Un texto inédito de Quevedo: "Memorial de don Francisco de Quevedo Villegas dado a la Inquisición General sobre los libros del Monte Santo de Granada"

This article presents an unknown and unpublished text written by Quevedo, the Memorial de don Francisco de Quevedo Villegas dado a la Inquisición General sobre los libros del Monte Santo de Granada, with an annotated edition and preceded by an introductory study. The study shows evidence for Quevedo’s authorship of the text and suggests an approximate date of composition. In the Memorial, Quevedo defends the fake nature of the texts and relics found in the Sacromonte de Granada and urges the Inquisition to burn them down instead of sending them to Rome for further examination, as Pope Urban VIII had requested. The text confirms Quevedo’s inclination to influence issues of government as well as his adhesion to Catholic orthodoxy and his aspiration to historiographical rigour.Este trabajo presenta un texto desconocido e inédito de Quevedo, el Memorial de don Francisco de Quevedo Villegas dado a la Inquisición General sobre los libros del Monte Santo de Granada, en una edición anotada y precedida de un estudio introductorio. El estudio determina la autoría de Quevedo y propone una fecha aproximada de composición. En el Memorial, Quevedo considera falsos los textos y reliquias encontrados en el Sacromonte granadino, y propone a la Inquisición que estos sean quemados ya en España y no enviados a Roma para su examen, como había solicitado el papa Urbano VIII. El memorial muestra la tendencia de Quevedo a influir en los asuntos de gobierno, así como su ortodoxia católica y su pretensión de rigor historiográfico

Algunas incógnitas, precisiones e incertidumbres sobre la vida y la muerte de Alonso Álvarez de Soria

It has been commonly assumed that the historical reference to the death of the Sevillian poet Alonso Álvarez de Soria made in Quevedo’s Buscón signals the terminus a quo for the composition of the work. In his biography of Álvarez de Soria, Rodríguez Marín argued that his execution did take place at the end of 1603 or at the beginning of 1604, and this hypothesis has been maintained and repeated so long without being questioned. But the fact is that there are no known documents that can help to verify the date of Álvarez de Soria’s execution. A systematic examination of the existing documentation on the poet and of the annals, ephemerides and local chronicles composed in Seville during the years related to Álvarez de Soria’s death have not allowed to find any mention or clue of the event. Only literary testimonies, which are here also provided, have transmitted this notice. A series of mysteries and uncertainties, which are underlined, arise as future lines of research.Se ha admitido de modo unánime que la referencia histórica en el Buscón a la muerte del poeta sevillano Alonso Álvarez de Soria representa el término a quo para la redacción del relato quevediano. Rodríguez Marín mantuvo en su biografía del poeta patibulario que su ejecución se produjo a finales de 1603 o al comienzo de 1604, conjetura que se ha tenido por cierta hasta ahora y que se ha aceptado sin apenas cuestionarse. Pero lo único cierto es que no hay ningún documento conocido que pueda verificar la fecha de la ejecución de Alonso Álvarez de Soria. El repaso sistemático de la documentación conservada sobre el poeta y de los anales, avisos, efemérides y todo género de crónicas locales que se compusieron en Sevilla durante los años en que se pudo producir la muerte de Álvarez de Soria no ha permitido hallar mención ni indicio del suceso. Solo los testimonios literarios que se repasan en este trabajo han transmitido la noticia. De ello se deriva una serie de incógnitas e incertidumbres que se ponen de relieve

Algunas incógnitas, precisiones e incertidumbres sobre la vida y la muerte de Alonso Álvarez de Soria

It has been commonly assumed that the historical reference to the death of the Sevillian poet Alonso Álvarez de Soria made in Quevedo’s Buscón signals the terminus a quo for the composition of the work. In his biography of Álvarez de Soria, Rodríguez Marín argued that his execution did take place at the end of 1603 or at the beginning of 1604, and this hypothesis has been maintained and repeated so long without being questioned. But the fact is that there are no known documents that can help to verify the date of Álvarez de Soria’s execution. A systematic examination of the existing documentation on the poet and of the annals, ephemerides and local chronicles composed in Seville during the years related to Álvarez de Soria’s death have not allowed to find any mention or clue of the event. Only literary testimonies, which are here also provided, have transmitted this notice. A series of mysteries and uncertainties, which are underlined, arise as future lines of research.Se ha admitido de modo unánime que la referencia histórica en el Buscón a la muerte del poeta sevillano Alonso Álvarez de Soria representa el término a quo para la redacción del relato quevediano. Rodríguez Marín mantuvo en su biografía del poeta patibulario que su ejecución se produjo a finales de 1603 o al comienzo de 1604, conjetura que se ha tenido por cierta hasta ahora y que se ha aceptado sin apenas cuestionarse. Pero lo único cierto es que no hay ningún documento conocido que pueda verificar la fecha de la ejecución de Alonso Álvarez de Soria. El repaso sistemático de la documentación conservada sobre el poeta y de los anales, avisos, efemérides y todo género de crónicas locales que se compusieron en Sevilla durante los años en que se pudo producir la muerte de Álvarez de Soria no ha permitido hallar mención ni indicio del suceso. Solo los testimonios literarios que se repasan en este trabajo han transmitido la noticia. De ello se deriva una serie de incógnitas e incertidumbres que se ponen de relieve

Un texto inédito de Quevedo: "Memorial de don Francisco de Quevedo Villegas dado a la Inquisición General sobre los libros del Monte Santo de Granada"

