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Este trabajo ha sido financiado por el proyecto de investigación del MICINN El autor bizantino III: metáfrasis, reescritura y recepción, AUTBIZIII (PID2019-105102GB-100), Se presenta en este artículo la primera edición de una breve colección de recetas recogidas en el manuscrito Città del Vaticano, Biblioteca Apostolica Vaticana, Vat. Urb. Gr. 67, un códice dedicado enteramente a Galeno y compuesto de dos partes bien diferenciadas. En su parte más antigua (ff. 53-275), datable hacia 1300, aparece esta colección de remedios de tradición galénica, que el copista ha añadido (ff. 186v-187v) para completar el cuaderno numerado iota zeta' (17) al final de la copia de Galeno, De compositione medicamentorum secundum locos., This article presents the first edition of a brief collection of recipes gathered in the manuscript Citta del Vaticano, Biblioteca Apostolica Vaticana, Vat. Urb. Gr. 67. This is a codex entirely dedicated to Galen and composed of two clearly differentiated parts. The collection of remedies from the Galenic tradition appears in the oldest part (ff. 53-275) of the codex, ca. 1300, and it has been added by the copyist (ff. 186v-187v) to complete the quire numbered iota zeta' (17) at the end of Galen's De compositione medicamentorum secundum locos., MICINN AUTBIZIII (PID2019-105102GB-100)

Dent disease 1; Cellular models Enfermedad de Dent 1; Modelos celulares Malaltia de Dent 1; Models cel·lulars Dent disease 1 (DD1) is a rare X-linked renal proximal tubulopathy characterized by low molecular weight proteinuria and variable degree of hypercalciuria, nephrocalcinosis and/or nephrolithiasis, progressing to chronic kidney disease. Although mutations in the electrogenic Cl−/H+ antiporter ClC-5, which impair endocytic uptake in proximal tubule cells, cause the disease, there is poor genotype–phenotype correlation and their contribution to proximal tubule dysfunction remains unclear. To further discover the mechanisms linking ClC-5 loss-of-function to proximal tubule dysfunction, we have generated novel DD1 cellular models depleted of ClC-5 and carrying ClC-5 mutants p.(Val523del), p.(Glu527Asp) and p.(Ile524Lys) using the human proximal tubule-derived RPTEC/TERT1 cell line. Our DD1 cellular models exhibit impaired albumin endocytosis, increased substrate adhesion and decreased collective migration, correlating with a less differentiated epithelial phenotype. Despite sharing functional features, these DD1 cell models exhibit different gene expression profiles, being p.(Val523del) ClC-5 the mutation showing the largest differences. Gene set enrichment analysis pointed to kidney development, anion homeostasis, organic acid transport, extracellular matrix organization and cell-migration biological processes as the most likely involved in DD1 pathophysiology. In conclusion, our results revealed the pathways linking ClC-5 mutations with tubular dysfunction and, importantly, provide new cellular models to further study DD1 pathophysiology. This work was supported in part by Asdent Patients Association and grants from Ministerio de Ciencia e Innovación (SAF201459945-R and SAF201789989-R to A.M.), the Fundación Senefro (SEN2019 to A.M.) and Red de Investigación Renal REDinREN (12/0021/0013). A.M. group holds the Quality Mention from the Generalitat de Catalunya (2017 SGR).

Baseline mucin secretion (BMS) is independent of external agonists and controlled by a small calcium binding protein named KChIP3. KChIP3 hosting mucin granules are not released until intracellular cytosolic calcium oscillations reach a threshold, KChIP3 binds calcium and detaches from granules, allowing their fusion to plasma membrane. Loss of KChIP3 or blocking its membrane attachment causes mucin hypersecretion. How is KChIP3 recruited to mucin granules? We show here that zDHHC (aspartate-histidine-histidine-cysteine motif in a cysteine-rich, zinc finger like domain) S-acyl-transferase dependent palmitoylation modulates binding of KChIP3 to mucin granules thereby affecting mucin secretion. We have found that inhibiting zDHHC-mediated palmitoylation in differentiated HT29-18N2, which express the Golgi-localized zDHHC3 and zDHHC4, releases KChIP3 from mucin granules and increases baseline mucin secretion. Mutation of the palmitoylation sites in KChIP3 (Cysteines 122 and 123 to Alanine) quantitatively reduces its attachment to mucin granules. Expression of KChIP3 WT in HT29-18N2 cell lines stably depleted of KChIP3 inhibits mucin secretion, whereas expression of non palmitoylated KChIP3 (KChIP3 AA) only partially rescues the effect of KChIP3 depletion and the cells maintain higher levels of baseline secretion compared to KChIP3-WT cells. Altogether, our data suggest that zDHHC3 or zDHHC4 dependent palmitoylation is involved in KChIP3 recruitment to mucin granules to control the baseline mucin secretion.

