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Skeletal muscle is more resilient to ischemia-reperfusion injury than other organs. Tissue specific post-translational modifications of cytochrome c (Cytc) are involved in ischemia-reperfusion injury by regulating mitochondrial respiration and apoptosis. Here, we describe an acetylation site of Cytc, lysine 39 (K39), which was mapped in ischemic porcine skeletal muscle and removed by sirtuin5 in vitro. Using purified protein and cellular double knockout models, we show that K39 acetylation and acetylmimetic K39Q replacement increases cytochrome c oxidase (COX) activity and ROS scavenging while inhibiting apoptosis via decreased binding to Apaf-1, caspase cleavage and activity, and cardiolipin peroxidase activity. These results are discussed with X-ray crystallography structures of K39 acetylated (1.50 Å) and acetylmimetic K39Q Cytc (1.36 Å) and NMR dynamics. We propose that K39 acetylation is an adaptive response that controls electron transport chain flux, allowing skeletal muscle to meet heightened energy demand while simultaneously providing the tissue with robust resilience to ischemia-reperfusion injury.

Surprising violations of outcome expectancies have long been known to enhance the associability of Pavlovian cues; that is, the rate at which the cue enters into further associations. The adaptive value of such enhancements resides in promoting new learning in the face of uncertainty. However, it is unclear whether associability enhancements reflect increased associative plasticity within a particular behavior system, or whether they can facilitate learning between a cue and any arbitrary outcome, as suggested by attentional models of conditioning. Here, we show evidence consistent with the latter hypothesis. Violating the outcome expectancies generated by a cue in an appetitive setting (feeding behavior system) facilitated subsequent learning about the cue in an aversive setting (defense behavior system). In addition to shedding light on the nature of associability enhancements, our findings offer the neuroscientist a behavioral tool to dissociate their neural substrates from those of other, behavior system- or valence-specific changes. Moreover, our results present an opportunity to utilize associability enhancements to the advantage of counterconditioning procedures in therapeutic contexts.

Post-translational modifications frequently modulate protein functions. Lysine acetylation in particular plays a key role in interactions between respiratory cytochrome c and its metabolic partners. To date, in vivo acetylation of lysines at positions 8 and 53 has specifically been identified in mammalian cytochrome c, but little is known about the structural basis of acetylation-induced functional changes. Here, we independently replaced these two residues in recombinant human cytochrome c with glutamine to mimic lysine acetylation and then characterized the structure and function of the resulting K8Q and K53Q mutants. We found that the physicochemical features were mostly unchanged in the two acetyl-mimetic mutants, but their thermal stability was significantly altered. NMR chemical shift perturbations of the backbone amide resonances revealed local structural changes, and the thermodynamics and kinetics of electron transfer in mutants immobilized on gold electrodes showed an increase in both protein dynamics and solvent involvement in the redox process. We also observed that the K8Q (but not the K53Q) mutation slightly increased the binding affinity of cytochrome c to its physiological electron donor, cytochrome c1—which is a component of mitochondrial complex III, or cytochrome bc1—thus suggesting that Lys8 (but not Lys53) is located in the interaction area. Finally, the K8Q and K53Q mutants exhibited reduced efficiency as electron donors to complex IV, or cytochrome c oxidase

Instrumental conditioning involves two different processes: Goal-directed behavior, characterized by its dependence on the causal relationship between action and outcome and the sensitivity of actions to changes in the value of the outcome; and habits, characterized for its persistence and insensitivity to changes after conditioning. It is known that the dopaminergic system is involved in both kind of learning. The present experiments analyzed two animal models of Parkinson's disease. The 6-OHDA model causes selective damage of the catecholaminergic neurons, specifically affecting the dopaminergic neurons in nigro-striatal system. This model simulates degenerative process symptomatology of Parkinson's disease. On the other hand, the LPS model generates an inflammation process in the infusion area. This model simulates the early symptoms of this disorder, including neuroinflammation and microglia activation. In order to validate both parkinsonian models, we studied if 6-OHDA and LPS models cause the same behavioral effects. The results showed that the 6-OHDA model interfered with the process involved in habit formation. In contrast, animals treated with LPS showed a goal-directed learning deficit. Differences between these models could be due to the different effects on Substantia Nigra neurons. 6-OHDA model might disrupt the nigrostriatal pathway, while LPS could interfere on efferences and afferences to Substantia Nigra.

Mitochondria are the powerhouses of the cell, whilst their malfunction is related to several human pathologies, including neurodegenerative diseases, cardiovascular diseases, and various types of cancer. In mitochondrial metabolism, cytochrome c is a small soluble heme protein that acts as an essential redox carrier in the respiratory electron transport chain. However, cytochrome c is likewise an essential protein in the cytoplasm acting as an activator of programmed cell death. Such a dual role of cytochrome c in cell life and death is indeed fine-regulated by a wide variety of protein post-translational modifications. In this work, we show how these modifications can alter cytochrome c structure and functionality, thus emerging as a control mechanism of cell metabolism but also as a key element in development and prevention of pathologies.

Increasing the thermal stability of immobilized proteins is a motivating goal for improving the performance of electrochemical biodevices. In this work, we propose the immobilization of crosslinked plastocyanin from the thermophilic cyanobacterium Phormidium laminosum by simultaneous incubation of a mixture of plastocyanin and the coupling reagents. The thermal stability of the so built covalently immobilized protein films has been assessed by cyclic voltammetry in the 0–90 °C temperature range and has been compared to that of physisorbed films. It is shown that the protein loss along a thermal cycle is significantly reduced in the case of the crosslinked films, whose redox properties remain unaltered along a cyclic heating-cooling thermal scan, and can withstand the contact with 70 °C solutions for four hours. Comparison of thermal unfolding curves obtained by circular dichroism spectroscopy of both free and crosslinked protein confirms the improved thermic resistance of the crosslinked plastocyanin. Notably, the electron transfer thermodynamics of physisorbed and crosslinked plastocyanin films are quite similar, suggesting that the formation of intra- and inter-protein amide bonds do not affect the integrity and functionality of the copper redox centers. UV–Vis absorption and circular dichroism measurements corroborate that protein crosslinking does not alter the coordination geometry of the metal center.

