Retablo mayor de la iglesia del Hospital de la Caridad. Investigación e intervención

A partir de las investigaciones y estudios preliminares recogidos en el proyecto inicial que se realizó en el Instituto Andaluz del Patrimonio Histórico, la restauración del retablo mayor de la iglesia del Hospital de la Santa Caridad de Sevilla corrió a cargo de la Dirección General de Bienes Culturales de la Junta de Andalucía, bajo la tutela del Proyecto de estudio, investigación y propuesta de intervención del retablo mayor de la iglesia de San Jorge del Hospital de la Caridad. La fase de intervención, iniciada en enero de 2006, ha supuesto para este retablo la oportunidad de profundizar en el estudio de su materialidad, mediante los análisis científicos de caracterización de materiales y la actualización de los datos histórico-artísticos y de historia material. Por otra parte, los tratamientos aplicados garantizarán la adecuada conservación de su arquitectura y esculturas en el futuro, contribuyendo de forma significativa a la recuperación de los valores históricos y artísticos de este magnífico retablo

Muscle-Type Nicotinic Receptor Blockade by Diethylamine, the Hydrophilic Moiety of Lidocaine

Lidocaine bears in its structure both an aromatic ring and a terminal amine, which can be protonated at physiological pH, linked by an amide group. Since lidocaine causes multiple inhibitory actions on nicotinic acetylcholine receptors (nAChRs), this work was aimed to determine the inhibitory effects of diethylamine (DEA), a small molecule resembling the hydrophilic moiety of lidocaine, on Torpedo marmorata nAChRs microtransplanted to Xenopus oocytes. Similarly to lidocaine, DEA reversibly blocked acetylcholine-elicited currents (IACh) in a dose-dependent manner (IC50 close to 70 μM), but unlike lidocaine, DEA did not affect IACh desensitization. IACh inhibition by DEA was more pronounced at negative potentials, suggesting an open-channel blockade of nAChRs, although roughly 30% inhibition persisted at positive potentials, indicating additional binding sites outside the pore. DEA block of nAChRs in the resting state (closed channel) was confirmed by the enhanced IACh inhibition when pre-applying DEA before its co-application with ACh, as compared with solely DEA and ACh co-application. Virtual docking assays provide a plausible explanation to the experimental observations in terms of the involvement of different sets of drug binding sites. So, at the nAChR transmembrane (TM) domain, DEA and lidocaine shared binding sites within the channel pore, giving support to their open-channel blockade; besides, lidocaine, but not DEA, interacted with residues at cavities among the M1, M2, M3, and M4 segments of each subunit and also at intersubunit crevices. At the extracellular (EC) domain, DEA and lidocaine binding sites were broadly distributed, which aids to explain the closed channel blockade observed. Interestingly, some DEA clusters were located at the α-γ interphase of the EC domain, in a cavity near the orthosteric binding site pocket; by contrast, lidocaine contacted with all α-subunit loops conforming the ACh binding site, both in α-γ and α-δ and interphases, likely because of its larger size. Together, these results indicate that DEA mimics some, but not all, inhibitory actions of lidocaine on nAChRs and that even this small polar molecule acts by different mechanisms on this receptor. The presented results contribute to a better understanding of the structural determinants of nAChR modulation.This work was supported by grants BFU2012-31359, BFU2012-39092-C02-01, BFU2011-25920, and CSD2008-00005 from the MINECO and PROMETEO/2014/11 from GVA (Spain)

On Some Sampling-Related Frames in U-Invariant Spaces

This paper is concerned with the characterization as frames of some sequences in -invariant spaces of a separable Hilbert space H where U denotes an unitary operator defined on H ; besides, the dual frames having the same form are also found. This general setting includes, in particular, shift-invariant or modulation-invariant subspaces in L2(R) , where these frames are intimately related to the generalized sampling problem. We also deal with some related perturbation problems. In doing so, we need the unitary operator to belong to a continuous group of unitary operators

Coercive and anisotropy fields in patterned amorphous FeSi submicrometric structures

Amorphous FexSi12x films have been prepared on Si substrates in order to fabricate submicrometric magnetic structures with soft magnetic behavior. The magnetic properties compositional dependence of the unpatterned samples has been analyzed to select the Fe content (x50.7) with the lowest coercive and anisotropy fields values. Arrays of Fe0.7Si0.3 lines have been fabricated by electron beam lithography combined with a liftoff technique, with typical dimensions of 200 nm linewidth and 1 mm line spacing. These arrays present coercive fields parallel to the line direction as small as 9 Oe.Peer reviewe

GD3 synthase overexpression sensitizes hepatocarcinoma cells to hypoxia and reduces tumor growth by suppressing the cSrc/NF-κB survival pathway