Restoration of kidney tubular epithelium following sublethal injury sequentially involves partial epithelial–mesenchymal transition (pEMT), proliferation, and further redifferentiation into specialized tubule epithelial cells (TECs). Because the immunosuppressant cyclosporine-A produces pEMT in TECs and inhibits the peptidyl-prolyl isomerase (PPIase) activity of cyclophilin (Cyp) proteins, we hypothesized that cyclophilins could regulate TEC phenotype. Here we demonstrate that in cultured TECs, CypA silencing triggers loss of epithelial features and enhances transforming growth factor β (TGFβ)-induced EMT in association with upregulation of epithelial repressors Slug and Snail. This pro-epithelial action of CypA relies on its PPIase activity. By contrast, CypB emerges as an epithelial repressor, because CypB silencing promotes epithelial differentiation, prevents TGFβ-induced EMT, and induces tubular structures in 3D cultures. In addition, in the kidneys of CypB knockout mice subjected to unilateral ureteral obstruction, inflammatory and pro-fibrotic events were attenuated. CypB silencing/knockout leads to Slug, but not Snail, downregulation. CypB support of Slug expression depends on its endoplasmic reticulum location, where it interacts with calreticulin, a calcium-buffering chaperone related to Slug expression. As CypB silencing reduces ionomycin-induced calcium release and Slug upregulation, we suggest that Slug expression may rely on CypB modulation of calreticulin-dependent calcium signaling. In conclusion, this work uncovers new roles for CypA and CypB in modulating TEC plasticity and identifies CypB as a druggable target potentially relevant in promoting kidney repair., Graphical abstract

This chapter is a didactic proposal for the teaching of Ancient Greek language and literature under an innovative and interdisciplinary approach. The history of teaching Ancient Greek shows different language acquisition methods that respond to the demands of their times, each of them with its advantages and disadvantages. The author combines diverse approaches to offer a new method for beginners in which students get involved in a stimulating practice that enables them to progress at the rhythm of their choice. The teaching materials are focused on real texts of Ancient Greek literature that work as starting point for an innovative and challenging language teaching for specific purposes approach. The final goal is to achieve student learning of Ancient Greek language through contextualized literary texts in order to get a better understanding of what Ancient Greek culture meant and why it has survived until today.

The identity and relevance of the ectomycorrhizal (ECM) fungal partners of Eucalyptus globulus was investigated in NW Spain, to detect which symbionts mainly support its invasiveness. Root tips of E. globulus and of three common native plant species (Quercus robur, Pinus pinaster and Halimium lasianthum) were collected in eucalypt plantations, Q. robur forests, P. pinaster plantations and shrublands. Fungal taxonomical identity was ascertained by use of rDNA and direct sequencing. We studied diversity, composition and colonization rate of the ECM fungal communities of E. globulus to determine if fungal assemblages are host specific (i.e. similar in different habitats) or more dependent on the neighbourhood context. We also identified the type of associations formed (i.e. co-introductions, familiar or novel associations). Twenty-six ECM taxa were associated with E. globulus. Most of them engaged in novel associations with eucalypts, whereas only three fungal species were co-introduced Australian aliens. Eucalypt fungal richness, diversity and colonization rate differed between habitats, being higher in native oak forests, whereas in shrublands E. globulus showed the lowest colonization rate and diversity. The Australian fungus Descolea maculata dominated the eucalypt fungal assemblage and also spread to the native host plants, in all the habitats, posing the risk of further co-invasion.

Cyclophilins (Cyp) are peptidil-prolyl-isomerases and the intracellular receptors for the immunosuppressant Cyclosporine-A (CsA), which produces epithelial-mesenchymal-transition (EMT) and renal tubule-interstitial fibrosis. Since CsA inhibits Cyp enzymatic activity, we hypothesized that Cyp could be involved in EMT and fibrosis. Here, we demonstrate that CypB is a critical regulator of tubule epithelial cell plasticity on the basis that: i) CypB silencing caused epithelial differentiation in proximal tubule-derived HK-2 cells, ii) CypB silencing prevented TGFβ-induced EMT in HK-2, and iii) CypB knockdown mice exhibited reduced UUO-induced inflammation and kidney fibrosis. By contrast, silencing of CypA induces a more undifferentiated phenotype and favors TGFβ effects. EMT mediators Slug and Snail were up-regulated in CypA-silenced cells, while in CypB silencing, Slug, but not Snail, was down-regulated; thus, reinforcing the role of Slug in kidney fibrosis. CypA regulates Slug through its PPIase activity whereas CypB depends on its ER location, where interacts with calreticulin, a calcium modulator which is involved in TGFβ signaling. In conclusion, this work uncovers new roles for CypA and CypB in modulating proximal tubular cell plasticity.

Res_eng:In this paper we compare the description of the legend of Arion and the Dolphin in Herodotus and Plutarch’s works in aim to elucidate the level of dependence of the latter from the former: Plutarch presents a more fi ctional version with particular additions and deletions in order to adapt the legend to his own convictions and probably to remake different Delphic themes.

Las mujeres en los Idilios de Teócrito es un viaje emocionante por el antiguo mundo de lo femenino a través de la mirada de su autor, poeta helenístico del s. III a. C. Gracias al análisis exhaustivo y a la vez lleno de sensibilidad que hace la investigadora de este aspecto de la obra de Teócrito, desmenuzando cada detalle y revelando los secretos escondidos detrás de cada verso y en cada palabra, descubriremos nuevas y sorprendentes conclusiones que alcanzan incluso a la propia personalidad del autor. Y todo ello en un lenguaje sencillo y ameno, apto tanto para el público iniciado como quien desee introducirse en la idea que se tenía de la mujer en la Antigüedad, de sus sentimientos y de su papel en el conjunto de la sociedad.

This work presents a Bayesian approach for estimating the reliability of a parallel multi-component system. It is assumed that the strengths of the components are independent random variables, which are subjected to a common stress with the same distribution. It is supposed that the failure times follow exponential and Weibull distributions, respectively. The Bayesian analysis is developed assuming a highly informative prior and a less informative prior distribution, respectively. A simulation based on certain data sets is used to study the performance of the Bayesian solutions. The solutions are computed by Markov Chain Monte Carlo (MCMC) methods. Finally, some observations are made in relation to the maximum likelihood method and some extensions are discussed.