Editorial: Aging, neurogenesis and neuroinflammation in hearing loss and protection

Editorial.-- This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).This work was supported by Spanish grant from the Ministerio de Economía y Competitividad SAF2014-53979-R and European FP7-PEOPLE-IAPP-TARGEAR. The cost of this publication has been paid in part by FEDER funds.Peer Reviewe

El ámbito en la ciudad del topos y locus: el proyecto del paisaje interior

Ponencia presentada a Session 9: Forma urbana y relaciones entre historia y proyecto: el medio ambiente como patrimonio / Urban form and relationships between design and history: environmental heritage, arquitecture and planningRememoremos las ciudades que han sido los motores de la civilización. Desde las asirias y mesopotámicas, hoy dolorosamente destruidas, hasta las contemporáneas en plena construcción o ya consolidadas. Todas han tenido la necesidad de conocer y dominar su entorno ambiental y la necesidad de crear un ámbito natural en ellas. Este texto busca reflexionar sobre la necesidad, la posibilidad y la realidad de hacer proyectos de paisaje en relación con el medio ambiente. La experiencia ha motivado que sepamos elegir los lugares con capacidad para facilitar la supervivencia. La necesidad de tener agua y protección ha excluido geografías. Sin embargo, determinados flujos económicos del comercio, minerales y combustibles han generado asentamientos urbanos de gran influencia en enclaves de riesgo. El dominio de la tecnología ha permitido al hombre a lo largo de todas las épocas aventurarse e imponerse al medio en el que vive

Pushing the limits of concertedness. A waltz of wandering carbocations.

Among the array of complex terpene-forming carbocation cyclization/rearrangement reactions, the so-called "triple shift" reactions are among the most unexpected. Such reactions involve the asynchronous combination of three 1,n-shifts into a concerted process, e.g., a 1,2-alkyl shift followed by a 1,3-hydride shift followed by a second 1,2-alkyl shift. This type of reaction so far has been proposed to occur during the biosynthesis of diterpenes and the sidechains of sterols. Here we describe efforts to push the limits of concertedness in this type of carbocation reaction by designing, and characterizing with quantum chemical computations, systems that could couple additional 1,n-shift events to a triple shift leading, in principle to quadruple, pentuple, etc. shifts. While our designs did not lead to clear-cut examples of quadruple, etc. shifts, they did lead to reactions with surprisingly flat energy surfaces where more than five chemical events connect reactants and plausible products. Ab initio molecular dynamics simulations demonstrate that the formal minima on these surfaces interchange on short timescales, both with each other and with additional unexpected structures, allowing us a glimpse into a very complex manifold that allows ready access to great structural diversity

El asesinato para facilitar la comisión de otro delito o para evitar que se descubra: La propuesta de dos nuevas modalidades de asesinato en el Código Penal español

El 23 de septiembre de 2013 se remitió a las Cortes Generales el Proyecto de Reforma del Código Penal Español. Entre otras muchas modifi caciones, éste incluye dos nuevas modalidades de asesinato, consistentes en matar a otro (i) para facilitar la comisión de otro delito o (ii) para evitar que se descubra. En este trabajo se abordan tres grupos de problemas planteados por cada una de estas dos nuevas circunstancias de cualifi cación: problemas de interpretación, problemas de fundamentación y problemas concursales. Su estudio conduce a la conclusión de que la modifi cación carece de justifi cación tanto desde un punto dogmático como desde un punto de vista político-criminal, además de que adolece de serias difi cultades de aplicación. Por todo ello, sería preferible que no llegara a prosperarOn September 23rd, 2013, the Draft Bill on the Reform of the Spanish Criminal Code was submitted to Parliament. Among other changes, two new forms of murder are willing to be introduced, consisting in killing another human being (i) to facilitate the commission of another offence or (ii) to prevent its discovery. This paper addresses three groups of problems posed by each of these two new qualifying circumstances: problems of interpretation, problems of justifi - cation and, lastly, problems of double incrimination. The conclusion is reached that the planned reform is unnecessary both from a dogmatic and political point of view. Its application would furthermore be extremely diffi cult, making it all in all desirable for these two new forms of murder to be withdrawn from the Draf

The Gardens of the Alhambra and the Search for Spanish Modernism, 1953–75.