This is an open-access article distributed under the terms of the Creative Commons Attribution License.[Background]: Hypoxia-mediated HIF-1a stabilization and NF-kB activation play a key role in carcinogenesis by fostering cancer cell survival, angiogenesis and tumor invasion. Gangliosides are integral components of biological membranes with an increasingly recognized role as signaling intermediates. In particular, ganglioside GD3 has been characterized as a proapoptotic lipid effector by promoting cell death signaling and suppression of survival pathways. Thus, our aim was to analyze the role of GD3 in hypoxia susceptibility of epatocarcinoma cells and in vivo tumor growth.[Methodology/Principal Findings]: We generated and characterized a human hepatocarcinoma cell line stably expressing GD3 synthase (Hep3B-GD3), which catalyzes the synthesis of GD3 from GM3. Despite increased GD3 levels (2–3 fold), no significant changes in cell morphology or growth were observed in Hep3B-GD3 cells compared to wild type Hep3B cells under normoxia. However, exposure of Hep3B-GD3 cells to hypoxia (2% O2) enhanced reactive oxygen species (ROS) generation, resulting in decreased cell survival, with similar findings observed in Hep3B cells exposed to increasing doses of exogenous GD3. In addition, hypoxia-induced c-Src phosphorylation at tyrosine residues, NF-kB activation and subsequent expression of Mn-SOD were observed in Hep3B cells but not in Hep3B-GD3 cells. Moreover, MnTBAP, an antioxidant with predominant SOD mimetic activity, reduced ROS generation, protecting Hep3B-GD3 cells from hypoxia-induced death. Finally, lower tumor growth, higher cell death and reduced Mn-SOD expression were observed in Hep3B-GD3 compared to Hep3B tumor xenografts.[Conclusion]: These findings underscore a role for GD3 in hypoxia susceptibility by disabling the c-Src/NF-kB survival pathway resulting in lower Mn-SOD expression, which may be of relevance in hepatocellular carcinoma therapy.Grant support: CIBEREHD and grants FIS06/0395, FIS07/1039, SAF2006-06789 and SAF2008-02199 by Instituto de Salud Carlos III and Ministry of Science and Innovation from Spain, and from the Research Center for Liver and Pancreatic Diseases, P50-AA-11999 funded by the US National Institute on Alcohol Abuse and Alcoholism.Peer reviewe

Mechanisms of Blockade of the Muscle-Type Nicotinic Receptor by Benzocaine, a Permanently Uncharged Local Anesthetic

Most local anesthetics (LAs) are amine compounds bearing one or several phenolic rings. Many of them are protonated at physiological pH, but benzocaine (Bzc) is permanently uncharged, which is relevant because the effects of LAs on nicotinic acetylcholine (ACh) receptors (nAChRs) depend on their presence as uncharged or protonated species. The aims of this study were to assess the effects of Bzc on nAChRs and to correlate them with its binding to putative interacting sites on this receptor. nAChRs from Torpedo electroplaques were microtransplanted to Xenopus oocytes and currents elicited by ACh (IAChs), either alone or together with Bzc, were recorded at different potentials. Co-application of ACh with increasing concentrations of Bzc showed that Bzc reversibly blocked nAChRs. IACh inhibition by Bzc was voltage-independent, but the IACh rebound elicited when rinsing Bzc suggests an open-channel blockade. Besides, ACh and Bzc co-application enhanced nAChR desensitization. When Bzc was just pre-applied it also inhibited IACh, by blocking closed (resting) nAChRs. This blockade slowed down the kinetics of both the IACh activation and the recovery from blockade. The electrophysiological results indicate that Bzc effects on nAChRs are similar to those of 2,6-dimethylaniline, an analogue of the hydrophobic moiety of lidocaine. Furthermore, docking assays on models of the nAChR revealed that Bzc and DMA binding sites on nAChRs overlap fairly well. These results demonstrate that Bzc inhibits nAChRs by multiple mechanisms and contribute to better understanding both the modulation of nAChRs and how LAs elicit some of their clinical side effects.This work was supported by grants BFU2012-31359, BFU2015-66612-P, SAF2015-66275-C2-1-R and SAF2017-82977-P (AEI/FEDER, UE) from MINECO, PROMETEO/2014/11 from Generalitat Valenciana (Spain) and GRE17-01 from Universidad de Alicante. R.C. held a predoctoral fellowship from Universidad de Alicante (FPUUA36) and M.N. a predoctoral industrial fellowship from Ministerio de Economía, Industria y Competitividad (DI-16-08303)

Durum and Bread Wheat Flours. Preliminary Mineral Characterization and Its Potential Health Claims

Wheat is one of the most important cereals in terms of its role in the human diet. The distribution of the nutrients in wheat grains depends largely on their morphology, the bran fraction being the richest in minerals, thus developing important functions related to human health. The main purpose of this study was to point out the potential nutritional and health claims related to the mineral composition based on the current European legislation in order to valorize the interesting wheat varieties traditionally consumed in Spain. The mineral composition (microelements: Fe, Cu, Mn, and Zn; and macrolements: Ca, Mg, Na, and K) were evaluated in different milling fractions (white flour, whole grain flour, and bran fraction) of 4 wheat varieties of durum (Triticum turgidum ssp. durum Linnaeus) and bread (Triticum aestivum Linnaeus) wheat. As expected, the mineral concentration was higher in the case of bran and whole grain flour, K and Mg being the principal minerals found. A difference between wheat genotype and harvesting year have been found. Moreover, regarding these preliminary results, some samples analysed in the present study met the conditions of use of different approved health claims that could support the possibility to consider wheat flours, especially whole grain flour and bran fraction as functional foods, but some did not.Depto. de Nutrición y Ciencia de los AlimentosFac. de FarmaciaTRUESpanish Ministry of Science and Technology (project reference AGL2012-38345)ALIMNOVA research group (UCM 252/2017)pu