparative genomic analysis of A1163 with the recently sequenced A. fumigatus isolate Af293 has identified core, variable and up to 2% unique genes in each genome. While the core genes are 99.8% identical at the nucleotide level, identity for variable genes can be as low 40%. The most divergent loci appear to contain heterokaryon incompatibility ( het) genes associated with fungal programmed cell death such as developmental regulator rosA. Cross-species comparison has revealed that 8.5%, 13.5% and 12.6%, respectively, of A. fumigatus, N. fischeri and A. clavatus genes are species-specific. These genes are significantly smaller in size than core genes, contain fewer exons and exhibit a subtelomeric bias. Most of them cluster together in 13 chromosomal islands, which are enriched for pseudogenes, transposons and other repetitive elements. At least 20% of A. fumigatus-specific genes appear to be functional and involved in carbohydrate and chitin catabolism, transport, detoxification, secondary metabolism and other functions that may facilitate the adaptation to heterogeneous environments such as soil or a mammalian host. Contrary to what was suggested previously, their origin cannot be attributed to horizontal gene transfer ( HGT), but instead is likely to involve duplication, diversification and differential gene loss (DDL). The role of duplication in the origin of lineage-specific genes is further underlined by the discovery of genomic islands that seem to function as designated ""gene dumps'' and, perhaps, simultaneously, as "" gene factories''.

The expression of efflux and uptake transporters are regulated by statins in Caco-2 and HepG2 cells

Aim: Statin disposition and response are greatly determined by the activities of drug metabolizing enzymes and efflux/uptake transporters. there is little information on the regulation of these proteins in human cells after statin therapy. In this study, the effects of atorvastatin and simvastatin on mRNA expression of efflux (ABCB1, ABCG2 and ABCC2) and uptake (SLCO1B1, SLCO2B1 and SLC22A1) drug transporters in Caco-2 and HepG2 cells were investigated. Methods: Quantitative real-time PCR was used to measure mRNA levels after exposure of HepG2 and Caco-2 cells to statins. Results: Differences in mRnA basal levels of the transporters were as follows: ABCC2>ABCG2>ABCB1>SLCO1B1>>>SLC22A1>SLC O2B1 for HepG2 cells, and SLCO2B1>>ABCC2>ABCB1>ABCG2>>>SLC22A1 for Caco-2 cells. While for HepG2 cells, ABCC2, ABCG2 and SLCO2B1 mRnA levels were significantly up-regulated at 1, 10 and 20 mu mol/L after 12 or 24 h treatment, in Caco-2 cells, only the efflux transporter ABCB1 was significantly down-regulated by two-fold following a 12 h treatment with atorvastatin. Interestingly, whereas treatment with simvastatin had no effect on mRNA levels of the transporters in HepG2 cells, in Caco-2 cells the statin significantly down-regulated ABCB1, ABCC2, SLC22A1, and SLCO2B1 mRnA levels after 12 or 24 h treatment. Conclusion: These findings reveal that statins exhibits differential effects on mRNA expression of drug transporters, and this effect depends on the cell type. Furthermore, alterations in the expression levels of drug transporters in the liver and/or intestine may contribute to the variability in oral disposition of statins.

One-pot synthesis of alpha,beta-epoxy ketones by palladium-catalyzed epoxidation-oxidation of terminal allylic alcohols

Described herein is a one-pot synthesis of a,p-epoxy ketones using a palladium-catalyzed epoxidation-oxidation sequence. Functionalized terminal allylic alcohols are treated with m-CPBA Under mild reaction conditions to obtain the alpha,beta-epoxy ketones. The main benefit of this approach is that the epoxidation of the terminal double bond and the oxidation of the secondary alcohol occured in the same reaction under mild reactions and both electron-donating and electron-withdrawing functionalities are tolerated in the reaction sequence. (C) 2010 Elsevier Ltd. All rights reserved.