Nuestra propuesta de trabajo tiene como objetivo analizar el actual aprovechamiento turístico de la antigua vía férrea Agost-Alcoy (iniciada en 1926), a través de los 2 tramos de vía verde que hay rehabilitados; La Vía Verde del Maigmó que se extiende por los términos de Agost, Petrer y Tibi con un total de 22,5 km. y está gestionada por la Diputación de Alicante y la Vía Verde de Alcoy con 10,5 km. gestionada por el Ayuntamiento de Alcoy, ambos tramos de vía suman 33 km. y pertenecían al mismo trazado ferroviario que quedó en desuso. Tanto la Vía del Maigmó como la de Alcoy se restauraron como “Vías Verdes” hace poco más de una década y actualmente quedan por acondicionar otros 33 km. de toda la parte central para completar los 66 km. de vía original y de los que forma parte los municipios de Tibi, Castalla e Ibi. La posible recuperación integral de todo el trazado vertebraría el territorio de la costa hacia el interior, siendo un eje estratégico en la provincia donde se podría desarrollar un turismo de calidad y promovería los valores históricos, culturales, paisajísticos y medioambientales, así como motivaría la participación de las comunidades locales implicadas en la reivindicación, restauración y mantenimiento de una marca “Vías Verdes” que está muy consolidada tanto en España como en Europa, cuya misión principal es la sostenibilidad y la innovación social., Our work proposal aims to analyze the current tourism development of the old railroad Agost - Alcoy (started in 1926), through the two sections of greenway that have been rehabilitated; The Greenway of Maigmó that extends to Agost, Petrer and Tibi with a total of 22.5 km. and it is managed by the Provincial Council of Alicante and the Greenway of Alcoy is 10.5 km and is managed by the town hall of Alcoy. Both railroads add up to 33 km and they belonged to the same railway line that fell into disuse. Both the Maigmó line as Alcoy were restored as “Greenways” a little more than a decade ago and currently remain to put another 33 km. to the entire center to complete the 66 km of the original line and of the ones that form part of the municipals of Tibi, Castalla and Ibi. The possible full recovery of the entire layout would structure the territory of the coast inland, being a strategic area in the province where they could develop quality tourism and promote the historical, cultural, scenic and environmental values and motivate participation of local communities involved in the claim, restoration and maintenance of the brand “Greenways” is well established both in Spain and in Europe, whose main mission is sustainability and social innovation.

Consulta en la Biblioteca ETSI Industriales (7601), [ES] Los métodos para la identificación, análisis y evaluación de riesgos son una herramienta muy valiosa para abordar con decisión su detección, causa y consecuencias que puedan acarrear, con la finalidad de eliminar o atenuar los propios riesgos así como limitar sus consecuencias, en el caso de no poder eliminarlos. En este proyecto se lleva a cabo el estudio de los escenarios accidentales y el riesgo asociado al almacenamiento y despacho de una planta de gas Butano, tomándose como referencia los criterios establecidos en el Real Decreto 1254/1999 y los que se establecen en la Directriz Básica para la elaboración y homologación de los planes especiales del sector Químico.

New realities have arisen in our world such as electronic trade via Internet, videoconferences, telemedicine or digital platforms.Our way of acting has been changing with them, for it changes our way of working, our way of enjoying ourselves, our way ofrelating and our way of learning. Elderly people can not be kept apart from this evolving movement; thus, they must also learn withthe new technologies. Throughout this report, we have intended to defend a position that advocates that getting older is living andthat pedagogy will never say no to man's ability to be educated in any given stage of life. In this article, we will have the opportunityto express as clearly and amply as possible, some ideas regarding the association of elderly people and Internet., Nous assistons aujourd'hui à une profusion remarquable des nouvelles réalités mondiales telles que le commerce électronique àtravers Internet, visioconférences, télé médecine ou plates-formes numériques. Ces phénomènes changent nos comportementsdans la mesure où ils affectent nos modes de travail, nos loisirs, nos relations et nos manières d'apprendre. Les personnes âgéesne peuvent rester à l'écart de cette évolution, elles doivent s'approprier des nouvelles technologies pour l'apprentissage.Ce texte vise la défense d'une prise de position dont la devise est « vieillir c'est aussi vivre » et que la pédagogie ne dira jamaisnon à l'éducabilité de l'homme à n'importe quel âge de sa vie. L'article présente de façon plus claire et large nos idées sur la relationdes personnes âgées avec Internet., En nuestro mundo han surgido nuevas realidades como el comercio electrónico a través de internet, las videoconferencias, latelemedicina o las plataformas digitales. Con ellas está cambiando nuestra manera de actuar, pues cambia nuestro modo de trabajarde divertirnos, de relacionarnos y de aprender. Las personas mayores no pueden quedar al margen de este movimiento enevolución; por ello han de aprender también con las nuevas tecnologías. A lo largo de este trabajo hemos querido defender unapostura que propugna que envejecer es vivir y que la pedagogía jamás dará un no a la educabilidad del hombre cualquiera que sea la etapa de su vida. En el presente artículo tendremos la oportunidad de expresar, lo más claro y ampliamente posible, unas ideasen torno a la relación de los mayores con internet.