This article presents an unknown and unpublished text written by Quevedo, the Memorial de don Francisco de Quevedo Villegas dado a la Inquisición General sobre los libros del Monte Santo de Granada, with an annotated edition and preceded by an introductory study. The study shows evidence for Quevedo’s authorship of the text and suggests an approximate date of composition. In the Memorial, Quevedo defends the fake nature of the texts and relics found in the Sacromonte de Granada and urges the Inquisition to burn them down instead of sending them to Rome for further examination, as Pope Urban VIII had requested. The text confirms Quevedo’s inclination to influence issues of government as well as his adhesion to Catholic orthodoxy and his aspiration to historiographical rigour.Este trabajo presenta un texto desconocido e inédito de Quevedo, el Memorial de don Francisco de Quevedo Villegas dado a la Inquisición General sobre los libros del Monte Santo de Granada, en una edición anotada y precedida de un estudio introductorio. El estudio determina la autoría de Quevedo y propone una fecha aproximada de composición. En el Memorial, Quevedo considera falsos los textos y reliquias encontrados en el Sacromonte granadino, y propone a la Inquisición que estos sean quemados ya en España y no enviados a Roma para su examen, como había solicitado el papa Urbano VIII. El memorial muestra la tendencia de Quevedo a influir en los asuntos de gobierno, así como su ortodoxia católica y su pretensión de rigor historiográfico

Dissecting Structural and Electrostatic Interactions of Charged Groups in α-Sarcin. An NMR Study of Some Mutants Involving the Catalytic Residues

The cytotoxic ribonuclease α-sarcin is the best characterized member of the ribotoxin family. Ribotoxins share a common structural core, catalytic residues, and active site topology with members of the broader family of nontoxic microbial extracellular RNases. They are, however, much more specific in their biological action. To shed light on the highly specific α-sarcin activity, we have evaluated the structural and electrostatic interactions of its charged groups, by combining the structural and pKa characterization by NMR of several variants with theoretical calculations based on the Tanford−Kirkwood and Poisson−Boltzmann models. The NMR data reveal that the global conformation of wild-type α-sarcin is preserved in the H50Q, E96Q, H137Q, and H50/137Q variants, and that His137 is involved in an H-bond that is crucial in maintaining the active site structure and in reinforcing the stability of the enzyme. The loss of this H-bond in the H137Q and H50/137Q variants modifies the local structure of the active site. The pKa values of active site groups H50, E96, and H137 in the four variants have been determined by two-dimensional NMR. The catalytic dyad of E96 and H137 is not sensitive to charge replacements, since their pKa values vary less than ±0.3 pH unit with respect to those of the wild type. On the contrary, the pKa of His50 undergoes drastic changes when compared to its value in the intact protein. These amount to an increase of 0.5 pH unit or a decrease of 1.1 pH units depending on whether a positive or negative charge is substituted at the active site. The main determinants of the pKa values of most of the charged groups in α-sarcin have been established by considering the NMR results in conjunction with those derived from theoretical pKa calculations. With regard to the active site residues, the H50 pKa is chiefly influenced by electrostatic interactions with E96 and H137, whereas the effect of the low dielectric constant and the interaction with R121 appear to be the main determinants of the altered pKa value of E96 and H137. Charge−charge interactions and an increased level of burial perturb the pKa values of the active site residues of α-sarcin, which can account for its reduced ribonucleolytic activity and its high specificity.This work was supported by Grants BIO2002-720 and BMC2000-0551 from the Ministerio de Ciencia y Tecnología and Educación y Cultura (Spain), respectively. M.F.G.-M. is the recipient of a fellowship from the Comunidad Autónoma de Madrid (CAM, Spain). J.M.P.-C. acknowledges the European Union and EMBO for support through their long-term postdoctoral fellowship programs

Prediction of long-term outcomes of HIV-infected patients developing non-AIDS events using a multistate approach

Outcomes of people living with HIV (PLWH) developing non-AIDS events (NAEs) remain poorly defined. We aimed to classify NAEs according to severity, and to describe clinical outcomes and prognostic factors after NAE occurrence using data from CoRIS, a large Spanish HIV cohort from 2004 to 2013. Prospective multicenter cohort study. Using a multistate approach we estimated 3 transition probabilities: from alive and NAE-free to alive and NAE-experienced ("NAE development"); from alive and NAE-experienced to death ("Death after NAE"); and from alive and NAE-free to death ("Death without NAE"). We analyzed the effect of different covariates, including demographic, immunologic and virologic data, on death or NAE development, based on estimates of hazard ratios (HR). We focused on the transition "Death after NAE". 8,789 PLWH were followed-up until death, cohort censoring or loss to follow-up. 792 first incident NAEs occurred in 9.01% PLWH (incidence rate 28.76; 95% confidence interval [CI], 26.80-30.84, per 1000 patient-years). 112 (14.14%) NAE-experienced PLWH and 240 (2.73%) NAE-free PLWH died. Adjusted HR for the transition "Death after NAE" was 12.1 (95%CI, 4.90-29.89). There was a graded increase in the adjusted HRs for mortality according to NAE severity category: HR (95%CI), 4.02 (2.45-6.57) for intermediate-severity; and 9.85 (5.45-17.81) for serious NAEs compared to low-severity NAEs. Male sex (HR 2.04; 95% CI, 1.11-3.84), ag