KISS1R Intracellular Trafficking and Degradation: Effect of the Arg386Pro Disease-Associated Mutation

The goal of this study was to investigate how the Arg386Pro mutation prolongs KiSS-1 receptor (KISS1R) responsiveness to kisspeptin, contributing to human central precocious puberty. Confocal imaging showed colocalization of wild-type (WT) KISS1R with a membrane marker, which persisted for up to 5 h of stimulation. Conversely, no colocalization with a lysosome marker was detected. Also, overnight treatment with a lysosome inhibitor did not affect WT KISS1R protein, whereas overnight treatment with a proteasome inhibitor increased protein levels by 24-fold. WT and Arg386Pro KISS1R showed time-dependent internalization upon stimulation. However, both receptors were recycled back to the membrane. The Arg386Pro mutation did not affect the relative distribution of KISS1R in membrane and internalized fractions when compared to WT KISS1R for up to 120 min of stimulation, demonstrating that this mutation does not affect KISS1R trafficking rate. Nonetheless, total Arg386Pro KISS1R was substantially increased compared with WT after 120 min of kisspeptin stimulation. This net increase was eliminated by blockade of detection of recycled receptors, demonstrating that recycled receptors account for the increased responsiveness of this mutant to kisspeptin. We therefore conclude the following: 1) WT KISS1R is degraded by proteasomes rather than lysosomes; 2) WT and Arg386Pro KISS1R are internalized upon stimulation, but most of the internalized receptors are recycled back to the membrane rather than degraded; 3) the Arg386Pro mutation does not affect the rate of KISS1R trafficking-instead, it prolongs responsiveness to kisspeptin by decreasing KISS1R degradation, resulting in the net increase on mutant receptor recycled back to the plasma membrane.(Endocrinology 152: 1616-1626,2011)

alpha-Melanocyte Stimulating Hormone Analogue AP214 Protects Against Ischemia Induced Acute Kidney Injury in a Porcine Surgical Model

Purpose: alpha-Melanocyte stimulating hormone protects kidneys against ischemia and sepsis induced acute kidney injury in rodents. We examined the efficacy of a-melanocyte stimulating hormone analogue AP214 to protect against acute kidney injury in higher vertebrates. Materials and Methods: We performed a prospective, blinded, randomized, placebo controlled study in 26 pigs. Laparoscopic technique was used for left nephrectomy and to induce complete warm ischemia in the right kidney for 120 minutes. AP214 (200 mu g/kg intravenously) was administered daily on the day of surgery and for 5 days thereafter. Kidney function was measured for 9 days. We measured changes in serum creatinine, estimated glomerular filtration rate, serum C-reactive protein and urine interleukin-18. Results: In the placebo control and AP214 groups mean peak serum creatinine was 10.2 vs 3.92 mg/dl and the estimated glomerular filtration rate nadir was 22.9 vs 62.6 ml per minute per kg (each p = 0.001). Functional nadir occurred at 72 vs 24 hours in the control vs AP214 groups. Estimated glomerular filtration rate outcome on postoperative day 9 was 118 vs 156 ml per minute per kg in the control vs AP214 groups (p = 0.04). Conclusions: We noted a robust renoprotective effect of AP214. A similar AP214 effect may be observed in humans. Future research includes mechanistic studies in pigs and a phase II human clinical trial of AP214 in kidney transplant and partial nephrectomy populations.

Cell homeostasis in a Leishmania major mutant overexpressing the spliced leader RNA is maintained by an increased proteolytic activity

Although several stage-specific genes have been identified in Leishmania, the molecular mechanisms governing developmental gene regulation in this organism are still not well understood. We have previously reported an attenuation of virulence in Leishmania major and L braziliensis carrying extra-copies of the spliced leader RNA gene. Here, we surveyed the major differences in proteome and transcript expression profiles between the spliced leader RNA overexpressor and control lines using two-dimensional gel electrophoresis and differential display reverse transcription PCR, respectively. Thirty-nine genes related to stress response, cytoskeleton, proteolysis, cell cycle control and proliferation, energy generation, gene transcription, RNA processing and post-transcriptional regulation have abnormal patterns of expression in the spliced leader RNA overexpressor line. The evaluation of proteolytic pathways in the mutant revealed a selective increase of cysteine protease activity and an exacerbated ubiquitin-labeled protein population. Polysome profile analysis and measurement of cellular protein aggregates showed that protein translation in the spliced leader RNA overexpressor line is increased when compared to the control line. We found that L major promastigotes maintain homeostasis in culture when challenged with a metabolic imbalance generated by spliced leader RNA surplus through modulation of intracellular proteolysis. However, this might interfere with a fine-tuned gene expression control necessary for the amastigote multiplication in the mammalian host. (c) 2010 Elsevier Ltd. All rights reserved.