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Ceramide Kinase inhibition blocks IGF-1-mediated survival of otic neurosensory progenitors by impairing AKT phosphorylation

Sphingolipids are bioactive lipid components of cell membranes with important signal transduction functions in health and disease. Ceramide is the central building block for sphingolipid biosynthesis and is processed to form structurally and functionally distinct sphingolipids. Ceramide can be phosphorylated by ceramide kinase (CERK) to generate ceramide-1-phosphate, a cytoprotective signaling molecule that has been widely studied in multiple tissues and organs, including the developing otocyst. However, little is known about ceramide kinase regulation during inner ear development. Using chicken otocysts, we show that genes for CERK and other enzymes of ceramide metabolism are expressed during the early stages of inner ear development and that CERK is developmentally regulated at the otic vesicle stage. To explore its role in inner ear morphogenesis, we blocked CERK activity in organotypic cultures of otic vesicles with a specific inhibitor. Inhibition of CERK activity impaired proliferation and promoted apoptosis of epithelial otic progenitors. CERK inhibition also compromised neurogenesis of the acoustic-vestibular ganglion. Insulin-like growth factor-1 (IGF-1) is a key factor for proliferation, survival and differentiation in the chicken otocyst. CERK inhibition decreased IGF-1-induced AKT phosphorylation and blocked IGF-1-induced cell survival. Overall, our data suggest that CERK is activated as a central element in the network of anti-apoptotic pro-survival pathways elicited by IGF-1 during early inner ear development.This work was supported by the Spanish Ministerio de Economia y Competitividad, project FEDER/SAF2017-86107-R to IVN and MM.Peer reviewe

La importancia de plantear los objetivos de una forma graduada y no en su totalidad en un caso de depresión

The case study presented shows a 19-session psycotherapeutic intervention in a patient who suffered from severe depression. The intervention consisted of a mixture of several cognitive, behavioural and emotional techniques. Beck's cognitive model of depression was used as a theoretical frame work. This article points out the importance of having gradual goals instead of the global ones. The results show a great success after a 19-session-treatment as the therapeutic goals were achieved.ResumenEl estudio de caso único que se presenta consiste en la intervención psicoterapéutica durante diecinueve sesiones con una paciente que sufría una depresión grave. La intervención consistió en diversas técnicas cognitivas, conductuales y emocionales. Se ha utilizado como marco de referencia el modelo cognitivo de la depresión de Beck. En este artículo nos planteamos la importancia que tiene el entender los objetivos de una forma graduada y no en su totalidad. Los resultados ponen de manifiesto el éxito conseguido tras las 19 sesiones de tratamiento habiéndose conseguido cumplir los objetivos propuestos.AbstractThe case study presented shows a 19-session psycotherapeutic intervention in a patient who suffered from severe depression. The intervention consisted of a mixture of several cognitive, behavioural and emotional techniques. Beck's cognitive model of depression was used as a theoretical frame work. This article points out the importance of having gradual goals instead of the global ones. The results show a great success after a 19-session-treatment as the therapeutic goals were achieved

Lipoteichoic acid and molecular weight of hyaluronic acid could explain the late inflammatory response trigger by hyaluronic acid fillers

Introduction: Hyaluronic acid is a safe dermal filler, but sometimes late granuloma is generated. This adverse effect is an inflammatory process, and its causes are not clear. Late granuloma generation could be due to the reaction to residual components of the bacterial wall present into hyaluronic acid, such as lipoteichoic acid (LTA). Other possibility is hyaluronic acid degraded could be trigger this inflammatory reaction. // Objective: Study possible molecular mechanism that could be implicated into the late granuloma formation. We wonder whereas inflammatory response activation is triggered by lower molecular weight hyaluronic acid or Gram-positive bacterial components as LTA. // Methods: We analyzed one adverse case generated by hyaluronic acid injections. Our study with one nodule through chemical and immunofluorescence histologic technics. // Results: In this case, observe a late granuloma without infectious process. Histological analysis shown few large Langerhans cells around fillers and multiple immunological cells infiltrated. Immunofluorescent study shown immunological cells (CD45 positives cells) with high TLR2 expression (hyaluronic acid and LTA receptor). // Limitations: The difficulty of obtaining biopsy samples of nodules implies that the number of cases analyzed is very low. // Conclusion: New model is proposed in which weight of hyaluronic acid and LTA could be able to trigger inflammation. This process could be mediated by TLR2 expressed in infiltrated immune cells