Specific infiltration of langerin-positive dendritic cells in EBV-infected tonsil, Hodgkin lymphoma and nasopharyngeal carcinoma

We report here the existence of a novel subset of langerin (CD207)-positive, immature dendritic cells (DCs) (CD83(neg)) abundantly infiltrating Epstein Barr virus (EBV)-infected areas in tonsil, Hodgkin lymphoma and nasopharyngeal carcinoma. These CD207(+) DCs differ from conventional epidermal Langerhans cells in their lack of CD1a and CCR6 and their unusual tissue localization. CD207(+) DC infiltration strongly correlates with EBV infection because it was neither detected in EBV negative specimens nor in tissues infected with other human viruses. These immature DCs might represent good candidates for induction of the EBV-specific immune response.

Caf?? com debate: lideran??a do professor-tutor

A Escola Nacional de Administra????o P??blica (ENAP) recebeu os professores Michel Bourdon, da Canada School of Public Service (CSPS), e Andrea Filatro, das universidades Paulista e Federal de Juiz de Fora. A atividade, realizada no Dia Nacional da Educa????o a Dist??ncia (EAD), teve como objetivo promover uma reflex??o sobre o papel do professor-tutor como l??der de processos de aprendizagem

Em torno do avigoramento dos modernos executivos

Um processo social, t??o atuante nos Estados Unidos como na Europa e noutras partes do mundo de hoje, vem, revolucionariamente ou evolucionariamente, fazendo declinar regimes predominantemente parlamentares e, ao mesmo tempo, grandemente dependentes de partidos apenas pol??ticos e de ritos de democracia convencionalmente eleitoral; e fazendo emergir, ou ressurgir, sob coloridos novos, e sob v??rias formas, um poder ou um executivo pol??tico administrativo como que sociologicamente monarquizado

Aula inaugural do curso de forma????o da carreira de EPPGG

A aula inaugural da primeira turma do curso de forma????o de Especialista em Pol??ticas P??blicas e Gest??o Governamental - EPPGG e da Escola Nacional de Administra????o P??blica - ENAP, preparada pelo presidente Jos?? Sarney e proferida pelo ministro Alu??zio Alves, em 1988, ?? documento de fundamental import??ncia para a carreira, para a ENAP e para a profissionaliza????o da Administra????o P??blica. A presente publica????o re??ne de maneira in??dita tr??s discursos que s??o refer??ncia obrigat??ria para os gestores governamentais: al??m da aula do presidente Jos?? Sarney, os pronunciamentos do ministro Alu??zio Alves e do presidente da Funda????o Centro de forma????o do Servidor P??blico - FUNCEP, Paulo Catalano, proferidos na mesma ocasi??o. Os textos traduzem as expectativas e as diretrizes para a consolida????o da ENAP e da carreira de EPPGGs, ressaltando sua import??ncia par uma gest??o p??blica voltada aos interesses dos cidad??os. Resgat??-los colabora para refor??ar a mem??ria e a hist??ria dos gestores governamentais, valorizando sua trajet??ria e seus objetivos. Vinte e cinco anos ap??s a aula inaugural, os prop??sitos e os princ??pios que nortearam a cria????o da carreira e da ENAP permanecem os mesmos, como ressaltado no discurso presidencial: "todos os atos do governo, do mais solene ao mais rotineiro, devem ter sempre no horizonte, o fim ??ltimo e a raz??o essencial do Estado que ?? a promo????o do bem-estar, a garantia de igualdade de chances, do direito ?? paz, ?? liberdade e ?? busca individual de felicidade para todos.